Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, 53100 Siena, Italy.
Int J Mol Sci. 2018 Nov 22;19(12):3705. doi: 10.3390/ijms19123705.
The insulin signaling pathway is composed of a large number of molecules that positively or negatively modulate insulin specific signal transduction following its binding to the cognate receptor. Given the importance of the final effects of insulin signal transduction, it is conceivable that many regulators are needed in order to tightly control the metabolic or proliferative functional outputs. MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively modulate gene expression through their specific binding within the 3'UTR sequence of messenger RNA (mRNA), thus causing mRNA decoy or translational inhibition. In the last decade, miRNAs have been addressed as pivotal cellular rheostats which control many fundamental signaling pathways, including insulin signal transduction. Several studies demonstrated that multiple alterations of miRNAs expression or function are relevant for the development of insulin resistance in type 2 diabetes (T2D); such alterations have been highlighted in multiple insulin target organs including liver, muscles, and adipose tissue. Indirectly, miRNAs have been identified as modulators of inflammation-derived insulin resistance, by controlling/tuning the activity of innate immune cells in insulin target tissues. Here, we review main findings on miRNA functions as modulators of insulin signaling in physiologic- or in T2D insulin resistance- status. Additionally, we report the latest hypotheses of prospective therapies involving miRNAs as potential targets for future drugs in T2D.
胰岛素信号通路由大量分子组成，这些分子在胰岛素与其同源受体结合后，正向或负向调节胰岛素的特异性信号转导。鉴于胰岛素信号转导的最终效应非常重要，可以想象，为了严格控制代谢或增殖功能的输出，需要许多调节剂。microRNAs (miRNAs) 是小的非编码 RNA 分子，通过在信使 RNA (mRNA) 的 3'UTR 序列中的特异性结合来负向调节基因表达，从而导致 mRNA 诱饵或翻译抑制。在过去的十年中，miRNAs 被认为是控制许多基本信号通路（包括胰岛素信号转导）的关键细胞变阻器。多项研究表明，miRNAs 表达或功能的多种改变与 2 型糖尿病 (T2D) 中的胰岛素抵抗的发展有关；这种改变在包括肝脏、肌肉和脂肪组织在内的多个胰岛素靶器官中都有被突出强调。间接的，miRNAs 通过控制/调节胰岛素靶组织中固有免疫细胞的活性，被鉴定为炎症来源的胰岛素抵抗的调节剂。在这里，我们综述了 miRNA 作为生理或 T2D 胰岛素抵抗状态下胰岛素信号转导调节剂的主要功能发现。此外，我们还报告了涉及 miRNA 的潜在治疗的最新假说，作为 T2D 中未来药物的潜在靶点。
