Diabetes 50:265-269, 2001
© 2001 by the American Diabetes Association, Inc.
Regulation of Glycogen Synthase Kinase-3 in Human Skeletal Muscle
Effects of Food Intake and Bicycle Exercise
Jørgen F.P. Wojtaszewski,
Pernille Nielsen,
Bente Kiens, and
Erik A. Richter
From the Copenhagen Muscle Research Centre, Department of Human
Physiology, University of Copenhagen, Copenhagen, Denmark.
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, hyper-insulinemic
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-
( 50% Vo2max for 1.5 h) and high-intensity ( 75%
Vo2max for 1 h) bicycle exercise as well as food intake. We
observed a small but significant increase in GSK3 (10-20%) activity in
biopsies obtained from vastus lateralis after both low- and high-intensity
exercise, whereas GSK3ß activity was unaffected. Subsequent food intake
increased Aktphosphorylation ( 2-fold) and deactivated GSK3
( 40%), whereas GSK3ß activity was unchanged. GS activity increased
in response to both exercise and food intake. We conclude that GSK3 but
not GSK3ß 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.
Address correspondence and reprint requests to Jørgen F.P.
Wojtaszewski, Copenhagen Muscle Research Centre, August Krogh Institute,
University of Copenhagen, 13, Universitetsparken, DK-2100 Copenhagen, Denmark.
Email:
jwojtaszewski{at}aki.ku.dk
.

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Copyright © 2001 by the American Diabetes Association.
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