Autoregulation of myocardial glycogen concentration during
intermittent hypoxia.
McNulty, Patrick H., Chin Ng, Wen-Xi Liu, Dinesh Jagasia, George V.
Letsou, John C. Baldwin, Robert Soufer.
Departments of Internal Medicine and Surgery, and the Positron
Emission Tomography Center, VA Medical Center, West Haven CT 06516
and Yale University School of Medicine, New Haven CT 06520
APStracts 3:0115R, 1996.
During hypoxia, the heart consumes glycogen to generate ATP. Tolerance
of repetitive hypoxia logically requires prompt replenishment of
glycogen, a process whose regulation is not fully understood. To
examine this, we imposed a defined hypoxic stimulus on the rat heart
while varying its workload. In intact rats, hypoxia reduced
myocardial glycogen 30%, and increased both the fraction of glycogen
synthase in its physiologically active (GS I) form (from 0.24 + 0.06
to 0.82 + 0.07 (p<0.005)), and glycogen synthesis (from 0.087 +
0.011 to 0.375 + 0.046 [mu]mol/g/min, p<0.005). Reducing cardiac
work (with propranolol or heterotopic transplantation) reduced
glycogen breakdown, glycogen synthase activation, and glycogen
synthesis in parallel, stepwise fashion in intact rats.
Correspondingly, hypoxia increased GS I activity in the perfused
heart in vitro, but only under conditions where glycogen was
consumed. This suggests myocardial glycogen synthase is activated by
systemic hypoxia, and catalyzes rapid post-hypoxic glycogen
synthesis. Hypoxic glycogen synthase activation appears to be a
proportionate, wholly intrisic response to local glycogenolysis,
operating to preserve myocardial glycogen stores independent of any
extra-cardiac mediator of carbohydrate metabolism.
Received 15 February 1995; accepted in final form 19 February
1996.
APS Manuscript Number R122-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 April 96