Studies on the interactions between insulin and epinephrine in the control of skeletal muscle glycogen metabolism.
Possible inhibitory effects of insulin on epinephrine-induced changes in the enzymes of glycogen metabolism in skeletal muscle were tested using a perfused rat hindlimb preparation. Epinephrine and/or insulin were infused over a wide range of concentrations. Insulin at 6 X 10(-9) M increased the activity ratio (--Glc-6-P/+Glc-6-P) of glycogen synthase from a basal value of 0.09 +/- 0.01 to 0.13 +/- 0.01 and caused a 23% decrease in the Ka for Glc-6-P. In contrast, epinephrine at 10(-7) M decreased the activity ratio to 0.05 +/- 0.01 and increased the Ka for Glc-6-P 6.3-fold. Insulin was without effect on the concentration of cAMP or the activity ratio (-cAMP/+cAMP) of cAMP-dependent protein kinase and caused a small decrease in the activity ratio (-AMP/+AMP) of phosphorylase, whereas epinephrine caused large increases in all these parameters. Insulin at 6 X 10(-11) to 6 X 10(-8) M had no inhibitory effect on the actions of 10(-8) or 10(-7) M epinephrine on glycogen synthase, phosphorylase or cAMP-dependent protein kinase at 30 min or at earlier times. Insulin (6 X 10(-9) M) also did not alter th concentration of cAMP in the presence of 10(-8) or 10(-7) M epinephrine. These data are not consistent with the view that insulin activates glycogen synthase by producing an inhibitor of cAMP-dependent protein kinase. Nor do they support the hypothesis that insulin acts by decreasing the activity of an inhibitor of a multisubstrate phosphoprotein phosphatase.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000201:enzymology*; D006005:Phosphorylases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats
D007328:Insulin; D006003:Glycogen; D000242:Cyclic AMP; D006005:Phosphorylases; D006006:Glycogen Synthase; D011494:Protein Kinases; D004837:Epinephrine