Effect of hypercorticism on regulation of skeletal muscle glycogen metabolism by epinephrine.
The effect of hypercorticism on the regulation of glycogen metabolism by epinephrine was examined in skeletal muscles using a hindlimb perfusion technique. Rats were injected with either saline or dexamethasone (0.4 mg.kg-1.day-1) for 14 days and were studied in the fed and fasted (24 h) states under saline or epinephrine (10(-7) M) treatment. In the fed state, dexamethasone administration did not affect basal glycogen concentration but decreased glycogen synthase activity ratio in white and red gastrocnemius muscles. Epinephrine failed to decrease glycogen content despite the expected activation of glycogen phosphorylase in the fed dexamethasone-treated rats. Dexamethasone treatment resulted in a threefold increase in the level of muscle adenosine, a phosphorylase a inhibitor. In control rats, fasting was associated with a decrease in muscle glycogen concentration (P less than 0.01) and with an increase in the glycogen synthase activity ratio. Dexamethasone treatment, however, totally abolished both the decreased muscle glycogen content and glycogen synthase activation observed in fasting controls. In the dexamethasone-treated group, fasting restored the glycogenolytic effect of epinephrine. Interestingly, it was associated with decreased muscle adenosine concentrations. These data indicate that, in the fed state, dexamethasone treatment inhibits skeletal muscle glycogenolysis in response to epinephrine despite phosphorylase activation and glycogen synthase inactivation. It is suggested that this abnormality could be due to the inhibition of phosphorylase a by increased muscle adenosine levels.
Coderre
L
L
Clinical Research Institutes of Montreal, University of Montreal, Quebec, Canada.
Srivastava
A K
AK
Chiasson
J L
JL
D000241:Adenosine / Q000494:pharmacology; D000308:Adrenocortical Hyperfunction / Q000378:metabolism*; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009711:Nucleotides / Q000378:metabolism; D009994:Osmolar Concentration; D010762:Phosphorylase a / Q000037:antagonists & inhibitors; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D005958:Glucosephosphates; D007773:Lactates; D009711:Nucleotides; D019344:Lactic Acid; D019298:Glucose-6-Phosphate; D006003:Glycogen; D010762:Phosphorylase a; D006005:Phosphorylases; D006006:Glycogen Synthase; D000241:Adenosine; D004837:Epinephrine