维生素D在糖尿病发生和发展中的作用

糖尿病是一类营养相关的代谢性疾病。近年来，维生素D与糖尿病的关系倍受关注。本项目受体内无活性维生素D的1α羟化酶基因敲除小鼠怀孕后胰岛β细胞凋亡高于同窝野生型小鼠现象的启发，提出了活性维生素D抑制胰岛β细胞凋亡的假设。采用1α羟化酶基因敲除小鼠模型研究阻断维生素D信号通路后小鼠胰岛β细胞凋亡率的变化。通过体内、体外实验验证假设，探索维生素D在糖尿病发生中的作用。 糖尿病肾病是糖尿病患者的主要死亡原因之一，目前无有效的防治方法。临床上发现糖尿病肾病患者多数存在维生素D缺乏。因此，本项目在研究维生素D信号通路对胰岛β细胞凋亡影响的基础上进一步研究基因敲除小鼠的糖尿病肾病发病情况并用不同剂量的维生素D进行干预观察疗效。同时，利用体外实验研究活性维生素D对高糖引起的肾脏系膜细胞和足细胞损伤的保护作用及机理。通过体内外实验探索维生素D对糖尿病肾病并发症的保护作用。

Diabetes mellitus is nutrition metabolic disease. A large numbers studies show that vitamin D play a role in Diabetes mellitus. In our previous studies, more apoptosis pancreatic beta cells were found in pregnancy 1 alpha hydroxylase gene knockout mice. It is suggested that vitamin D might inhibit the apoptosis of islet β cell. So, in this study, apoptosis of pancreatic beta cells are explored after vitamin D signal pathway is blocked and stimulated. The effects of vitamin D in diabetes mellitus occurrence are investigated in vivo and in vitro. Diabetic nephropathy is one of the main causes of death in patients with diabetes and there are no effective prevention methods currently. Vitamin D deficiency is popular in the patients with diabetic nephropathy. Therefore, this project studies the incidence of diabetic nephropathy in gene knockout mice and protective effect of different doses of vitamin D on diabetic nephropathy in knockout mice. At the same time, the protective effect and mechanism of vitamin D on high glucose-induced injury in renal mesangial cells and podocytes are studied in vitro.The effects of vitamin D in diabetes mellitus development are studied in vivo and in vitro.