Roles of adenosine monophosphate-activated protein kinase in skeletal muscle: fatty acid oxidation, glucose transport, and gene regulation

摘要

Adenosine monophpsphate-activated protein kinase (AMPK) is activated in response to an increase in 5-AMP and a decrease in creatine phosphate (CP) as muscle contracts. The extent of activation of AMPK depends on work rate. The activated kinase phosphorylates acetyl-CoA carboxylase and malonyl-CoA decarboxylase, resulting in a decline in muscle malonyl-CoA, an inhibitor of carnitine palmitoyl-transferase 1. Accumulating evidence indicates that AMPK activation also mediates the contraction-induced increase in glucose transport, particularly in fast-twitch (type II) muscle fibers. Putative downstream phosphorylation targets such as nitric oxide synthase are being investigated. Evidence is accumulating for AMPK involvement in control of gene expression and of specific protein levels in muscle, including GLUT4, hexokinase, mitochondrial oxidative enzymes, and uncoupling protein (UCP)-3. AMPK is emerging as a key player in control of fatty acid oxidation and glucose uptake during exercise and in mediating the effect of repeated bouts of muscle contraction on expression of muscle proteins.