Phosphate as a novel signal in the intracellular signal transduction

新規シグナルとしてのリン酸(<特集>ビタミンB研究委員会平成26年度シンポジウム「ビタミン・バイオファクターの生理機能に関する最新の話題」)

The phosphate (Pi)-mediated signal transduction pathways in renal proximal tubular cells and endothelial cells were examined, because Pi depletion and overloading are known to influence gene expression and cellular function. In renal proximal tubular calls (LLC-PK1), Pi depletion resulted in increases in intracellular inositol triphosphate (IP3) and calcium ion (Ca^<2+>) levels, the latter of which may be associated with the maintenance of Pi homeostasis. On the other hand, exposing bovine aortic endothelial cells to excessive Pi load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Pi loading in rat aortic rings inhibited endothelium-dependent vasodilation. A high dietary Pi load in human subjects increased serum Pi level at 2 h and significantly decreased flow-mediated dilation. Thus, it was found that the function of endothelial cells was damaged by the high dietary Pi loading. Taken together, these findings suggest that the changes in serum Pi level are associated with human health by affecting the intracellular Pi signal transduction pathway.


新規シグナルとしてのリン酸

新規シグナルとしてのリン酸


小児疾患および成人疾患からみたビタミンD栄養学

Nutritional science of vitamin D in pediatric and adult diseases was summarized. Vitamin D-dependency type II is a rare disease caused by a disorder of the human vitamin D receptor (VDR). Except for the alopecia, severe rickets and other biochemical abnormalities of 6 patients were reversed by treatment with 3 g/kg/d of 1-hydroxyvitamin D_3. A polymorphism at the translation initiation codon of the human VDR gene also affects the bone mineral density (BMD) in Japanese. Attention to phosphorus intake is important because both phosphorus deficiency and overloading impair bone health and quality of life (QOL). Elevation of extracellular phosphorus level causes endothelial dysfunction and medial calcification, which are closely associated with the development of cardiovascular disease (CVD). A dietary approach to limit phosphorus intake is particularly important to prevent bone impairment and CVD in patients with chronic kidney disease (CKD). Increased serum fibroblast growth factor 23 (FGF23)level is an early finding of abnormal mineral metabolism in CKD which causes secondary hyperparathyroidism and resistance of the parathyroid gland to the action of FGF23. In order to improve bone health and QOL in the general population, it should be important that attention to phosphorous intake from processed foods containing phosphorus additive is paied.


小児疾患および成人からみたビタミンD栄養学

小児疾患および成人からみたビタミンD栄養学


「日本食」の食卓を科学的に評価する③ニュートリゲノミクスを用いた日本食の評価

「日本食」の食卓を科学的に評価する③ニュートリゲノミクスを用いた日本食の評価


「日本食」の食卓を科学的に評価する②日本食を用いたボリュメトリクス(Volumetrics):エネルギー密度(ED)に注目した低エネルギーでも満腹度・満足度の高い食事


「日本食」の食卓を科学的に評価する①食後高血糖を抑制する食事

「日本食」の食卓を科学的に評価する①食後高血糖を抑制する食事


慢性腎不全時のリン制限食を用いた栄養療法は，腎性貧血の発症進展を予防する

慢性腎不全時のリン制限食を用いた栄養療法は，腎性貧血の発症進展を予防する


リンの栄養学 健康と疾患(解説)

リンの栄養学 健康と疾患(解説)


うつ病と栄養 (特集 メンタルヘルスと栄養)

Severe and prolonged stress exposure impairs homeostatic mechanisms, particularly associatedwith the onset of depressive illness. Brain food is aimed at preventing as well as treating a growingnumber of depression. An increase in brain tryptophan levels on the order of that produced byeating a carbohydrate-rich/protein-poor meal causes parallel increases in the amounts of serotoninreleased into synapses. Dietary antioxidants present in fruits and vegetables may also improvemood. Furthermore, lifestyle of breakfast, lunch and dinner with family or friends is a very importantfactor to reduce depression.


