Tokushima University / Educator and Researcher Directory --- Funaki, Makoto

Personal Web Page

https://researchmap.jp/makotofunaki (researchmap)

Field of Study

○	Diabetology, Metabolic Syndrome, Regenerative Medicine, Tissue Engineering, Cell Biomechanics

Subject of Study

○	Epidemiological study to elucidate a linkage between life style and metabolic diseases, Signal transduction that leads to metabolic disorder, Mechanical signal transduction that regulates cellular functions

Book / Paper

Book:

1.	Yosuke Shikama, Naozumi Ishimaru, Yasusei Kudo, Rieko Arakaki, Yukiko Bandou, Nanako Aki and Makoto Funaki : High Levels of Saturated Fatty Acids may Exacerbate the Pathogenesis of Primary Sjögrens Syndrome, Springer, Dec. 2014.

Academic Paper (Judged Full Paper):

1.	吉川紘平, 金子遥祐, 辻誠士郎, 河田沙紀, 川原綾香, 森建介, 遠藤ふうり, Tomoyo Hara, Kiyoe Kurahashi, Sumiko Yoshida, Akio Kuroda, 明比祐子, Itsuro Endo, Makoto Funaki, Seiji Fukumoto, Masahiro Abe and Munehide Matsuhisa : TIA様症状を契機に診断されたインスリノーマの1例, Shikoku Acta Medica, Vol.77, No.5-6, 275-280, 2021. (Summary) We report the case of a67-year-old woman who had symptoms suggestive of a transient ischemic attack(TIA), such as lightheadedness and transient visual changes before meals for 4 months. She experienced altered consciousness before lunch and was taken to the emergency room2weeks ago. She had repeated hypoglycemia with a blood glucose level of 31 mg/dL. Insulin secretion was not suppressed, with an immunoreactive insulin level of 14．0 μU/mL and connecting peptide immunoreactivity of 1．83 ng/mL for occasional blood glucose levels of 49 mg/dL. Dynamic CT revealed a 17‐mm mass enhanced during the arterial phase in the pancreatic uncinate process, suggestive of a pancreatic neuroendocrine tumor. A selective arterial secretagogue(calcium)injection test revealed the localization of insulinoma in the head of the pancreas. Therefore, pancreatoduodenectomy was performed. Hyperglycemia occurred after the surgery, and it was judged that the insulinoma was resected. This case showed TIA-like symptoms without signs of sympathetic overdrive associated with hypoglycemia. Thus, the diagnosis was delayed. Insulinoma may present with symptoms of neuroglycopenia but not autonomic activity due to hypoglycemia. Insulinoma should be distinguished in patients with unknown neurological symptoms since neuroglycopenia caused by insulinoma is diverse. (Keyword) Insulinoma / Hypoglycemia / Neuroglycopenia / Transient ischemic attack (Tokushima University Institutional Repository) ● Metadata: 116831 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1050855112792865536 (Tokushima University Institutional Repository: 116831, CiNii: 1050855112792865536)
2.	Yumi Kuwamura, Sumiko Yoshida, Kiyoe Kurahashi, 澄川真珠子, Eijiro Sakamoto, Akio Kuroda, Ken-ichi Aihara, Makoto Funaki, Hiromichi Yumoto, Hirokazu Uemura, 岡本美鈴, 大和光, Munehide Matsuhisa, Itsuro Endo and Sachi Kishida : 糖尿病患者の口腔保健行動アセスメントツールを用いた看護支援プログラムの評価, Journal of the The Japan Diabetes Society, Vol.63, No.Supplement, S117, 2020. (Keyword) diabetes mellitus / oral health behaviors / assessment / 看護支援
3.	Toshihiro Watanabe, Yuki Fujimoto, Aya Morimoto, Mai Nishiyama, Akinori Kawai, Seiki Okada, Motohiro Aiba, Tomoharu Kawano, Mina Kawahigashi, Masashi Ishizu, Hiroyasu Mori, Munehide Matsuhisa, Akiko Hata, Makoto Funaki and Seiichi Hashida : Development of fully automated and ultrasensitive assays for urinary adiponectin and their application as novel biomarkers for diabetic kidney disease., Scientific Reports, Vol.10, No.1, 15869, 2020. (Summary) Glomerular filtration rate (GFR) and urinary albumin excretion rate (UAER) are used to diagnose and classify the severity of chronic kidney disease. Total adiponectin (T-AN) and high molecular weight adiponectin (H-AN) assays were developed using the fully automated immunoassay system, HI-1000 and their significance over conventional biomarkers were investigated. The T-AN and H-AN assays had high reproducibility, good linearity, and sufficient sensitivity to detect trace amounts of adiponectin in the urine. Urine samples after gel filtration were analyzed for the presence of different molecular isoforms. Low molecular weight (LMW) forms and monomers were the major components (93%) of adiponectin in the urine from a diabetic patient with normoalbuminuria. Urine from a microalbuminuria patient contained both high molecular weight (HMW) (11%) and middle molecular weight (MMW) (28%) adiponectin, although the LMW level was still high (52%). The amount of HMW (32%) and MMW (42%) were more abundant than that of LMW (24%) in a diabetic patient with macroalbuminuria. T-AN (r = - 0.43) and H-AN (r = - 0.38) levels showed higher correlation with estimated GFR (eGFR) than UAER (r = - 0.23). Urinary levels of both T-AN and H-AN negatively correlated with renal function in diabetic patients and they may serve as new biomarkers for diabetic kidney disease. (Tokushima University Institutional Repository) ● Metadata: 115617 (Link to Publication Site) ● Publication site (DOI): 10.1038/s41598-020-72494-6 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32985540 ● Search Scopus @ Elsevier (PMID): 32985540 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-020-72494-6 (Tokushima University Institutional Repository: 115617, DOI: 10.1038/s41598-020-72494-6, PubMed: 32985540)
4.	Mariko Nakamoto, Yuna Yun, Mariko Omine, Sarasa Mori, Emi Shuto, Akiko Nakamoto, Akiko Hata, Nanako Aki, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Ayako Tamura, Yumi Kuwamura, Makoto Funaki and Tohru Sakai : Dietary diversity and characteristics of lifestyle and awareness of health in Japanese workers:a cross-sectional study., The Journal of Medical Investigation : JMI, Vol.67, No.3.4, 255-264, 2020. (Summary) The aim of this study was to clarify the characteristics of lifestyle and health awareness according to dietary diversity in a Japanese worksite population. The participants were 1,312 men and women aged 20 to 63 years who were living in Tokushima Prefecture, Japan during the period 2012-2013. We obtained anthropometric data and information on lifestyle characteristics using a self-administered questionnaire. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). The characteristics of lifestyle and health awareness according to quartiles of the QUANTIDD score were assessed using the chi-square test and a general linear model. The higher the QUANTIDD score was, the larger were the proportions of participants who knew the appropriate amount of dietary intake and participants who referred to nutritional component information when choosing and/or buying food. Among participants with higher QUANTIDD scores, the proportion of participants who considered their current diet was good was high in women, whereas the proportion of participants who wanted to improve their diet in the future was high in men. Those results indicate that higher dietary diversity was related to better characteristics of lifestyle and awareness of health. J. Med. Invest. 67 : 255-264, August, 2020. (Tokushima University Institutional Repository) ● Metadata: 115420 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.67.255 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33148898 ● Search Scopus @ Elsevier (PMID): 33148898 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.67.255 (Tokushima University Institutional Repository: 115420, DOI: 10.2152/jmi.67.255, PubMed: 33148898)
5.	Hiroyasu Mori, Akio Kuroda, Masashi Ishizu, Mami Ohishi, Yuichi Takashi, Yinhua Otsuka, Satoshi Taniguchi, Motoyuki Tamaki, Kiyoe Kurahashi, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki, Yuko Akehi and Munehide Matsuhisa : Association of accumulated advanced glycation end-products with a high prevalence of sarcopenia and dynapenia in patients with type 2 diabetes., Journal of Diabetes Investigation, 2019. (Summary) Advanced glycation end-products (AGEs), which are a major cause of diabetic vascular complications, accumulate in various tissues under chronic hyperglycemic conditions, as well as with aging in patients with diabetes. The loss of muscle mass and strength, so-called sarcopenia and dynapenia, has recently been recognized as a diabetic complication. However, the influence of accumulated AGEs on muscle mass and strength remains unclear. The present study aimed to evaluate the association of sarcopenia and dynapenia with accumulated AGEs in patients with type 2 diabetes. We recruited 166 patients with type 2 diabetes aged 30 years (mean age 63.2 ± 12.3 years; body mass index 26.3 ± 4.9 kg/m ; glycated hemoglobin 7.1 ± 1.1%). Skin autofluorescence as a marker of AGEs, limb skeletal muscle mass index, grip strength, knee extension strength and gait speed were assessed. Sarcopenia and dynapenia were observed in 7.2 and 13.9% of participants, respectively. Skin autofluorescence was significantly higher in patients with sarcopenia and dynapenia. Skin autofluorescence was the independent determinant for skeletal muscle mass index, grip strength, knee extension strength, sarcopenia and dynapenia. Accumulated AGEs could contribute to reduced muscle mass and strength, leading to sarcopenia and dynapenia in patients with type 2 diabetes. (Tokushima University Institutional Repository) ● Metadata: 114022 (Link to Publication Site) ● Publication site (DOI): 10.1111/jdi.13014 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30677242 ● Search Scopus @ Elsevier (PMID): 30677242 ● Search Scopus @ Elsevier (DOI): 10.1111/jdi.13014 (Tokushima University Institutional Repository: 114022, DOI: 10.1111/jdi.13014, PubMed: 30677242)
6.	Mariko Nakamoto, Mariko Omine, Yuna Yun, Emi Shuto, Akiko Nakamoto, Akiko Hata, Nanako Aki, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Ayako Tamura, Yumi Kuwamura, Makoto Funaki and Tohru Sakai : Associations of dietary diversity with allergic diseases in Japanese workers: a cross-sectional study., Asia Pacific Journal of Clinical Nutrition, Vol.28, No.4, 857-869, 2019. (Summary) The aim of this study was to determine the associations of dietary diversity with prevalences of allergic diseases. The participants were 1,317 men and women aged 20 to 63 years who were living in Tokushima Prefecture, Japan during the period 2012-2013. We obtained anthropometric data and information on lifestyle characteristics and current medical histories of allergic diseases using a self-administered questionnaire. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). The ORs and 95% CIs for each of the allergic diseases with a 1 standard deviation (SD) increase in the QUANTIDD score were estimated, controlling for age, family history of allergic diseases, education, smoking, drinking, physical activity, energy intake and BMI. Higher dietary diversity showed significant inverse dose-response relationships with allergic diseases and allergic rhinitis in women. Multivariate-adjusted ORs (95% CI) for allergic diseases and allergic rhinitis with 1 SD increase in the QUANTIDD score were 0.77 (95% CI: 0.60-0.98, p=0.037) and 0.69 (95% CI: 0.53-0.90, p=0.007), respectively, in women. There were no significant associations between dietary diversity and allergic diseases in men. The results indicate that there is an inverse association between higher dietary diversity and allergic rhinitis in Japanese female workers. (Keyword) Adult / Asthma / Cross-Sectional Studies / Dermatitis, Atopic / Diet / Female / Food / Humans / Japan / Male / Middle Aged / Rhinitis, Allergic / Risk Factors / Young Adult (Link to Publication Site) ● Publication site (DOI): 10.6133/apjcn.201912_28(4).0023 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31826384 ● Summary page in Scopus @ Elsevier: 2-s2.0-85076486533 (DOI: 10.6133/apjcn.201912_28(4).0023, PubMed: 31826384, Elsevier: Scopus)
7.	Mariko Nakamoto, Emi Shuto, Akiko Nakamoto, Akiko Hata, Nanako Aki, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Ayako Tamura, Yumi Kuwamura, Makoto Funaki and Tohru Sakai : Soy product and isoflavone intake associations with allergic diseases in Japanese workers: rhinitis, dermatitis and asthma., Asia Pacific Journal of Clinical Nutrition, Vol.27, No.6, 1277-1285, 2018. (Summary) The aim of this study was to determine the associations of intake of soy products and isoflavones with allergic diseases. We conducted a cross-sectional study in 1437 participants (aged 20-64 years) who were living in Tokushima Prefecture, Japan during the period 2010- 2011. We obtained anthropometric data and information on life style characteristics including dietary intake and current medical histories of allergic diseases using a structural self-administered questionnaire. Multiple logistic regression models were used to assess the associations of soy products and isoflavones with allergic diseases after controlling for age, family history of allergic diseases, smoking, drinking, physical activity, energy intake, BMI and dietary factors. Intake of soy products showed significant inverse dose-response relationships with allergic rhinitis. The third quartile for soy products had an adjusted OR of 0.56 (95% CI: 0.35-0.91) compared to the reference group (first quartile), though intake of soy products showed no dose-response relationship with atopic dermatitis. Intake of soy isoflavones showed a significant inverse dose-response relationship with atopic dermatitis, though the association between intake of soy isoflavones and atopic dermatitis was U-shaped after adjustments for potential confounders. On the other hand, the associations between intake of soy isoflavones and other allergic diseases were not significant. The results indicate that higher intake of soy products is associated with reduced risk of allergic rhinitis in Japanese workers. Furthermore, moderate intake amounts of soy products and soy isoflavones are associated with inverse risk of atopic dermatitis. (Keyword) epidemiology / nutrition (Link to Publication Site) ● Publication site (DOI): 10.6133/apjcn.201811_27(6).0015 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30485927 ● Search Scopus @ Elsevier (PMID): 30485927 ● Search Scopus @ Elsevier (DOI): 10.6133/apjcn.201811_27(6).0015 (DOI: 10.6133/apjcn.201811_27(6).0015, PubMed: 30485927)
8.	Xiaolin Yang, Mariko Nakamoto, Emi Shuto, Akiko Hata, Nanako Aki, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Ayako Tamura, Hirokazu Uemura, Kokichi Arisawa, Makoto Funaki and Tohru Sakai : Associations between intake of dietary fermented soy food and concentrations of inflammatory markers: a cross-sectional study in Japanese workers, The Journal of Medical Investigation : JMI, Vol.65, No.1-2, 74-80, 2018. (Summary) Epidemiological investigations have shown that consumption of soybeans or soy foods reduces the risk of the development of cardiovascular disease, cancer and osteoporosis. The aim of this study was to determine the associations between different soy foods and inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, and IL-18, in Japanese workers. The cross-sectional study included 1,426 Japanese workers (1,053 men and 373 women) aged 20 to 64 years. Intake of 12 soy foods was estimated by a validated food frequency questionnaire. Associations of total soy foods, fermented soy food, non-fermented soy food, soy isoflavone with hs-CRP, IL-6, and IL-18 levels were examined by general linear model regression analysis. We found that total fermented soy food intake was inversely associated with multivariable-adjusted geometric concentration of IL-6 in men (Q1:1.03 pg/mL, Q5:0.94 pg /mL;P for trend = 0.031). Furthermore, it was shown that IL-6 concentrations were inversely associated with miso intake (β = -0.068;p = 0.034) and soy sauce intake in men (β = -0.074;p = 0.018). This study suggests that intake of total fermented soy food, miso and soy sauce be associated with IL-6 concentrations in Japanese men. J. Med. Invest. 65:74-80, February, 2018. (Tokushima University Institutional Repository) ● Metadata: 111414 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.65.74 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29593198 ● CiNii @ National Institute of Informatics (CRID): 1390282679224674560 ● Summary page in Scopus @ Elsevier: 2-s2.0-85044467994 (Tokushima University Institutional Repository: 111414, DOI: 10.2152/jmi.65.74, PubMed: 29593198, CiNii: 1390282679224674560, Elsevier: Scopus)
9.	Yosuke Shikama, Yasusei Kudo, Naozumi Ishimaru and Makoto Funaki : Possible involvement of palmitate in pathogensis of periodontitis., Journal of Cellular Physiology, Vol.230, No.12, 2981-2989, 2015. (Summary) Type 2 diabetes (T2D) is characterized by decreased insulin sensitivity and higher concentrations of free fatty acids (FFAs) in plasma. Among FFAs, saturated fatty acids (SFAs), such as palmitate, have been suggested to promote inflammatory responses. Although many epidemiological studies have shown a link between periodontitis and T2D, little is known about the clinical significance of SFAs in periodontitis. In this study, we showed that gingival fibroblasts have cell-surface expression of CD36, which is also known as FAT/fatty acid translocase. Moreover, CD36 expression was increased in gingival fibroblasts of high-fat diet-induced T2D model mice, compared with gingival fibroblasts of mice fed a normal diet. DNA microarray analysis revealed that palmitate increased mRNA expression of pro-inflammatory cytokines and chemokines in human gingival fibroblasts (HGF). Consistent with these results, we confirmed that palmitate-induced interleukin (IL)-6, IL-8, and CXCL1 secretion in HGF, using a cytokine array and ELISA. SFAs, but not an unsaturated fatty acid, oleate, induced IL-8 production. Docosahexaenoic acid (DHA), which is one of the omega-3 polyunsaturated fatty acids, significantly suppressed palmitate-induced IL-6 and IL-8 production. Treatment of HGF with a CD36 inhibitor also inhibited palmitate-induced pro-inflammatory responses. Finally, we demonstrated that Porphyromonas gingivalis (P.g.) lipopolysaccharide and heat-killed P.g. augmented palmitate-induced chemokine secretion in HGF. These results suggest a potential link between SFAs in plasma and the pathogenesis of periodontitis. J. Cell. Physiol. 230: 2981-2989, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. (Link to Publication Site) ● Publication site (DOI): 10.1002/jcp.25029 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25921577 ● Summary page in Scopus @ Elsevier: 2-s2.0-84939824337 (DOI: 10.1002/jcp.25029, PubMed: 25921577, Elsevier: Scopus)
10.	Jun-ichi Kido, Yukiko Bandou, Mika Bandou, Yukari Kajiura, Yuka Hiroshima, Yuji Inagaki, Hiromi Murata, Takahisa Ikuta, Reiko Kido, Koji Naruishi, Makoto Funaki and Toshihiko Nagata : YKL-40 level in gingival crevicular fluid from patients with periodontitis and type 2 diabetes, Oral Diseases, Vol.21, No.5, 667-673, 2015. (Summary) YKL-40 is a chitin-binding glycoprotein, the level of which increases in inflammatory diseases, diabetes mellitus (DM), cardiovascular diseases, and tumors. Gingival crevicular fluid (GCF) contains many proteins and markers of periodontitis. The purpose of this study was to investigate YKL-40 level in GCF from patients with periodontitis and DM and the association between YKL-40 level and chronic periodontitis (CP) or DM. The subjects were 121 patients with DM, CP, DM and periodontitis (DM-P), and healthy subjects (H). GCF was collected using paper strips after the sites for GCF collection were clinically evaluated for probing depth (PD), gingival index (GI), and bleeding on probing (BOP). YKL-40 in GCF was identified by Western blotting, and its level was determined by ELISA. YKL-40 was contained in GCF samples from H, DM, CP, and DM-P sites, and its levels (amount and concentration) in CP and DM-P were significantly higher than those in H and DM. GCF YKL-40 level significantly correlated with PD and GI, and its level in BOP-positive sites was significantly higher than that in BOP-negative ones. GCF YKL-40 level was elevated in periodontitis, but not DM. YKL-40 in GCF may be an inflammatory marker for periodontitis. (Link to Publication Site) ● Publication site (DOI): 10.1111/odi.12334 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25740558 ● Summary page in Scopus @ Elsevier: 2-s2.0-84930271794 (DOI: 10.1111/odi.12334, PubMed: 25740558, Elsevier: Scopus)
11.	Yosuke Shikama, Nanako Aki, Akiko Hata, Miho Nishimura, Seiichi Oyadomari and Makoto Funaki : Palmitate-stimulated monocytes induce adhesion molecule expression in endothelial cells via IL-1 signaling pathway., Journal of Cellular Physiology, Vol.230, No.3, 732-742, 2015. (Summary) Increased intake of saturated fatty acids (SFAs), such as palmitate (Pal), is linked to a higher risk of type 2 diabetes and cardiovascular disease. Although recent studies have investigated the direct effects of SFAs on inflammatory responses in vascular endothelial cells, it remains unknown whether SFAs also induce these responses mediated by circulating cells. In this study, especially focused on adhesion molecules and monocytes, we investigated the indirect effects of Pal on expression and release of ICAM-1 and E-selectin in vascular endothelial cells. Phorbol 12-myristate 13-acetate (PMA)-treated THP-1 (pTHP-1) cells and human monocytes were stimulated with various free fatty acids (FFAs). SFAs, but not unsaturated fatty acids (UFAs), increased interleukin (IL)-1 secretion and decreased IL-1 receptor antagonist (IL-1Ra) secretion, resulting in an increase in the IL-1/IL-1Ra secretion ratio. UFAs dose-dependently inhibited the increase in IL-1 secretion and decrease in IL-1Ra secretion induced by Pal. Moreover, in human aortic and vein endothelial cells, expression and release of ICAM-1 and E-selectin were induced by treatment with conditioned medium collected from Pal-stimulated pTHP-1 cells and human monocytes, but not by Pal itself. The up-regulated expression and release of adhesion molecules by the conditioned medium were mostly abolished by recombinant human IL-1Ra supplementation. These results suggest that the Pal-induced increase in the ratio of IL-1/IL-1Ra secretion in monocytes up-regulates endothelial adhesion molecules, which could enhance leukocyte adhesion to endothelium. This study provides further evidence that IL-1 neutralization through receptor antagonism may be useful for preventing the onset and development of cardiovascular disease. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc. (Keyword) Cell Adhesion Molecules / E-Selectin / Endothelial Cells / Gene Expression Regulation / Humans / Intercellular Adhesion Molecule-1 / Interleukin-1 / Monocytes / Palmitates / Phorbols / Signal Transduction (Link to Publication Site) ● Publication site (DOI): 10.1002/jcp.24797 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25201247 ● Summary page in Scopus @ Elsevier: 2-s2.0-84920885356 (DOI: 10.1002/jcp.24797, PubMed: 25201247, Elsevier: Scopus)
12.	Akiko Hata, Koji Yonemoto, Yosuke Shikama, Nanako Aki, Chisato Kosugi, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Masashi Miyoshi, Takayuki Nakao and Makoto Funaki : Cut-off value of total adiponectin for managing risk of developing metabolic syndrome in male Japanese workers., PLoS ONE, Vol.10, No.2, e0118373, 2015. (Summary) To determine the optimal cut-off value of serum total adiponectin for managing the risk of developing metabolic syndrome (MetS) in male Japanese workers. A total of 365 subjects without MetS aged 20-60 years were followed up prospectively for a mean of 3.1 years. The accelerated failure-time model was used to estimate time ratio (TR) and cut-off value for developing MetS. During follow-up, 45 subjects developed MetS. Age-adjusted TR significantly declined with decreasing total adiponectin level (≤ 4.9, 5.0-6.6, 6.7-8.8 and ≥ 8.9 μg/ml, P for trend = 0.003). In multivariate analyses, TR of MetS was 0.12 (95% CI 0.02-0.78; P = 0.03) in subjects with total adiponectin level of 5.0-6.6 μg/ml, and 0.15 (95% CI 0.02-0.97; P = 0.047) in subjects with total adiponectin level ≤ 4.9 μg/ml compared with those with total adiponectin level ≥ 8.9 μg/ml. The accelerated failure-time model showed that the optimal cut-off value of total adiponectin for managing the risk of developing MetS was 6.2 μg/ml. In the multivariate-adjusted model, the mean time to the development of MetS was 78% shorter for total adiponectin level ≤ 6.2 μg/ml compared with > 6.2 μg/ml (TR 0.22, 95% CI: 0.08-0.64, P = 0.005). Our findings suggest that the cut-off value for managing the risk of developing MetS is 6.2 μg/ml in male Japanese workers. Subjects with total adiponectin level ≤ 6.2 μg/ml developed MetS more rapidly than did those with total adiponectin level > 6.2 μg/ml. (Tokushima University Institutional Repository) ● Metadata: 114931 (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0118373 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25705909 ● Summary page in Scopus @ Elsevier: 2-s2.0-84923361347 (Tokushima University Institutional Repository: 114931, DOI: 10.1371/journal.pone.0118373, PubMed: 25705909, Elsevier: Scopus)
13.	Qing-Ri Jin, Yukiko Bandou, Katsuyuki Miyawaki, Yosuke Shikama, Chisato Kosugi, Nanako Aki, Makoto Funaki and Sumihare Noji : Correlation of fibroblast growth factor 21 serum levels with metabolic parameters in Japanese subjects, The Journal of Medical Investigation : JMI, Vol.61, No.1.2, 28-34, 2014. (Summary) Since serum level of fibroblast growth factor 21 (FGF21) has been implicated as a potential biomarker for the early detection of the metabolic syndrome and type 2 diabetes, we examined how FGF21 serum levels are correlated with metabolic parameters in Japanese subjects. FGF21 levels were analyzed by enzyme-linked immunosorbent assays. Spearman's correlation and multiple stepwise regression analyses were used to examine the relationship between serum FGF21 and other factors. A Mann-Whitney U test was performed between the normal and high groups for triglycerides and systolic blood pressure (BP) respectively. By univariate correlation analysis, serum FGF21 levels were significantly associated with triglyceride levels, systolic BP, diastolic BP, pulse pressure, body mass index (BMI), age, fasting plasma glucose (FPG) levels, and total cholesterol levels. Multiple regression analysis (adjusted for age, gender, and BMI) showed that serum FGF21 levels were independently and significantly associated with triglyceride levels and systolic BP. Serum FGF21 levels were significantly higher in subjects with high triglyceride levels and high systolic BP compared with those who had normal triglyceride levels and normal systolic BP respectively. This study found that FGF21 levels might be a biomarker for some metabolic disorders associated with metabolic syndrome. (Keyword) Adult / Aged / Asian Continental Ancestry Group / Biological Markers / Blood Glucose / blood pressure / Body Mass Index / Cross-Sectional Studies / Female / Fibroblast Growth Factors / Humans / Male / Metabolic Syndrome X / Middle Aged / Regression Analysis / Triglycerides (Tokushima University Institutional Repository) ● Metadata: 109493 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.61.28 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24705745 ● Search Scopus @ Elsevier (PMID): 24705745 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.61.28 (Tokushima University Institutional Repository: 109493, DOI: 10.2152/jmi.61.28, PubMed: 24705745)
14.	Tomoyuki Watanabe, Masao Saotome, Mamoru Nobuhara, Atsushi Sakamoto, Tsuyoshi Urushida, Hideki Katoh, Hiroshi Satoh, Makoto Funaki and Hideharu Hayashi : Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance., Experimental Cell Research, Vol.323, No.2, 314-325, 2014. (Summary) A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. (Keyword) Animals / Cell Line / Dynamins / hydrogen peroxide / insulin / Insulin Resistance / Membrane Potential, Mitochondrial / Mitochondria, Heart / Myocytes, Cardiac / Palmitates / Porphyrins / Rats / reactive oxygen species (Link to Publication Site) ● Publication site (DOI): 10.1016/j.yexcr.2014.02.027 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24631294 ● Search Scopus @ Elsevier (PMID): 24631294 ● Search Scopus @ Elsevier (DOI): 10.1016/j.yexcr.2014.02.027 (DOI: 10.1016/j.yexcr.2014.02.027, PubMed: 24631294)
15.	O Naujok, Yukiko Bandou, Yosuke Shikama, Makoto Funaki and S Lenzen : Effect of substrate rigidity in tissue culture on the function of insulin-secreting INS-1E cells., Journal of Tissue Engineering and Regenerative Medicine, Vol.epub ahead of print, 2014. (Summary) Insulin-secreting INS-1E cells are a useful tool in diabetes research. However, during permanent culture the cells tend to lose their β cell phenotype, with resultant loss of insulin-secretory responsiveness. This can be at least partially attributed to inappropriate cell culture conditions. One of the important causative factors is the rigidity of the extracellular matrix. We have therefore systematically studied the performance of INS-1E insulin-secreting cells cultured on polyacrylamide gels of different stiffnesses and analysed changes in insulin content and secretion, glucokinase enzyme activity, gene expression of β cell transcription factors and cell death and proliferation rates. INS-1E cells were cultured on polyacrylamide gels with a wide range of rigidities, including the one that simulates the stiffness of the pancreas. We detected changes in insulin content and the insulin-secretory response to glucose stimulation in parallel to the increasing stiffness of the polyacrylamide gels in the range 1700-111 000 Pa. On substrates with the highest and lowest rigidities, 322 and 111 000 Pa, the cells mainly formed pseudo-islets, while at rigidities of 1700-64800 Pa, including the rigidity of native pancreas tissue (3100 Pa), cells grew as a monolayer attached to the polyacrylamide gel surface. These observations provide evidence for an apparent mechanosensitivity of insulin-secreting INS-1E cells affecting morphology and cellular functions. The results can also provide practical advice regarding a selection of the materials appropriate for successful cell culture of insulin-secreting cells. Copyright © 2014 John Wiley & Sons, Ltd. (Link to Publication Site) ● Publication site (DOI): 10.1002/term.1857 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24399617 ● Summary page in Scopus @ Elsevier: 2-s2.0-84891761765 (DOI: 10.1002/term.1857, PubMed: 24399617, Elsevier: Scopus)
16.	Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura, Chisato Kosugi, 安藝菜奈子, Toshio Hosaka, Emi Shuto, Tohru Sakai and Makoto Funaki : Epidemiology : Relationship between Physical Activity and Metabolic Syndrome in Male Workers, Journal of the The Japan Diabetes Society, Vol.56, No.9, 637-645, 2013. (Keyword) メタボリックシンドローム / 身体活動 / 勤労男性 / 横断調査 (Link to Publication Site) ● Publication site (DOI): 10.11213/tonyobyo.56.637 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390282679885162752 ● Summary page in Scopus @ Elsevier: 2-s2.0-84886613919 (DOI: 10.11213/tonyobyo.56.637, CiNii: 1390282679885162752, Elsevier: Scopus)
17.	中本真理子, Tohru Sakai, Emi Shuto, 安藝菜奈子, Chisato Kosugi, Akiko Hata, Kaori Shinoda, Yumi Kuwamura, Takako Minagawa, Takako Ichihara, Ayako Tamura and Makoto Funaki : Period between Dinner and Bedtime Is Related to Hypertension, Journal of Japanese Society of Nutrition and Food Science, Vol.66, No.4, 185-193, 2013. (Summary) The aim of this study was to examine the association between the period between dinner and bedtime, and various adult lifestyle-related diseases in the workplace. We analyzed 470 men and 252 women aged 20-65 years who had been enrolled in baseline surveys conducted for the Tokushima Diabetes Cohort Study in a workplace setting in Tokushima prefecture. Multiple logistic regression models were used for analyzing the association of the time between dinner and bedtime and the prevalence rates of adult lifestyle-related diseases. The period between dinner and bedtime tended to show an inverse dose-response relationship with hypertension (p for trend = 0.04) after adjustment for age, sex and other potential confounders. The group with the longest period between dinner and bedtime had an adjusted odds ratio of 0.38 (95% confidence interval 0.17-0.82) compared to the reference group (first quartile group) . Additionally, the period between dinner and bedtime showed an inverse dose-response relationship with hypertension for subjects who ate dinner after 21:00 (p for trend = 0.02) . These results indicate that the period between dinner and bedtime is inversely associated with the prevalence of hypertension. (Keyword) hypertension / lifestyle / cross-sectional study / work site population (Link to Publication Site) ● Publication site (DOI): 10.4327/jsnfs.66.185 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390282681268995200 ● Search Scopus @ Elsevier (DOI): 10.4327/jsnfs.66.185 (DOI: 10.4327/jsnfs.66.185, CiNii: 1390282681268995200)
18.	Aya Umeno, Mototada Shichiri, Noriko Ishida, Yoshiko Hashimoto, Kaori Abe, Masatoshi Kataoka, Kohzoh Yoshino, Yoshihisa Hagihara, Nanako Aki, Makoto Funaki, Yasuhiko Asada and Yasukazu Yoshida : Singlet oxygen induced products of linoleates, 10- and 12-(Z,E)-hydroxyoctadecadienoic acids (HODE), can be potential biomarkers for early detection of type 2 diabetes., PLoS ONE, Vol.8, No.5, e63542, 2013. (Summary) Current diagnostic tests such as glycemic indicators have limitations for early detection of impaired glucose tolerance (IGT), which leads to diabetes. Oxidative stress induced by various oxidants in a random and destructive manner is considered to play an important role in the pathophysiology of a number of human disorders and diseases such as impaired glucose tolerance. We have developed an improved method for the measurement of in vivo lipid peroxidation, where the presence of 8-iso-prostaglandin F2α (8-iso-PGF2α), hydroxyoctadecadienoic acids (HODEs), hydroxyeicosatetraenoic acids (HETEs), and 7-hydroxycholesterol (7-OHCh), as well as their parent molecules, linoleic acid (LA) and cholesterol (Ch), was determined by performing LC-MS/MS (for 8-iso-PGF2α, HODE, and HETE) and GC-MS (for 7-OHCh, LA, and Ch) after reduction with triphenyl phosphine and saponification by potassium hydroxide. We then applied this method to volunteers (n = 57), including normal type (n = 43), "high-normal" (fasting plasma glucose, 100-109 mg/dL, n = 7), pre-diabetic type (IGT, n = 5), and diabetic type (n = 2) subjects who are diagnosed by performing oral glucose tolerance tests (OGTTs). Several biomarkers in plasma, such as insulin, leptin, adiponectin, interleukin-6, tumor necrosis factor-α, high sensitivity-C-reactive protein, HbA1c, and glucose levels were measured during OGTT. We found that the fasting levels of (10- and 12-(Z,E)- HODE)/LA increased significantly with increasing levels of HbA1c and glucose during OGTT and with insulin secretion and resistance index. In conclusion, 10- and 12-(Z,E)-HODE may be prominent biomarkers for the early detection of IGT and "high-normal" type without OGTT. (Keyword) Adipokines / Adult / Biomarkers / Diabetes Mellitus, Type 2 / Early Diagnosis / Fatty Acids, Unsaturated / Female / Gas Chromatography-Mass Spectrometry / Glucose Tolerance Test / Humans / Linoleic Acids / Male / Middle Aged / oxidative stress / Singlet Oxygen (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0063542 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23691063 ● Search Scopus @ Elsevier (PMID): 23691063 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0063542 (DOI: 10.1371/journal.pone.0063542, PubMed: 23691063)
19.	Yosuke Shikama, Naozumi Ishimaru, Yasusei Kudo, Yukiko Bandou, N Aki, Yoshio Hayashi and Makoto Funaki : Effects of Free Fatty Acids on Human Salivary Gland Epithelial Cells., Journal of Dental Research, Vol.92, No.6, 540-546, 2013. (Summary) Obesity and type 2 diabetes (T2D) are characterized by decreased insulin sensitivity and higher concentrations of free fatty acids (FFAs) in plasma. Among FFAs, saturated fatty acids (SFAs), such as palmitate, have been proposed to promote inflammatory responses. Primary Sjögren's syndrome (SS) is an autoimmune disease characterized by inflammatory mononuclear cell infiltration and destruction of epithelial cells in the salivary and lacrimal glands. IL-6 production and -fodrin degradation are increased in salivary gland epithelial cells of patients with primary SS. Although previous studies have shown a link between SS and either dyslipidemia or T2D, little is known about the clinical significance of FFAs in primary SS. Here we report that SFAs, but not unsaturated fatty acids, induced IL-6 production via NF-B and p38 MAPK activation in human salivary gland epithelial cells. Moreover, palmitate induced apoptosis and -fodrin degradation by caspase-3 activation. Unlike salivary gland epithelial cells, induction of IL-6 production and the degradation of -fodrin in response to palmitate were undetectable in squamous carcinoma cells and keratinocytes. Taken together, SFAs induced IL-6 production and -fodrin degradation in salivary gland epithelial cells, implicating a potential link between the pathogenesis of primary SS and SFAs level in plasma. (Link to Publication Site) ● Publication site (DOI): 10.1177/0022034513487378 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23603335 ● Search Scopus @ Elsevier (PMID): 23603335 ● Search Scopus @ Elsevier (DOI): 10.1177/0022034513487378 (DOI: 10.1177/0022034513487378, PubMed: 23603335)
20.	Mamoru Nobuhara, Masao Saotome, Tomoyuki Watanabe, Tsuyoshi Urushida, Hideki Katoh, Hiroshi Satoh, Makoto Funaki and Hideharu Hayashi : Mitochondrial dysfunction caused by saturated fatty acid loading induces myocardial insulin-resistance in differentiated H9c2 myocytes: a novel ex vivo myocardial insulin-resistance model., Experimental Cell Research, Vol.319, No.7, 955-966, 2013. (Summary) Heart failure (HF) is often accompanied with metabolic disorders and insufficient energy production. Some previous studies have suggested an elevated serum free fatty acid (FA) due to chronic adrenergic stimulation induces myocardial insulin-resistance, which further impairs myocardial energy production. Because little is known about the pathogenesis of FA-induced cardiac insulin-resistance, we established an ex vivo cardiac insulin-resistant model and investigated the relationship between insulin-resistance and mitochondrial dysfunction. The ex vivo insulin-resistant myocytes, which was produced by treating differentiated H9c2 myocytes with palmitate (saturated FA; 0.2mM) for 24h, exhibited insulin-signaling deficiency and attenuated 2-deoxy-d-glucose (2-DG) uptake. When myocytes were pretreated with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP, a ROS scavenger; 200 M), the insulin-signaling deficiency by palmitate was restored, whereas the attenuated 2-DG uptake was remained. In contrast to TMPyP, the pretreatment with perhexiline (a mitochondrial FA uptake inhibitor; 2 M) restored the insulin-signaling deficiency and the attenuated 2-DG uptake by palmitate. Perhexiline restored the depolarized mitochondrial membrane potential (m) and the reduced intracellular ATP by palmitate, and thereby improved the impaired GLUT4 recruitment to plasma membrane after insulin, whereas TMPyP failed to do so. These results suggested that the mitochondrial dysfunction by saturated FA loading and consequent intracellular energy shortage induced myocardial insulin-resistance in our ex vivo insulin-resistant model. (Keyword) Animals / Cell Differentiation / Cells, Cultured / Energy Metabolism / Fatty Acids / Glucose / Heart / Insulin / Insulin Resistance / Mitochondria / Myocardium / Rats / Signal Transduction (Link to Publication Site) ● Publication site (DOI): 10.1016/j.yexcr.2013.02.004 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23416068 ● Search Scopus @ Elsevier (PMID): 23416068 ● Search Scopus @ Elsevier (DOI): 10.1016/j.yexcr.2013.02.004 (DOI: 10.1016/j.yexcr.2013.02.004, PubMed: 23416068)
21.	Qinkai Li, Toshio Hosaka, Nagakatsu Harada, Yutaka Nakaya and Makoto Funaki : Activation of Akt through 5-HT2A receptor ameliorates serotonin-induced degradation of insulin receptor substrate-1 in adipocytes, Molecular and Cellular Endocrinology, Vol.365, No.1, 25-35, 2013. (Summary) Serotonin (5-hydroxytryptamine, 5-HT) was found to be elevated in the serum of diabetic patients. In this study, we investigate the mechanism of insulin desensitization caused by 5-HT. In 3T3-L1 adipocytes, 5-HT treatment induced the translocation of insulin receptor substrate-1 (IRS-1) from low density microsome (LDM), the important intracellular compartment for its functions, to cytosol, inducing IRS-1 ubiquitination and degradation. Moreover, inhibition of 5-HT-stimulated Akt activation by either ketanserin (a specific 5-HT2A receptor antagonist) or knocking-down the expression of 5-HT2A receptor promoted 5-HT-stimulated IRS-1 dissociation from 14-3-3β in LDM, leading to drastic ubiquitination. Interestingly, sarpogrelate, another antagonist of 5-HT2A receptor, protected IRS-1 from degradation through activation of Akt. This implicates the importance of Akt activation in extending IRS-1 life span through maintaining their optimal sub-location into adipocytes. Taken together, this study suggest that activation of Akt may be able to compensate the adverse effects of 5-HT by stabilizing IRS-1 in LDM. (Keyword) 14-3-3 Proteins / 3T3-L1 Cells / Adipocytes, White / Animals / Cytosol / Insulin Receptor Substrate Proteins / Insulin Resistance / Male / Mice / Mice, Inbred C57BL / Mice, Obese / Microsomes / Protein Stability / Protein Transport / Proteolysis / Proto-Oncogene Proteins c-akt / RNA Interference / Receptor, Serotonin, 5-HT2A / Serotonin / Serotonin 5-HT2 Receptor Agonists / Serotonin 5-HT2 Receptor Antagonists / Ubiquitination (Link to Publication Site) ● Publication site (DOI): 10.1016/j.mce.2012.08.022 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22975078 ● Search Scopus @ Elsevier (PMID): 22975078 ● Search Scopus @ Elsevier (DOI): 10.1016/j.mce.2012.08.022 (DOI: 10.1016/j.mce.2012.08.022, PubMed: 22975078)
22.	Qinkai Li, Toshio Hosaka, Yosuke Shikama, Yukiko Bandou, Chisato Kosugi, Nanako Kataoka, Yutaka Nakaya and Makoto Funaki : Heparin-binding EGF-like growth factor (HB-EGF) mediates 5-HT-induced insulin resistance through activation of EGF receptor-ERK1/2-mTOR pathway., Endocrinology, Vol.153, No.1, 56-68, 2012. (Summary) Although an inverse correlation between insulin sensitivity and the level of Gq/11-coupled receptor agonists, such as endothelin-1, thrombin, and 5-hydroxytryptamine (5-HT), has been reported, its precise mechanism remains unclear. In this report, we provide evidence that 5-HT induced production of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and caused insulin resistance in 3T3-L1 adipocytes, primary adipocytes, and C2C12 myotubes. In 3T3-L1 adipocytes, 5-HT stimulated HB-EGF production by promoting metalloproteinase-dependent shedding of transmembrane protein pro-HB-EGF. HB-EGF then bound and tyrosine-phosphorylated EGF receptors, which activated the mammalian target of rapamycin pathway through ERK1/2 phosphorylation. Mammalian target of rapamycin activation caused serine phosphorylation of insulin receptor substrate-1, which attenuated insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 and glucose uptake. Pharmacological inhibition of either Gq/11-coupled receptors or metalloproteinases, as well as either inhibition or knockdown of HB-EGF or Gq/11, restored insulin signal transduction impaired by 5-HT. Inhibition of metalloproteinase activity also abolished HB-EGF production and subsequent EGF receptor activation by other Gq/11-coupled receptor agonists known to cause insulin resistance, such as endothelin-1 and thrombin. These results suggest that transactivation of the EGF receptor through HB-EGF processing plays a pivotal role in 5-HT-induced insulin resistance. (Keyword) 3T3-L1 Cells / Adipocytes / Animals / Cell Line / Cells, Cultured / Endothelin-1 / GTP-Binding Protein alpha Subunits, Gq-G11 / Glucose / Insulin / Insulin Receptor Substrate Proteins / Insulin Resistance / Intercellular Signaling Peptides and Proteins / MAP Kinase Signaling System / Mice / Muscle Fibers, Skeletal / Proto-Oncogene Proteins c-akt / Receptor, Epidermal Growth Factor / Serotonin / Signal Transduction / TOR Serine-Threonine Kinases / Thrombin / Transcriptional Activation (Link to Publication Site) ● Publication site (DOI): 10.1210/en.2011-1418 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22028447 ● Search Scopus @ Elsevier (PMID): 22028447 ● Search Scopus @ Elsevier (DOI): 10.1210/en.2011-1418 (DOI: 10.1210/en.2011-1418, PubMed: 22028447)
23.	Mariko Nakamoto, Tohru Sakai, Emi Shuto, Toshio Hosaka, Nanako Kataoka, Chisato Kosugi, Akiko Hata, Kaori Shinoda, Yumi Kuwamura, Takako Minagawa, Takako Ichihara, Ayako Tamura and Makoto Funaki : Does food intake and life style relate to the prevalence of allergic disease?, Journal of rehabilitation and health science, Vol.8, 15-21, 2010. (Keyword) allergy / 栄養調査 / 豆類 / vitamin A / lifestyle-related disease (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390573242531347328 (CiNii: 1390573242531347328)
24.	Qinkai Li, Akiko Hata, Chisato Kosugi, Nanako Kataoka and Makoto Funaki : The density of extracellular matrix proteins regulates inflammation and insulin signaling in adipocytes., FEBS Letters, Vol.584, No.19, 4145-4150, 2010. (Summary) Cells can not only sense the type of extracellular matrix (ECM) protein that is present in the microenvironment, but they can also sense its density. Here, we investigated the effects of ECM protein density on adipokine secretion and insulin signaling in adipocytes. To this end, 3T3-L1 adipocytes were cultured on the surface of polyacrylamide gels that were coated with gradient densities of a collagen type I and fibronectin mixture. We found that high density ECM causes a decrease in insulin signaling and adiponectin secretion, whereas the secretion of monocyte chemoattractant protein-1 (MCP-1) was increased via the activation of nuclear factor-κB (NF-κB). These results indicate that the density of the ECM directly regulates the inflammatory response and insulin sensitivity of adipocytes. (Keyword) 3T3-L1 Cells / Adipocytes / Adiponectin / Animals / Chemokine CCL2 / Extracellular Matrix Proteins / Inflammation / Insulin / Insulin Resistance / Mice / NF-kappa B / Signal Transduction (Link to Publication Site) ● Publication site (DOI): 10.1016/j.febslet.2010.08.033 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20804756 ● Search Scopus @ Elsevier (PMID): 20804756 ● Search Scopus @ Elsevier (DOI): 10.1016/j.febslet.2010.08.033 (DOI: 10.1016/j.febslet.2010.08.033, PubMed: 20804756)
25.	島健二, 小松まち子, 福島泰江, 新谷保実, 斎藤泰憲, 中川洋一, 石本寛子, 播紀子, Makoto Funaki, 野間喜彦, 藤中雄一, Masako Sei, 白神敦久, 鶴尾美穂, 松永慶子, 竹田信也, 田中俊夫, 宮本道代, 田中利子, 古田結花 and 大塚明廣 : 糖尿病死亡率ワーストワンからの脱却を目指して徳島県医師会生活習慣病予防対策委員会糖尿病対策班の活動, Diabetes Frontier, Vol.21, No.3, 367-376, 2010.
26.	Qinkai Li, Weidong Yin, Manbo Cai, Yi Liu, Hongjie Hou, Qingyun Shen, Chi Zhang, Junxia Xiao, Xiaobo Hu, Qishisan Wu, Makoto Funaki and Yutaka Nakaya : NO-1886 suppresses diet-induced insulin resistance and cholesterol accumulation through STAT5-dependent upregulation of IGF1 and CYP7A1., The Journal of Endocrinology, Vol.204, No.1, 47-56, 2010. (Summary) Insulin resistance and dyslipidemia are both considered to be risk factors for metabolic syndrome. Low levels of IGF1 are associated with insulin resistance. Elevation of low-density lipoprotein cholesterol (LDL-C) concomitant with depression of high-density lipoprotein cholesterol (HDL-C) increase the risk of obesity and type 2 diabetes mellitus (T2DM). Liver secretes IGF1 and catabolizes cholesterol regulated by the rate-limiting enzyme of bile acid synthesis from cholesterol 7alpha-hydroxylase (CYP7A1). NO-1886, a chemically synthesized lipoprotein lipase activator, suppresses diet-induced insulin resistance with the improvement of HDL-C. The goal of the present study is to evaluate whether NO-1886 upregulates IGF1 and CYP7A1 to benefit glucose and cholesterol metabolism. By using human hepatoma cell lines (HepG2 cells) as an in vitro model, we found that NO-1886 promoted IGF1 secretion and CYP7A1 expression through the activation of signal transducer and activator of transcription 5 (STAT5). Pretreatment of cells with AG 490, the inhibitor of STAT pathway, completely abolished NO-1886-induced IGF1 secretion and CYP7A1 expression. Studies performed in Chinese Bama minipigs pointed out an augmentation of plasma IGF1 elicited by a single dose administration of NO-1886. Long-term supplementation with NO-1886 recovered hyperinsulinemia and low plasma levels of IGF1 suppressed LDL-C and facilitated reverse cholesterol transport by decreasing hepatic cholesterol accumulation through increasing CYP7A1 expression in high-fat/high-sucrose/high-cholesterol diet minipigs. These findings indicate that NO-1886 upregulates IGF1 secretion and CYP7A1 expression to improve insulin resistance and hepatic cholesterol accumulation, which may represent an alternative therapeutic avenue of NO-1886 for T2DM and metabolic syndrome. (Keyword) Animal Feed / Animals / Benzamides / Cell Line, Tumor / Cholesterol / Cholesterol 7-alpha-Hydroxylase / Cholesterol, HDL / Cholesterol, LDL / Dietary Fats / Drug Administration Schedule / Humans / Hyperglycemia / Hyperinsulinism / Hypolipidemic Agents / Insulin Resistance / Insulin-Like Growth Factor I / Liver / Male / Organophosphorus Compounds / STAT5 Transcription Factor / Swine / Swine, Miniature / Up-Regulation (Link to Publication Site) ● Publication site (DOI): 10.1677/JOE-09-0278 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19815588 ● Search Scopus @ Elsevier (PMID): 19815588 ● Search Scopus @ Elsevier (DOI): 10.1677/JOE-09-0278 (DOI: 10.1677/JOE-09-0278, PubMed: 19815588)
27.	Le Thi Kim Chung, Toshio Hosaka, Nagakatsu Harada, Bayasgalan Jambaldorj, Keiko Fukunaga, Yuka Nishiwaki, Kiyoshi Teshigawara, Tohru Sakai, Yutaka Nakaya and Makoto Funaki : Myosin IIA participates in docking of Glut4 storage vesicles with the plasma membrane in 3T3-L1 adipocytes., Biochemical and Biophysical Research Communications, Vol.391, No.1, 995-999, 2009. (Summary) In adipocytes and myocytes, insulin stimulation translocates glucose transporter 4 (Glut4) storage vesicles (GSVs) from their intracellular storage sites to the plasma membrane (PM) where they dock with the PM. Then, Glut4 is inserted into the PM and initiates glucose uptake into these cells. Previous studies using chemical inhibitors demonstrated that myosin II participates in fusion of GSVs and the PM and increase in the intrinsic activity of Glut4. In this study, the effect of myosin IIA on GSV trafficking was examined by knocking down myosin IIA expression. Myosin IIA knockdown decreased both glucose uptake and exposures of myc-tagged Glut4 to the cell surface in insulin-stimulated cells, but did not affect insulin signal transduction. Interestingly, myosin IIA knockdown failed to decrease insulin-dependent trafficking of Glut4 to the PM. Moreover, in myosin IIA knockdown cells, insulin-stimulated binding of GSV SNARE protein, vesicle-associated membrane protein 2 (VAMP2) to PM SNARE protein, syntaxin 4 was inhibited. These data suggest that myosin IIA plays a role in insulin-stimulated docking of GSVs to the PM in 3T3-L1 adipocytes through SNARE complex formation. (Keyword) 3T3-L1 Cells / Adipocytes / Animals / Cell Membrane / Cytoplasmic Vesicles / Gene Knockdown Techniques / Glucose / Glucose Transporter Type 4 / Insulin / Mice / Nonmuscle Myosin Type IIA / Protein Transport / SNARE Proteins / signal transduction / Vesicle-Associated Membrane Protein 2 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2009.12.004 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19968963 ● Search Scopus @ Elsevier (PMID): 19968963 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2009.12.004 (DOI: 10.1016/j.bbrc.2009.12.004, PubMed: 19968963)
28.	Li Qinkai, Toshio Hosaka, Jambaldorj Bayasglan, Yutaka Nakaya and Makoto Funaki : Extracellular Matrix with the Rigidity of Adipose Tissues Helps 3T3-L1 Adipocytes Maintain Insulin Responsiveness, The Journal of Medical Investigation : JMI, Vol.56, No.3,4, 142-149, 2009. (Summary) Despite the popularity of 3T3-L1 adipocytes as a model system of adipocytes in vivo, they do not carry all of the cellular functions of adipocytes in vivo. In this study, we investigated the effect of extracellular matrix (ECM) rigidity on insulin signal transduction in 3T3-L1 adipocytes. On 250 Pa polyacrylamide gel (soft gel) laminated with a mixture of collagen type 1 and fibronectin, whose rigidity matches that of adipose tissue, expression of the insulin receptor, IRS-1 and AKT was upregulated and their insulin-stimulated phosphorylation was enhanced. Furthermore, the expression of GLUT1 was downregulated, whereas the expression of GLUT4 was unaffected as ECM rigidity decreased. Insulin-stimulated GLUT4 recruitment to the plasma membrane was significantly enhanced in cells seeded on soft gel. These results suggest that adjusting the ECM rigidity to that of adipose tissue augments insulin signaling in 3T3-L1 adipocytes and enhances insulin-stimulated GLUT4 recruitment to the plasma membrane. (Keyword) 3T3-L1 Cells / Adipocytes / Animals / Biophysical Phenomena / Extracellular Matrix / Glucose Transporter Type 1 / Glucose Transporter Type 4 / Insulin / Mice / Recombinant Fusion Proteins / Signal Transduction / Transfection (Tokushima University Institutional Repository) ● Metadata: 111321 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.56.142 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19763027 ● Search Scopus @ Elsevier (PMID): 19763027 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.56.142 (Tokushima University Institutional Repository: 111321, DOI: 10.2152/jmi.56.142, PubMed: 19763027)
29.	Makoto Funaki, Kate Benincasa and K Paramjeet Randhawa : Peptide rescues GLUT4 recruitment, but not GLUT4 activation, in insulin resistance., Biochemical and Biophysical Research Communications, Vol.360, No.4, 891-896, 2007. (Summary) Insulin-stimulated GLUT4 recruitment to the plasma membrane is impaired in insulin resistance. We recently reported that a cell permeable phosphoinositide-binding peptide induces GLUT4 recruitment as potently as insulin, but does not activate GLUT4 to initiate glucose uptake. Here we investigated whether the peptide-induced GLUT4 recruitment is intact in insulin resistance. The expression levels of GLUT1 and GLUT4 were unaffected by chronically treating 3T3-L1 adipocytes with insulin. GLUT4 recruitment by acute insulin stimulation after chronic insulin treatment was significantly reduced, but was fully restored by the peptide treatment. However, subsequent acute insulin stimulation to activate GLUT4 failed to increase glucose uptake in peptide-pretreated cells. Insulin-stimulated GLUT1 recruitment was unaffected by the peptide pretreatment. These results suggest that the GLUT4 recruitment signal caused by the peptide is intact in insulin resistance, but GLUT4 activation that occurs subsequent to recruitment is not rescued by the peptide treatment. (Keyword) 3T3-L1 Cells / Adipocytes / Animals / glucose / Glucose Transporter Type 4 / insulin / insulin resistance / Mice / Peptides (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2007.06.153 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17631270 ● Search Scopus @ Elsevier (PMID): 17631270 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2007.06.153 (DOI: 10.1016/j.bbrc.2007.06.153, PubMed: 17631270)
30.	Makoto Funaki, Lesley DiFransico and A Paul Janmey : PI 4,5-P2 stimulates glucose transport activity of GLUT4 in the plasma membrane of 3T3-L1 adipocytes., Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol.1763, No.8, 889-899, 2006. (Summary) Insulin-stimulated glucose uptake through GLUT4 plays a pivotal role in maintaining normal blood glucose levels. Glucose transport through GLUT4 requires both GLUT4 translocation to the plasma membrane and GLUT4 activation at the plasma membrane. Here we report that a cell-permeable phosphoinositide-binding peptide, which induces GLUT4 translocation without activation, sequestered PI 4,5-P2 in the plasma membrane from its binding partners. Restoring PI 4,5-P2 to the plasma membrane after the peptide treatment increased glucose uptake. No additional glucose transporters were recruited to the plasma membrane, suggesting that the increased glucose uptake was attributable to GLUT4 activation. Cells overexpressing phosphatidylinositol-4-phosphate 5-kinase treated with the peptide followed by its removal exhibited a higher level of glucose transport than cells stimulated with a submaximal level of insulin. However, only cells treated with submaximal insulin exhibited translocation of the PH-domains of the general receptor for phosphoinositides (GRP1) to the plasma membrane. Thus, PI 4,5-P2, but not PI 3,4,5-P3 converted from PI 4,5-P2, induced GLUT4 activation. Inhibiting F-actin remodeling after the peptide treatment significantly impaired GLUT4 activation induced either by PI 4,5-P2 or by insulin. These results suggest that PI 4,5-P2 in the plasma membrane acts as a second messenger to activate GLUT4, possibly through F-actin remodeling. (Keyword) 3T3-L1 Cells / Actins / Adipocytes / Animals / Biological Transport, Active / Cell Membrane / glucose / Glucose Transporter Type 1 / Glucose Transporter Type 4 / insulin / Intracellular Signaling Peptides and Proteins / Mice / Phosphatidylinositol 4,5-Diphosphate / Second Messenger Systems (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbamcr.2006.05.012 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16828894 ● Search Scopus @ Elsevier (PMID): 16828894 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbamcr.2006.05.012 (DOI: 10.1016/j.bbamcr.2006.05.012, PubMed: 16828894)
31.	J Jennifer Pastore, Makoto Funaki, A Paul Janmey and Robert Bucki : Flavonoid-mediated inhibition of actin polymerization in cold-activated platelets., Platelets, Vol.16, No.6, 362-367, 2005. (Summary) The response of human platelets to low temperature (below 15 degrees C) requires that they are stored at elevated temperatures and limits their storage time to 5 days for use in transfusion. Prolonged storage at room temperature leads to loss of platelet function and risk of septic conditions. The need for improved platelet storage is an important issue, and finding a key component allowing platelets to be maintained at low temperatures would have significant practical benefit. Developing such a component is challenging, because the process of cold-activation resembles that of a physiological agonist-mediated activation, but without a specific receptor that can be inhibited. A component preventing platelets' low temperature response will potentially inhibit their physiological function, making them less useful after transfusion. In the present study, we report that pretreatment of platelets with flavonoids before chilling prevents an increase in cytosolic calcium concentration, actin polymerization and platelet shape change. After warming, platelets that were chilled in the presence of flavonoids retain a normal shape change and aggregation response after stimulation by thrombin. Additionally, cold platelet activation does not increase platelet procoagulant activity evaluated by annexin V-FITC binding in the presence and absence of flavonoids. These data confirm the important links that exist between agonist- and cold-mediated platelet activation, suggesting a possible advantage of incorporating the use of flavonoids to allow platelet hypothermic-storage. (Keyword) Actins / Blood Platelets / Blood Preservation / calcium / Cold Temperature / flavonoids / Humans / Platelet Activation / Platelet Aggregation / Platelet Transfusion / Reference Values (Link to Publication Site) ● Publication site (DOI): 10.1080/09537100500124442 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16194866 ● Search Scopus @ Elsevier (PMID): 16194866 ● Search Scopus @ Elsevier (DOI): 10.1080/09537100500124442 (DOI: 10.1080/09537100500124442, PubMed: 16194866)
32.	Robert Bucki, C Penelope Georges, Quentin Espinassous, Makoto Funaki, J Jennifer Pastore, Richard Chaby and A Paul Janmey : Inactivation of endotoxin by human plasma gelsolin., Biochemistry, Vol.44, No.28, 9590-9597, 2005. (Summary) Septic shock from bacterial endotoxin, triggered by the release of lipopolysaccharide (LPS) molecules from the outer wall of Gram-negative bacteria, is a major cause of human death for which there is no effective treatment once the complex inflammatory pathways stimulated by these small amphipathic molecules are activated. Here we report that plasma gelsolin, a highly conserved human protein, binds LPS from various bacteria with high affinity. Solid-phase binding assays, fluorescence measurements, and functional assays of actin depolymerizing effects show that gelsolin binds more tightly to LPS than it does to its other known lipid ligands, phosphatidylinositol 4,5-bisphosphate and lysophosphatidic acid. Gelsolin also competes with LPS-binding protein (LBP), a high-affinity carrier for LPS. One result of gelsolin-LPS binding is inhibition of the actin binding activity of gelsolin as well as the actin depolymerizing activity of blood serum. Simultaneously, effects of LPS on cellular functions, including cytoskeletal actin remodeling, and collagen-induced platelet activation by pathways independent of toll-like receptors (TLRs) are neutralized by gelsolin and by a peptide based on gelsolin residues 160-169 (GSN160-169) which comprise part of gelsolin's phosphoinositide binding site. Additionally, TLR-dependent NF-kappaB translocation in astrocytes appears to be blocked by gelsolin. These results show a strong effect of LPS on plasma gelsolin function and suggest that some effects of endotoxin in vivo may be mediated or inhibited by plasma gelsolin. (Keyword) Actin Cytoskeleton / Acute-Phase Proteins / Animals / Astrocytes / Binding, Competitive / Carrier Proteins / Cell Line / Cells, Cultured / Gelsolin / Humans / Lipopolysaccharides / Membrane Glycoproteins / NF-kappa B / Peptide Fragments / Phosphatidylinositol Phosphates / Platelet Aggregation Inhibitors / Protein Binding / Protein Transport / Rabbits / Rats (Link to Publication Site) ● Publication site (DOI): 10.1021/bi0503504 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16008344 ● Search Scopus @ Elsevier (PMID): 16008344 ● Search Scopus @ Elsevier (DOI): 10.1021/bi0503504 (DOI: 10.1021/bi0503504, PubMed: 16008344)
33.	T Sasaoka, K Fukui, T Wada, S Murakami, J Kawahara, H Ishihara, Makoto Funaki, T Asano and M Kobayashi : Inhibition of endogenous SHIP2 ameliorates insulin resistance caused by chronic insulin treatment in 3T3-L1 adipocytes., Diabetologia, Vol.48, No.2, 336-344, 2005. (Summary) Our results indicate that the inhibition of endogenous SHIP2 is effective in improving the state of insulin resistance caused by chronic insulin treatment. (Keyword) 3T3 Cells / Adipocytes / Animals / Biological Transport / Deoxyglucose / insulin / Insulin Receptor Substrate Proteins / insulin resistance / Isoenzymes / Mice / Phosphoproteins / Phosphoric Monoester Hydrolases / Protein Kinase C / signal transduction / Sirolimus / src Homology Domains (Link to Publication Site) ● Publication site (DOI): 10.1007/s00125-004-1636-8 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15654601 ● Search Scopus @ Elsevier (PMID): 15654601 ● Search Scopus @ Elsevier (DOI): 10.1007/s00125-004-1636-8 (DOI: 10.1007/s00125-004-1636-8, PubMed: 15654601)
34.	Tony Yeung, C Penelope Georges, A Lisa Flanagan, Beatrice Marg, Miguelina Ortiz, Makoto Funaki, Nastaran Zahir, Wenyu Ming, Valerie Weaver and A Paul Janmey : Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion., Cell Motility and the Cytoskeleton, Vol.60, No.1, 24-34, 2005. (Summary) The morphology and cytoskeletal structure of fibroblasts, endothelial cells, and neutrophils are documented for cells cultured on surfaces with stiffness ranging from 2 to 55,000 Pa that have been laminated with fibronectin or collagen as adhesive ligand. When grown in sparse culture with no cell-cell contacts, fibroblasts and endothelial cells show an abrupt change in spread area that occurs at a stiffness range around 3,000 Pa. No actin stress fibers are seen in fibroblasts on soft surfaces, and the appearance of stress fibers is abrupt and complete at a stiffness range coincident with that at which they spread. Upregulation of alpha5 integrin also occurs in the same stiffness range, but exogenous expression of alpha5 integrin is not sufficient to cause cell spreading on soft surfaces. Neutrophils, in contrast, show no dependence of either resting shape or ability to spread after activation when cultured on surfaces as soft as 2 Pa compared to glass. The shape and cytoskeletal differences evident in single cells on soft compared to hard substrates are eliminated when fibroblasts or endothelial cells make cell-cell contact. These results support the hypothesis that mechanical factors impact different cell types in fundamentally different ways, and can trigger specific changes similar to those stimulated by soluble ligands. (Keyword) Actins / Animals / Aorta / Cattle / Cell Adhesion / Cell Line / Cells, Cultured / collagen / Cytoskeleton / Endothelium, Vascular / extracellular matrix / Fibroblasts / Fibronectins / Glass / Green Fluorescent Proteins / Humans / Integrin alpha5 / Mice / Microscopy, Confocal / NIH 3T3 Cells / Neutrophils / Stress Fibers / surface properties (Link to Publication Site) ● Publication site (DOI): 10.1002/cm.20041 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15573414 ● Search Scopus @ Elsevier (PMID): 15573414 ● Search Scopus @ Elsevier (DOI): 10.1002/cm.20041 (DOI: 10.1002/cm.20041, PubMed: 15573414)
35.	Makoto Funaki, Paramjeet Randhawa and A Paul Janmey : Separation of insulin signaling into distinct GLUT4 translocation and activation steps., Molecular and Cellular Biology, Vol.24, No.17, 7567-7577, 2004. (Summary) GLUT4 (glucose transporter 4) plays a pivotal role in insulin-induced glucose uptake to maintain normal blood glucose levels. Here, we report that a cell-permeable phosphoinositide-binding peptide induced GLUT4 translocation to the plasma membrane without inhibiting IRAP (insulin-responsive aminopeptidase) endocytosis. However, unlike insulin treatment, the peptide treatment did not increase glucose uptake in 3T3-L1 adipocytes, indicating that GLUT4 translocation and activation are separate events. GLUT4 activation can occur at the plasma membrane, since insulin was able to increase glucose uptake with a shorter time lag when inactive GLUT4 was first translocated to the plasma membrane by pretreating the cells with this peptide. Inhibition of phosphatidylinositol (PI) 3-kinase activity failed to inhibit GLUT4 translocation by the peptide but did inhibit glucose uptake when insulin was added following peptide treatment. Insulin, but not the peptide, stimulated GLUT1 translocation. Surprisingly, the peptide pretreatment inhibited insulin-induced GLUT1 translocation, suggesting that the peptide treatment has both a stimulatory effect on GLUT4 translocation and an inhibitory effect on insulin-induced GLUT1 translocation. These results suggest that GLUT4 requires translocation to the plasma membrane, as well as activation at the plasma membrane, to initiate glucose uptake, and both of these steps normally require PI 3-kinase activation. (Keyword) 3T3 Cells / Adipocytes / Aminopeptidases / Animals / Cell Membrane / Cystinyl Aminopeptidase / Endocytosis / Enzyme Activation / Fluorescent Dyes / glucose / Glucose Transporter Type 4 / Humans / insulin / Mice / Monosaccharide Transport Proteins / Muscle Proteins / Peptides / Phosphatidylinositol 3-Kinases / Protein Transport / Protein-Serine-Threonine Kinases / Proto-Oncogene Proteins / Proto-Oncogene Proteins c-akt / signal transduction (Link to Publication Site) ● Publication site (DOI): 10.1128/MCB.24.17.7567-7577.2004 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15314166 ● Search Scopus @ Elsevier (PMID): 15314166 ● Search Scopus @ Elsevier (DOI): 10.1128/MCB.24.17.7567-7577.2004 (DOI: 10.1128/MCB.24.17.7567-7577.2004, PubMed: 15314166)
36.	Y Onishi-Haraikawa, Makoto Funaki, N Gotoh, M Shibuya, K Inukai, H Katagiri, Y Fukushima, M Anai, T Ogihara, H Sakoda, H Ono, M Kikuchi, Y Oka and T Asano : Unique phosphorylation mechanism of Gab1 using PI 3-kinase as an adaptor protein., Biochemical and Biophysical Research Communications, Vol.288, No.2, 476-482, 2001. (Summary) Grb2-associated binder-1 (Gab1) undergoes tyrosine phosphorylation in response to stimulation by growth factors and hormones including insulin, epidermal growth factor (EGF), nerve growth factor (NGF), and hepatocyte growth factor (HGF). However, the HGF receptor is the only one known to associate directly with Gab1. Herein, we explore the mechanism of Gab1 phosphorylation by other receptor protein-tyrosine kinases unable to bind to Gab1 directly. The Src homology 2 (SH2) domain of the phosphatidylinositol 3-kinase (PI3K) regulatory subunit binds Gab1 in a phosphorylation-independent manner. Moreover, the regulatory subunit of PI3K can mediate the association of Gab1 and receptor protein-tyrosine kinases including the insulin, EGF, and NGF receptors, all of which phosphorylate Gab1. Thus, it appears that the PI3K regulatory subunit acts as an adaptor protein via a phosphotyrosyl-independent SH2 interaction, allowing Gab1 to serve as a substrate for several tyrosine kinases. This is a new role for the PI3K regulatory subunit. (Keyword) Adaptor Proteins, Signal Transducing / Animals / CHO Cells / Cells, Cultured / Cricetinae / Humans / Insects / Insulin Receptor Substrate Proteins / Phosphatidylinositol 3-Kinases / Phosphoproteins / phosphorylation / Protein Structure, Tertiary / Protein-Tyrosine Kinases (Link to Publication Site) ● Publication site (DOI): 10.1006/bbrc.2001.5791 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11606067 ● Search Scopus @ Elsevier (PMID): 11606067 ● Search Scopus @ Elsevier (DOI): 10.1006/bbrc.2001.5791 (DOI: 10.1006/bbrc.2001.5791, PubMed: 11606067)
37.	C C Cunningham, R Vegners, R Bucki, Makoto Funaki, N Korde, H J Hartwig, P T Stossel and A P Janmey : Cell permeant polyphosphoinositide-binding peptides that block cell motility and actin assembly., The Journal of Biological Chemistry, Vol.276, No.46, 43390-43399, 2001. (Summary) Polyphosphoinositides (PPIs) affect the localization and activities of many cellular constituents, including actin-modulating proteins. Several classes of polypeptide sequences, including pleckstrin homology domains, FYVE domains, and short linear sequences containing predominantly hydrophobic and cationic residues account for phosphoinositide binding by most such proteins. We report that a ten-residue peptide derived from the phosphatidylinositol 4,5-bisphosphate (PIP(2)) binding region in segment 2 of gelsolin, when coupled to rhodamine B has potent PIP(2) binding activity in vitro; crosses the cell membrane of fibroblasts, platelets, melanoma cells, and neutrophils by a process not involving endocytosis; and blocks cell motility. This peptide derivative transiently disassembles actin filament structures in GFP-actin-expressing NIH3T3 fibroblasts and prevents thrombin- or chemotactic peptide-stimulated actin assembly in platelets and neutrophils, respectively, but does not block the initial [Ca(2+)] increase caused by these agonists. The blockage of actin assembly and motility is transient, and cells recover motility within an hour after their immobilization by 5-20 microm peptide. This class of reagents confirms the critical relation between inositol lipids and cytoskeletal structure and may be useful to probe the location and function of polyphosphoinositides in vivo. (Keyword) 3T3 Cells / Actins / Animals / Blood Platelets / calcium / Cell Movement / Cytoskeleton / Detergents / Dose-Response Relationship, Drug / Fibroblasts / Humans / Immunoblotting / Mice / Microscopy, Fluorescence / Neutrophils / Octoxynol / Peptides / Phosphatidylinositol 4,5-Diphosphate / Phosphatidylinositol Phosphates / Protein Binding / signal transduction / Spectrometry, Fluorescence / Time Factors / Tumor Cells, Cultured (Link to Publication Site) ● Publication site (DOI): 10.1074/jbc.M105289200 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11533030 ● Search Scopus @ Elsevier (PMID): 11533030 ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M105289200 (DOI: 10.1074/jbc.M105289200, PubMed: 11533030)
