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.

OBJECTIVES:MicroRNAs 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. METHODS:In 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. RESULTS:We 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. CONCLUSIONS:These 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.

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