Exercise Effects of Muscle Insulin Signaling and Action
Invited Review: Exercise training-induced changes in insulin signaling in skeletal muscle
Juleen R. Zierath
Department of Clinical Physiology, Karolinska Hospital, Karolinska Institutet, SE-171 77 Stockholm, Sweden
This review will provide insight on the current understanding of the intracellular signaling mechanisms by which exercisetraining increases glucose metabolism and gene expression in skeletalmuscle. Participation in regular exercise programs can have importantclinical implications, leading to improved health in insulin-resistantpersons. Evidence is emerging that insulin signal transductionat the level of insulin receptor substrates 1 and 2, as well asphosphatidylinositol 3-kinase, is enhanced in skeletal muscleafter exercise training. This is clinically relevant because insulinsignaling is impaired in skeletal muscle from insulin-resistantType 2 diabetic and obese humans. The molecular mechanism forenhanced insulin-stimulated glucose uptake after exercise trainingmay be partly related to increased expression and activity ofkey proteins known to regulate glucose metabolism in skeletalmuscle. Exercise also leads to an insulin-independent increasein glucose transport, mediated in part by AMP-activated proteinkinase. Changes in protein expression may be related to increasedsignal transduction through the mitogen-activated protein kinasesignaling cascades, a pathway known to regulate transcriptionalactivity. Understanding the molecular mechanism for the activationof insulin signal transduction pathways after exercise trainingmay provide novel entry points for new strategies to enhance glucosemetabolism and for improved health in the generalpopulation.
AMP-activated protein kinase; diabetes; gene expression; insulin receptor substrates; mitogen-activated protein kinase; phosphatidylinositol 3-kinase
Source: J Appl Physiol Vol. 93, Issue 2, 773-781, August 2002.