38.	H Ono, H Katagiri, Makoto Funaki, M Anai, K Inukai, Y Fukushima, H Sakoda, T Ogihara, Y Onishi, M Fujishiro, M Kikuchi, Y Oka and T Asano : Regulation of phosphoinositide metabolism, Akt phosphorylation, and glucose transport by PTEN (phosphatase and tensin homolog deleted on chromosome 10) in 3T3-L1 adipocytes., Molecular Endocrinology, Vol.15, No.8, 1411-1422, 2001. (Summary) To investigate the roles of PTEN (phosphatase and tensin homolog deleted on chromosome 10) in the regulation of 3-position phosphorylated phosphoinositide metabolism as well as insulin-induced Akt phosphorylation and glucose metabolism, wild-type PTEN and its phosphatase-dead mutant (C124S) with or without an N-terminal myristoylation tag were overexpressed in Sf-9 cells and 3T3-L1 adipocytes using baculovirus and adenovirus systems, respectively. When expressed in Sf-9 cells together with the p110alpha catalytic subunit of phosphoinositide 3-kinase, myristoylated PTEN markedly reduced the accumulations of both phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate induced by p110alpha. In contrast, overexpression of the C124S mutants apparently increased these accumulations. In 3T3-L1 adipocytes, insulin-induced accumulations of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate were markedly suppressed by overexpression of wild-type PTEN with the N-terminal myristoylation tag, but not by that without the tag. On the contrary, the C124S mutants of PTEN enhanced insulin-induced accumulations of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Interestingly, the phosphorylation level of Akt at Thr308 (Akt2 at Thr309), but not at Ser473 (Akt2 at Ser474), was revealed to correlate well with the accumulation of phosphatidylinositol 3,4,5-trisphosphate modified by overexpression of these PTEN proteins. Finally, insulin-induced increases in glucose transport activity were significantly inhibited by the overexpression of myristoylated wild-type PTEN, but were not enhanced by expression of the C124S mutant of PTEN. Therefore, in conclusion, 1) PTEN dephosphorylates both phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate in vivo, and the C124S mutants interrupt endogenous PTEN activity in a dominant-negative manner. 2) The membrane targeting process of PTEN may be important for exerting its function. 3) Phosphorylations of Thr309 and Ser474 of Akt2 are regulated differently, and the former is regulated very sensitively by the function of PTEN. 4) The phosphorylation level of Ser474, but not that of Thr309, in Akt2 correlates well with insulin-stimulated glucose transport activity in 3T3-L1 adipocytes. 5) The activity of endogenous PTEN may not play a major role in the regulation of glucose transport activity in 3T3-L1 adipocytes. (Keyword) 3T3 Cells / Adipocytes / Animals / Baculoviridae / Biological Transport / Blotting, Western / Cell Line / Deoxyglucose / gene expression / Glucose / insulin / Mice / Mutation / PTEN Phosphohydrolase / Phosphatidylinositol 3-Kinases / Phosphatidylinositol Phosphates / Phosphatidylinositols / Phosphoric Monoester Hydrolases / phosphorylation / Protein-Serine-Threonine Kinases / Proto-Oncogene Proteins / Proto-Oncogene Proteins c-akt / Rats / Spodoptera / Tumor Suppressor Proteins (Link to Publication Site) ● Publication site (DOI): 10.1210/mend.15.8.0684 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11463863 ● Search Scopus @ Elsevier (PMID): 11463863 ● Search Scopus @ Elsevier (DOI): 10.1210/mend.15.8.0684 (DOI: 10.1210/mend.15.8.0684, PubMed: 11463863)
39.	Y Fukushima, T Saitoh, M Anai, T Ogihara, K Inukai, Makoto Funaki, H Sakoda, Y Onishi, H Ono, M Fujishiro, T Ishikawa, K Takata, R Nagai, M Omata and T Asano : Palmitoylation of the canine histamine H2 receptor occurs at Cys(305) and is important for cell surface targeting., Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol.1539, No.3, 181-191, 2001. (Summary) To determine the presence and functional role of the histamine H2 receptor (H2R) palmitoylation, a receptor with a Cys(305) to Ala (A(305) receptor) mutation was generated. Wild-type (WT) and A(305) receptors were tagged at their N-termini with a hemagglutinin (HA) epitope. WT, but not A(305), receptors incorporated [3H]palmitate by metabolic labeling, indicating that the H2R is palmitoylated at Cys(305). Immunocytochemistry of WT and A(305) receptors expressed in COS7 cells revealed WT receptors to be distributed at the plasma membrane, while the majority of A(305) receptors were localized intracellularly with only a small portion being at the plasma membrane. However, the affinity of the A(305) receptor for tiotidine was comparable to that of the WT receptor. In addition, when the amounts of cell surface receptors as determined by anti-HA antibody binding were equivalent, A(305) receptors mediated production of more cAMP than WT receptors. Preincubation of COS7 cells expressing each receptor with 10(-5) M histamine for 30 min reduced subsequent cAMP production in response to histamine via the receptors to similar extents, indicating that palmitoylation is not necessary for desensitization. In addition, cell surface A(305) receptors were capable of being internalized from the cell surface at a rate and extent similar to those of WT receptors. Finally, CHO cell lines stably expressing either WT or A(305) receptors were incubated with 10(-5) M histamine for 1, 6, 12 and 24 h. Total amounts of WT and A(305) receptors, as determined by tiotidine binding, were reduced by incubation, indicating downregulation. Downregulation of the A(305) receptor was more extensive than that of the WT receptor. Thus, palmitoylation of the H2R might be important for targeting to the cell surface and stability. (Keyword) Adenylyl Cyclases / Animals / CHO Cells / COS Cells / Cricetinae / Cyclic AMP / Cysteine / Dogs / Down-Regulation / Endocytosis / Histamine Agonists / Insects / Mutagenesis, Site-Directed / Palmitates / Receptors, Histamine H2 / Subcellular Fractions (Link to Publication Site) ● Publication site (DOI): 10.1016/S0167-4889(01)00104-5 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11420116 ● Search Scopus @ Elsevier (PMID): 11420116 ● Search Scopus @ Elsevier (DOI): 10.1016/S0167-4889(01)00104-5 (DOI: 10.1016/S0167-4889(01)00104-5, PubMed: 11420116)
40.	A Oku, M Nawano, K Ueta, T Fujita, I Umebayashi, K Arakawa, T Kano-Ishihara, A Saito, M Anai, Makoto Funaki, M Kikuchi, Y Oka and T Asano : Inhibitory effect of hyperglycemia on insulin-induced Akt/protein kinase B activation in skeletal muscle., American Journal of Physiology, Endocrinology and Metabolism, Vol.280, No.5, E816-824, 2001. (Summary) To determine the molecular mechanism underlying hyperglycemia-induced insulin resistance in skeletal muscles, postreceptor insulin-signaling events were assessed in skeletal muscles of neonatally streptozotocin-treated diabetic rats. In isolated soleus muscle of the diabetic rats, insulin-stimulated 2-deoxyglucose uptake, glucose oxidation, and lactate release were all significantly decreased compared with normal rats. Similarly, insulin-induced phosphorylation and activation of Akt/protein kinase B (PKB) and GLUT-4 translocation were severely impaired. However, the upstream signal, including phosphorylation of the insulin receptor (IR) and insulin receptor substrate (IRS)-1 and -2 and activity of phosphatidylinositol (PI) 3-kinase associated with IRS-1/2, was enhanced. The amelioration of hyperglycemia by T-1095, a Na(+)-glucose transporter inhibitor, normalized the reduced insulin sensitivity in the soleus muscle and the impaired insulin-stimulated Akt/PKB phosphorylation and activity. In addition, the enhanced PI 3-kinase activation and phosphorylation of IR and IRS-1 and -2 were reduced to normal levels. These results suggest that sustained hyperglycemia impairs the insulin-signaling steps between PI 3-kinase and Akt/PKB, and that impaired Akt/PKB activity underlies hyperglycemia-induced insulin resistance in skeletal muscle. (Keyword) Animals / Biological Transport / Deoxyglucose / Diabetes Mellitus, Experimental / Enzyme Activation / glucose / Glucose Transporter Type 4 / Hyperglycemia / insulin / Intracellular Membranes / Lactic Acid / Male / Monosaccharide Transport Proteins / Muscle Proteins / Muscle, Skeletal / oxidation and reduction / Protein-Serine-Threonine Kinases / Proto-Oncogene Proteins / Proto-Oncogene Proteins c-akt / Rats / Rats, Sprague-Dawley / signal transduction (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11287365 ● Search Scopus @ Elsevier (PMID): 11287365 (PubMed: 11287365)
41.	T Wada, T Sasaoka, Makoto Funaki, H Hori, S Murakami, M Ishiki, T Haruta, T Asano, W Ogawa, H Ishihara and M Kobayashi : Overexpression of SH2-containing inositol phosphatase 2 results in negative regulation of insulin-induced metabolic actions in 3T3-L1 adipocytes via its 5'-phosphatase catalytic activity., Molecular and Cellular Biology, Vol.21, No.5, 1633-1646, 2001. (Summary) Phosphatidylinositol (PI) 3-kinase plays an important role in various metabolic actions of insulin including glucose uptake and glycogen synthesis. Although PI 3-kinase primarily functions as a lipid kinase which preferentially phosphorylates the D-3 position of phospholipids, the effect of hydrolysis of the key PI 3-kinase product PI 3,4,5-triphosphate [PI(3,4,5)P3] on these biological responses is unknown. We recently cloned rat SH2-containing inositol phosphatase 2 (SHIP2) cDNA which possesses the 5'-phosphatase activity to hydrolyze PI(3,4,5)P3 to PI 3,4-bisphosphate [PI(3,4)P2] and which is mainly expressed in the target tissues of insulin. To study the role of SHIP2 in insulin signaling, wild-type SHIP2 (WT-SHIP2) and 5'-phosphatase-defective SHIP2 (Delta IP-SHIP2) were overexpressed in 3T3-L1 adipocytes by means of adenovirus-mediated gene transfer. Early events of insulin signaling including insulin-induced tyrosine phosphorylation of the insulin receptor beta subunit and IRS-1, IRS-1 association with the p85 subunit, and PI 3-kinase activity were not affected by expression of either WT-SHIP2 or Delta IP-SHIP2. Because WT-SHIP2 possesses the 5'-phosphatase catalytic region, its overexpression marked by decreased insulin-induced PI(3,4,5)P3 production, as expected. In contrast, the amount of PI(3,4,5)P3 was increased by the expression of Delta IP-SHIP2, indicating that Delta IP-SHIP2 functions in a dominant-negative manner in 3T3-L1 adipocytes. Both PI(3,4,5)P3 and PI(3,4)P2 were known to possibly activate downstream targets Akt and protein kinase C lambda in vitro. Importantly, expression of WT-SHIP2 inhibited insulin-induced activation of Akt and protein kinase C lambda, whereas these activations were increased by expression of Delta IP-SHIP2 in vivo. Consistent with the regulation of downstream molecules of PI 3-kinase, insulin-induced 2-deoxyglucose uptake and Glut4 translocation were decreased by expression of WT-SHIP2 and increased by expression of Delta IP-SHIP2. In addition, insulin-induced phosphorylation of GSK-3beta and activation of PP1 followed by activation of glycogen synthase and glycogen synthesis were decreased by expression of WT-SHIP2 and increased by the expression of Delta IP-SHIP2. These results indicate that SHIP2 negatively regulates metabolic signaling of insulin via the 5'-phosphatase activity and that PI(3,4,5)P3 rather than PI(3,4)P2 is important for in vivo regulation of insulin-induced activation of downstream molecules of PI 3-kinase leading to glucose uptake and glycogen synthesis. (Keyword) 3T3 Cells / Adenoviridae / Adipocytes / Animals / Arabidopsis Proteins / Blotting, Western / enzyme catalysis / Chromatography, High Pressure Liquid / Cloning, Molecular / DNA, Complementary / Deoxyglucose / Gene Transfer Techniques / Genes, Dominant / Glucose Transporter Type 1 / Glucose Transporter Type 4 / Glycogen / Glycogen Synthase / insulin / Insulin Receptor Substrate Proteins / Isoenzymes / Lac Operon / Mice / Microscopy, Confocal / Models, Genetic / Monosaccharide Transport Proteins / Muscle Proteins / Phosphatidylinositol 3-Kinases / Phosphatidylinositols / Phosphoproteins / Phosphoric Monoester Hydrolases / phosphorylation / Plant Proteins / Potassium Channels / Precipitin Tests / Protein Kinase C / Rats / signal transduction / Time Factors / Transfection / src Homology Domains (Link to Publication Site) ● Publication site (DOI): 10.1128/MCB.21.5.1633-1646.2001 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11238900 ● Search Scopus @ Elsevier (PMID): 11238900 ● Search Scopus @ Elsevier (DOI): 10.1128/MCB.21.5.1633-1646.2001 (DOI: 10.1128/MCB.21.5.1633-1646.2001, PubMed: 11238900)
42.	M Fujishiro, Y Gotoh, H Katagiri, H Sakoda, T Ogihara, M Anai, Y Onishi, H Ono, Makoto Funaki, K Inukai, Y Fukushima, M Kikuchi, Y Oka and T Asano : MKK6/3 and p38 MAPK pathway activation is not necessary for insulin-induced glucose uptake but regulates glucose transporter expression., The Journal of Biological Chemistry, Vol.276, No.23, 19800-19806, 2001. (Summary) p38 mitogen-activated protein kinase (MAPK), which is situated downstream of MAPK kinase (MKK) 6 and MKK3, is activated by mitogenic or stress-inducing stimuli, as well as by insulin. To clarify the role of the MKK6/3-p38 MAPK pathway in the regulation of glucose transport, dominant negative p38 MAPK and MKK6 mutants and constitutively active MKK6 and MKK3 mutants were overexpressed in 3T3-L1 adipocytes and L6 myotubes using an adenovirus-mediated transfection procedure. Constitutively active MKK6/3 mutants up-regulated GLUT1 expression and down-regulated GLUT4 expression, thereby significantly increasing basal glucose transport but diminishing transport induced by insulin. Similar effects were elicited by chronic (24 h) exposure to tumor necrosis factor alpha, interleukin-1beta, or 200 mm sorbitol, all activate the MKK6/3-p38 MAPK pathway. SB203580, a specific p38 MAPK inhibitor, attenuated these effects, further confirming that both MMK6 and MMK3 act via p38 MAPK, whereas they had no effect on the increase in glucose transport induced by a constitutively active MAPK kinase 1 (MEK1) mutant or by myristoylated Akt. In addition, suppression of p38 MAPK activation by overexpression of a dominant negative p38 MAPK or MKK6 mutant did not diminish insulin-induced glucose uptake by 3T3-L1 adipocytes. It is thus apparent that activation of p38 MAPK is not essential for insulin-induced increases in glucose uptake. Rather, p38 MAPK activation leads to a marked down-regulation of insulin-induced glucose uptake via GLUT4, which may underlie cellular stress-induced insulin resistance caused by tumor necrosis factor alpha and other factors. (Keyword) 3T3 Cells / Animals / Calcium-Calmodulin-Dependent Protein Kinases / Enzyme Activation / Enzyme Inhibitors / glucose / Glucose Transporter Type 1 / Glucose Transporter Type 4 / Imidazoles / insulin / Interleukin-1 / MAP Kinase Kinase 3 / MAP Kinase Kinase 6 / Mice / Mitogen-Activated Protein Kinase Kinases / Mitogen-Activated Protein Kinases / Monosaccharide Transport Proteins / Muscle Proteins / Osmolar Concentration / phosphorylation / Protein-Tyrosine Kinases / Pyridines / RNA, Messenger / Tumor Necrosis Factor-alpha / p38 Mitogen-Activated Protein Kinases (Link to Publication Site) ● Publication site (DOI): 10.1074/jbc.M101087200 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11279172 ● Search Scopus @ Elsevier (PMID): 11279172 ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M101087200 (DOI: 10.1074/jbc.M101087200, PubMed: 11279172)
43.	K Inukai, Makoto Funaki, M Anai, T Ogihara, H Katagiri, Y Fukushima, H Sakoda, Y Onishi, H Ono, M Fujishiro, M Abe, Y Oka, M Kikuchi and T Asano : Five isoforms of the phosphatidylinositol 3-kinase regulatory subunit exhibit different associations with receptor tyrosine kinases and their tyrosine phosphorylations., FEBS Letters, Vol.490, No.1-2, 32-38, 2001. (Summary) There are five isoforms of the regulatory subunit for the heterodimeric type of phosphatidylinositol 3-kinase. These five regulatory subunit isoforms were overexpressed using an adenovirus transfection system, and their own tyrosine phosphorylations and associations with various tyrosine kinase receptors were investigated. When overexpressed in CHO-PDGFR cells, the associations of these regulatory subunit isoforms with the platelet-derived growth factor receptor were similar. However, when overexpressed in CHO-IR cells, p55gamma exhibited a significantly lower ability to bind with IRS-1 upon insulin stimulation, as compared with other regulatory subunit isoforms. Furthermore, p55alpha and p55gamma were found to be tyrosine-phosphorylated. Finally, interestingly, when overexpressed in CHO-EGFR cells or A431 cells and stimulated with epidermal growth factor (EGF), phosphorylated EGF receptor was detected in p85alpha, p85beta and p50alpha immunoprecipitates, but not in p55alpha and p55gamma immunoprecipitates. In addition, EGF-induced tyrosine phosphorylation was observed in p85alpha, p85beta, p55alpha and p55gamma, but not in p50alpha, immunoprecipitates. Thus, each regulatory subunit exhibits specific responses regarding both the association with tyrosine-phosphorylated substrates and its own tyrosine phosphorylation. These results suggest that each isoform possesses specific roles in signal transduction, based on its individual tyrosine kinase receptor. (Keyword) Adenoviridae / Animals / Arabidopsis Proteins / Blotting, Western / CHO Cells / Cell Line / Cricetinae / Electrophoresis, Polyacrylamide Gel / Epidermal Growth Factor / Humans / Immunoblotting / Insulin Receptor Substrate Proteins / Ligands / Phosphatidylinositol 3-Kinases / Phosphoproteins / phosphorylation / Plant Proteins / Potassium Channels / Precipitin Tests / Protein Isoforms / Protein-Tyrosine Kinases / Receptor, Epidermal Growth Factor / signal transduction / Transfection / Tyrosine (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11172806 ● Search Scopus @ Elsevier (PMID): 11172806 (PubMed: 11172806)
44.	Y Fukushima, T Saitoh, M Anai, K Tsukuda, Y Onishi, H Sakoda, K Inukai, T Ogihara, Makoto Funaki, H Ono, M Fujishiro, T Ishikawa, R Nagai, M Omata and T Asano : G649, an allelic variant of the human H2 receptor with low basal activity, is resistant to upregulation upon antagonist exposure., The Pharmacogenomics Journal, Vol.1, No.1, 78-83, 2001. (Summary) Orange et al reported an allelic variant of the human histamine H2 receptor, in which adenine 649 was replaced with guanine, to be more frequent in the schizophrenic population than controls in British Caucasians. The A649 to G change causes an Asn to Asp transition at amino acid position 217 in the third intracellular region, which is postulated to be important for receptor function. Herein, we analyzed the functional significance of this variant using wild-type and variant receptors expressed in Chinese hamster ovary cells. The variant receptor was associated with markedly lower basal cAMP productions than the wild-type receptor. Histamine-dependent cAMP productions via the variant receptor were lower as well. Treatment of cells expressing variant receptors with 10(-5) M ranitidine for 24 h resulted in a reduced degree of receptor upregulation as compared with the wild-type receptor. Thus, this is the first report of an allelic variant of the human H2 receptor which confers altered receptor function. To analyze gastric acid secretion in individuals with this variant, we examined 100 Japanese control subjects. However, neither heterozygotes nor homozygotes were found, suggesting that this variant, if present, is uncommon in the Japanese population. (Keyword) Alleles / Animals / CHO Cells / Cimetidine / Cricetinae / Cyclic AMP / histamine / Histamine H2 Antagonists / Humans / Mutation / Receptors, Histamine H2 / Up-Regulation (Link to Publication Site) ● Publication site (DOI): 10.1038/sj.tpj.6500011 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11913732 ● Search Scopus @ Elsevier (PMID): 11913732 ● Search Scopus @ Elsevier (DOI): 10.1038/sj.tpj.6500011 (DOI: 10.1038/sj.tpj.6500011, PubMed: 11913732)
45.	H Sakoda, T Ogihara, M Anai, Makoto Funaki, K Inukai, H Katagiri, Y Fukushima, Y Onishi, H Ono, M Fujishiro, M Kikuchi, Y Oka and T Asano : Dexamethasone-induced insulin resistance in 3T3-L1 adipocytes is due to inhibition of glucose transport rather than insulin signal transduction., Diabetes, Vol.49, No.10, 1700-1708, 2000. (Summary) Glucocorticoids reportedly induce insulin resistance. In this study, we investigated the mechanism of glucocorticoid-induced insulin resistance using 3T3-L1 adipocytes in which treatment with dexamethasone has been shown to impair the insulin-induced increase in glucose uptake. In 3T3-L1 adipocytes treated with dexamethasone, the GLUT1 protein expression level was decreased by 30%, which possibly caused decreased basal glucose uptake. On the other hand, dexamethasone treatment did not alter the amount of GLUT4 protein in total cell lysates but decreased the insulin-stimulated GLUT4 translocation to the plasma membrane, which possibly caused decreased insulin-stimulated glucose uptake. Dexamethasone did not alter tyrosine phosphorylation of insulin receptors, and it significantly decreased protein expression and tyrosine phosphorylation of insulin receptor substrate (IRS)-1. Interestingly, however, protein expression and tyrosine phosphorylation of IRS-2 were increased. To investigate whether the reduced IRS-1 content is involved in insulin resistance, IRS-1 was overexpressed in dexamethasone-treated 3T3-L1 adipocytes using an adenovirus transfection system. Despite protein expression and phosphorylation levels of IRS-1 being normalized, insulin-induced 2-deoxy-D-[3H]glucose uptake impaired by dexamethasone showed no significant improvement. Subsequently, we examined the effect of dexamethasone on the glucose uptake increase induced by overexpression of GLUT2-tagged p110alpha, constitutively active Akt (myristoylated Akt), oxidative stress (30 mU glucose oxidase for 2 h), 2 mmol/l 5-aminoimidazole-4-carboxamide ribonucleoside for 30 min, and osmotic shock (600 mmol/l sorbitol for 30 min). Dexamethasone treatment clearly inhibited the increases in glucose uptake produced by these agents. Thus, in conclusion, the GLUT1 decrease may be involved in the dexamethasone-induced decrease in basal glucose transport activity, and the mechanism of dexamethasone-induced insulin resistance in glucose transport activity (rather than the inhibition of phosphatidylinositol 3-kinase activation resulting from a decreased IRS-1 content) is likely to underlie impaired glucose transporter regulation. (Keyword) 3T3 Cells / Adipocytes / Aminoimidazole Carboxamide / Animals / Biological Transport / Dexamethasone / Enzyme Activation / gene expression / Glucocorticoids / glucose / Glucose Transporter Type 1 / Glucose Transporter Type 4 / insulin / Insulin Receptor Substrate Proteins / Insulin Resistance / Intracellular Signaling Peptides and Proteins / Mice / Monosaccharide Transport Proteins / Muscle Proteins / Osmotic Pressure / oxidative stress / Phosphatidylinositol 3-Kinases / Phosphoproteins / phosphorylation / Phosphotyrosine / Receptor, Insulin / Ribonucleotides / signal transduction (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11016454 ● Search Scopus @ Elsevier (PMID): 11016454 (PubMed: 11016454)
46.	T Asano, A Kanda, H Katagiri, M Nawano, T Ogihara, K Inukai, M Anai, Y Fukushima, Y Yazaki, M Kikuchi, R Hooshmand-Rad, H C Heldin, Y Oka and Makoto Funaki : p110beta is up-regulated during differentiation of 3T3-L1 cells and contributes to the highly insulin-responsive glucose transport activity., The Journal of Biological Chemistry, Vol.275, No.23, 17671-17676, 2000. (Summary) Activation of p85/p110 type phosphatidylinositol kinase is essential for aspects of insulin-induced glucose metabolism, including translocation of GLUT4 to the cell surface and glycogen synthesis. The enzyme exists as a heterodimer containing a regulatory subunit (e.g. p85alpha) and one of two widely distributed isoforms of the p110 catalytic subunit: p110alpha or p110beta. In the present study, we compared the two isoforms in the regulation of insulin action. During differentiation of 3T3-L1 cells into adipocytes, p110beta was up-regulated approximately 10-fold, whereas expression of p110alpha was unaltered. The effects of the increased p110 expression were further assessed by expressing epitope tagged p110beta and p110alpha in 3T3-L1 cells using adenovirus transduction systems, respectively. In vitro, the basal lipid kinase activity of p110beta was lower than that of p110alpha. When p110alpha and p110beta were overexpressed in 3T3-L1 adipocytes, exposing cells to insulin induced each of the subunits to form complexes with p85alpha and tyrosine-phosphorylated IRS-1 with similar efficiency. However, whereas the kinase activity of p110beta, either endogenous or exogeneous, was markedly enhanced by insulin stimulation, only very small increases of the activity of p110alpha were observed. Interestingly, overexpression of p110beta increased insulin-induced glucose uptake by 3T3-L1 cells without significantly affecting basal glucose transport, whereas overexpression of p110alpha increased both basal and insulin-stimulated glucose uptake. Finally, microinjection of anti-p110beta neutralizing antibody into 3T3-L1 adipocytes abolished insulin-induced translocation of GLUT4 to the cell surface almost completely, whereas anti-p110alpha neutralizing antibody did only slightly. Together, these findings suggest that p110beta plays a crucial role in cellular activities evoked acutely by insulin. (Keyword) 3T3 Cells / Adipocytes / Animals / CCAAT-Enhancer-Binding Proteins / cell differentiation / Class Ia Phosphatidylinositol 3-Kinase / DNA-Binding Proteins / Deoxyglucose / Gene Expression Regulation, Enzymologic / glucose / Glucose Transporter Type 4 / insulin / Isoenzymes / enzyme kinetics / Mice / Monosaccharide Transport Proteins / Muscle Proteins / Nuclear Proteins / Phosphatidylinositol 3-Kinases / Transfection (Link to Publication Site) ● Publication site (DOI): 10.1074/jbc.M910391199 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10748220 ● Search Scopus @ Elsevier (PMID): 10748220 ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M910391199 (DOI: 10.1074/jbc.M910391199, PubMed: 10748220)
47.	T Ijuin, Y Mochizuki, K Fukami, Makoto Funaki, T Asano and T Takenawa : Identification and characterization of a novel inositol polyphosphate 5-phosphatase., The Journal of Biological Chemistry, Vol.275, No.15, 10870-10875, 2000. (Summary) We have identified a cDNA encoding a novel inositol polyphosphate 5-phosphatase. It contains two highly conserved catalytic motifs for 5-phosphatase, has a molecular mass of 51 kDa, and is ubiquitously expressed and especially abundant in skeletal muscle, heart, and kidney. We designated this 5-phosphatase as SKIP (Skeletal muscle and Kidney enriched Inositol Phosphatase). SKIP is a simple 5-phosphatase with no other motifs. Baculovirus-expressed recombinant SKIP protein exhibited 5-phosphatase activities toward inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol (PtdIns) 4,5-bisphosphate, and PtdIns 3,4, 5-trisphosphate but has 6-fold more substrate specificity for PtdIns 4,5-bisphosphate (K(m) = 180 microM) than for inositol 1,4, 5-trisphosphate (K(m) = 1.15 mM). The ectopic expression of SKIP protein in COS-7 cells and immunostaining of neuroblastoma N1E-115 cells revealed that SKIP is expressed in cytosol and that loss of actin stress fibers occurs where the SKIP protein is concentrated. These results imply that SKIP plays a negative role in regulating the actin cytoskeleton through hydrolyzing PtdIns 4,5-bisphosphate. (Keyword) Amino Acid Sequence / Animals / Base Sequence / Blotting, Northern / COS Cells / Cloning, Molecular / DNA, Complementary / Humans / Molecular Sequence Data / Phosphoric Monoester Hydrolases / Rabbits / Substrate Specificity (Link to Publication Site) ● Publication site (DOI): 10.1074/jbc.275.15.10870 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10753883 ● Search Scopus @ Elsevier (PMID): 10753883 ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.275.15.10870 (DOI: 10.1074/jbc.275.15.10870, PubMed: 10753883)
48.	K Inukai, Makoto Funaki, M Nawano, H Katagiri, T Ogihara, M Anai, Y Onishi, H Sakoda, H Ono, Y Fukushima, M Kikuchi, Y Oka and T Asano : The N-terminal 34 residues of the 55 kDa regulatory subunits of phosphoinositide 3-kinase interact with tubulin., The Biochemical Journal, Vol.346 Pt 2, 483-489, 2000. (Summary) There are five regulatory subunit isoforms of phosphoinositide 3-kinase (PI 3-kinase), which are classified into three groups: proteins of 85 kDa (p85alpha and p85beta), 55 kDa (p55alpha and p55gamma) and 50 kDa (p50alpha). Structural differences between the three groups reside in the N-terminus. To elucidate the unique functional role of the 55 kDa regulatory subunits, GST (glutathione S-transferase) fusion proteins containing a unique N-terminal portion consisting of a 34-amino-acid sequence of p55alpha or p55gamma (GST-p55alpha/gammaN(1-34)) were used as affinity matrices to screen rat brain cell extracts for proteins to which this portion binds specifically. A protein that bound was identified as beta-tubulin by protein sequencing. In addition, not only the beta isoform of tubulin, but also the alpha and gamma isoforms, were detected in the protein absorbed from cell lysates with GST-p55gammaN(1-34) and GST-p55alphaN(1-34) by immunoblotting. Indeed, the only regulatory subunit present in the purified microtubule assembly from rat brain was the 55 kDa isoform; neither 85 kDa nor 50 kDa subunits were detected. These results indicate endogenous binding of 55 kDa regulatory subunits of PI 3-kinase to tubulin in the brain. Finally, we measured tubulin-associated PI 3-kinase activity in CHO/IR cells overexpressing each of the five regulatory subunit isoforms. Only in cells expressing p55alpha or p55gamma was there a significant elevation of tubulin-associated PI 3-kinase activity in response to insulin. These results suggest that the p55alpha and p55gamma regulatory subunits have important roles in regulating PI 3-kinase activity, particularly for microtubules at the cell periphery. (Keyword) Amino Acid Sequence / Animals / Binding Sites / CHO Cells / Cricetinae / Molecular Sequence Data / Peptide Fragments / Phosphatidylinositol 3-Kinases / Protein Binding / Protein Isoforms / Rats / Recombinant Fusion Proteins / Tubulin (Link to Publication Site) ● Publication site (DOI): 10.1042/bj3460483 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10677370 ● Search Scopus @ Elsevier (PMID): 10677370 ● Search Scopus @ Elsevier (DOI): 10.1042/bj3460483 (DOI: 10.1042/bj3460483, PubMed: 10677370)
49.	M Nawano, K Ueta, A Oku, K Arakawa, A Saito, Makoto Funaki, M Anai, M Kikuchi, Y Oka and T Asano : Hyperglycemia impairs the insulin signaling step between PI 3-kinase and Akt/PKB activations in ZDF rat liver., Biochemical and Biophysical Research Communications, Vol.266, No.1, 252-256, 1999. (Summary) Akt/PKB activation is reportedly essential for insulin-induced glucose metabolism in the liver. During the hypoinsulinemic and hyperglycemic phase in the Zucker diabetic fatty (ZDF) rat liver, insulin-induced phosphorylations of the insulin receptor (IR) and insulin receptor substrate (IRS)-1/2 were significantly enhanced. Similarly, phosphatidylinositol (PI) 3-kinase activities associated with IRS-1/2 were markedly increased in ZDF rat liver compared with those in the control lean rat liver. However, interestingly, insulin-induced phosphorylation and kinase activation of Akt/PKB were severely suppressed. The restoration of normoglycemia by sodium-dependent glucose transporter (SGLT) inhibitor to ZDF rats normalized elevated PI 3-kinase activation and phosphorylation of IR and IRS-1/2 to lean control rat levels. In addition, impaired insulin-induced Akt/PKB activation was also normalized. These results suggest that chronic hyperglycemia reduces the efficiency of the activation step from PI 3-kinase to Akt/PKB kinase and that this impairment is the molecular mechanism underlying hyperglycemia-induced insulin resistance in the liver. (Keyword) Animals / Blood Glucose / Body Weight / Carbonates / Dose-Response Relationship, Drug / Enzyme Activation / Glucosides / Hyperglycemia / insulin / Insulin Receptor Substrate Proteins / Intracellular Signaling Peptides and Proteins / Liver / Membrane Glycoproteins / Monosaccharide Transport Proteins / Phosphatidylinositol 3-Kinases / Phosphoproteins / phosphorylation / Protein-Serine-Threonine Kinases / Proto-Oncogene Proteins / Proto-Oncogene Proteins c-akt / Rats / Rats, Zucker / Receptor, Insulin / signal transduction / Sodium-Glucose Transporter 1 / Time Factors (Link to Publication Site) ● Publication site (DOI): 10.1006/bbrc.1999.1797 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10581198 ● Search Scopus @ Elsevier (PMID): 10581198 ● Search Scopus @ Elsevier (DOI): 10.1006/bbrc.1999.1797 (DOI: 10.1006/bbrc.1999.1797, PubMed: 10581198)
50.	Y Fukushima, Y Ohmachi, T Asano, M Nawano, Makoto Funaki, M Anai, T Ogihara, K Inukai, Y Onishi, H Sakoda, T Saitoh, N Matsuhashi, Y Yazaki and K Sugano : Localization of the histamine H(2) receptor, a target for antiulcer drugs, in gastric parietal cells., Digestion, Vol.60, No.6, 522-527, 1999. (Summary) The H(2) receptor is localized in the gastric parietal cell. (Keyword) Amino Acid Sequence / Animals / Anti-Ulcer Agents / Antibodies, Monoclonal / Basement Membrane / COS Cells / Cell Membrane / DNA Primers / gene expression / H(+)-K(+)-Exchanging ATPase / Histamine H2 Antagonists / Mice / Mice, Inbred ICR / Microscopy, Confocal / Molecular Sequence Data / Parietal Cells, Gastric / Receptors, Histamine H2 / Sequence Homology, Amino Acid / Transfection (Link to Publication Site) ● Publication site (DOI): 10.1159/000007701 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10545721 ● Search Scopus @ Elsevier (PMID): 10545721 ● Search Scopus @ Elsevier (DOI): 10.1159/000007701 (DOI: 10.1159/000007701, PubMed: 10545721)
51.	M Nawano, M Anai, Makoto Funaki, H Kobayashi, A Kanda, Y Fukushima, K Inukai, T Ogihara, H Sakoda, Y Onishi, M Kikuchi, Y Yazaki, Y Oka and T Asano : Imidapril, an angiotensin-converting enzyme inhibitor, improves insulin sensitivity by enhancing signal transduction via insulin receptor substrate proteins and improving vascular resistance in the Zucker fatty rat., Metabolism: Clinical and Experimental, Vol.48, No.10, 1248-1255, 1999. (Summary) Angiotensin-converting enzyme (ACE) inhibitors are antihypertensive agents, that inhibit the conversion of angiotensin I to angiotensin II, resulting in smooth-muscle relaxation and a reduction of vascular resistance. Recently, it has been suggested that ACE inhibitors improve insulin resistance in diabetic patients. To investigate the effect of an ACE inhibitor on insulin sensitivity, insulin signaling, and circulation, imidapril was administered orally or intraduodenally to Zucker fatty rats. Oral administration of imidapril improved insulin sensitivity based on the results of an oral glucose tolerance test (OGTT) and a decrease in urinary glucose secretion. Phosphatidylinositol 3-kinase (PI 3-kinase) activity associated with hepatic insulin receptor substrate-1 (IRS-1) in the insulin-stimulated condition was significantly enhanced 110% without a significant alteration in tyrosine phosphorylation of IRS-1 in the imidapril-treated group. In muscle, IRS-1 tyrosine phosphorylation and PI 3-kinase activity associated with IRS-1 in the insulin-stimulated condition were enhanced 70% and 20%, respectively, in the imidapril-treated group. In contrast, an alteration of the IRS-2 pathway was observed only in liver; a significant insulin-induced increase in the IRS-2-associated PI 3-kinase over the basal level was observed in the imidapril-treated group but not in the control. In addition, treatment with imidapril was shown to significantly reduce blood pressure and increase blood flow in the liver and muscle. These results suggest that the ACE inhibitor imidapril may improve insulin sensitivity not only by acting directly on the insulin signaling pathway but also by increasing blood flow in tissues via normalization of vascular resistance, a major cause of hypertension. (Keyword) Angiotensin-Converting Enzyme Inhibitors / Animals / Blood Glucose / blood pressure / Female / Glucose Tolerance Test / Heart Rate / Imidazoles / Imidazolidines / insulin / Insulin Receptor Substrate Proteins / Liver / Liver Circulation / Muscle, Skeletal / obesity / Phosphatidylinositol 3-Kinases / Phosphoproteins / phosphorylation / Rats / Rats, Zucker / Receptor, Insulin / Regional Blood Flow / signal transduction / Vascular Resistance (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10535386 ● Search Scopus @ Elsevier (PMID): 10535386 (PubMed: 10535386)
52.	Makoto Funaki, H Katagiri, A Kanda, M Anai, M Nawano, T Ogihara, K Inukai, Y Fukushima, H Ono, Y Yazaki, M Kikuchi, Y Oka and T Asano : p85/p110-type phosphatidylinositol kinase phosphorylates not only the D-3, but also the D-4 position of the inositol ring., The Journal of Biological Chemistry, Vol.274, No.31, 22019-22024, 1999. (Summary) Activation of p85/p110-type phosphatidylinositol (PI) kinase has been implicated in various cellular activities. This PI kinase phosphorylates the D-4 position with a similar or higher efficiency than the D-3 position when trichloroacetic acid-treated cell membrane is used as a substrate, although it phosphorylates almost exclusively the D-3 position of the inositol ring in phosphoinositides when purified PI is used as a substrate. Furthermore, the lipid kinase activities of p110 for both the D-3 and D-4 positions were completely abolished by introducing kinase-dead point mutations in their lipid kinase domains (DeltaKinalpha and DeltaKinbeta, respectively). In addition, both PI 3- and PI 4-kinase activities of p110alpha and p110beta immunoprecipitates were similarly inhibited by either wortmannin or LY294002, specific inhibitors of p110. Insulin induced phosphorylation of not only the D-3 position, but also the D-4 position. Indeed, overexpression of p110 in Sf9 or 3T3-L1 cells induced marked phosphorylation of the D-4 position to a level comparable to or much greater than that of D-3, whereas inhibition of endogenous p85/p110-type PI kinase via overexpression of dominant-negative p85alpha (Deltap85alpha) in 3T3-L1 adipocytes abolished insulin-induced synthesis of both. Thus, p85/p110-type PI kinase phosphorylates the D-4 position of phosphoinositides more efficiently than the D-3 position in vivo, and each of the D-3- or D-4-phosphorylated phosphoinositides may transmit signals downstream. (Keyword) 1-Phosphatidylinositol 4-Kinase / 3T3 Cells / Androstadienes / Animals / Cell Line / Chromones / Enzyme Activation / Enzyme Inhibitors / Mice / Morpholines / Mutagenesis, Site-Directed / Phosphatidylinositol 3-Kinases / Phosphatidylinositols / Phosphorus Radioisotopes / phosphorylation / Point Mutation / Recombinant Proteins / Spodoptera / Substrate Specificity / Transfection (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10419527 ● Search Scopus @ Elsevier (PMID): 10419527 (PubMed: 10419527)
53.	H Sakoda, T Ogihara, M Anai, Makoto Funaki, K Inukai, H Katagiri, Y Fukushima, Y Onishi, H Ono, Y Yazaki, M Kikuchi, Y Oka and T Asano : No correlation of plasma cell 1 overexpression with insulin resistance in diabetic rats and 3T3-L1 adipocytes., Diabetes, Vol.48, No.7, 1365-1371, 1999. (Summary) Membrane glycoprotein plasma cell 1 (PC-1) has been shown to be increased in type 2 diabetes and involved in insulin resistance through inhibiting the insulin receptor tyrosine kinase, which was demonstrated using cultured breast cancer cells. However, other reports have shown contradictory results in Chinese hamster ovary cells and in vitro kinase assay. Thus, we considered it necessary to investigate the effect of PC-1 using highly insulin-sensitive cells. Here, we used two of the following approaches: 1) investigating PC-1 expression levels in insulin-responsive tissues in rat models of diabetes and 2) overexpressing PC-1 in 3T3-L1 adipocytes. We found that PC-1 was highly expressed in insulin-responsive tissues, such as liver and adipose tissue, in normal rats. However, high-fat feeding or streptozotocin-induced diabetes did not change its expression levels in liver, adipose tissue, and skeletal muscle. Thus, PC-1 expression levels were not associated with high-fat-diet-induced insulin resistance or hyperglycemia. Although PC-1 was increased in adipose tissue in Zucker fatty rats (protein level, by 50%; mRNA level, by 90%), its expression levels in liver and skeletal muscle, tissues that are more responsible for whole body glucose metabolism than adipose tissue, did not significantly differ from those in normal rats. Next, we overexpressed PC-1 in 3T3-L1 adipocytes using an adenovirus transfection system. PC-1 expression was markedly increased to a level 16-fold greater than that in normal human adipose tissue, which is higher than the previously reported levels in diabetic patients. However, insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1, activation of phosphatidylinositol 3-kinase, and glucose uptake were not affected by PC-1 overexpression. These results strongly suggest that increased PC-1 expression is not causally related to insulin resistance. (Keyword) 3T3 Cells / Adipocytes / Amino Acid Sequence / Animals / Base Sequence / Diabetes Mellitus, Experimental / Gene Expression Regulation, Enzymologic / Humans / insulin resistance / Male / Membrane Glycoproteins / Mice / Molecular Sequence Data / obesity / Phosphoric Diester Hydrolases / Pyrophosphatases / Rats / Rats, Sprague-Dawley / Rats, Zucker / Sequence Homology, Amino Acid (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10389840 ● Search Scopus @ Elsevier (PMID): 10389840 (PubMed: 10389840)
54.	M Anai, Makoto Funaki, T Ogihara, A Kanda, Y Onishi, H Sakoda, K Inukai, M Nawano, Y Fukushima, Y Yazaki, M Kikuchi, Y Oka and T Asano : Enhanced insulin-stimulated activation of phosphatidylinositol 3-kinase in the liver of high-fat-fed rats., Diabetes, Vol.48, No.1, 158-169, 1999. (Summary) Insulin receptor substrate (IRS)-1 and IRS-2, which mediate phosphatidylinositol (PI) 3-kinase activation, play essential roles in insulin-induced translocation of GLUT4 and in glycogen synthesis. In this study, we investigated the process of PI 3-kinase activation via binding with IRS-1 and -2 in liver, muscle, and fat of high-fat-fed rats, a model of insulin-resistant diabetes. In the liver of high-fat-fed rats, insulin increased the PI 3-kinase regulatory subunit p85alpha and the PI 3-kinase activities associated with IRS-1 3.6- and 2.4-fold, and with IRS-2, 4.7- and 3.0-fold, respectively, compared with those in control rats. The tyrosine phosphorylation levels of IRS-1 and IRS-2 were not significantly altered, however. In contrast with the liver, tyrosine phosphorylation levels and associated PI 3-kinase proteins and activities were decreased in the muscle and adipose tissue of high-fat-fed rats. Thus, high-fat feeding appears to cause insulin resistance in the liver by a mechanism different from the impaired PI 3-kinase activation observed in muscle and adipose tissue. Taking into consideration that hepatic PI 3-kinase activation is severely impaired in obese diabetic models such as Zucker fatty rats, it is possible that the mechanism by which a high-fat diet causes insulin resistance is quite different from that associated with obesity and overeating due to abnormality in the leptin system. This is the first report to show increased PI 3-kinase activation by insulin in an insulin-resistant diabetic animal model. These findings may be important for understanding the mechanism of insulin resistance in human NIDDM, since a high-fat diet is considered to be one of the major factors exacerbating insulin insensitivity in humans. (Keyword) Adipose Tissue / Animals / Dietary Fats / Enzyme Activation / Epididymis / insulin / Insulin Receptor Substrate Proteins / insulin resistance / Intracellular Signaling Peptides and Proteins / Liver / Male / Muscles / Phosphatidylinositol 3-Kinases / Phosphoproteins / phosphorylation / RNA, Messenger / Rats / Rats, Sprague-Dawley / Reference Values / Tyrosine (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9892238 ● Search Scopus @ Elsevier (PMID): 9892238 (PubMed: 9892238)
55.	M Anai, H Ono, Makoto Funaki, Y Fukushima, K Inukai, T Ogihara, H Sakoda, Y Onishi, Y Yazaki, M Kikuchi, Y Oka and T Asano : Different subcellular distribution and regulation of expression of insulin receptor substrate (IRS)-3 from those of IRS-1 and IRS-2., The Journal of Biological Chemistry, Vol.273, No.45, 29686-29692, 1998. (Summary) Adipocytes contain three major substrate proteins of the insulin receptor, termed IRS-1, IRS-2, and IRS-3. We demonstrated that IRS-1 and IRS-2 are located mainly in the low density microsome (LDM) fraction and are tyrosine phosphorylated in response to insulin stimulation, leading to phosphatidylinositol (PI) 3-kinase activation. In contrast, IRS-3 is located mainly in the plasma membrane (PM) fraction and contributes to PI 3-kinase activation in the PM fraction. The different cellular localizations of IRS proteins may account for the mechanism of insulin resistance induced by a high fat diet, considering that PI 3-kinase activation in the LDM fraction is reportedly essential for the translocation of GLUT4 in adipocytes. High fat feeding in rats increased both protein and mRNA levels of IRS-3 but decreased those of IRS-1 and IRS-2 in epididymal adipocytes. As a result, selective impairment of insulin-induced PI 3-kinase activation was observed in the LDM fraction, whereas PI 3-kinase activation was conserved in the PM fraction. This is the first report showing that different IRS proteins function in different subcellular compartments, which may contribute to determining the insulin sensitivity in adipocytes. (Keyword) Adipocytes / Animals / Cell Membrane / Dietary Fats / Gene Expression Regulation / insulin / Insulin Receptor Substrate Proteins / insulin resistance / Intracellular Signaling Peptides and Proteins / Male / Microsomes / Phosphatidylinositol 3-Kinases / Phosphoproteins / Precipitin Tests / Rats / Rats, Sprague-Dawley / Subcellular Fractions (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9792680 ● Search Scopus @ Elsevier (PMID): 9792680 (PubMed: 9792680)
56.	J Terasaki, M Anai, Makoto Funaki, T Shibata, K Inukai, T Ogihara, H Ishihara, H Katagiri, Y Onishi, H Sakoda, Y Fukushima, Y Yazaki, M Kikuchi, Y Oka and T Asano : Role of JTT-501, a new insulin sensitiser, in restoring impaired GLUT4 translocation in adipocytes of rats fed a high fat diet., Diabetologia, Vol.41, No.4, 400-409, 1998. (Summary) JTT-501 is an insulin-sensitising compound with an isoxazolidinedione rather than a thiazolidionedione structure. Sprague-Dawley rats fed a high fat diet for 2 weeks were used as an animal model of insulin resistance, and JTT-501 was administered for the final week of the diet. An euglycaemic glucose clamp study showed that the glucose infusion rate (GIR) required to maintain euglycaemia was 57% lower in rats fed a high fat diet than in control rats, and that JTT-501 treatment restored the reduction in GIR produced by the high fat diet. To explain the mechanisms underlying the effects of a high fat diet and JTT-501 treatment, epididymal fat pads were excised and used in the analysis of insulin action. The high fat diet caused: (1) a 58% decrease in insulin receptor substrate-1 (IRS-1) content with a 58% decrease in IRS-1 tyrosine phosphorylation; (2) reductions of 56% and 73% respectively in insulin-induced maximal PI 3-kinase activation in anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates; (3) a 46% reduction in the glucose transporter protein, GLUT4 content and, consequently, (4) severely impaired insulin-induced GLUT4 translocation to the plasma membrane and glucose uptake in adipocytes. JTT-501 treatment restored appreciably the protein content and tyrosine phosphorylation level of IRS-1. Insulin-stimulated PI 3-kinase activation was also restored in anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates. As reflected by these improvements in insulin signalling, JTT-501 treatment improved considerably insulin-induced GLUT4 translocation to the plasma membrane as well as insulin-induced glucose uptake. However, JTT-501 had no effect on the decrease in GLUT4 content produced by the high fat diet. These observations suggest that JTT-501 enhances insulin signalling and may be effective in reducing insulin resistance. (Keyword) Adipocytes / Animals / Blood Glucose / Body Weight / Cell Membrane / Cells, Cultured / Dietary Fats / Glucose Clamp Technique / Glucose Transporter Type 4 / Humans / Hypoglycemic Agents / Infusions, Intravenous / insulin / Isoxazoles / enzyme kinetics / Male / Monosaccharide Transport Proteins / Muscle Proteins / Rats / Rats, Sprague-Dawley / Recombinant Proteins (Link to Publication Site) ● Publication site (DOI): 10.1007/s001250050922 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9562343 ● Search Scopus @ Elsevier (PMID): 9562343 ● Search Scopus @ Elsevier (DOI): 10.1007/s001250050922 (DOI: 10.1007/s001250050922, PubMed: 9562343)
57.	M Anai, Makoto Funaki, T Ogihara, J Terasaki, K Inukai, H Katagiri, Y Fukushima, Y Yazaki, M Kikuchi, Y Oka and T Asano : Altered expression levels and impaired steps in the pathway to phosphatidylinositol 3-kinase activation via insulin receptor substrates 1 and 2 in Zucker fatty rats., Diabetes, Vol.47, No.1, 13-23, 1998. (Summary) To elucidate the mechanism of obesity-related insulin resistance, we investigated the impaired steps in the processes of phosphatidylinositol (PI) 3-kinase activation through binding with insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in liver and muscle of Zucker fatty rats. The expressions of IRS-1 and IRS-2 were shown to be downregulated in both liver and muscle in fatty rats (hepatic IRS-1, 83%; hepatic IRS-2, 45%; muscle IRS-1, 60%; muscle IRS-2, 78%), resulting in decreased tyrosine phosphorylation in response to insulin stimulation. Despite the decrease in the tyrosine phosphorylation levels of hepatic IRS-1 and IRS-2 being mild to moderate, associated PI 3-kinase activities were dramatically decreased in fatty rats (IRS-1, 14%; IRS-2, 10%), which may suggest alteration in the sites of phosphorylated tyrosine residues of hepatic IRS-1 and IRS-2. In addition, we demonstrated that the expressions of p85alpha and p55alpha regulatory subunits of PI 3-kinase were reduced (p85alpha, 67%; p55alpha, 54%), and that the p50alpha regulatory subunit was markedly upregulated (176%) in the livers of fatty rats without apparent alterations in expressions of the catalytic subunits p110alpha and p110beta. These alterations may reflect the obesity-related insulin resistance commonly observed in human NIDDM. (Keyword) Albumins / Amino Acid Sequence / Animals / Base Sequence / Blood Glucose / Down-Regulation / Enzyme Activation / Female / Gene Expression Regulation, Enzymologic / insulin / Insulin Receptor Substrate Proteins / insulin resistance / Intracellular Signaling Peptides and Proteins / Liver / Molecular Sequence Data / Muscle, Skeletal / Myosins / Phosphatidylinositol 3-Kinases / Phosphoproteins / phosphorylation / RNA, Messenger / Rats / Rats, Zucker / signal transduction / Tyrosine (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9421369 ● Search Scopus @ Elsevier (PMID): 9421369 (PubMed: 9421369)
58.	T Ogihara, T Isobe, T Ichimura, M Taoka, Makoto Funaki, H Sakoda, Y Onishi, K Inukai, M Anai, Y Fukushima, M Kikuchi, Y Yazaki, Y Oka and T Asano : 14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain., The Journal of Biological Chemistry, Vol.272, No.40, 25267-25274, 1997. (Summary) Insulin binding to its receptor induces the phosphorylation of cytosolic substrates, insulin receptor substrate (IRS)-1 and IRS-2, which associate with several Src homology-2 domain-containing proteins. To identify unique IRS-1-binding proteins, we screened a human heart cDNA library with 32P-labeled recombinant IRS-1 and obtained two isoforms (epsilon and zeta) of the 14-3-3 protein family. 14-3-3 protein has been shown to associate with IRS-1 in L6 myotubes, HepG2 hepatoma cells, Chinese hamster ovary cells, and bovine brain tissue. IRS-2, a protein structurally similar to IRS-1, was also shown to form a complex with 14-3-3 protein using a baculovirus expression system. The amount of 14-3-3 protein associated with IRS-1 was not affected by insulin stimulation but was increased significantly by treatment with okadaic acid, a potent serine/threonine phosphatase inhibitor. Peptide inhibition experiments using phosphoserine-containing peptides of IRS-1 revealed that IRS-1 contains three putative binding sites for 14-3-3 protein (Ser-270, Ser-374, and Ser-641). Among these three, the motif around Ser-270 is located in the phosphotyrosine binding domain of IRS-1, which is responsible for the interaction with the insulin receptor. Indeed, a truncated mutant of IRS-1 consisting of only the phosphotyrosine binding domain retained the capacity to bind to 14-3-3 protein in vivo. Finally, the effect of 14-3-3 protein binding on the insulin-induced phosphorylation of IRS-1 was investigated. Phosphoamino acid analysis revealed that IRS-1 coimmunoprecipitated with anti-14-3-3 antibody to be weakly phosphorylated after insulin stimulation, on tyrosine as well as serine residues, compared with IRS-1 immunoprecipitated with anti-IRS-1 antibody. Thus, the association with 14-3-3 protein may play a role in the regulation of insulin sensitivity by interrupting the association between the insulin receptor and IRS-1. (Keyword) 14-3-3 Proteins / adenosine triphosphate / Amino Acid Sequence / Animals / Binding Sites / brain / CHO Cells / Carcinoma, Hepatocellular / Cattle / Cell Line / Cricetinae / Gene Library / Humans / insulin / Insulin Receptor Substrate Proteins / Intracellular Signaling Peptides and Proteins / Liver Neoplasms / Mice / Molecular Sequence Data / myocardium / Okadaic Acid / Phosphoproteins / Phosphorus Radioisotopes / Phosphotyrosine / Protein Biosynthesis / Proteins / Rats / Receptor, Insulin / Recombinant Proteins / Sequence Alignment / Sequence Homology, Amino Acid / Spodoptera / Transfection / Tumor Cells, Cultured / Tyrosine 3-Monooxygenase (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9312143 ● Search Scopus @ Elsevier (PMID): 9312143 (PubMed: 9312143)
59.	Y Fukushima, T Asano, T Saitoh, M Anai, Makoto Funaki, T Ogihara, H Katagiri, N Matsuhashi, Y Yazaki and K Sugano : Oligomer formation of histamine H2 receptors expressed in Sf9 and COS7 cells., FEBS Letters, Vol.409, No.2, 283-286, 1997. (Summary) A histamine H2 receptor, which had been mutated at its glycosylation site and tagged at its N-terminus with an HA tag (HA-H2 receptor), was expressed in Sf9 cells and COS7 cells. Immunoprecipitation and immunoblotting of HA-H2 receptors with alphaHA antibody revealed four bands of 31.5 +/- 2.5 kDa, 59.0 +/- 6.0 kDa, 80.5 +/- 4.5 kDa and 120 kDa. These bands were also detected by immunoblot using anti-H2 receptor serum (C-terminus). In addition, H2 receptors without the HA-tag coimmunoprecipitated with HA-tagged H2 receptors devoid of the 51 C-terminal amino acids, via immunoprecipitation with alphaHA antibody, when the two receptors were coexpressed. These results suggest that H2 receptors are present as receptor oligomers and that the C-terminal portion is not involved in the formation of these oligomers. (Keyword) Animals / COS Cells / Cloning, Molecular / Hemagglutinins / Immunoblotting / molecular weight / Precipitin Tests / Receptors, Histamine H2 / Spodoptera (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9202162 ● Search Scopus @ Elsevier (PMID): 9202162 (PubMed: 9202162)
60.	T Ogihara, C B Shin, M Anai, H Katagiri, K Inukai, Makoto Funaki, Y Fukushima, H Ishihara, K Takata, M Kikuchi, Y Yazaki, Y Oka and T Asano : Insulin receptor substrate (IRS)-2 is dephosphorylated more rapidly than IRS-1 via its association with phosphatidylinositol 3-kinase in skeletal muscle cells., The Journal of Biological Chemistry, Vol.272, No.19, 12868-12873, 1997. (Summary) Insulin receptor substrate (IRS)-2 is structurally and functionally similar to IRS-1. Indeed, stimulation with insulin or insulin-like growth factor I led to the rapid tyrosine phosphorylation of both IRS-1 and IRS-2, which in turn activated phosphatidylinositol (PI) 3-kinase in L6 cells and rat skeletal muscle. However, IRS-2 was rapidly dephosphorylated (3-10 min after the addition of insulin/insulin-like growth factor I), whereas IRS-1 phosphorylation continued for at least 60 min. The time courses of the PI 3-kinase activity associated with IRS-1 and IRS-2 paralleled the tyrosine phosphorylation of these proteins. Preincubation with sodium orthovanadate, an inhibitor of protein tyrosine phosphatase, blocked the rapid dephosphorylation of IRS-2, suggesting the involvement of tyrosine phosphatase. The activation of PI 3-kinase apparently plays an important role in the rapid dephosphorylation of IRS-2, as IRS-2 dephosphorylation was inhibited markedly by suppressing PI 3-kinase activity with wortmannin or overexpression of the dominant negative p85 subunit of PI 3-kinase, which cannot bind the p110 catalytic subunit. In addition, platelet-derived growth factor stimulation prior to insulin stimulation decreased IRS-associated PI 3-kinase and significantly inhibited the dephosphorylation of IRS-2. Taken together, these observations suggest that IRS-2 plays a unique role in mediating the signals from the insulin receptor to downstream molecules and that this effect is more transient than that of IRS-1. Tyrosine phosphatase and IRS-associated PI 3-kinase activity thus contribute to the rapid dephosphorylation of IRS-2. (Keyword) Androstadienes / Animals / Cells, Cultured / Enzyme Inhibitors / Insulin Receptor Substrate Proteins / Intracellular Signaling Peptides and Proteins / Muscle, Skeletal / Phosphatidylinositol 3-Kinases / Phosphoproteins / phosphorylation / Phosphotransferases (Alcohol Group Acceptor) / Platelet-Derived Growth Factor / Rats / Tyrosine (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9139749 ● Search Scopus @ Elsevier (PMID): 9139749 (PubMed: 9139749)
61.	K Inukai, Makoto Funaki, T Ogihara, H Katagiri, A Kanda, M Anai, Y Fukushima, T Hosaka, M Suzuki, C B Shin, K Takata, Y Yazaki, M Kikuchi, Y Oka and T Asano : p85alpha gene generates three isoforms of regulatory subunit for phosphatidylinositol 3-kinase (PI 3-Kinase), p50alpha, p55alpha, and p85alpha, with different PI 3-kinase activity elevating responses to insulin., The Journal of Biological Chemistry, Vol.272, No.12, 7873-7882, 1997. (Summary) Phosphatidylinositol 3-kinase (PI 3-kinase) is stimulated by association with a variety of tyrosine kinase receptors and intracellular tyrosine-phosphorylated substrates. We isolated a cDNA that encodes a 50-kDa regulatory subunit of PI 3-kinase with an expression cloning method using 32P-labeled insulin receptor substrate-1 (IRS-1). This 50-kDa protein contains two SH2 domains and an inter-SH2 domain of p85alpha, but the SH3 and bcr homology domains of p85alpha were replaced by a unique 6-amino acid sequence. Thus, this protein appears to be generated by alternative splicing of the p85alpha gene product. We suggest that this protein be called p50alpha. Northern blotting using a specific DNA probe corresponding to p50alpha revealed 6.0- and 2.8-kb bands in hepatic, brain, and renal tissues. The expression of p50alpha protein and its associated PI 3-kinase were detected in lysates prepared from the liver, brain, and muscle using a specific antibody against p50alpha. Taken together, these observations indicate that the p85alpha gene actually generates three protein products of 85, 55, and 50 kDa. The distributions of the three proteins (p85alpha, p55alpha, and p50alpha), in various rat tissues and also in various brain compartments, were found to be different. Interestingly, p50alpha forms a heterodimer with p110 that can as well as cannot be labeled with wortmannin, whereas p85alpha and p55alpha associate only with p110 that can be wortmannin-labeled. Furthermore, p50alpha exhibits a markedly higher capacity for activation of associated PI 3-kinase via insulin stimulation and has a higher affinity for tyrosine-phosphorylated IRS-1 than the other isoforms. Considering the high level of p50alpha expression in the liver and its marked responsiveness to insulin, p50alpha appears to play an important role in the activation of hepatic PI 3-kinase. Each of the three alpha isoforms has a different function and may have specific roles in various tissues. (Keyword) Amino Acid Sequence / Animals / Blotting, Western / brain / CHO Cells / enzyme catalysis / Cricetinae / DNA, Complementary / Enzyme Activation / Humans / insulin / Insulin Receptor Substrate Proteins / Kidney / Liver / Molecular Sequence Data / Phosphatidylinositol 3-Kinases / Phosphoproteins / Phosphotransferases (Alcohol Group Acceptor) / RNA, Messenger / Rats / Receptor, Insulin / Recombinant Proteins / Sequence Homology, Amino Acid / Tumor Cells, Cultured (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9065454 ● Search Scopus @ Elsevier (PMID): 9065454 (PubMed: 9065454)
62.	Y Fukushima, T Asano, H Katagiri, M Aihara, T Saitoh, M Anai, Makoto Funaki, T Ogihara, K Inukai, N Matsuhashi, Y Oka, Y Yazaki and K Sugano : Interaction between the two signal transduction systems of the histamine H2 receptor: desensitizing and sensitizing effects of histamine stimulation on histamine-dependent cAMP production in Chinese hamster ovary cells., The Biochemical Journal, Vol.320 ( Pt 1), 27-32, 1996. (Summary) The histamine H2 receptor is a member of the family of G-protein-coupled receptors and is linked to the activation of adenylate cyclase phospholipase C (PLC). In this study we examined the effects of protein kinase C (PKC) activation in Chinese hamster ovary (CHO) cells stably expressing canine histamine H2 receptors. Pretreatment with 100 nM phorbol 12-myristate 13-acetate at 37 degrees C for 15 min led to significant potentiation of histamine-dependent and forskolin-dependent cAMP production, whereas the biologically inactive phorbol ester, 4 alpha-phorbol 12, 13-didecanoate, was without effect. These potentiating effects were abolished by preincubation with 0.5 microM bisindolylmaleimide, a PKC inhibitor. Thus the activation of PKCs seems to be involved in the potentiation of cAMP production by acting on a post-receptor mechanism. Preincubation of a CHO cell line, CHO-H2R, with 10 microM histamine for 30 min had two effects. Maximal histamine-dependent cAMP production and forskolin-dependent cAMP production were potentiated by 36% and 105.2% respectively. The other effect was a desensitization of the histamine-dependent adenylate cyclase response as demonstrated by a three-fold increase in EC50. Administration of 0.5 microM bisindolylmaleimide before preincubation of CHO-H2R with 10 microM histamine did not alter the desensitizing effect on cAMP production, but did abolish the sensitizing effect. Preincubation of CHO-H2R cells with 10 nM histamine resulted in moderate potentiation, which was also abolished by bisindolylmaleimide, but not in desensitization of the histamine-dependent cAMP production. Thus these results suggest that preincubation with histamine had a sensitizing effect on cAMP production mediated by PLC and PKC activation, as well as a desensitizing effect on the H2 receptor. The former effect is dependent on the intensity of PLC and PKC signals delivered by H2 receptors. The latter effect requires a higher concentration of histamine. (Keyword) Animals / CHO Cells / Colforsin / Cricetinae / Cricetulus / Cyclic AMP / Dogs / histamine / Histamine Agonists / Indoles / Maleimides / Receptors, Histamine H2 / Recombinant Proteins / signal transduction / Tetradecanoylphorbol Acetate (Link to Publication Site) ● Publication site (DOI): 10.1042/bj3200027 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8947463 ● Search Scopus @ Elsevier (PMID): 8947463 ● Search Scopus @ Elsevier (DOI): 10.1042/bj3200027 (DOI: 10.1042/bj3200027, PubMed: 8947463)
63.	K Inukai, M Anai, E Breda Van, Toshio Hosaka, H Katagiri, Makoto Funaki, Y Fukushima, T Ogihara, Y Yazaki, M Kikuchi, Y Oka and T Asano : A novel 55-kDa regulatory subunit for phosphatidylinositol 3-kinase structurally similar to p55PIK Is generated by alternative splicing of the p85alpha gene., The Journal of Biological Chemistry, Vol.271, No.10, 5317-5320, 1996. (Summary) Phosphatidylinositol 3-kinase, which is composed of a 110-kDa catalytic subunit and a regulatory subunit, plays important roles in various cellular signaling mechanisms. We screened a rat brain cDNA expression library with 32P-labeled human IRS-1 protein and cloned cDNAs that were very likely to be generated by alternative splicing of p85alpha gene products. These cDNAs were demonstrated to encode a 55-kDa protein (p55alpha) containing two SH2 domains and an inter-SH2 domain of p85alpha but neither a bcr domain nor a SH3 homology domain. Interestingly, p55 alpha contains a unique 34-amino acid sequence at its NH2 terminus, which is not included in the p85alpha amino acid sequence. This 34-amino acid portion was revealed to be comparable with p55PIK (p55gamma) in length, with a high homology between the two, suggesting that these NH2-terminal domains of p55alpha and p5 gamma may have a specific role that p85 does not. The expression of p55alpha mRNA is most abundant in the brain, but expression is ubiquitous in most rat tissues. Furthermore, it should be noted that the expression of p85alpha mRNA in muscle is almost undetectably low by Northern blotting with a cDNA probe coding for the p85alpha SH3 domain, while the expression of p55alpha can be readily detected. These results suggest that p55 alpha may play an unique regulatory role for phosphatidylinositol 3-kinase in brain and muscle. (Keyword) Alternative Splicing / Amino Acid Sequence / Animals / Base Sequence / brain / Cloning, Molecular / DNA, Complementary / gene expression / Gene Library / Genomic Library / homeostasis / Humans / Immunoblotting / Insulin Receptor Substrate Proteins / Isoenzymes / Macromolecular Substances / Molecular Sequence Data / molecular weight / Muscle, Skeletal / Oligodeoxyribonucleotides / Organ Specificity / Phosphatidylinositol 3-Kinases / Phosphoproteins / Phosphotransferases (Alcohol Group Acceptor) / RNA, Messenger / Rats / Recombinant Proteins / Sequence Homology, Amino Acid / src Homology Domains (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8621382 ● Search Scopus @ Elsevier (PMID): 8621382 (PubMed: 8621382)
64.	K Inukai, T Asano, H Katagiri, M Anai, Makoto Funaki, H Ishihara, K Tsukuda, M Kikuchi, Y Yazaki and Y Oka : Replacement of both tryptophan residues at 388 and 412 completely abolished cytochalasin B photolabelling of the GLUT1 glucose transporter., The Biochemical Journal, Vol.302 ( Pt 2), 355-361, 1994. (Summary) A mutated GLUT1 glucose transporter, a Trp-388, 412 mutant whose tryptophans 388 and 412 were both replaced by leucines, was constructed by site-directed mutagenesis and expressed in Chinese hamster ovary cells. Glucose transport activity was decreased to approx. 30% in the Trp-388, 412 mutant compared with that in the wild type, a similar decrease in transport activity had been observed previously in the Trp-388 mutant and the Trp-412 mutant which had leucine at 388 and 412 respectively. Cytochalasin B labelling of the Trp-388 mutant was only decreased rather than abolished, a result similar to that obtained previously for the Trp-412 mutant. Cytochalasin B labelling was finally abolished completely in the Trp-388, 412 mutant, while cytochalasin B binding to this mutant was decreased to approx. 30% of that of the wild-type GLUT1 at the concentration used for photolabelling. This level of binding is thought to be adequate to detect labelling, assuming that the labelling efficiency of these transporters is similar. These findings suggest that cytochalasin B binds to the transmembrane domain of the glucose transporter in the vicinity of helix 10-11, and is inserted covalently by photoactivation at either the 388 or the 412 site. (Keyword) Animals / Binding Sites / Blotting, Western / CHO Cells / Cricetinae / Cytochalasin B / Deoxyglucose / Electrophoresis, Polyacrylamide Gel / glucose / Glucose Transporter Type 1 / Leucine / Monosaccharide Transport Proteins / Mutagenesis, Site-Directed / Mutation / Tryptophan (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8092986 ● Search Scopus @ Elsevier (PMID): 8092986 (PubMed: 8092986)
65.	E Yano, K Tanaka, Makoto Funaki, K Maeda, C Matsunaga and K Yamaoka : Effect of smoking on pleural thickening in asbestos workers., British Journal of Industrial Medicine, Vol.50, No.10, 898-901, 1993. (Summary) It is well known that an interaction exists between smoking and exposure to asbestos in the occurrence of lung cancer, whereas occurrence of malignant mesothelioma has not been related to smoking. In the case of pleural thickening related to asbestos, there is a disagreement in previous studies as to the effect of smoking. This could be because the diagnosis of pleural changes has a subjective element. Taking this into account, in the present work the maximum width of the pleura was used as an index of pleural changes. Study subjects were 134 asbestos workers of a brake manufacturing company who had received medical checks in 1978 and in 1990. The maximum width of the pleura on the chest x ray films of the workers was measured by two examiners who did not know the year of examination or smoking state of the worker. A general linear model was applied to analyse the effects of smoking, the year of examination, age, and duration of exposure to asbestos. The difference between maximum widths measured in 1978 and 1990 suggested chronological progression. The increase in width during the 12 years, however, did not differ significantly between smokers and nonsmokers. This suggests that smoking does not significantly increase pleural thickening in asbestos workers. (Keyword) Aged / Asbestos / Humans / Male / Middle Aged / Occupational Diseases / Occupational Exposure / Pleura / Pleural Diseases / smoking (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8217848 ● Search Scopus @ Elsevier (PMID): 8217848 (PubMed: 8217848)

