Attenuation of epinephrine-induced increase in liver cyclic AMP by endogeneous insulin in vivo.
1. Epinephrine-induced increase in rat liver cyclic AMP in vivo was potentiated when the circulating insulin was suppressed by injection of anti-insulin serum or by induction of diabetes. Consequently, phosphorylase was activated, glycogen synthetase was inactivated and glycogen accumulation induced by glucose load was prevented by epinephrine in the insulin-deficient rats to a much larger extent than in normal rats. 2. Insulin lack was effective in potentiating epinephrine-induced increase in liver and muscule cyclic AMP even after the treatment of rats with theophylline; the potentiation could not be solely accounted for by the inhibition of cyclic AMP phosphodiesterase. Thus, it is likely that insulin lack enhaces epinephrine activation of adenylate cyclase. 3. Unlike epinephrine, glucagon increased liver cyclic AMP to essentially the same extent whether the rat was treated with anti-insulin serum or not. 4. Based on the difference in dose-response curves between normal and insulin-deficient rats, a possibility is discussed that there are two adenylate cylase in the liver with higher and lower affinities for epinephrine and that circulating insulin blocks the high affinity enzyme selectively.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000302:Adrenal Cortex / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000502:physiology*; D007330:Insulin Antibodies; D008099:Liver / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D013311:Streptozocin; D013806:Theophylline / Q000494:pharmacology
D007328:Insulin; D007330:Insulin Antibodies; D013311:Streptozocin; D000324:Adrenocorticotropic Hormone; D006003:Glycogen; D013806:Theophylline; D000242:Cyclic AMP; D006005:Phosphorylases; D006006:Glycogen Synthase; D000262:Adenylyl Cyclases; D004837:Epinephrine