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

João Victor Esteves,Ubiratan Fabres Machado,Francisco Javier Enguita

doi:10.1155/2017/7267910

João Victor Esteves, Ubiratan Fabres Machado + Show 1 more

Open Access

https://doi.org/10.1155/2017/7267910

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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.

Highlights

Diabetes mellitus (DM) is a metabolic disorder with high prevalence in the world [1]
As in the adipose tissue, the insulin-stimulated glucose uptake is performed through the solute carrier family 2, facilitated glucose transporter member 4 (GLUT4), which is rapidly translocated to the plasma membrane in response to the hormone [5, 6]
This review summarizes the potential participation of miRNAs in the regulation of GLUT4 protein and proteins related to its translocation, in skeletal muscle, exploring their involvement in the pathophysiology of diabetes, as well as their potential role in preventive or therapeutic approaches for diabetes

Summary

Introduction

Diabetes mellitus (DM) is a metabolic disorder with high prevalence in the world [1]. As in the adipose tissue, the insulin-stimulated glucose uptake is performed through the solute carrier family 2, facilitated glucose transporter member 4 (GLUT4), which is rapidly translocated to the plasma membrane in response to the hormone [5, 6]. This review summarizes the potential participation of miRNAs in the regulation of GLUT4 protein (codified by the SLC2A4 gene) and proteins related to its translocation, in skeletal muscle, exploring their involvement in the pathophysiology of diabetes, as well as their potential role in preventive or therapeutic approaches for diabetes. The GLUT4 protein (codified by the gene solute carrier family 2 member 4, SLC2A4) is the major glucose transporter of brown and white adipose tissues and of skeletal and cardiac muscles [21]. Considering what was described above, it becomes evident that insulin and muscle contraction modulate glycemic homeostasis by regulating both translocation and expression of GLUT4

Skeletal Muscle GLUT4 Expression and Translocation

Findings

Conclusions