栄養素輸送システムと食品機能

栄養素輸送システムと食品機能


臨床栄養管理の意義とエビデンス，臨床栄養管理法―栄養アセスメントから経済評価まで―


大麦を利用した食後高血糖抑制割合の検討と食品評価

大麦を利用した食後高血糖抑制割合の検討と食品評価


内科医のための骨粗鬆症・カルシウム・リン代謝からあらためて骨を考える

内科医のための骨粗鬆症・カルシウム・リン代謝からあらためて骨を考える


Vitamin D and phosphate metabolism --- relationship with aging-regulating gene

ビタミンDとリン代謝 --- 加齢遺伝子とのかかわり


栄養・食糧学データハンドブック

栄養・食糧学データハンドブック


第6章ストレス制御をめざす栄養科学

第6章ストレス制御をめざす栄養科学


座談会・経腸栄養の素材と生体機能調節

座談会・経腸栄養の素材と生体機能調節

Japanese Journal of Nutritional Assessment


健康・栄養科学シリーズ人体の構造と機能及び疾病の成り立ち各論Ⅰ

健康・栄養科学シリーズ人体の構造と機能及び疾病の成り立ち各論Ⅰ


ビタミンDレセプター遺伝子多型と骨代謝

ビタミンDレセプター遺伝子多型と骨代謝


分子栄養学とは? 食事で遺伝子の発現が変わるのか?

分子栄養学とは? 食事で遺伝子の発現が変わるのか?


ストレス制御をめざす栄養科学

ストレス制御をめざす栄養科学

日本学術会議中国・四国地区ニュース

日本学術会議中国・四国地区ニュース


1α,25-Dihydroxyvitamin D3 is a preventive factor in the metastasis of lung cancer

1alpha,25-Dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], the major regulator of calcium homeostasis, has potent antiproliferative and anti-invasive properties in vitro in cancer cells. Studies in vivo demonstrated that 1alpha,25(OH)(2)D(3) slows the progression of breast, prostate and other carcinomas. A key question is whether 1alpha,25(OH)(2)D(3) exerts its anticarcinogenic effects in vivo by a mechanism that is dependent on its capacity to limit the proliferation and invasiveness of cancer cells in vitro. It has not been clear whether the calcemic activity and regulation of the host defenses by 1alpha,25(OH)(2)D(3) contribute to the effect on cancer cells. In this study we have focused on the influence of 1alpha,25(OH)(2)D(3) on the metastasis of lung cancer, without involvement of the calcemic activity and other effects of 1alpha,25(OH)(2)D(3) in the host. We used metastatic Lewis lung carcinoma cells expressing green fluorescent protein (LLC-GFP cells) and examined metastatic activity in vitamin D receptor (VDR) null mutant (VDR(-/-)) mice and their wild-type counterparts (VDR(+/+) mice). VDR(-/-) mice exhibit hypocalcemia and extremely high serum levels of 1alpha,25(OH)(2)D(3). We expected that serum 1alpha,25(OH)(2)D(3) would act in vivo to directly inhibit the metastatic growth of VDR-positive LLC-GFP cells in VDR(-/-) mice. The metastatic activities of LLC-GFP cells were remarkably reduced in VDR(-/-) mice compared with VDR(+/+) mice. To test the hypothesis that serum 1alpha,25(OH)(2)D(3) is an intrinsic factor that inhibits metastatic growth of lung cancer cells, we corrected hypocalcemia and/or hypervitaminosis D in VDR(-/-) mice by dietary manipulation. The metastatic growth of LLC-GFP cells was remarkably reduced in response to serum levels of 1alpha,25(OH)(2)D(3), but not to serum calcium levels. Furthermore, we found that VDR(+/+) mice fed the manipulated diets displayed an apparent inverse relationship between the physiological levels of serum 1alpha,25(OH)(2)D(3) (8-15 pg/ml) and tumorigenesis. Here we show that 1alpha,25(OH)(2)D(3) inhibits the metastatic growth of lung cancer cells in a defined animal model.


