Ghrelin对胰岛β细胞分泌胰岛素和增殖的影响及分子机制

项目名称： Ghrelin对胰岛β细胞分泌胰岛素和增殖的影响及分子机制

项目编号： No.81200596

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 王颖

作者单位： 扬州大学

项目金额： 23万元

中文摘要： 由胰岛β细胞分泌胰岛素减少及凋亡引起的β细胞数量减少所导致的胰岛β细胞功能缺陷是糖尿病发生的重要机制之一，但其分子机制尚不清楚。近来研究发现，促摄食激素ghrelin参与抑制β细胞胰岛素分泌。本研究前期工作利用胰岛β细胞系MIN6细胞，证实ghrelin通过AMP激活的蛋白激酶(AMPK)-解偶联蛋白2(UCP2)通路抑制胰岛素的分泌。而最近报道ghrelin对下丘脑AMPK的激活作用依赖于NAD（辅酶）依赖的去乙酰化酶SIRT1。在此基础上，本研究旨在探讨ghrelin对MIN6细胞和大鼠胰岛细胞胰岛素分泌与增殖的影响及SIRT1在ghrelin调控的AMPK-UCP2通路中的作用，在整体、细胞和分子水平阐明ghrelin对胰岛β细胞功能的影响，为寻求有效的糖尿病治疗新方法提供实验基础。

中文关键词： Ghrelin；胰岛；β细胞；胰岛素；增殖

英文摘要： Functional defect in islet β cells is one of the important mechanisms of diabetes. The biological factors of it include insufficient insulin secretion and decrease in the amount of β cells caused by apoptosis. But the intrinsic molecular mechanism is still not clear. The orexigenic hormone ghrelin was showed taking part in the inhibition of insulin secretion in β cells in recent studies. We have proved that ghrelin inhibited insulin secretion through adenosine monophosphate activated protein kinase(AMPK)-uncoupling protein 2 (UCP2) pathway using MIN6 cells. Moreover, it was reported that the effect of ghrelin on AMPK activation in hypothalamus was blocked by EX-527, inhibitor of nicotinamide adenine dinucleotide (NAD, coenzyme)-dependent deacetylase SIRT1, showing that the action of ghrelin on AMPK is dependent on SIRT1 recently. On account of these, this research aims at investigating the impact of ghrelin on insulin secretion and proliferation in MIN6 and rat islet cells and the role SIRT1 plays in the ghrelin regulated AMPK-UCP2 pathway as well. Then we are able to not only get approach to consider the influence of ghrelin on islet cells from the integrated, the cellular and the molecular levels together but also set up laboratory foundation for a new way to treat diabetes.

英文关键词： Ghrelin；Islets；β cells；Insulin；Proliferation