Dibutyryl guanosine 3',5'-monophosphate inhibits cholecystokinin potentiation of insulin release in the isolated perfused rat pancreas.
(Bu)2cGMP is known to act as a specific competitive inhibitor for gastrin and cholecystokinin (CCK) peptides. We have examined the effects of (Bu)2cGMP on CCK octapeptide (CCK-8) stimulation of insulin release in the isolated perfused pancreas and compared them with those on protein output. Addition of (Bu)2cGMP after a 20-min perfusion with 100 pM CCK-8 resulted in two distinctly different phases of insulin suppression. There was a sharp initial decline in insulin release for 3 min, followed by transient recovery toward the control level for 5 min, and then a small decline until termination of (Bu)2cGMP infusion. (Bu)2cGMP produced a concentration-dependent inhibition of both phases of insulin decrement. (Bu)2cGMP also produced a concentration-dependent inhibition of protein output. Addition of 1 mM (Bu)2cGMP rapidly and completely abolished CCK-8-stimulated protein output. Since CCK is released by meal intake and exogenous CCK stimulates insulin release and augments glucose-induced insulin release, it is possible that endogenous CCK plays an important role in the enteroinsular axis. The present findings of blockade of CCK-8-induced insulin release by selective antagonist of the action of CCK provide evidence for CCK as a mediator in the enteroinsular axis.
D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects; D012844:Sincalide / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D007328:Insulin; D003995:Dibutyryl Cyclic GMP; D006152:Cyclic GMP; D012844:Sincalide