MicroRNA-29a is up-regulated in beta-cells by glucose and decreases glucose-stimulated insulin secretion
MicroRNA-29a is up-regulated in beta-cells by glucose and decreases glucose-stimulated insulin secretion
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DOI：
10.1016/j.bbrc.2012.08.082
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发表时间：
2012-09-21
影响因子：
3.1
通讯作者：
Dalgaard, Louise T.
中科院分区：
文献类型：
--
作者：
Bagge, Annika;Clausen, Trine R.;Dalgaard, Louise T.
长期升高的葡萄糖水平损害胰腺β细胞功能，同时诱导β细胞增殖。MicroRNA-29a （miR-29a）水平在糖尿病动物的几个组织中升高，并介导胰岛素刺激的脂肪细胞葡萄糖转运减少。目的是研究葡萄糖对INS-1E β细胞和朗格汉斯人胰岛中miR-29a水平的影响，并进一步评估miR-29a对β细胞功能和增殖的影响。葡萄糖水平升高可上调β细胞、人和大鼠朗格汉斯胰岛中的miR-29a。通过强制表达miR-29a， INS-1E β细胞的葡萄糖刺激胰岛素分泌（GSIS）降低，而内源性miR-29a的消耗改善了GSIS。过表达miR-29a可增加INS-1E的增殖。因此，miR-29a上调参与了葡萄糖诱导的β细胞增殖。此外，由于miR-29a的缺失可以改善β细胞功能，miR-29a是葡萄糖诱导的β细胞功能障碍的介质。葡萄糖诱导的β细胞中miR-29a的上调可能与糖耐量受损到2型糖尿病的进展有关。(C) 2012爱思唯尔公司版权所有。
Chronically elevated levels of glucose impair pancreatic beta-cell function while inducing beta-cell proliferation. MicroRNA-29a (miR-29a) levels are increased in several tissues in diabetic animals and mediate decreased insulin-stimulated glucose-transport of adipocytes. The aim was to investigate the impact of glucose on miR-29a levels in INS-1E beta-cells and in human islets of Langerhans and furthermore to evaluate the impact of miR-29a on beta-cell function and proliferation. Increased glucose levels up-regulated miR-29a in beta-cells and human and rat islets of Langerhans. Glucose-stimulated insulin-secretion (GSIS) of INS-1E beta-cells was decreased by forced expression of miR-29a, while depletion of endogenous miR-29a improved GSIS. Over-expression of miR-29a increased INS-1E proliferation. Thus, miR-29a up-regulation is involved in glucose-induced proliferation of beta-cells. Furthermore, as depletion of miR-29a improves beta-cell function, miR-29a is a mediator of glucose-induced beta-cell dysfunction. Glucose-induced up-regulation of miR-29a in beta-cells could be implicated in progression from impaired glucose tolerance to type 2 diabetes. (C) 2012 Elsevier Inc. All rights reserved.