Site of insulin inhibition of cAMP-stimulated glycogenolysis.
Insulin antagonized the glycogenolytic actions of cAMP in isolated hepatocytes even in the presence of the phosphodiesterase inhibitors, 1-methyl-3-isobutylxanthine or d-4-(3-butoxy-4-methoxybenzyl)-2- imidizolidione . Stimulation of glucose release by 8-bromo-cAMP, which is not appreciably hydrolyzed by phosphodiesterase, was also inhibited by insulin in the presence of d-4-(3-butoxy-4-methoxybenzyl)-2- imidizolidione . This demonstrates that insulin can antagonize cAMP stimulation of glycogenolysis independent of possible effects of insulin on adenylate cyclase or phosphodiesterase. Under conditions where changes in cyclic adenine nucleotide concentrations (cAMP and 8-bromo-cAMP) were prevented, insulin depressed the 8-bromo-cAMP-stimulated protein kinase activity ratio. We conclude that phosphodiesterase activation is not required for insulin antagonism of cAMP-stimulated glycogenolysis. The effect of insulin under these conditions can be explained by an action of insulin on cAMP-dependent protein kinase independent of changes in cAMP levels.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects*; D008112:Liver Glycogen / Q000378:metabolism*; D051381:Rats
D007328:Insulin; D008112:Liver Glycogen; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine