AMP-activated protein kinase-mediated expression of heat shock protein beta 1 enhanced insulin sensitivity in the skeletal muscle

Abstract

Activation of AMP-activated protein kinase (AMPK) has been viewed as an important target for the treatment of insulin resistance. Here, by proteomic analysis, we found that expression of heat shock protein beta-1 (HSPB1) was induced by the AMP analog 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside in palmitate-induced insulin-resistant cells. Overexpression of AMPKα2, or activation of AMPKα via acute/chronic exercise training, increased HSPB1 expression in the skeletal muscle. In AMPKα2−/− mice, HSPB1 expression was downregulated in the quadriceps muscles. Exercise did not increase HSPB1 expression in AMPKα2−/− mice. Moreover, overexpression of HSPB1 enhanced insulin sensitivity in palmitate-induced insulin-resistant cells and restored metabolic phenotypes associated with defective AMPK. Finally, HSPB1 was required for AMPK-mediated activation of the class IIa histone deacetylases and glucose uptake in the skeletal muscle. Our results demonstrate that AMPK-mediated HSPB1 expression enhanced insulin sensitivity in the skeletal muscle.