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

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 ( HSPB 1) was induced by the AMP analog 5‐aminoimidazole‐4‐carboxamide 1‐β‐D‐ribofuranoside in palmitate‐induced insulin‐resistant cells. Overexpression of AMPK α2, or activation of AMPK α via acute/chronic exercise training, increased HSPB 1 expression in the skeletal muscle. In AMPK α2 −/− mice, HSPB 1 expression was downregulated in the quadriceps muscles. Exercise did not increase HSPB 1 expression in AMPK α2 −/− mice. Moreover, overexpression of HSPB 1 enhanced insulin sensitivity in palmitate‐induced insulin‐resistant cells and restored metabolic phenotypes associated with defective AMPK . Finally, HSPB 1 was required for AMPK ‐mediated activation of the class II a histone deacetylases and glucose uptake in the skeletal muscle. Our results demonstrate that AMPK ‐mediated HSPB 1 expression enhanced insulin sensitivity in the skeletal muscle.