特集「透析患者の栄養評価における新理論と新技術」Ⅰ総論:最近の栄養評価における理論と技術およびその問題点


特集 - エビデンスからみた機能性食品の現状 2. 耐糖能改善食品(1)食物繊維


生体におけるリンの役割と制御

生体におけるリンの役割と制御


III 食事療法 肝疾患合併時

III 食事療法 肝疾患合併時


小児のこころと身体の健康を支援する栄養科学

小児のこころと身体の健康を支援する栄養科学


炎症性腸疾患に対する栄養管理の進歩

炎症性腸疾患に対する栄養管理の進歩


The regulation and function of phosphate in the human body

Inorganic phosphate (Pi) is required for cellular function and skeletal mineralization. Serum Pi level is maintained within a narrow range through a complex interplay between intestinal absorption, exchange with intracellular and bone storage pools, and renal tubular reabsorption. Pi is abundant in the diet, and intestinal absorption of Pi is efficient and minimally regulated. The kidney is a major regulator of Pi homeostasis and can increase or decrease its Pi reabsorptive capacity to accommodate Pi need. The crucial regulated step in Pi homeostasis is the transport of Pi across the renal proximal tubule. Type II sodium-dependent phosphate (Na/Pi) cotransporter (NPT2) is the major molecule in the renal proximal tubule and is regulated by hormones and nonhormonal factors. Recent studies of inherited and acquired hypophosphatemia which exhibit similar biochemical and clinical features, have led to the identification of novel genes, phosphate regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and fibroblast growth factor-23 (FGF-23), that play a role in the regulation of Pi homeostasis. The PHEX gene encodes an endopeptidase, predominantly expressed in bone and teeth but not in kidney. FGF-23 may be a substrate of this endopeptidase and inhibit renal Pi reabsorption. In a survey in the United States and in Japan, the amount of phosphorus from food is gradually increasing. It is thought that excess amounts of phosphorus intake for long periods are a strong factor in bone impairment and ageing. The restriction of phosphorus intake seems to be important under low calcium intake to keep QOL on high level.


Ⅶ．骨粗鬆症 ビタミンD至適摂取量-活性型ビタミンDを使用した場合の対応も含めて


分子栄養学からみた糖尿病の予防と治療

分子栄養学からみた糖尿病の予防と治療


栄養食品学-基礎と応用-

栄養食品学-基礎と応用-


肝疾患における低栄養の病態と治療

肝疾患における低栄養の病態と治療


ビタミン欠乏症 微量元素欠乏症

ビタミン欠乏症 微量元素欠乏症


重症心身障害児の至適投与熱量と栄養基質

重症心身障害児の至適投与熱量と栄養基質


ミネラルの生体での代謝と吸収

ミネラルの生体での代謝と吸収


耐糖能障害を予防・改善する機能性食品の開発

耐糖能障害を予防・改善する機能性食品の開発


肝硬変の栄養療法-夜食による早朝空腹時のエネルギー代謝改善効果-

肝硬変の栄養療法-夜食による早朝空腹時のエネルギー代謝改善効果-


低Glycemic Index食品は2型糖尿病の発症を予防し治療効果を有する

低Glycemic Index食品は2型糖尿病の発症を予防し治療効果を有する


先天性異常症 --- 病態と栄養療法の基礎的理解のために

先天性異常症 --- 病態と栄養療法の基礎的理解のために


Journal of Clinical and Experimental Medicine


腎尿細管・消化吸収機能異常症

腎尿細管・消化吸収機能異常症


「病態栄養専門士」とその認定制度

「病態栄養専門士」とその認定制度

The Japanese Journal of Clinical Nutrition


認定病態栄養士のための病態栄養ガイドブック

認定病態栄養士のための病態栄養ガイドブック


ヒトビタミンD受容体の腸管での発現と骨粗鬆症

ヒトビタミンD受容体の腸管での発現と骨粗鬆症

臨床栄養Update 生活習慣と消化器疾患

臨床栄養Update 生活習慣と消化器疾患


カルシウム・リン酸輸送とカベオラ

カルシウム・リン酸輸送とカベオラ


炎症性腸疾患の栄養アセスメント

炎症性腸疾患の栄養アセスメント


Parathyroid Hormone-Mediated Regulation of Renal Phosphate Co-Transporter

副甲状腺ホルモンによるリントランスポーター遺伝子の調節

PTHは，IIa 型リントランスポーターのエンドサイトーシスを誘導することによって腎臓のリン再吸収を抑制する．PTHは刷子縁膜および基底膜に局在するPTH受容体を介して，PKAあるいはPKCの活性化を促進する．これらのシグナル伝達の活性化は，直接NPT2をリン酸化するのではなく，エンドサイトーシスに関連する分子がPTHの作用に重要な役割を果たしていると考えられる．


