Musclin Inhibits Insulin Activation of Akt/Protein Kinase B in Rat Skeletal Muscle

Abstract

Musclin is a muscle-derived secretory peptide that induces insulin resistance in vitro We studied the effect of musclin (0.5 μg/ml) on insulin-stimulated glucose uptake in rat skeletal muscles and also the effect of rosiglitazone (0.4 μg/ml). Pre-incubation of muscles with musclin resulted in decreased insulin-stimulated glucose uptake. Musclin also reduced expression of peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor α (LXRα) mRNAs, although expression of glucose transporter 4 mRNA was unaltered. Rosiglitazone attenuated the effects of musclin on glucose uptake and PPARγ and LXRα mRNA expression. Western blotting demonstrated that activation of protein kinase B (Akt/PKB) in the insulin-signalling cascade was decreased by musclin but corrected by rosiglitazone. These findings suggest that musclin-induced impairment of insulin-stimulated glucose uptake in skeletal muscle is related to Akt/PKB inhibition and might be modulated by PPARγ/LXRα.