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microRNAs 在 2 型糖尿病并发症发展中的作用。

The Role of microRNAs in the Development of Type 2 Diabetes Complications.

机构信息

Department of Cardiology, Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, 11527Athens, Greece.

First Department of Internal Medicine, Diabetes Centre, Division of Endocrinology and Metabolism, AHEPA University Hospital, Thessaloniki, Greece.

出版信息

Curr Pharm Des. 2020;26(46):5969-5979. doi: 10.2174/1381612826666201102102233.

Abstract

MicroRNAs represent a class of small (19-25 nucleotides) single-strand pieces of RNA that are noncoding ones. They are synthesized by RNA polymerase II from transcripts that fold back on themselves. They mostly act as gene regulatory agents that pair with complementary sequences on mRNA and produce silencing complexes, which, in turn, suppress coding genes at a post-transcriptional level. There is now evidence that microRNAs may affect insulin secretion or insulin action, as they can alter pancreatic beta cells development, insulin production, as well as insulin signaling. Any molecular disorder that affects these pathways can deteriorate insulin resistance and lead to type 2 diabetes mellitus (T2DM) onset. Furthermore, the expression of several microRNAs is up- or down-regulated in the presence of diabetic microvascular complications (i.e., peripheral neuropathy, nephropathy, retinopathy, foot ulcers), as well as in patients with coronary heart disease, stroke, and peripheral artery disease. However, more evidence is needed, specifically regarding T2DM patients, to establish the use of such microRNAs as diagnostical biomarkers or therapeutic targets in daily practice.

摘要

MicroRNAs 是一类小的(19-25 个核苷酸)单链 RNA 非编码分子。它们由 RNA 聚合酶 II 从自身回折的转录本中合成。它们主要作为基因调节因子,与 mRNA 上的互补序列结合,产生沉默复合物,从而在转录后水平抑制编码基因。现在有证据表明 microRNAs 可能影响胰岛素分泌或胰岛素作用,因为它们可以改变胰岛 β 细胞的发育、胰岛素的产生以及胰岛素信号转导。任何影响这些途径的分子紊乱都会导致胰岛素抵抗,并导致 2 型糖尿病(T2DM)的发生。此外,在存在糖尿病微血管并发症(即周围神经病、肾病、视网膜病变、足部溃疡)的情况下,以及在患有冠心病、中风和外周动脉疾病的患者中,几种 microRNAs 的表达上调或下调。然而,还需要更多的证据,特别是针对 T2DM 患者,以确定将这些 microRNAs 用作日常实践中的诊断生物标志物或治疗靶点。

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