title: AMPK binds to Sestrins and mediates the effect of exercise to increase insulin-sensitivity through autophagy.
abstract: OBJECTIVE
  Exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes. However, the cellular mechanisms underlying the metabolic effects of exercise are not completely understood. We know that autophagy plays an important role in maintaining cellular homeostasis. In this study, we aimed to better understand the metabolic effects of autophagy in skeletal muscle and the role of Sestrins/AMPK in mediating the beneficial effects of physical exercise through autophagy.
  
  
  METHODS
  We used wild type and AMPKα2(-/-) C57BL/6 mice as animal models to elucidate the role of AMPK in autophagy activation and the metabolism-promoting effects of acute and regular exercise. C2C12 myotubes were used to study the metabolic effects of autophagy in vitro.
  
  
  RESULTS
  Autophagy promotes glucose uptake in skeletal muscle. A single bout of exercise increased the activity of autophagy in the skeletal muscle of wild type mice but not of AMPKα2(-/-) mice. This difference was associated with increased amounts of both Sestrin2 and Sestrin3 coimmunoprecipitated with AMPKα2. Long-term physical exercise significantly increased the basal level of muscle autophagy and protein expression of Sestrin2 and Sestrin3 in both normal chow and high-fat diet-fed mice.
  
  
  CONCLUSIONS
  We believe that exercise-induced AMPK and Sestrins interaction may be involved in the beneficial metabolic effects of exercise by activating autophagy. This interaction provides a molecular mechanism that is a potential target in metabolic syndromes.
authors: Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China.
authors: Xiaolei
authors: X
authors: Liu
authors: Department of Rehabilitation and Sports Medicine, Tianjin Medical University, Tianjin 300070, China.
authors: Yanmei
authors: Y
authors: Niu
authors: Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China.
authors: Hairui
authors: H
authors: Yuan
authors: Department of Pathology and Laboratory Medicine, School of Medicine, Temple University, Philadelphia, PA 19103.
authors: Jian
authors: J
authors: Huang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China. Electronic address: lifu@tijmu.edu.cn.
authors: Li
authors: L
authors: Fu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002478:Cells, Cultured; D059305:Diet, High-Fat; D005947:Glucose / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*
chemical_list: D006360:Heat-Shock Proteins; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMP-activated protein kinase; Autophagy; Exercise; Metabolism; Sestrins