Role of Akt substrate of 160 kDa in insulin-stimulated and contraction-stimulated glucose transport.
Insulin and exercise, the most important physiological stimuli to increase glucose transport in skeletal muscle, trigger a redistribution of GLUT4 glucose transporter proteins from the cell interior to the cell surface, thereby increasing glucose transport capacity. The most distal insulin signaling protein that has been linked to GLUT4 translocation, Akt substrate of 160 kDa (AS160), becomes phosphorylated in insulin-stimulated 3T3-L1 adipocytes; this is important for insulin-stimulated GLUT4 translocation and glucose transport. Insulin also induces a rapid and dose-dependent increase in AS160 phosphorylation in skeletal muscle. Available data from skeletal muscle support the concepts developed in adipocytes with regard to the role AS160 plays in the regulation of insulin-stimulated glucose transport. In vivo exercise, in vitro contractions, or in situ contractions can also stimulate AS160 phosphorylation. AMP-activated protein kinase (AMPK) is likely important for phosphorylating AS160 in response to exercise/contractile activity, whereas Akt2 appears to be important for insulin-stimulated AS160 phosphorylation in muscle. Evidence of a role for AS160 in exercise/contraction-stimulated glucose uptake is currently inconclusive. The distinct signaling pathways that are stimulated by insulin and exercise/contraction converge at AS160. Although AS160 phosphorylation is apparently important for insulin-stimulated GLUT4 translocation and glucose transport, it is uncertain whether elevated AS160 phosphorylation plays a similar role with exercise/contraction.
Cartee
Gregory D
GD
Muscle Biology Laboratory, Division of Kinesiology, Room 3040E, 401 Washtenaw Avenue, University of Michigan, Ann Arbor, MI 48109-2214, USA. gcartee@umich.edu
Wojtaszewski
Jørgen F P
JF
D041721:3T3-L1 Cells; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D015444:Exercise / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; C518767:TBC1D4 protein, human; C505647:Tbc1d4 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose