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首页> 外文期刊>Diabetes research and clinical practice >MicroRNA-15a positively regulates insulin synthesis by inhibiting uncoupling protein-2 expression.
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MicroRNA-15a positively regulates insulin synthesis by inhibiting uncoupling protein-2 expression.

机译:MicroRNA-15a通过抑制解偶联蛋白2的表达积极调节胰岛素的合成。

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MicroRNAs are small noncoding RNAs that have been highly conserved during evolution and have been implicated to play an important role in many diseases, including diabetes. Several reports indicated the function of miRNAs in insulin production. However, the mechanisms by which miRNAs regulate this process remain poorly understood. Here we found that the expression of miR-15a was up-regulated in the presence of high glucose for 1h, whereas prolonged periods of high glucose exposure resulted in depressed expression of miR-15a, and the change in expression levels of miR-15a coincided with insulin biosynthesis. Moreover, ectopic expression of miR-15a promoted insulin biosynthesis in MIN6 cells, whereas its repression was sufficient to inhibit insulin biosynthesis. Further, we verified that miR-15a directly targeted and inhibited uncoupling protein-2 (UCP-2) gene expression. miR-15a mimics inhibited UCP-2 3'UTR luciferase reporter activity. Western blot analysis showed that miR-15a inhibited endogenous UCP-2 protein levels, and resulted in the increase in oxygen consumption and reduced ATP generation. This study suggests miR-15a is a mediator of beta cell function and insulin biosynthesis, thus offering a new target for the development of preventive or therapeutic agents against diabetes.
机译:微小RNA是小的非编码RNA,在进化过程中高度保守,并被暗示在包括糖尿病在内的许多疾病中起着重要作用。一些报道表明miRNA在胰岛素生产中的功能。然而,miRNA调节这一过程的机制仍然知之甚少。在这里,我们发现在高葡萄糖存在1h时miR-15a的表达上调,而长时间的高葡萄糖暴露导致miR-15a的表达降低,并且miR-15a的表达水平发生了变化与胰岛素的生物合成。此外,miR-15a的异位表达促进了MIN6细胞中胰岛素的生物合成,而其阻遏作用足以抑制胰岛素的生物合成。此外,我们证实了miR-15a直接靶向并抑制了解偶联蛋白2(UCP-2)基因的表达。 miR-15a模拟物抑制UCP-2 3'UTR荧光素酶报道分子的活性。蛋白质印迹分析表明,miR-15a抑制内源性UCP-2蛋白水平,并导致耗氧量增加和ATP生成减少。这项研究表明miR-15a是β细胞功能和胰岛素生物合成的介体,从而为开发预防或治疗糖尿病的药物提供了新的靶点。

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