ビタミンD欠乏性くる病とビタミンD依存性くる病

ビタミンD欠乏性くる病とビタミンD依存性くる病


食物成分と薬剤との相互作用

食物成分と薬剤との相互作用


骨粗鬆症のリスクファクターである日本人リン摂取過剰に関する研究

骨粗鬆症のリスクファクターである日本人リン摂取過剰に関する研究


高齢者の食と栄養管理に関する対策と提言

高齢者の食と栄養管理に関する対策と提言


医師のための糖尿病栄養学

医師のための糖尿病栄養学

メディカルジャーナルDITN

メディカルジャーナルDITN


骨代謝の基礎と最近の知見

骨代謝の基礎と最近の知見


治療指針今日の治療指針 - 私はこう治療している

治療指針今日の治療指針 - 私はこう治療している


ビタミンD受容体遺伝子多型からみた骨粗鬆症に対する栄養管理

ビタミンD受容体遺伝子多型からみた骨粗鬆症に対する栄養管理


肝硬変患者のエネルギー代謝の評価法

肝硬変患者のエネルギー代謝の評価法


肝疾患と病態栄養-予防と治療を考える-

肝疾患と病態栄養-予防と治療を考える-

最新肝臓病学 全国現状調査から将来展望まで

最新肝臓病学 全国現状調査から将来展望まで


エネルギー代謝からみた肝硬変患者の栄養管理-肝硬変患者のエネルギー代謝

エネルギー代謝からみた肝硬変患者の栄養管理-肝硬変患者のエネルギー代謝


糖尿病予防・治療のための食品の組み合わせ効果に関するヒト試験，Ⅲ-3ヒト試験等による生活習慣病・メタボリックシンドロームの予防機能の検証，食品・農産物の表示の信頼性確保と機能性解析のための基盤技術の開発-機能性-(食品・農産物の新たな機能性解析技術の開発)

平成20年度運営委員会報告 農林水産省農林水産技術会議事務局 独立行政法人農業・食品産業技術総合研究機構 食品総合研究所


Evaluation of anti-stress nutrients in the endothelial cells with fluorescence indicator

Oxidative stress has emerged as an important pathogenic factor in the development of long-term complications, such as hypertension, atherosclerosis, nephropathy, and cancer. Taking many antioxidants from natural food may be effective to prevent us from those diseases. We have attempted to evaluate the effect of improvement by dietary antioxidants on the endothelial dysfunction induced by hyperglycemia. Fluorescence indicators for reactive oxygen species and nitric oxide were employed to the evaluation. The combination of those fluorescence indicators could be powerful tool to evaluate the effect of anti-stress nutrients on both oxidative stress and endothelial dysfunction.

The Journal of Medical Investigation : JMI


Control of oxidative stress and metabolic homeostasis by the suppression of postprandial hyperglycemia

Repeated mental stress may lead to chronic alterations in cortisol and catecholamine concentrations and to insulin resistance. Furthermore, chronically elevated cortisol concentrations may favour the development of abdominal obesity and of the metabolic syndrome. Oxidative stress impairs glucose uptake in muscle and fat and correlates with BMI. Obese subjects with type 2 diabetes, especially soon after the onset of diabetes, usually exhibit postprandial hyperglycemia with delayed hyperinsulinemia. It is recognized that insulin resistance causes postprandial hyperglycemia; however, it is also possible that impairment of early insulin secretion in response to an oral glucose load is the reason why postprandial hyperglycemia occurs. Since even modest increases in postprandial glucose values can be a risk factor for cardiovascular disease. Therefore, the effects of palatinose based functional food which reduces postprandial hyperglycemia and hyperinsulinemia were investigated in rats. This novel food definitely reduced visceral fat accumulation and improved insulin sensitivity. Therefore, it is suggested that functional food which suppresses postprandial glucose level is beneficial for both stress and metabolic controls.


Human nutritional science on stress control

Severe and prolonged stress exposure impairs homeostatic mechanisms, particularly associated with the onset of depressive illness. The establishment of functional foods that correctly regulate stress response must be an important and new field for human nutrition. This exciting science has been vigorously achieving in the 21st century COE program of University of Tokushima Graduate School.


臨床栄養管理に対する基礎的および実践的研究

臨床栄養管理に対する基礎的および実践的研究


昼食後耐糖能におよぼす朝食での糖質調整流動食(インスロー)摂取の効果

昼食後耐糖能におよぼす朝食での糖質調整流動食(インスロー)摂取の効果

The Japanese Society of Digestion and Absorption