Department of Science, Systems and Models, Roskilde University, Roskilde, Denmark.
Biochem Biophys Res Commun. 2012 Sep 21;426(2):266-72. doi: 10.1016/j.bbrc.2012.08.082. Epub 2012 Aug 23.
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.
慢性升高的葡萄糖水平会损害胰腺β细胞功能，同时诱导β细胞增殖。在糖尿病动物的几种组织中，miR-29a（miR-29a）的水平增加，并介导脂肪细胞胰岛素刺激的葡萄糖转运减少。本研究旨在探讨葡萄糖对 INS-1E 胰岛β细胞和人胰岛中 miR-29a 水平的影响，进一步评估 miR-29a 对β细胞功能和增殖的影响。高葡萄糖水平可上调β细胞和人胰岛和大鼠胰岛中 miR-29a 的表达。miR-29a 的强制表达可降低 INS-1E 胰岛β细胞的葡萄糖刺激胰岛素分泌（GSIS），而内源性 miR-29a 的耗竭则可改善 GSIS。miR-29a 的过表达可增加 INS-1E 细胞的增殖。因此，miR-29a 的上调参与了葡萄糖诱导的β细胞增殖。此外，由于 miR-29a 的耗竭可改善β细胞功能，因此 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 的上调可能与从糖耐量受损进展为 2 型糖尿病有关。
