AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism.
The AMP-activated protein kinase (AMPK) is an evolutionarily conserved sensor of cellular energy status, and recent data demonstrate that it also plays a critical role in systemic energy balance. AMPK integrates nutritional and hormonal signals in peripheral tissues and the hypothalamus. It mediates effects of adipokines (leptin, adiponectin, and possibly resistin) in regulating food intake, body weight, and glucose and lipid homeostasis. AMPK is regulated by upstream kinases of which the tumor suppressor, LKB1, is the first to be identified. Complex signaling networks suggest that AMPK may prevent insulin resistance, in part by inhibiting pathways that antagonize insulin signaling. Through signaling, metabolic, and gene expression effects, AMPK enhances insulin sensitivity and fosters a metabolic milieu that may reduce the risk for obesity and type 2 diabetes.
Kahn
Barbara B
BB
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA. bkahn@bidmc.harvard.edu
Alquier
Thierry
T
Carling
David
D
Hardie
D Grahame
DG
D055372:AMP-Activated Protein Kinases; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D015444:Exercise; D006706:Homeostasis; D006729:Hormones, Ectopic / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D010805:Physical Conditioning, Animal; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D052243:Resistin; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D006729:Hormones, Ectopic; D007328:Insulin; D009097:Multienzyme Complexes; C499624:RETN protein, human; D052243:Resistin; C499623:Retn protein, mouse; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases