硫酸脱氢表雄酮在胰岛β细胞中的作用及其机制的研究

项目名称： 硫酸脱氢表雄酮在胰岛β细胞中的作用及其机制的研究

项目编号： No.81471029

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李圣贤

作者单位： 上海交通大学

项目金额： 73万元

中文摘要： 近年，我国糖尿病患病率显著增加，已达到了惊人的11.6%。 相对于糖尿病患者的激增，治疗手段的进展较为缓慢。β细胞功能减退和胰岛素分泌不足是导致糖尿病发生的主要原因。目前鲜有降糖药能同时满足促进胰岛素分泌、改善胰岛素敏感性和促进β细胞增生。幸运的是，我们课题组发现硫酸脱氢表雄酮（DHEAS）能促进β细胞分泌胰岛素、提高胰岛素敏感性和修复受损的β细胞。由于DHEAS作用机制未明等原因，限制了其临床使用。结合我们前期的研究工作，我们推测：1）G蛋白偶联受体(GPCRs)信号通路介导DHEAS短时相的胰岛素分泌,还参与β细胞的增殖；2）丙酮酸循环通路及葡萄糖代谢的中间产物参与长时相的促泌调节。我们拟通过本研究，阐明DHEAS促进胰岛素分泌和β细胞增殖的分子机制，以填补DHEAS在β细胞中作用机制的空白，有助于DHEAS或其小分子类似物走向临床，或以此为靶点研制新药。

中文关键词： 硫酸脱氢表雄酮；胰岛β细胞；胰岛素分泌；信号通路；G蛋白偶联受体

英文摘要： Diabetes has becoming a worldwide epidemic in the general population. The prevalence of diabetes is up to 11.6% according to the data released in 2013 by the China Noncommunicable Disease Surveillance Group. However, the development of treatment is slow. The decreased insulin secretion and beta cell dysfunction, are the main characteristics of type 2 diabetes. and , There are few antidiabetic medications which increase insulin secretion, improve insulin sensitivity, and promote beta cell proliferation. In our previous study, we found that dehydroepiandrosterone sulfate (DHEAS) increased insulin secretion, improved the insulin sensitivity and restored the beta cells function.　However, the mechanism of it is still unknown. we hypothesize that: 1) the G protein coupled receptors (GPCRs) signaling pathways may mediate the short-term phase insulin secretion and beta cell proliferation, 2) pyruvic acid circulation path and its intermediate may be involved in the regulation of long phase insulin secretion. We aim to clarify the potential mechanism of DHEAS in the stimulation of insulin secretion and beta cell proliferation. We would be able to reveal the physiological function and mechanism of DHEAS and provide the possibility of DHEAS and its analogues in the clinical treatment in the future.

英文关键词： dehydroepiandrosterone sulfate;islet β cell;insulin secretion;signaling pathway;G protein coupled receptors