DIABETES, KIDNEY, CALCIUM TRANSPORT, AND AGING

拟议研究的目的是分析其生物学效应。 维生素D代谢产物对体内磷酸盐和钙转运的影响 肠和肾。正常的生理状态和两种截然不同的 将对病理生理状态进行研究。每种产品的特点都是 维生素D代谢的改变，以及两者中的功能紊乱 钙和/或磷的运输。该计划基于以下内容 假设。第一，遗传性肾磷酸盐稳态的改变 家族性低磷血症性软骨病(FHR)是由肾脏支出引起的 肾小管磷酸盐转运和对维生素D的生物反应。 第二，后天钙、磷和维生素D的紊乱 糖尿病状态下的新陈代谢由激素控制缺陷所致 肾细胞代谢和磷酸盐转运机制。这些研究将 重点研究：(1)25(OH)D3在FHR小鼠模型中的肾脏代谢， 以及维生素D代谢物与磷酸盐转运和 蛋白质磷酸化；(2)维生素D代谢产物对血管内皮生长因子的影响 肾细胞膜的磷酸盐转运和磷酸化，(3) 胰岛素对肾脏葡萄糖和环核苷酸代谢的影响 它们与刷状缘膜蛋白磷酸化和蛋白表达的关系 磷酸盐转运；(4)肾代谢缺陷的性质 胰岛素缺乏状态下的25-羟基胆钙化醇：和(5) 这些缺陷与获得性肠道和骨骼肌紊乱的关系 1，25-二羟基胆钙醇的肾脏生物学反应(S)。

The objective of the proposed research is to analyze the biological effects of vitamin D metabolites on phosphate and calcium transport in the intestine and kidney. Normal physiological states and two distinct pathophysiological states will be studied. Each is characterized by alterations in vitamin D metabolism, and functional derangements in either calcium and/or phosphate transport. The program is based on the following hypotheses. First, inherited alterations in renal phosphate homeostasis in Familial Hypophosphatemic Rickets (FHR) result from disburbances in renal tubular phosphate transport, and biological responses to vitamin D. Second, acquired derangements in calcium, phosphate, and vitamin D metabolism in the diabetic state result from defective hormonal control of renal cell metabolism and phosphate transport mechanisms. The studies will focus on: (1) the renal metabolism of 25(OH)D3 in a mouse model of FHR, and the relationship of vitamin D metabolites to phosphate transport and protein phosphorylation; (2) the effects of vitamin D metabolites on phosphate transport and phosphorylation of renal cell membranes, (3) the effects of insulin on renal glucose and cyclic nucleotide metabolism and their relationship to brush border membrane protein phosphorylation and phosphate transport; (4) the nature of the defects in renal metabolism of 25-hydroxycholecalciferol in the insulinopenic state: and (5) the relationship of these defects to acquired derangements in intestinal and renal biological response(s) to 1,25-dihydroxycholecalciferol.