Regulation of hexokinase ii and glycogen synthase mrna, protein,
and catalytic activity in human skeletal muscle in vivo.
Mandarino, Lawrence J., Richard L. Printz, Kenneth A. Cusi, Paul
Kinchington, Robert M. O'doherty, Haruhiko Osawa, Charles Sewell,
Agostino Consoli, Daryl K. Granner, and Ralph A. Defronzo.
Division of Diabetes, Department of Medicine, and the Department of
Biochemistry, The University of Texas Health Science Center at San
Antonio, San Antonio, Texas, and the Department of Molecular
Physiology and Biophysics, Vanderbilt University School of Medicine,
Nashville, Tennessee
APStracts 2:0114E, 1995.
Insulin regulates the activity of key enzymes of glucose metabolism in
skeletal muscle by altering transcription or translation or by
producing activity-altering modifications of pre-existing enzyme
molecules. Because of the small size of percutaneous muscle biopsies,
these phenomena have been difficult to study in humans. This study
was performed to determine how physiologic hyperinsulinemia regulates
the activities of hexokinase (HK), glycogen synthase (GS), and GLUT4
in human skeletal muscle in vivo. We determined mRNA abundance,
protein content, and activities for these proteins in muscle biopsies
before and after a hyperinsulinemic clamp in normal subjects. HKI,
HKII, GS, and GLUT4 were expressed in muscle. HKII accounted for 80%
of total hexokinase activity and was increased by insulin from a
basal value of 2.11+/-0.26 to 3.35+/-0.47 pmoles/min.mg protein
(P<0.05); HKI activity was unaffected. Insulin increased GS
activity from 3.85+/-0.82 to 6.06+/-0.49 nmoles/min.mg (P<0.01).
HKII mRNA was increased by 3.3+/-1.3-fold (P<0.05) by insulin
infusion. HKI, GS, and GLUT4 mRNA and protein and were unaffected..
Since insulin infusion increased HKII but not GS mRNA, we conclude
that HKII and GS may be regulated by insulin by different mechanisms
in human skeletal muscle.
Received 23 February 1995; accepted in final form 9 May 1995.
APS Manuscript Number E77-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.