Review, Commentary:

1.	Makoto Funaki : Saturated fatty acids and insulin resistance., The Journal of Medical Investigation : JMI, Vol.56, No.3-4, 88-92, Aug. 2009. (Summary) Insulin resistance is one of the pathophysiological features of obesity and type 2 diabetes. Recent findings have linked insulin resistance to chronic low-grade inflammation in white adipose tissue. Excess storage of saturated fat in white adipose tissue due to a modern life style causes hypertrophy and hyperplasia of adipocytes, which exhibit attenuated insulin signaling due to their production and release of saturated fatty acids. These adipocytes recruit macrophages to white adipose tissue and, together with them, initiate a proinflammatory response. Proinflammatory factors and saturated fatty acids secreted into the bloodstream from white adipose tissue impair insulin signaling in non-adipose tissues, which causes whole-body insulin resistance. (Keyword) Adipose Tissue, White / Endocrine System / energy metabolism / fatty acids β-oxidation / Humans / inflammation / insulin resistance / Macrophages / obesity / signal transduction (Tokushima University Institutional Repository) ● Metadata: 111313 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.56.88 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19763019 ● Search Scopus @ Elsevier (PMID): 19763019 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.56.88 (Tokushima University Institutional Repository: 111313, DOI: 10.2152/jmi.56.88, PubMed: 19763019)
2.	Makoto Funaki, H Katagiri, K Inukai, M Kikuchi and T Asano : Structure and function of phosphatidylinositol-3,4 kinase., Cellular Signalling, Vol.12, No.3, 135-142, Mar. 2000. (Summary) Activation of phosphatidylinositol (PI)-kinase is involved in the regulation of a wide array of cellular activities. The enzyme exists as a dimer, consisting of a catalytic and a regulatory subunit. Five isoforms of the regulatory subunit have been identified and classified into three groups comprising respectively 85-kDa, 55-kDa, and 50-kDa proteins. Structural differences in the N-terminal regions of the different group members contribute to defining their binding specificity, their subcellular distributions, and their capacity to activate the 110-kDa catalytic subunit. Two widely distributed isoforms of the catalytic subunit have been identified-p110alpha and p110beta. Despite the fact that they bind to the p85alpha regulatory subunit similarly, p110alpha and p110beta appear to have separate functions within cells and to be activated by different stimuli. Moreover, although p85/p110 PI-kinase almost exclusively phosphorylates the D-3 position of the inositol ring in phosphoinositides when purified PI is used as a substrate in vitro, it appears to phosphorylate the D-4 position with similar or higher efficiency in vivo. Thus, it is highly probable that p85/p110 PI-kinase transmits signals to downstream targets via both D-3- and D-4-phosphorylated phosphoinositides. (Keyword) Animals / Class Ia Phosphatidylinositol 3-Kinase / Humans / Isoenzymes / Phosphatidylinositol 3-Kinases / Phosphatidylinositols / phosphorylation / structureactivity relationship (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10704820 ● Search Scopus @ Elsevier (PMID): 10704820 (PubMed: 10704820)

