title: 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.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, China.|Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, China.
authors.forename: Hairui
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Rehabilitation and Sports Medicine, Tianjin Medical University, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D010641:Phenotype; D040901:Proteomics; D012265:Ribonucleotides / Q000494:pharmacology; D053719:Tandem Mass Spectrometry
chemical_list: D055551:HSP27 Heat-Shock Proteins; D007328:Insulin; D012265:Ribonucleotides; D019308:Palmitic Acid; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; D006655:Histone Deacetylases; C031143:AICA ribonucleotide; D005947:Glucose
keywords: AMP-activated protein kinase; heat shock protein beta-1; insulin resistance; skeletal muscle