Regulation of glycogen synthase kinase-3 in human skeletal muscle: effects of food intake and bicycle exercise.
Studies of skeletal muscle from rodents performed both in vivo and in vitro suggest a regulatory role of glycogen synthase kinase (GSK) 3 in glycogen synthase (GS) activation in response to insulin. Recently, hyperinsulinemic clamp studies in humans support such a role under nearly physiological conditions. In addition, in rats the activation of GS in skeletal muscle during treadmill running is time-related to the deactivation of GSK3. We investigated whether GSK3 was deactivated in human muscle during low- (approximately 50% VO2max for 1.5 h) and high-intensity (approximately 75% VO2max for 1 h) bicycle exercise as well as food intake. We observed a small but significant increase in GSK3alpha (10-20%) activity in biopsies obtained from vastus lateralis after both low- and high-intensity exercise, whereas GSK3beta activity was unaffected. Subsequent food intake increased Aktphosphorylation (approximately 2-fold) and deactivated GSK3alpha (approximately 40%), whereas GSK3beta activity was unchanged. GS activity increased in response to both exercise and food intake. We conclude that GSK3alpha but not GSK3beta may have a role in the regulation of GS activity in response to meal-associated hyperinsulinemia in humans. However, in contrast to findings in muscle from rats, exercise does not deactivate GSK3 in humans, suggesting a GSK3-independent mechanism in the regulation of GS activity in muscle during physical activity.
Copenhagen Muscle Research Centre, Department of Human Physiology, University of Copenhagen, Denmark. jwojtaszewski@aki.ku.dk
J F
JF
Wojtaszewski
P
P
Nielsen
B
B
Kiens
E A
EA
Richter
J F
JF
Wojtazsewski
D000328:Adult; D001642:Bicycling; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D015444:Exercise / Q000502:physiology; D006003:Glycogen / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt
D007328:Insulin; D011518:Proto-Oncogene Proteins; D006003:Glycogen; D038341:Glycogen Synthase Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3