Proceeding of International Conference:

1.	Akiko Hata, Nanako Aki, Takako Ichihara, Takako Minagawa, Ayako Tamura, Yumi Kuwamura and Makoto Funaki : Serum Adipocyte Fatty Acid Binding Protein Is Related to the Development of Prediabetes: Tokushima Cohort Study, Diabetes, Vol.72, No.Suppl.1, San Diego, Jun. 2023.
2.	Makoto Funaki, Akiko Hata, Mitsuteru Yoshida, Naoki Miyamoto, Takahisa Ikuta, Yuta Uemura, MINATO AKIZUKI, Akira Tangoku, Hiromichi Yumoto, Hirohisa Ogawa and Takeshi Oya : Quiescence Abrogates Stress-Induced Senescence-Associated Secretion Phenotype in Adipose-Derived Stem Cells and May Enhance Their Therapeutic Effects on Diabetic Complications, Diabetes, Vol.71, No.Suppl_1, 305-OR, New Orleans, Jun. 2022.
3.	Akiko Hata, Nanako Aki, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : Serum Fatty Acid Composition as a Biomarker of Diabetes Development: Tokushima Cohort Study, Diabetes, Vol.Vol.71, No.Suppl.1, 1234-P, New Orleans, Jun. 2022.
4.	Akiko Hata, Masashi Miyoshi, Takayuki Nakao, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : Serum Total Adiponectin Level is Associated with Onset of Diabetes in Male Japanese: Tokushima Cohort Study, Diabetes, Vol.70, No.Suppl.1, Chicago, Jun. 2021.
5.	Akiko Hata, Nanako Aki, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : Decreased Serum 1,5-Anhydroglucitol Level is Associated with Development of Abnormal Glucose Metabolism or Metabolic Syndrome in Male Japanese: Tokushima Cohort Study, Diabetes, Vol.69, No.Suppl.1, 1583-P, Jun. 2020. (Link to Publication Site) ● Publication site (DOI): 10.2337/db20-1583-P (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.2337/db20-1583-P (DOI: 10.2337/db20-1583-P)
6.	Akiko Hata, Nanako Aki, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : Serum Fatty Acid Proportions Are Associated with Development of Abnormal Glucose Metabolism in Male Japanese: Tokushima Cohort Study, Diabetes, Vol.68, No.Suppl.1, Jun. 2019. (Link to Publication Site) ● Publication site (DOI): 10.2337/db19-1617-P (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.2337/db19-1617-P (DOI: 10.2337/db19-1617-P)
7.	Yumi Kuwamura, Sumiko Yoshida, Kiyoe Kurahashi, Masuko Sumikawa, Eijiro Sakamoto, Akio Kuroda, Hikari Yamato, Misuzu Okamoto, Hirokazu Uemura, Daisuke Hinode, Hiromichi Yumoto, Ken-ichi Aihara, Makoto Funaki, Munehide Matsuhisa, Itsuro Endo and Sachi Kishida : Oral health behaviors of outpatients with diabetes based on the Revised Diabetes Oral Health Assessment Tool for nurses, Journal of Diabetes Investigation, Vol.10, No.Supplement1, 26, Sendai-City, Miyagi Prefecture, May 2019. (Keyword) oral health behaviors / diabetes nursing / assessment
8.	Akiko Hata, Masashi Miyoshi, Takayuki Nakao, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : Serum total adiponectin level and new onset of prediabetes in Japanese workers: Tokushima Cohort Study, 12th IDF-WPR Congress&10th ASSD Scientific Meeting, Nov. 2018.
9.	Munehide Matsuhisa, Hiroyasu Mori, Mami Ohishi, Masashi Ishizu, Reiko Suzuki, Ineko Takikawa, Satoshi Taniguchi, Motoyuki Tamaki, Yuko Akehi, Kiyoe Kurahashi, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki and Akio Kuroda : The risk factors for rapid decline of renal function in Japanese patients with diabetes mellitus, American Diabetes Association 78th Scientific Sessions, Orlando, Jun. 2018.
10.	Akiko Hata, Masashi Miyoshi, Takayuki Nakao, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : Serum Total Adiponectin Level is Associated with Incident Prediabetes in Japanese Workers, Diabetes, Vol.67, No.Suppl.1, A403, Jun. 2018. (Link to Publication Site) ● Publication site (DOI): 10.2337/db18-1505-P (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.2337/db18-1505-P (DOI: 10.2337/db18-1505-P)
11.	Kana Morimoto, Masuda Shiho, Kiyoe Kurahashi, Motoyuki Tamaki, Takeshi Kondo, Sumiko Yoshida, Tomoyuki Yuasa, Akio Kuroda, Itsuro Endo, Akehi Yuko, Makoto Funaki, Seiji Fukumoto, Munehide Matsuhisa and Ken-ichi Aihara : Identification of clinical determinants for coefficient of variation of - intervals in patients with type 2 diabetes., International Conference on Diabetes and Its Complications 2017, Baltimore, Nov. 2017. (Keyword) therapy / 合併症
12.	Masaki Morishima, Kazuki Horikawa and Makoto Funaki : Mechanically Physiological Microenvironment Sensitizes Primary Cardiomyocytes to Glucotoxicity; New In Vitro Diabetic Heart Research Model, Diabetes, San Diego, Jun. 2017.
13.	Akiko Hata, Koji Yonemoto, Nanako Aki, Masashi Miyoshi, Takayuki Nakao, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : Serum Apoptosis Inhibitor of Macrophage is Related to Development of Metabolic Syndrome in Japanese Male Workers, Diabetes, Vol.66, No.Suppl.1, A444, Jun. 2017.
14.	Akiko Hata, Koji Yonemoto, Nanako Aki, Tohru Sakai, Emi Shuto, Takayuki Nakao, Masashi Miyoshi and Makoto Funaki : Identifying a Dietary Pattern Associated with Metabolic Syndrome by Reduced Rank Regression in Japanese Male Workers, Diabetes, Vol.65, No.Suppl.1, A604-A605, Jun. 2016.
15.	Akiko Hata, Yosuke Shikama, Nanako Aki, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : Serum Fatty Acid Proportions Are Related to Development of Metabolic Syndrome in Japanese Male Workers, Diabetes, Vol.64, No.Suppl.1, A.444-A.445, Jun. 2015.
16.	Akiko Hata, Yosuke Shikama, Nanako Aki, Chisato Kosugi, Hiroya Kobayashi, Masashi Miyoshi, Takayuki Nakao, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Toshio Matsumoto and Makoto Funaki : Serum Adipocyte Fatty Acid-binding Protein Is Related to the Development of Metabolic Syndrome in Japanese Male Workers, Diabetes, Vol.63, No.Suppl.1, A.388, Jun. 2014.
17.	Yosuke Shikama, Nanako Aki, Akiko Hata, Miho Nishimura and Makoto Funaki : Palmitate-Stimulated Monocytes Induce ICAM-1 and E-selectin Expression in Vascular Endothelial Cells via an IL-1-Dependent Pathway, Diabetes, Vol.63, No.Suppl.1, A127, Jun. 2014.
18.	Jun-ichi Kido, Mika Bandou, Yuji Inagaki, Yuka Hiroshima, Hiromi Murata, Chie Wada -Mihara, 梶浦由加里, 生田貴久, 篠原宏貴, 橋本万里, Yukiko Nakajima, Yukiko Bandou, Makoto Funaki, Haruhiko Saito and Toshihiko Nagata : Diagnosis of diabetes-associated periodontitis using glycoalbumin and calprotectin in gingival crevicular fluid, 10th Asian Pacific Society of Periodontology Meeting, Nara, Sep. 2013.
19.	Yosuke Shikama, Naozumi Ishimaru, Yasusei Kudo, Yukiko Bandou, Nanako Aki, Yoshio Hayashi and Makoto Funaki : High Levels of Free Fatty Acids May Advance the Severity of Primary Sjögrens Syndrome, Diabetes, Vol.62, No.Supplement 1, A166, Jul. 2013.
20.	Toshihiko Nagata, Jun-ichi Kido, Mika Bandou, Yuka Hiroshima, Yuji Inagaki, Hiromi Murata, Chie Wada -Mihara, Mika Bandou and Makoto Funaki : Diagnosis of diabetes-associated periodontitis using biomarkers in gingival crevicular fluid, 91th General Session & Exhibition of the International Association for Dental Research. Seattle, USA, May 2013.
21.	Toshihiko Nagata, Jun-ichi Kido, Mika Bandou, Yuka Hiroshima, Yuji Inagaki, Masami Ninomiya, Chie Wada -Mihara, Hiromi Murata, Yukiko Bandou and Makoto Funaki : Diagnosis of diabetes-associated periodontitis by measuring biomarkers in gingival crevicular fluid, The 9th International Diabetes Federation Western Pacific Region Congress/ The 4th AASD Scientific Meeting, Nov. 2012.
22.	Takako Ichihara, Ayako Tamura, Yumi Kuwamura, Takako Minagawa, Nanako Kataoka, Chisato Kosugi, Hata Akiko, Emi Shuto, Tohru Sakai and Makoto Funaki : The Effects of physical Activity on Metabolic Symdrome, --- From the 2009 Cross-Sectional Syudy on Working Men in Tokushima ---, 9th International Diabetes Federation Westeran Pacific Region Congress,4th Scientific Meeting of the Asian Association Study of Diabetes, Vol.3, No.Supplement 1, 269, Kyoto, Nov. 2012.
23.	Yosuke Shikama, Qinkai Li, Yukiko Bandou, Nanako Aki, Chisato Kosugi and Makoto Funaki : Crosstalk between Salivary Gland Chronic Inflammation and the Endocrine Function of Adipocytes in Insulin Resistance, Diabetes, Vol.61, No.supplement1, A161, Jun. 2012.
24.	LI QINKAI, Toshio Hosaka, JAMBALDORJ BAYASGLAN, Yutaka Nakaya and Makoto Funaki : Extracellular Matrix with the Rigidity of Adipose Tissues Helps 3T3-L1 Adipocytes Maintain Insulin Responsiveness, The American Diabetes Association 69th Scientific Sessions, New Orleans, Jun. 2009.
25.	Li Qinkai, Toshio Hosaka, Jambaldorj Bayasglan, Otsuka Ryo, Hirata Yohko, Teshigawara Kiyoshi, Chisato Kosugi, Yutaka Nakaya and Makoto Funaki : Serotonin Induces Insulin-Resistance in 3T3-L1 Adipocytes, 68th scientific sessions American Diabetes Association, San Francisco, Jun. 2008.

Proceeding of Domestic Conference:

1.	Ayumi Tohjoh, Mariko Nakamoto, Kana Yamada, Koki Torami, Akiko Nakamoto, Akiko Hata, 安藝菜奈子, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Ayako Tamura, Yumi Kuwamura, Makoto Funaki and Tohru Sakai : 徳島県勤労者における食事摂取の多様性と炎症性マーカーとの横断的検討, 第8回日本栄養改善学会四国支部学術総会, May 2023.
2.	Makoto Funaki, Akiko Hata, Mitsuteru Yoshida, Naoki Miyamoto, Takahisa Ikuta, Yuta Uemura, Minato Akizuki, Akira Tangoku, Hiromichi Yumoto, Hirohisa Ogawa and Takeshi Oya : 休眠状態の脂肪組織由来間葉系幹細胞による細胞老化随伴分泌現象の解除と糖尿病性合併症治療への応用の可能性, Journal of the The Japan Diabetes Society, Vol.66, No.Suppl.1, S.246, May 2023.
3.	Mariko Nakamoto, Ayumi Tohjoh, Kana Yamada, Koki Torami, Akiko Nakamoto, Akiko Hata, 安藝菜奈子, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Ayako Tamura, Yumi Kuwamura, Makoto Funaki and Tohru Sakai : 徳島県勤労者における食事摂取の多様性と炎症マーカーとの関連, Journal of Japanese Society of Nutrition and Food Science, 74, May 2023.
4.	Akiko Hata, Nanako Aki, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : 血中全脂質中脂肪酸分画と糖尿病発症との関連に対する肥満の影響:Tokushima Cohort Study, Journal of the The Japan Diabetes Society, Vol.66, No.Suppl.1, S.308, May 2023.
5.	Kana Yamada, Mariko Nakamoto, Akiko Nakamoto, Akiko Hata, Nanako Aki, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Ayako Tamura, Yumi Kuwamura, Makoto Funaki and Tohru Sakai : 徳島県勤労者のイソフラボン摂取量とメタボリックシンドローム構成因子との関連, The Japanese Journal of Nutrition and Dietetics, Vol.80, No.5, 207, Sep. 2022. (Keyword) epidemiology / 公衆栄養 / 栄養疫学
6.	Makoto Funaki, Mitsuteru Yoshida, Naoki Miyamoto, Takahisa Ikuta, Yuta Uemura, MINATO AKIZUKI, Akiko Hata, Akira Tangoku, Hiromichi Yumoto, Hirohisa Ogawa and Takeshi Oya : 休眠状態の導入・維持による脂肪組織由来間葉系幹細胞の若返りを通じた，糖尿病性合併症治療への応用の可能性, Journal of the The Japan Diabetes Society, Vol.65, No.Suppl.1, S257, May 2022.
7.	Akiko Hata, Nanako Aki, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : 血清脂肪細胞特異的脂肪酸結合蛋白質とメタボリックシンドローム発症と関連:Tokushima Cohort Study, Journal of the The Japan Diabetes Society, Vol.65, No.Suppl.1, S227, May 2022.
8.	Kana Yamada, Mariko Nakamoto, Akiko Nakamoto, Akiko Hata, 安藝菜奈子, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Ayako Tamura, Yumi Kuwamura, Makoto Funaki and Tohru Sakai : 徳島県勤労者の大豆イソフラボン摂取量とメタボリックシンドロームとの関連, 第264回徳島医学会学術集会, 32, Feb. 2022.
9.	Kana Yamada, Mariko Nakamoto, Akiko Nakamoto, Akiko Hata, 安藝菜奈子, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Ayako Tamura, Yumi Kuwamura, Makoto Funaki and Tohru Sakai : 徳島県勤労者のイソフラボン摂取量とメタボリックシンドロームとの関連, 第6回日本糖尿病・生活習慣病ヒューマンデータ学会年次学術集会, Dec. 2021.
10.	Akiko Hata, Nanako Aki, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : 血中脂肪酸分画と糖尿病発症との関連:Tokushima Cohort Study, 第6回日本糖尿病・生活習慣病ヒューマンデータ学会, Dec. 2021.
11.	Akiko Hata, Nanako Aki, Masashi Miyoshi, Takayuki Nakao, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : 徳島県における血中総アディポネクチン濃度と糖尿病発症との関連:Tokushima Cohort Study, Journal of the The Japan Diabetes Society, Vol.64, No.Suppl, S356, May 2021.
12.	辻誠士郎, Sumiko Yoshida, 平岡栞名, Kohsuke Miyataka, Minae Hosoki, Tomoyo Hara, 三井由加里, Kiyoe Kurahashi, Akio Kuroda, 明比祐子, Itsuro Endo, Makoto Funaki, Seiji Fukumoto, Masahiro Abe and Munehide Matsuhisa : 行動療法を中心とした2週間の減量入院プログラムの退院後の減量効果, 第64回日本糖尿病学会年次学術集会, May 2021.
13.	Akiko Hata, Nanako Aki, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : 徳島県における血中1,5AG濃度と糖代謝異常発症及びメタボリックシンドローム発症との関連, Journal of the The Japan Diabetes Society, Vol.63, No.Suppl, S275, Oct. 2020.
14.	Sumiko Yoshida, 工藤千晶, 辻本賀美, 安井沙耶, 遠藤ふうり, 桝田志保, 三井由加里, Kiyoe Kurahashi, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki, Seiji Fukumoto, Masahiro Abe and Munehide Matsuhisa : 血糖管理入院でのテストステロン値の変化の検討, 第63回日本糖尿病学会年次学術集会, Oct. 2020.
15.	Mariko Nakamoto, Mariko Ohmine, Yuna Yun, Emi Shuto, Akiko Nakamoto, Akiko Hata, Nanako Aki, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Ayako Tamura, Yumi Kuwamura, Makoto Funaki and Tohru Sakai : Associations of dietary diversity with allergic diseases in Japanese workers: a cross-sectional study, Journal of Shikoku Public Health Society, Vol.65, No.1, 32, Feb. 2020. (Keyword) epidemiology / nutrition / allergy / Japan
16.	安井沙耶, 桝田志保, Sumiko Yoshida, 辻本賀美, 工藤千晶, 遠藤ふうり, 三井由加里, Kiyoe Kurahashi, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki, Munehide Matsuhisa, Masahiro Abe and Seiji Fukumoto : 成長ホルモン分泌不全症と甲状腺機能低下症を呈した小児がん経験者の一例, 第259回徳島医学会学術集会(令和元年度夏期), Aug. 2019.
17.	宮高絋輔, Sumiko Yoshida, Furi Endo, 枡田志保, 三井由加里, Kiyoe Kurahashi, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Seiji Fukumoto, Makoto Funaki, Yoshihiro Matsudate, Hiroshi Nokihara, Yasuhiko Nishioka, Masahiro Abe and Munehide Matsuhisa : 免疫チェックポイント阻害薬投与後に1型糖尿病を発症した2例, 第62回日本糖尿病学会年次学術集会, May 2019.
18.	Makoto Funaki, Koji Yonemoto, Takahiro Tachiki, Satoyo Ikehara, Kuniyasu Kamiya, Akemi Nitta, Katsuyasu Kouda, Jyunko Tamaki, Masayuki Iki, Etsuko Kajita, Sadanobu Kagamimori, Masashi Miyoshi, Takayuki Nakao and Akiko Hata : 女性におけるメタボリックシンドローム発症予防のための血清総アディポネクチンの基準値の策定, Journal of the The Japan Diabetes Society, Vol.62, No.Suppl.1, S303, Apr. 2019.
19.	Akiko Hata, Nanako Aki, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : 血中脂肪酸分画と糖代謝異常発症との関連:Tokushima Cohort Study, Journal of the The Japan Diabetes Society, Vol.62, No.Suppl.1, S216, Apr. 2019.
20.	Kohsuke Miyataka, Furi Endo, 三井由加里, 枡田志保, Kiyoe Kurahashi, Sumiko Yoshida, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki, Seiji Fukumoto, Hiroshi Nokihara, Yasuhiko Nishioka, Masahiro Abe and Munehide Matsuhisa : 抗PD-1抗体投与後に1型糖尿病を発症した1例, 第258回徳島医学会学術集会ポスターセッション, Feb. 2019.
21.	Ken-ichi Aihara, Sumiko Yoshida, Furi Endo, 筒井康継, Tomoyo Hara, 桝田志保, Kiyoe Kurahashi, Toshiki Otoda, Tomoyuki Yuasa, Itsuro Endo, Kana Morimoto, Akio Kuroda, 明比祐子, Makoto Funaki, Munehide Matsuhisa, Seiji Fukumoto and Masahiro Abe : 原発性アルドステロン症におけるミネラルコルチコイド受容体拮抗薬の血管機能への影響, 第18回日本内分泌学会四国支部学術集会, Sep. 2018.
22.	Sumiko Yoshida, 原倫世, 細井美希, 山上紘規, 山口佑樹, 桝田志保, Kiyoe Kurahashi, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki, Seiji Fukumoto, Masahiro Abe and Munehide Matsuhisa : 糖尿病教育入院における筋肉量の変化, 第61回日本糖尿病学会年次学術集会, May 2018.
23.	山上紘規, Sumiko Yoshida, 原倫世, 細井美希, 山口佑樹, 桝田志保, Kiyoe Kurahashi, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki, Seiji Fukumoto, Masahiro Abe, Yoshihiro Matsudate and Munehide Matsuhisa : 免疫チェックポイント阻害薬投与後に甲状腺機能異常と劇症1型糖尿病を発症した1例, 第61回日本糖尿病学会年次学術集会, May 2018.
24.	Motoyuki Tamaki, Yuichi Takashi, Toshiki Otoda, Seiji Fukumoto, Akio Kuroda, 明比祐子, Hiroyasu Mori, Satoshi Taniguchi, 鈴木麗子, Misuzu Yamada, Masashi Ishizu, Mami Ohishi, 白神敦久, Ken-ichi Aihara, Makoto Funaki and Munehide Matsuhisa : かかりつけ患者に対するSGLT2阻害薬の投与開始タイミングの特徴と投与開始後の体重・eGFR・ALT・脂質代謝の変化, 第61回日本糖尿病学会年次学術集会, May 2018.
25.	Ken-ichi Aihara, 上元良子, 石川カズ江, Kana Morimoto, 桝田志保, Hiroki Yamagami, Yuki Yamaguchi, Tomoyo Hara, 細井美希, Kiyoe Kurahashi, Sumiko Yoshida, Toshiki Otoda, Tomoyuki Yuasa, Akio Kuroda, 明比祐子, Itsuro Endo, Makoto Funaki, Seiji Fukumoto, Munehide Matsuhisa, Hiroyuki Azuma and Masahiro Abe : 生活習慣病患者の尿中酸化ストレス指標における糖尿病および薬物療法の影響, 第61回日本糖尿病学会年次学術集会, May 2018.
26.	Akiko Hata, Nanako Aki, Masashi Miyoshi, Takayuki Nakao, Takako Ichihara, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : 徳島県における血中アディポネクチンとPrediabetes発症との関連, Journal of the The Japan Diabetes Society, Vol.61, No.Suppl.1, S270, May 2018.
27.	Sumiko Yoshida, 原倫世, 細井美希, 山上紘規, 山口佑樹, 桝田志保, Kiyoe Kurahashi, Akio Kuroda, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki, Seiji Fukumoto, Daisuke Hamada, Munehide Matsuhisa and Masahiro Abe : 待機的高リスク整形外科手術における血糖管理の効果, 第91回日本内分泌学会学術総会, Apr. 2018.
28.	Yuki Fujimoto, Toshihiro Watanabe, Aya Morimoto, Hana Kumamoto, Kouzou Sudou, Tomokazu Yoshida, Hiroyasu Mori, Munehide Matsuhisa, Akiko Hata, Makoto Funaki, Mayumi Yamamoto and Seiichi Hashida : 腎障害予測指標としての尿中アディポネクチンに関する検討, 第21回日本病態栄養学会年次学術集会, Jan. 2018.
29.	桝田志保, 明比祐子, Sumiko Yoshida, Hiroki Yamagami, Yuki Yamaguchi, 細井美希, Tomoyo Hara, Kiyoe Kurahashi, Itsuro Endo, Akio Kuroda, Ken-ichi Aihara, Munehide Matsuhisa, Makoto Funaki and 福本誠ニ : 123I-MIBGシンチグラフィ陽性の副腎皮質腺腫の一例, 第27回臨床内分泌代謝Update抄録集, Nov. 2017.
30.	Yuki Yamaguchi, Sumiko Yoshida, Tomoyo Hara, 細井美希, Hiroki Yamagami, 桝田志保, Kiyoe Kurahashi, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki, 福本誠ニ, Masahiro Abe, Hideya Kashihara, Kouzou Yoshikawa and Munehide Matsuhisa : 高度肥満症に対するスリーブ状胃切除術の長期の耐糖能異常改善効果の検討, 日本糖尿病学会中国四国地方会第55回総会抄録集, Nov. 2017.
31.	Naoto Kunikata, Sumiko Yoshida, Tomoyo Hara, 細井美希, Hiroki Yamagami, Yuki Yamaguchi, 桝田志保, Kiyoe Kurahashi, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki, 福本誠ニ, Masahiro Abe, Daisuke Hamada and Munehide Matsuhisa : 待機的整形外科手術の術後経過における糖尿病の影響, 日本糖尿病学会中国四国地方会第55回総会抄録集, Nov. 2017.
32.	細井美希, Kiyoe Kurahashi, Tomoyo Hara, Yuki Yamaguchi, Hiroki Yamagami, 桝田志保, Sumiko Yoshida, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki, 福本誠ニ and Munehide Matsuhisa : 低血糖脳症をきたしたACTH単独欠損症合併1型糖尿病の一例, 日本糖尿病学会中国四国地方会第55回総会抄録集, Nov. 2017.
33.	Hiroyasu Mori, Mami Ohishi, 鈴木麗子, Akio Kuroda, Satoshi Taniguchi, Motoyuki Tamaki, 明比祐子, Kiyoe Kurahashi, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki and Munehide Matsuhisa : 2型糖尿病患者における末梢神経障害の合併が骨格筋力の質的低下に及ぼす影響, 第32回日本糖尿病合併症学会, Oct. 2017.
34.	原倫世, Sumiko Yoshida, 山上紘規, 山口佑樹, 細井美希, 桝田志保, Kiyoe Kurahashi, Itsuro Endo, 明比祐子, Akio Kuroda, Ken-ichi Aihara, Munehide Matsuhisa, Makoto Funaki and Seiji Fukumoto : Frequent syncope and marked blood pressure fluctuation due to antiparkinson drugs: A case report, 2017年10月20日-22日ひめぎんホール, Oct. 2017.
35.	Tomoyo Hara, Sumiko Yoshida, 山上紘規, 山口佑樹, 細井美希, 桝田志保, Kiyoe Kurahashi, Itsuro Endo, 明比祐子, Akio Kuroda, Ken-ichi Aihara, Munehide Matsuhisa, Makoto Funaki and Seiji Fukumoto : 抗パーキンソン病薬により頻回な失神と著明な血圧変動をきたした一例, 第40回日本高血圧学会総会, Oct. 2017.
36.	山上紘規, Kiyoe Kurahashi, 山口佑樹, 細井美希, 原倫世, 桝田志保, Sumiko Yoshida, Itsuro Endo, 明比祐子, Akio Kuroda, Ken-ichi Aihara, Munehide Matsuhisa, Makoto Funaki and Seiji Fukumoto : バセドウ病とTSH産生下垂体腺腫の合併の一例, 第60回日本甲状腺学会学術集会, Oct. 2017.
37.	細井美希, Sumiko Yoshida, 山上紘規, 山口佑樹, 原倫世, 桝田志保, Kiyoe Kurahashi, Itsuro Endo, 明比祐子, Akio Kuroda, Ken-ichi Aihara, Munehide Matsuhisa, Makoto Funaki and Seiji Fukumoto : 無セルロプラスミン血症に合併した甲状腺乳頭癌の一例, 第60回日本甲状腺学会学術集会, Oct. 2017.
38.	桝田志保, Kiyoe Kurahashi, Takeshi Kondo, 細井美希, Yuki Yamaguchi, Tomoyo Hara, Hiroki Yamagami, Sumiko Yoshida, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Munehide Matsuhisa, Makoto Funaki and 福本誠ニ : デノスマブ投与により術後の血清Ca/P値を容易に管理しえた巨大異所性副甲状腺腺腫の一例, 第17回日本内分泌学会四国支部学術集会抄録集, Sep. 2017.
39.	Tomoyo Hara, Sumiko Yoshida, Yuki Yamaguchi, 細井美希, Hiroki Yamagami, 桝田志保, Kiyoe Kurahashi, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Munehide Matsuhisa, Makoto Funaki, 福本誠ニ and Masahiro Abe : 当院での免疫チェックポイント阻害薬による下垂体機能低下症の5例, 第17回日本内分泌学会四国支部学術集会抄録集, Sep. 2017.
40.	山口佑樹, Sumiko Yoshida, 細井美希, 山上紘規, 原倫世, 桝田志保, Kiyoe Kurahashi, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Munehide Matsuhisa, Makoto Funaki, Seiji Fukumoto and Hiromitsu Takizawa : 当院での免疫チェックポインント阻害薬による内分泌異常の発生と有害事象対策, 第255回徳島医学会学術集会(平成29年度夏期), Aug. 2017.
41.	Sumiko Yoshida, Ken-ichi Aihara, Kiyoe Kurahashi, Takeshi Kondo, Kana Morimoto, Motoyuki Tamaki, Tomoyuki Yuasa, Akio Kuroda, 明比祐子, Itsuro Endo, Makoto Funaki, 福本誠ニ and Munehide Matsuhisa : 糖尿病教育入院での酸化ストレスマーカーの変化の検討, 第60回日本糖尿病学会年次学術集会抄録集, May 2017.
42.	Kana Morimoto, 桝田志保, Kiyoe Kurahashi, Motoyuki Tamaki, Takeshi Kondo, Sumiko Yoshida, Tomoyuki Yuasa, Akio Kuroda, 明比祐子, Itsuro Endo, Makoto Funaki, 福本誠ニ, Munehide Matsuhisa, Masahiro Abe and Ken-ichi Aihara : 糖尿病患者における自律神経機能をアルブミン尿の相互関連および各病態に影響を及ぼす因子解析, 第60回日本糖尿病学会年次学術集会, May 2017.
43.	Michiko Araki, Hiroyasu Mori, Akio Kuroda, 鈴木麗子, Mami Ohishi, Satoshi Taniguchi, Motoyuki Tamaki, 明比祐子, Hiroshi Sakaue, Kiyoe Kurahashi, Takeshi Kondo, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki and Munehide Matsuhisa : 1型糖尿病患者における血清IGF-1とサルコペニア罹患との関連, 第60回日本糖尿病学会年次学術集会, May 2017.
44.	Hiroyasu Mori, Akio Kuroda, Michiko Araki, 鈴木麗子, Mami Ohishi, Satoshi Taniguchi, Motoyuki Tamaki, 明比祐子, Kiyoe Kurahashi, Takeshi Kondo, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki and Munehide Matsuhisa : 2型糖尿病患者における皮下AGE蓄積が筋機能低下に及ぼす影響, 第60回日本糖尿病学会年次学術集会抄録集, May 2017.
45.	Yuki Fujimoto, Toshihiro Watanabe, Aya Morimoto, Hana Kumamoto, Kouzou Sudo, Tomokazu Yoshida, Hiroyasu Mori, Munehide Matsuhisa, Akiko Hata, Makoto Funaki, Mayumi Yamamoto and Seiichi Hashida : 尿中アディポネクチンの腎障害予測マーカーに関する研究, Journal of the The Japan Diabetes Society, Vol.60, No.Suppl.1, May 2017.
46.	Akiko Hata, Nanako Aki, Masashi Miyoshi, Takayuki Nakao, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : 血中AIMとメタボリックシンドローム発症に関する疫学的検討, Journal of the The Japan Diabetes Society, Vol.60, No.Suppl.1, May 2017.
47.	Hiroyasu Mori, Akio Kuroda, Michiko Araki, 鈴木麗子, Mami Ohishi, Satoshi Taniguchi, Motoyuki Tamaki, 明比祐子, Kiyoe Kurahashi, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki and Munehide Matsuhisa : 2型糖尿病患者におけるサルコペニアのリスク因子解析, 第51回日本成人病学会学術集会, Jan. 2017.
48.	岡本恵暢, Sumiko Yoshida, Kiyoe Kurahashi, Takeshi Kondo, Kana Morimoto, Motoyuki Tamaki, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki, Munehide Matsuhisa and Seiji Fukumoto : IGF-2産生神経内分泌癌による重症低血糖の一例, 第26回臨床内分泌代謝Update, Nov. 2016.
49.	Sumiko Yoshida, Kiyoe Kurahashi, Takeshi Kondo, Kana Morimoto, Motoyuki Tamaki, Akio Kuroda, 明比祐子, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki, Munehide Matsuhisa and Seiji Fukumoto : 当院のニボルマブおよびイピリムマブ投与21例の内分泌異常の検討, 第26回臨床内分泌代謝Update, Nov. 2016.
50.	山下沙織, Sumiko Yoshida, 高橋優花, Ken-ichi Aihara, Kiyoe Kurahashi, Takeshi Kondo, Kana Morimoto, Motoyuki Tamaki, Tomoyuki Yuasa, Akio Kuroda, 明比祐子, Itsuro Endo, Makoto Funaki, Seiji Fukumoto, Munehide Matsuhisa and Masahiro Abe : 糖尿病教育入院における酸化ストレス減少に影響を及ぼす因子の検討, 日本糖尿病学会中国四国地方会第54回総会, Nov. 2016.
51.	Michiko Araki, Hiroyasu Mori, Akio Kuroda, 鈴木麗子, Mami Ohishi, Satoshi Taniguchi, Motoyuki Tamaki, 明比祐子, Hiroshi Sakaue, Kiyoe Kurahashi, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki and Munehide Matsuhisa : 1型糖尿病患者の血清IGF-1がサルコペニア罹患に及ぼす影響, 日本糖尿病学会中国四国地方会第54回総会, Nov. 2016.
52.	Hiroyasu Mori, Akio Kuroda, Michiko Araki, 鈴木麗子, Mami Ohishi, Satoshi Taniguchi, Motoyuki Tamaki, 明比祐子, Kiyoe Kurahashi, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki and Munehide Matsuhisa : 2型糖尿病患者におけるAGE蓄積とサルコペニアとの関連の検討, 日本糖尿病学会中国四国地方会第54回総会, Nov. 2016.
53.	Kana Morimoto, 桝田志保, Kiyoe Kurahashi, Motoyuki Tamaki, Takeshi Kondo, Sumiko Yoshida, Tomoyuki Yuasa, Akio Kuroda, 明比祐子, Itsuro Endo, Makoto Funaki, Seiji Fukumoto, Munehide Matsuhisa, Masahiro Abe and Ken-ichi Aihara : 糖尿病患者における心電図R-R間隔変動係数に影響を及ぼす因子の検討, 日本糖尿病学会中国四国地方会第54回総会, Nov. 2016.
54.	Michiko Araki, Hiroyasu Mori, Akio Kuroda, 鈴木麗子, Mami Ohishi, Satoshi Taniguchi, Motoyuki Tamaki, 明比祐子, Hiroshi Sakaue, Kiyoe Kurahashi, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki and Munehide Matsuhisa : 1型糖尿病患者の血清IGF-1がサルコペニア罹患に及ぼす影響, 第14回1型糖尿病研究会, Nov. 2016.
55.	楊暁琳, Mariko Nakamoto, Tohru Sakai, Emi Shuto, 篠原尚子, Akiko Hata, Takako Minagawa, Takako Ichihara, Ayako Tamura, Yumi Kuwamura and Makoto Funaki : 徳島県男性勤労者の大豆発酵食品摂取は血清IL-6濃度を低下させる, 第63回日本栄養改善学会学術総会, Sep. 2016.
56.	篠原尚子, Mariko Nakamoto, Tohru Sakai, Emi Shuto, 楊暁琳, Akiko Hata, Takako Minagawa, Takako Ichihara, Ayako Tamura, Yumi Kuwamura and Makoto Funaki : 徳島県男性勤労者における珈琲，緑茶およびその他のお茶摂取と高尿酸血症との関連, 第63回日本栄養改善学会学術総会, Sep. 2016.
57.	Takako Ichihara, Akiko Hata, Toshimi Onishi, Mariko Nakamoto, Emi Shuto, Tohru Sakai, Ayako Tamura, Takako Minagawa, Yukari Hisaka and Makoto Funaki : Association between daily life activities and blood pressure increaseThree-year longitudinal study in Japanese male employees living in suburban cities, The 6th Joint Symposium between Kagawa University and Chiang Mai University, Aug. 2016.
58.	遠藤ふうり, Kiyoe Kurahashi, Kana Morimoto, Takeshi Kondo, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara, Akio Kuroda, 明比祐子, Makoto Funaki, Munehide Matsuhisa, Seiji Fukumoto and Masahiro Abe : 日和見感染を合併したACTH依存性Cushing症候群の1例, 第253回徳島医学会学術集会(平成28年度夏期), Jul. 2016.
59.	篠原尚子, Mariko Nakamoto, Tohru Sakai, Emi Shuto, 楊暁琳, Akiko Hata, 安藝菜奈子, 四釜洋介, 板東由記子, Yukari Hisaka, Takako Minagawa, Ayako Tamura, Yumi Kuwamura, Takako Ichihara and Makoto Funaki : 徳島県男性勤労者におけるリスク保有状況別の嗜好飲料摂取と高尿酸血症の関連の検討, 第253回徳島医学会, Jul. 2016.
60.	Sumiko Yoshida, Ken-ichi Aihara, Kana Morimoto, Kiyoe Kurahashi, Takeshi Kondo, Motoyuki Tamaki, Akio Kuroda, Itsuro Endo, 明比祐子, Makoto Funaki, Seiji Fukumoto and Munehide Matsuhisa : 当院検診受診者における筋肉量がメタボリックパラメーターに及ぼす影響の検討, 第59回日本糖尿病学会年次学術集会, May 2016.
61.	Kana Morimoto, Ken-ichi Aihara, Sumiko Yoshida, Kiyoe Kurahashi, Takeshi Kondo, Motoyuki Tamaki, Akio Kuroda, Itsuro Endo, Makoto Funaki, Seiji Fukumoto, Munehide Matsuhisa and Masahiro Abe : 減塩による2型糖尿病入院症例の降圧予測指標, 第59回日本糖尿病学会年次学術集会, May 2016.
62.	Sumiko Yoshida, Ken-ichi Aihara, Kana Morimoto, Kiyoe Kurahashi, Takeshi Kondo, Motoyuki Tamaki, Akio Kuroda, Itsuro Endo, 明比祐子, Makoto Funaki, Seiji Fukumoto and Munehide Matsuhisa : 当院検診受診者における筋肉量が高血圧に及ぼす影響の検討, 第5回臨床高血圧フォーラム, May 2016.
63.	楊曉琳, Mariko Nakamoto, Tohru Sakai, Emi Shuto, 篠原尚子, Akiko Hata, 安藝菜奈子, Chisato Kosugi, Yosuke Shikama, Yukiko Bandou, Takako Minagawa, Takako Ichihara, Ayako Tamura, Yumi Kuwamura and Makoto Funaki : 徳島県勤労者を対象とした大豆摂取と炎症マーカーとの関連について, 第70回日本栄養食糧学会, May 2016.
64.	篠原尚子, Mariko Nakamoto, Tohru Sakai, Emi Shuto, 楊暁琳, Akiko Hata, 安藝菜奈子, Yosuke Shikama, Yukiko Bandou, Takako Minagawa, Takako Ichihara, Ayako Tamura, Yumi Kuwamura and Makoto Funaki : 徳島県勤労者における珈琲摂取と高尿酸血症との関連, 第70回日本栄養・食糧学会, May 2016.
65.	Mariko Nakamoto, Tohru Sakai, Emi Shuto, 安藝菜奈子, Akiko Hata, Yumi Kuwamura, Takako Minagawa, Takako Ichihara, Ayako Tamura and Makoto Funaki : 徳島県勤労者のイソフラボン摂取量とアレルギー疾患との関係, 第70回日本栄養・食糧学会, May 2016.
66.	Akiko Hata, Koji Yonemoto, Nanako Aki, Tohru Sakai, Emi Shuto, Takayuki Nakao, Masashi Miyoshi and Makoto Funaki : 徳島県におけるメタボリックシンドロームと関連する食事パターンの検討, Journal of the The Japan Diabetes Society, Vol.59, No.Suppl.1, May 2016.
67.	篠原尚子, Mariko Nakamoto, Tohru Sakai, Emi Shuto, 楊暁琳, Akiko Hata, 安藝菜奈子, Yosuke Shikama, Yukiko Bandou, Takako Minagawa, Takako Ichihara, Ayako Tamura, Yumi Kuwamura and Makoto Funaki : 第3回日本栄養改善学会(四国支部会), 第3回日本栄養改善学会(四国支部会), Apr. 2016.
68.	山上紘規, Kiyoe Kurahashi, 森本佳奈, Takeshi Kondo, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara, Akio Kuroda, 明比祐子, Makoto Funaki, Munehide Matsuhisa, Seiji Fukumoto and Masahiro Abe : インターフェロンβ治療中に糖尿病ケトアシドーシスを契機とし，急性発症1A型糖尿病と診断された一例, 第252回徳島医学会学術集会長井記念ホール, Feb. 2016.
69.	Ken-ichi Aihara, Sumiko Yoshida, Kana Morimoto, Kiyoe Kurahashi, Takeshi Kondo, Motoyuki Tamaki, Akio Kuroda, 明比祐子, Itsuro Endo, Makoto Funaki, Seiji Fukumoto, Munehide Matsuhisa and Masahiro Abe : 2型糖尿病患者の左室形態および機能における強化インスリン療法の効果, 日本糖尿病学会第53回中国四国地方会, Oct. 2015.
70.	Ken-ichi Aihara, Sumiko Yoshida, 森本佳奈, Kiyoe Kurahashi, Takeshi Kondo, Motoyuki Tamaki, Akio Kuroda, 明比祐子, Itsuro Endo, Makoto Funaki, Seiji Fukumoto, Munehide Matsuhisa and Masahiro Abe : 2型糖尿病患者の左室形態および機能における強化インスリン療法の効果, 第53回日本糖尿病学会中国・四国地方会米子コンベンションセンター, Oct. 2015.
71.	林亜紀, Sumiko Yoshida, Akio Kuroda, 七篠あつ子, Minoru Irahara, 鶴尾美穂, 森本佳奈, 倉橋清衛, Takeshi Kondo, Motoyuki Tamaki, 明比祐子, Itsuro Endo, Makoto Funaki, Munehide Matsuhisa, Seiji Fukumoto, Ken-ichi Aihara and Masahiro Abe : 分娩前に10g/日以上の蛋白尿を合併し，出産に至った糖尿病腎症の1例, 日本糖尿病学会中国四国地方会第53回総会, Oct. 2015.
72.	Mayuka Sakaguchi, Akiko Hata, Yosuke Shikama, Nanako Aki, Tohru Sakai, Emi Shuto, Rie Tsutsumi, Takayuki Nakao, Masashi Miyoshi, Makoto Funaki and Koji Yonemoto : Reduced Rank Regressionにより抽出された食事パターンの一般化可能性に関する検討∼メタボリックシンドローム発症追跡データを用いて∼, Journal of the The Japan Diabetes Society, Vol.58, No.Suppl.1, May 2015.
73.	Akiko Hata, Yosuke Shikama, Nanako Aki, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : 徳島県における全脂質中脂肪酸分画とメタボリックシンドローム発症との関連, Journal of the The Japan Diabetes Society, Vol.58, No.Suppl.1, May 2015.
74.	Takako Ichihara, 西村美穂, 安藝菜奈子, Ayako Tamura, Takako Minagawa, Yumi Kuwamura, Yukari Hisaka and Makoto Funaki : 2型糖尿者に対する医療チームの職場訪問により，訪問中に積極介入を行わないにもかかわらず血糖値と体重が改善した2事例, 第19回日本糖尿病教育・看護学会学術集会, 209, Sep. 2014. (Keyword) 2型糖尿病 / 介入研究 / 生活指導 / 職場 / 生活指導
75.	Yosuke Shikama, Yasusei Kudo, Naozumi Ishimaru and Makoto Funaki : 飽和脂肪酸が歯周病の病態形成に関与する可能性(Possibility of involvement of saturated fatty acids in pathogenesis of periodontitis), Journal of Oral Biosciences Supplement, Vol.2014, 161, Sep. 2014.
76.	Yosuke Shikama, 安藝菜奈子, 秦明子, 西村美穂 and Makoto Funaki : 単球における遊離脂肪酸のIL-1betaおよび IL-1 receptor antagonist(Ra)産生に対する効果:血管内皮細胞の接着因子発現との関連性, Journal of the The Japan Diabetes Society, Vol.57, No.supplement1, S-459, May 2014.
77.	Akiko Hata, Yosuke Shikama, 安藝菜奈子, Chisato Kosugi, 小林寛也, 三好雅士, 中尾隆之, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Toshio Matsumoto and Makoto Funaki : 徳島県における血清脂肪細胞特異的脂肪酸結合蛋白質とメタボリックシンドローム発症との関連, Journal of the The Japan Diabetes Society, Vol.Vol.57, No.Suppl.1, May 2014.
78.	Yosuke Shikama, 安藝菜奈子, Akiko Hata, 西村美穂 and Makoto Funaki : 単球における遊離脂肪酸のIL-1βおよびIL-1 receptor antagonist(Ra)産生に対する効果血管内皮細胞の接着因子発現との関連性, Journal of the The Japan Diabetes Society, Vol.Vol.57, No.Suppl.1, May 2014.
79.	Takako Ichihara, 西村美穂, 安藝菜奈子, Ayako Tamura, Yumi Kuwamura, Takako Minagawa, 庄野真代, Yukari Hisaka, Akiko Hata, Yosuke Shikama and Makoto Funaki : 医療職の職場訪問による男性2型糖尿病者に対する生活指導の効果血糖値・体重が改善した3事例の分析を中心に, Journal of the The Japan Diabetes Society, Vol.57, No.Suppl.1, May 2014.
80.	Takako Ichihara, 西村美穂, 安藝菜奈子, Ayako Tamura, Takako Minagawa, Yukari Hisaka and Makoto Funaki : 2型糖尿病に対する医療チームの職場訪問により，訪問中に積極介入を行わなかぅたにもかかわらず血糖値と体重が改善した2事例, 日本糖尿病教育・看護学会誌, Vol.18, 209, Sep. 2013. (Keyword) 2型糖尿病 / 患者指導 / 職場 / 教育プログラム
81.	Takako Ichihara, 西村美穂, Ayako Tamura, Takako Minagawa, Yumi Kuwamura and Makoto Funaki : 2型糖尿病患者の行動変容を目指した医療職派遣による教育プログラム:血糖値・体重の改善が少なかった事例の面接記録の分析から, 日本糖尿病教育・看護学会誌, Vol.17, 197, Sep. 2013. (Keyword) 2型糖尿病 / 患者指導 / 職場 / 教育プログラム
82.	Jun-ichi Kido, Mika Bandou, Yukiko Bandou, Yuji Inagaki, Yuka Hiroshima, 梶浦由加里, Chie Wada -Mihara, Hiromi Murata, 生田貴久, 篠原宏貴, Makoto Funaki and Toshihiko Nagata : 糖尿病関連歯周炎の診断マーカーとしての歯肉溝滲出液中グリコアルブミンとカルプロテクチンの有用性, 第56回日本糖尿病学会, May 2013.
83.	Jun-ichi Kido, Mika Bandou, Yukiko Bandou, Yuji Inagaki, Yuka Hiroshima, 梶浦由加里, 美原智恵, Hiromi Murata, 生田貴久, 篠原宏貴, 橋本万里, Makoto Funaki, Haruhiko Saito and Toshihiko Nagata : --, 第56回日本糖尿病学会年次学術集会, May 2013.
84.	中本真理子, Tohru Sakai, Emi Shuto, 安藝菜奈子, Chisato Kosugi, Akiko Hata, Kaori Shinoda, Yumi Kuwamura, Takako Minagawa, Takako Ichihara, Ayako Tamura and Makoto Funaki : 徳島県勤労者の血清脂肪酸濃度とインスリン抵抗性との関係に関する疫学研究, 第67回日本栄養・食糧学会大会, May 2013.
85.	Akiko Hata, Yukiko Bandou, Yosuke Shikama, 安藝菜奈子, Chisato Kosugi, 西村美穂, 阿部房代, 佐藤美子, 中奥真理子, 片山りか, 赤松康代, Tohru Sakai, Emi Shuto, Rie Tsutsumi, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, 中尾隆之, 三好雅士, Hiroki Moriguchi, Yuu Tamaki, Toshio Matsumoto and Makoto Funaki : 徳島県におけるadiponectinや高感度CRPとメタボリックシンドロームとの関連, Journal of the The Japan Diabetes Society, Vol.Vol.56, No.Suppl.1, S.208, May 2013.
86.	秦明子, Yukiko Bandou, Yosuke Shikama, 安藝菜奈子, Chisato Kosugi, 西村美穂, 阿部房代, 佐藤美子, 中奥真理子, 片山りか, 赤松康代, 丹下幸子, Tohru Sakai, Emi Shuto, Rie Tsutsumi, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Yumi Kuwamura, Takayuki Nakao, Masashi Miyoshi, Hiroki Moriguchi, Yuu Tamaki, Toshio Matsumoto and Makoto Funaki : 徳島県におけるadiponectinや高感度CRPとメタボリックシンドロームとの関連, Journal of the The Japan Diabetes Society, Vol.56, Apr. 2013.
87.	Yosuke Shikama, 安藝菜奈子, Akiko Hata, Yukiko Bandou, 西村美穂 and Makoto Funaki : ヒト単球における遊離脂肪酸のIL-1受容体アンタゴニスト産生に対する効果, 第86回日本内分泌学会学術総会, Apr. 2013.
88.	Yosuke Shikama, Naozumi Ishimaru, Yukiko Bandou, Nanako Aki and Makoto Funaki : Palmitate induces IL-6 production and α-fodrin degradation in salivary gland epithelial cells, Journal of the The Japan Diabetes Society, Vol.56, No.Suppl.1, S-186, 2013. (Keyword) Carrier Proteins Interleukin 6 ミクロフィラメント蛋白質 Palmitic Acid Sjoegren症候群自己免疫疾患上皮細胞唾液腺 *Fodrin
89.	Yosuke Shikama, 安藝菜奈子, 秦明子, 坂東由記子, 西村美穂 and Makoto Funaki : ヒト単球における遊離脂肪酸のIL-1受容体アンタゴニスト産生に対する効果, Folia endocrinologica Japonica, Vol.89, No.1, 312, 2013.
90.	中本真理子, Tohru Sakai, Emi Shuto, Nanako Kataoka, Chisato Kosugi, 秦明子, Kaori Shinoda, Yumi Kuwamura, Takako Minagawa, Takako Ichihara, Ayako Tamura and Makoto Funaki : 徳島県勤労者の夕食終了から就寝時間までの間隔と生活習慣病有病状況との関係に関する疫学研究, 第66回日本栄養食糧学会大会, May 2012.
91.	Jun-ichi Kido, Yuji Inagaki, Mika Bandou, Yukiko Bandou, Yuka Hiroshima, Hiromi Murata, Makoto Funaki, Haruhiko Saito and Toshihiko Nagata : 歯肉溝滲出液中のバイオマーカーを用いた糖尿病関連歯周炎の診断, 第55回日本糖尿病学会年次学術集会抄録集, 186, May 2012.
92.	中本真理子, Tohru Sakai, Emi Shuto, Nanako Kataoka, Chisato Kosugi, Akiko Hata, Kaori Shinoda, Yumi Kuwamura, Takako Minagawa, Takako Ichihara, Ayako Tamura and Makoto Funaki : 徳島県勤労者の夕食終了から就寝時間までの間隔と生活習慣病有病状況との関係に関する疫学研究, 第66回日本栄養・食糧学会大会, May 2012.
93.	Yukiko Bandou, Yosuke Shikama, 西村美穂, Chisato Kosugi, 安芸菜奈子, Akiko Hata, 赤松康代, 片山りか, 阿部房代, Tohru Sakai, Emi Shuto, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Hiroki Moriguchi, Tomiaki Morikawa, Yuu Tamaki and Makoto Funaki : 徳島県におけるadiponectinの糖代謝異常予測因子としての検討, Journal of the The Japan Diabetes Society, Vol.Vol.55, No.Suppl.1, S.359, May 2012.
94.	Chisato Kosugi, 安藝菜奈子, Yukiko Bandou, Yosuke Shikama, 西村美穂, 片山りか, 丹下幸子, 阿部房代, 赤松康代, Akiko Hata, 木宿由佳, Kaori Shinoda, Tohru Sakai, Emi Shuto, Rie Tsutsumi, Toshio Hosaka, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Tomiaki Morikawa, Yuu Tamaki and Makoto Funaki : 初期糖代謝異常を発見する指標としてのIL-18測定有用性の検討, Journal of the The Japan Diabetes Society, Vol.Vol.55, No.Suppl.1, S.290, May 2012.
95.	Akiko Hata, Yasufumi Doi, Naoko Mukai, Yoichiro Hirakawa, Toshiharu Ninomiya, Jun Hata, Masayo Fukuhara, Kentaro Shikata, Mio Ozawa, Kazuhiro Uchida, Tomoko Shirota, Makoto Funaki, Takanari Kitazono and Yutaka Kiyohara : 地域一般住民におけるマグネシウム摂取量と2型糖尿病の発症リスク:久山町研究, Journal of the The Japan Diabetes Society, Vol.Vol.55, No.Suppl.1, S.289, May 2012.
96.	Yosuke Shikama, Qinkai Li, Yukiko Bandou, 安芸菜奈子, 小杉知里, 西村美穂 and Makoto Funaki : 遊離脂肪酸の内因性リガンドとしての唾液腺上皮細胞に対する影響: アディポネクチンの効果, Journal of the The Japan Diabetes Society, Vol.55, No.Suppl.1, S-312, Apr. 2012.
97.	Yukiko Bandou, Jun-ichi Kido, Yuka Hiroshima, Mika Bandou, Yuji Inagaki, Hiromi Murata, Yosuke Shikama, Makoto Funaki and Toshihiko Nagata : 歯肉溝滲出液中のNKL-40の分析, 日本歯周病学会会誌秋季特別号, Vol.53, 106, Sep. 2011.
98.	中本真理子, Tohru Sakai, Emi Shuto, Toshio Hosaka, Nanako Kataoka, Chisato Kosugi, 秦明子, Kaori Shinoda, Yumi Kuwamura, Takako Minagawa, Takako Ichihara, Ayako Tamura and Makoto Funaki : 徳島県勤労者の豆類摂取量とアレルギー既往との関係に関する疫学研究, 第65回日本栄養食糧学会大会, May 2011.
99.	中本真理子, Tohru Sakai, Emi Shuto, Toshio Hosaka, Nanako Kataoka, Chisato Kosugi, Akiko Hata, Kaori Shinoda, Yumi Kuwamura, Takako Minagawa, Takako Ichihara, Ayako Tamura and Makoto Funaki : 徳島県勤労者の豆類摂取量とアレルギー既往との関係に関する疫学研究, 第65回日本栄養・食糧学会大会, May 2011.
100.	Yosuke Shikama, Chisato Kosugi, Nanako Kataoka, Yukiko Bandou, Akiko Hata, Kaori Shinoda, 木村純子, 赤松康代, 片山りか, 庄野真代, 簾馨, 藤森洋子, Tohru Sakai, Emi Shuto, Toshio Hosaka, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Hiroki Moriguchi, Tomiaki Morikawa, Yuu Tamaki and Makoto Funaki : 非肥満者に見られる糖・脂質代謝異常，高血圧に脂肪組織の機能異常が関与する可能性の検討, Journal of the The Japan Diabetes Society, Vol.Vol.54, No.Suppl.1, May 2011.
101.	Yukiko Bandou, Chisato Kosugi, Nanako Kataoka, Yosuke Shikama, Akiko Hata, 赤松康代, 片山りか, 庄野真代, 簾馨, Kaori Shinoda, Tohru Sakai, Emi Shuto, Toshio Hosaka, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Hiroki Moriguchi, Tomiaki Morikawa, Yuu Tamaki and Makoto Funaki : 徳島県におけるadiponectinおよびHOMA-IRと糖・脂質早期代謝異常との相関性についての考察, Journal of the The Japan Diabetes Society, Vol.Vol.54, No.Suppl.1, May 2011.
102.	Makoto Funaki, Yosuke Shikama, Yukiko Bando, Chisato Kosugi, Nanako Kataoka, Xin Lian and Qinkai Li : 肥満におけるMatrix Rigidityセンシングに対するRho-ROCK経路の関与(An Involvement of Rho-ROCK Pathway for Sensing Matrix Rigidity in Obesity), Journal of the The Japan Diabetes Society, Vol.54, No.Suppl.1, S-158, 2011. (Keyword) NF-Kappa B 肥満(実験的) rho GTP-Binding Proteins 3T3-L1細胞マウス動物
103.	Qinkai Li, Yosuke Shikama, Yukiko Bando, Chisato Kosugi, Nanako Kataoka, Xin Lian and Makoto Funaki : 脂肪細胞においてHB-EGFはEGFR-ERK1/2-mTOR経路の活性化によってGPCRアゴニスト-誘導インスリン抵抗を生じさせる(HB-EGF Mediates GPCR Agonist-induced Insulin Resistance through Activation of EGFR-ERK1/2-mTOR PATHWAY in Adipocytes), Journal of the The Japan Diabetes Society, Vol.54, No.Suppl.1, S-330, 2011. (Keyword) Epidermal Growth Factor Polymerase Chain Reaction / インスリン抵抗性 / Protein-Serine-Threonine Kinases / 脂肪細胞 / G-Protein-Coupled Receptors / 細胞内シグナルペプチドと蛋白質 / Heparin-Binding EGF-Like Growth Factor / TOR Serine-Threonine Kinases / ヒト
104.	Qinkai Li, Yosuke Shikama, Yukiko Bandou, Chisato Kosugi, Nanako Kataoka and Makoto Funaki : 5-HTは5HT2A受容体活性化を通じてIRS-1分解を誘発し，インスリン抵抗性を引き起す, Journal of Japan Society for the Study of Obesity, Vol.17, No.Suppl., 146, 2011. (Keyword) Serotonin / インスリン抵抗性 / 脂肪細胞 / Serotonin 5-HT2A Receptor / Insulin Receptor Substrate Proteins / *Insulin Receptor Substrate-1 Protein
105.	Yukiko Bandou, Chisato Kosugi, Nanako Kataoka, Yosuke Shikama, 秦明子, 木村純子, 赤松康代, 片山りか, 庄野真代, 簾馨, Kaori Shinoda, Tohru Sakai, Emi Shuto, Toshio Hosaka, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Hiroki Moriguchi, Tomiaki Morikawa, Yuu Tamaki and Makoto Funaki : 徳島県におけるadiponectinおよびHOMA-IRと糖・脂質早期代謝異常との相関性についての考察, Journal of the The Japan Diabetes Society, Vol.54, No.Suppl.1, S-248, 2011.
106.	Yosuke Shikama, Chisato Kosugi, Nanako Kataoka, Yukiko Bandou, 秦明子, Kaori Shinoda, 木村純子, 赤松康代, 片山りか, 庄野真代, 簾馨, 藤森洋子, Tohru Sakai, Emi Shuto, Toshio Hosaka, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Hiroki Moriguchi, Tomiaki Morikawa, Yuu Tamaki and Makoto Funaki : 非肥満者に見られる糖・脂質代謝異常，高血圧に脂肪組織の機能異常が関与する可能性の検討, Journal of the The Japan Diabetes Society, Vol.54, No.Suppl.1, S-355, 2011.
107.	Chisato Kosugi, Nanako Kataoka, Kaori Shinoda, Akiko Hata, 木村純子, 赤松康代, 片山りか, 藤森洋子, Tohru Sakai, Emi Shuto, Toshio Hosaka, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Yutaka Nakaya, Bayasgalan Jambaldorj, Hiroki Moriguchi, Tomiaki Morikawa, Yuu Tamaki, 福原俊一, 竹上美沙 and Makoto Funaki : 初期糖代謝異常状態の慢性炎症管理におけるIL-18の有用性についての検討, Journal of the The Japan Diabetes Society, Vol.Vol.53, No.Suppl.1, S.299, May 2010.
108.	Nanako Kataoka, Kaori Shinoda, Chisato Kosugi, Akiko Hata, 木村純子, 赤松康代, 片山りか, 藤森洋子, Tohru Sakai, Emi Shuto, Toshio Hosaka, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Yutaka Nakaya, Bayasgalan Jambaldorj, Hiroki Moriguchi, Tomiaki Morikawa, Yuu Tamaki, 福原俊一, 竹上美沙 and Makoto Funaki : 徳島県における糖代謝異常発生過程でのインスリン抵抗性の関与, Journal of the The Japan Diabetes Society, Vol.Vol.53, No.Suppl.1, S.298, May 2010.
109.	Qinkai Li, Akiko Hata, Kaori Shinoda, Chisato Kosugi, Nanako Kataoka and Makoto Funaki : 高弾性細胞外基質上では，パルミチン酸による3T3-L1脂肪細胞のアディポネクチン分泌抑制が見られない, Journal of the The Japan Diabetes Society, Vol.Vol.53, No.Suppl.1, S.205, May 2010.
110.	Akiko Hata, Chisato Kosugi, Nanako Kataoka, Kaori Shinoda, 木村純子, 赤松康代, 片山りか, 藤森洋子, Tohru Sakai, Emi Shuto, Toshio Hosaka, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Yutaka Nakaya, Bayasgalan Jambaldorj, Hiroki Moriguchi, Tomiaki Morikawa, Yuu Tamaki, 福原俊一, 竹上美沙 and Makoto Funaki : インスリン抵抗性を伴う高リスク糖尿病発症者となる危険因子の探索, Journal of the The Japan Diabetes Society, Vol.Vol.53, No.Suppl 1, S207, May 2010.
111.	秦明子, Chisato Kosugi, Nanako Kataoka, Kaori Shinoda, 木村純子, 赤松康代, 片山りか, 藤森洋子, Tohru Sakai, Emi Shuto, Toshio Hosaka, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Yutaka Nakaya, Jambaldorj Baysaglan, Hiroki Moriguchi, Tomiaki Morikawa, Yuu Tamaki, 福原俊一 and Makoto Funaki : インスリン抵抗性を伴う高リスク糖尿病発症者となる危険因子の探索, Journal of the The Japan Diabetes Society, Vol.53, No.Suppl.1, S-207, May 2010.
112.	Nanako Kataoka, Kaori Shinoda, Chisato Kosugi, 秦明子, 木村純子, 赤松康代, 片山りか, 藤森洋子, Tohru Sakai, Emi Shuto, Toshio Hosaka, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Yutaka Nakaya, Jambaldorj Baysaglan, Hiroki Moriguchi, Tomiaki Morikawa, Yuu Tamaki, 福原俊一, 竹上美沙 and Makoto Funaki : 徳島県における糖代謝異常発生過程でのインスリン抵抗性の関与, Journal of the The Japan Diabetes Society, Vol.53, No.Suppl.1, S-298, May 2010.
113.	Chisato Kosugi, Nanako Kataoka, Kaori Shinoda, 秦明子, 木村純子, 赤松康代, 片山りか, 藤森洋子, Tohru Sakai, Emi Shuto, Toshio Hosaka, Ayako Tamura, Takako Ichihara, Takako Minagawa, Yumi Kuwamura, Yutaka Nakaya, Jambaldorj Baysaglan, Hiroki Moriguchi, Tomiaki Morikawa, Yuu Tamaki, 福原俊一, 竹上美沙 and Makoto Funaki : 初期糖代謝異常状態の慢性炎症管理におけるIL-18の有用性についての検討, Journal of the The Japan Diabetes Society, Vol.53, No.Suppl.1, S-299, May 2010.
114.	LI QINKAI, Toshio Hosaka, Jambaldorj Bayasglan, Fukunaga Keiko, Nishiwak Yuka, Yutaka Nakaya and Makoto Funaki : Extracellular matrix with the rigidity of adipose tissues helps 3T3-L1 adipocytes maintain insulin responsiveness, 第52回日本糖尿病学会年次学術集会, May 2009.
115.	Le Thi Kim Chung, Toshio Hosaka, Jambaldorj Bayasglan, Fukunaga Keiko, Nishiwak Yuka, Yutaka Nakaya and Makoto Funaki : Myosin A enhances membrane fusion of GLUT4-containing vesicles, but not recycling endosomes, with the plasma membrane., 第52回日本糖尿病学会年次学術集会, May 2009.
116.	Qinkai Li, Kazuaki Mawatari, Nagakatsu Harada, 中野政之, Akira Takahashi, Yutaka Nakaya, Toshio Hosaka, Bayasgalan Jambaldorj, 大塚良 and Makoto Funaki : Chronic 5-Hydroxytryptamine Treatment Induces Insulin Resistance in 3T3-L1 Adipocytes by mTOR-dependent modification of IRS-1, 第238回徳島医学会学術集会, Feb. 2009.

Et cetera, Workshop:

1.	Hiroyasu Mori, Akio Kuroda, Michiko Araki, Reiko Suzuki, Mami Ohishi, Satoshi Taniguchi, Motoyuki Tamaki, Yuko Akehi, Hiroshi Sakaue, Kiyoe Kurahashi, Takeshi Kondo, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara, Makoto Funaki and Munehide Matsuhisa : Advanced glycation end-products are a risk for muscle weakness in patients with type2 diabetes., American Diabetes Association 78th Scientific Sessions, Jun. 2017.

Report:

1.	Mariko Nakamoto, Sarasa Mori, Emi Shuto, Akiko Nakamoto, Akiko Hata, Nanako Aki, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Ayako Tamura, Yumi Kuwamura, Makoto Funaki and Tohru Sakai : Soy and Isoflavone Intake and Lifestyle and Health Awareness in Japanese Workers, SOY PROTEIN RESEARCH, Japan, Vol.24, 154-161, Jul. 2022.
2.	Mariko Nakamoto, Sarasa Mori, Akimitsu Ohkohji, Emi Shuto, Akiko Nakamoto, Akiko Hata, Nanako Aki, Yosuke Shikama, Yukiko Bandou, Takako Ichihara, Takako Minagawa, Ayako Tamura, Yumi Kuwamura, Makoto Funaki and Tohru Sakai : 大豆製品・大豆含有成分摂取と推定腎機能との関係を探る臨床疫学研究, Soy protein research, Vol.23, 182-191, 2020.

Patent:

1.	Makoto Funaki : 血中因子の測定による健常人のインスリン抵抗性の早期診断方法, (Feb. 2010), .

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)

Development of an innovative method to modify life style using a dietary pattern score (Project/Area Number: 16K09785 )
Development of methodology for science of lifestyle habits in epidemiological research (Project/Area Number: 16K00063 )
Epidemiological study of association between serum level of apoptosis inhibitor of macrophage (AIM) and incidence of metabolic syndrome or abnormal glucose metabolism (Project/Area Number: 15K19229 )
力学的刺激によるエナメル芽細胞の分化誘導方法の開発 (Project/Area Number: 15K11013 )
Development of a patient support model linking living and hospital for early type 2 diabetes patients (Project/Area Number: 26463304 )
Epidemiological study on the association between serum adipocyte fatty acid-binding protein, fatty acid proportions and abnormal glucose metabolism. (Project/Area Number: 25860439 )
The development of an education model by which dispatched nurses provide advice to patients who have recently developed type 2 diabetes at their workplaces (Project/Area Number: 23660036 )
An attempt to deal with saturated fatty acid-induced insulin resistance by the stiffness of the extracellular matrix (Project/Area Number: 22616005 )
細胞支持基盤の弾性調節による初代培養脂肪・肝臓・骨格筋細胞の長期間機能保持の試み (Project/Area Number: 21650119 )
Alteration in cellular metabolism and substrate transporters in insulin resistant cardiac myocytes (Project/Area Number: 21590926 )
Search by Researcher Number (10467821)