MiR-26b modulates insulin sensitivity in adipocytes by interrupting the PTEN/PI3K/AKT pathway

Abstract

Background:MicroRNAs (miRNAs) have emerged as epigenetic regulators of metabolism and energy homeostasis. There is a growing body of evidence pointing to miRNAs that have important regulatory roles in insulin sensitivity.Objective:The aim of this work was to explore the expression and mechanism of action of miR-26b in obesity-related insulin resistance (IR) in adipocytes.Methods:Quantitative real-time PCR was performed to determine miR-26b expression in obese rodent models, human obesity subjects and insulin-resistant adipocytes. We analysed the roles of miR-26b overexpression and inhibition on glucose uptake in adipocytes. Western blotting was used to detect the levels of protein molecules involved in the phosphoinositide-3-kinase (PI3K) pathway. Bioinformatics and the Dual Luciferase Assay were used to identify the target gene of miR-26b. We assessed the regulatory roles of miR-26b on the phosphatase and tensin homologue (PTEN)/PI3K/AKT pathway and the relationship between miR-26b and the metabolism of human obese subjects.Results:Levels of miR-26b are reduced in visceral adipose tissue (VAT) in obese rodent models, human obesity and insulin-resistant adipocytes. MiR-26b promotes insulin-stimulated glucose uptake and increases insulin-stimulated glucose transporter type 4 translocation to the plasma membrane in human mature adipocytes. MiR-26b modulates insulin-stimulated AKT activation via inhibition of its target gene, PTEN, and significantly increases insulin sensitivity via the PTEN/PI3K/AKT pathway. The expression level of miR-26b negatively correlates with increasing body mass index and homeostasis model assessment for IR in human obese subjects.Conclusion:Decreased miR-26b expression in VAT may be involved in obesity-related IR by interrupting the PTEN/PI3K/AKT pathway.