DIABETES, KIDNEY, CALCIUM TRANSPORT, AND AGING

拟议研究的目的是分析生物效应 维生素D代谢产物对磷酸盐和钙转运的影响 肠和肾。 正常的生理状态和两种不同的 将研究病理生理状态。 每一个的特点是， 维生素D代谢的改变， 钙和/或磷酸盐转运。 该计划基于以下内容 假设 第一，肾磷酸盐稳态的遗传性改变， 家族性低磷血症性佝偻病（FHR）是由肾脏疾病引起的。 肾小管磷酸盐转运和对维生素D的生物反应。 其次，钙、磷酸盐和维生素D的获得性紊乱 糖尿病状态下的代谢是由激素控制缺陷引起的， 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代谢产物与磷酸盐转运的关系， 蛋白质磷酸化;（2）维生素D代谢产物对 磷酸盐转运和肾细胞膜的磷酸化，（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 磷酸盐转运;（4）肾脏代谢缺陷的性质， 25-胰岛素减少状态下的羟基胆钙化醇：和（5） 这些缺陷与获得性肠道紊乱和 对1，25-二羟基胆钙化醇的肾脏生物学反应。

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.