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微小RNA介导的胰岛素抵抗状态下骨骼肌葡萄糖转运蛋白4表达及转位的调控

MicroRNAs-Mediated Regulation of Skeletal Muscle GLUT4 Expression and Translocation in Insulin Resistance.

作者信息

Esteves João Victor, Enguita Francisco Javier, Machado Ubiratan Fabres

机构信息

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.

出版信息

J Diabetes Res. 2017;2017:7267910. doi: 10.1155/2017/7267910. Epub 2017 Mar 27.

Abstract

The solute carrier family 2 facilitated glucose transporter member 4 (GLUT4) plays a key role in the insulin-induced glucose uptake by muscle and adipose tissues. In prediabetes and diabetes, GLUT4 expression/translocation has been detected as reduced, participating in mechanisms that impair glycemic control. Recently, a class of short endogenous noncoding RNAs named microRNAs (miRNAs) has been increasingly described as involved in the posttranscriptional epigenetic regulation of gene expression. The present review focuses on miRNAs potentially involved in the expression of GLUT4 expression, and proteins related to GLUT4 and translocation in skeletal muscle, seeking to correlate them with insulin resistance and diabetes. So far, miR-21a-5p, miR-29a-3p, miR-29c-3p, miR-93-5p, miR-106b-5p, miR-133a-3p, miR-133b-3p, miR-222-3p, and miR-223-3p have been reported to directly and/or indirectly regulate the GLUT4 expression; and their expression is altered under diabetes-related conditions. Besides, some miRNAs that have been linked to the expression of proteins involved in GLUT4 translocation machinery in muscle could also impact glucose uptake. That makes these miRNAs promising targets for preventive and/or therapeutic approaches, which could improve glycemic control, thus deserving future new investigations.

摘要

溶质载体家族2促进葡萄糖转运蛋白成员4(GLUT4)在胰岛素诱导的肌肉和脂肪组织葡萄糖摄取中起关键作用。在糖尿病前期和糖尿病中,已检测到GLUT4的表达/转位降低,这参与了损害血糖控制的机制。最近,一类名为微小RNA(miRNA)的短内源性非编码RNA越来越多地被描述为参与基因表达的转录后表观遗传调控。本综述重点关注可能参与GLUT4表达以及与骨骼肌中GLUT4及其转位相关的蛋白质表达的miRNA,旨在将它们与胰岛素抵抗和糖尿病联系起来。到目前为止,据报道miR-21a-5p、miR-29a-3p、miR-29c-3p、miR-93-5p、miR-106b-5p、miR-133a-3p、miR-133b-3p、miR-222-3p和miR-223-3p可直接和/或间接调节GLUT4的表达;并且它们的表达在糖尿病相关条件下会发生改变。此外,一些与肌肉中GLUT4转位机制相关蛋白质表达有关的miRNA也可能影响葡萄糖摄取。这使得这些miRNA成为预防和/或治疗方法的有希望的靶点,有望改善血糖控制,因此值得未来进行新的研究。

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