Acute inhibition of protein deacetylases does not impact skeletal muscle insulin action.

Abstract

INTRODUCTION\nWhether the histone deacetylase (HDAC) and sirtuin families of protein deacetylases regulate insulin-stimulated glucose uptake, independent of their transcriptional effects, has not been studied. Our objective herein was to determine the non-transcriptional role of HDACs and sirtuins in regulating skeletal muscle insulin action.\n\n\nMETHODS\nBasal and insulin-stimulated glucose uptake and signaling, and acetylation were assessed in L6 myotubes and skeletal muscle from C57BL/6J mice that were treated acutely (1 hour) with HDAC (trichostatin A, panobinostat, TMP195) and sirtuin inhibitors (nicotinamide).\n\n\nRESULTS\nTreatment of L6 myotubes with HDAC inhibitors, or skeletal muscle with a combination of HDAC and sirtuin inhibitors increased tubulin and pan-protein acetylation, demonstrating effective impairment of HDAC and sirtuin deacetylase activities. Despite this, neither basal or insulin-stimulated glucose uptake or insulin signaling were impacted.\n\n\nCONCLUSIONS\nAcutely reducing the deacetylase activity of HDACs and/or sirtuins does not impact insulin action in skeletal muscle.