AJP - Endocrinology and Metabolism, Vol 263, Issue 6 E1086-E1091, Copyright © 1992 by American Physiological Society
Hypoxia causes glycogenolysis without an increase in percent phosphorylase a in rat skeletal muscle
J. M. Ren, E. A. Gulve, G. D. Cartee and J. O. Holloszy
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Stimulation of skeletal muscle to contract activates phosphorylase b-to-a
conversion and glycogenolysis. Despite reversal of the increase in
percentage of phosphorylase a after a few minutes, continued glycogen
breakdown can occur during strenuous exercise. Hypoxia causes sustained
glycogenolysis in skeletal muscle without an increase in percentage of
phosphorylase a. We used this model to obtain insights regarding how
glycogenolysis is mediated in the absence of an increase in percentage of
phosphorylase a. Hypoxia caused a 70% decrease in glycogen in
epitrochlearis muscles during an 80-min incubation despite no increase in
percentage of phosphorylase a above the basal level of approximately 10%.
Muscle Pi concentration increased from 3.8 to 8.6 mumol/g muscle after 5
min and 15.7 mumol/g after 20 min. AMP concentration doubled, attaining a
steady state of 0.23 mumol/g in 5 min. Incubation of oxygenated muscles
with 0.1 microM epinephrine induced an approximately sixfold increase in
percentage of phosphorylase a but resulted in minimal glycogenolysis.
Muscle Pi concentration was not altered by epinephrine. Despite no increase
in percentage of phosphorylase a, hypoxia resulted in a fivefold greater
depletion of glycogen over 20 min than did epinephrine. To evaluate the
role of phosphorylase b, muscles were loaded with 2-deoxyglucose
6-phosphate, which inhibits phosphorylase b. The rate of glycogenolysis
during 60 min of hypoxia was reduced by only approximately 14% in
2-deoxyglucose 6-phosphate-loaded muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
