MicroRNA-15a Inhibits Glucose Transporter 4 Translocation and Impairs Glucose Metabolism in L6 Skeletal Muscle Via Targeting of Vesicle-Associated Membrane Protein-Associated Protein A.

Abstract

OBJECTIVES\nMicroRNAs have been reported to participate in various important cell biological processes, such as glucose metabolism. The aim of this study was to explore the roles of microRNA-15a (miR-15a) in regulating insulin sensitivity.\n\n\nMETHODS\nIn L6 rat skeletal muscle cells, we observed the effect of miR-15a on glucose metabolism and glucose transporter 4 (GLUT4) translocation by targeting vesicle-associated membrane protein-associated protein A (VAP-A) after insulin treatment. Luciferase reporter assays were performed to demonstrate a direct interaction between miR-15a and the 3 -untranslated region of VAP-A microRNA.\n\n\nRESULTS\nWe identified miR-15a as an extremely important regulator of GLUT4 translocation via targeting of VAP-A. Additionally, knockdown of endogenous miR-15a or overexpression of VAP-A could increase extracellular glucose by inhibiting the translocation of GLUT4 to the cell membrane after insulin treatment. However, overexpression of miR-15a or knockdown of VAP-A had no significant effect on glucose metabolism.\n\n\nCONCLUSIONS\nThese findings reveal the following: 1) VAP-A is a marker of skeletal muscle glucose disposal and 2) a novel mechanism for GLUT4 translocation by miR-15a.