Effects of two cholecystokinin variants, CCK-39 and CCK-8, on basal and stimulated insulin secretion.
The effects of two different cholecystokinin variants, CCK-39 and the carboxyl-terminal octa-peptide CCK-8, on basal and stimulated insulin secretion were studied in the mouse. It was found that both peptides had a dose-dependent stimulating action on insulin secretion with a maximal response of similar magnitude at a dose level of about 5 nmol/kg body weight. This dose induced an increase of plasma concentrations of immunoreactive insulin of about 100 microU/ml. The calculated half-maximal dose was 2.12 nmol/kg for CCK-39 and 3.18 nmol/kg for CCK-8. The insulin-secretory response to CCK-39 and CCK-8 in the absence of other secretagogues was partially abolished by pretreatment with the cholinergic blocker methylatropine as well as with the beta-adrenoceptor blocker L-propranolol. Thus, this great insulin-secretory response to the two peptides seemed to be dependent on intact muscarinic and beta-adrenergic receptors. CCK-39 or CCK-8 administered in a threshold dose prior to half-maximal doses of D-glucose, the cholinergic agonist carbachol, or the beta-adrenergic agonist L-isopropylnoradrenaline (L-IPNA), respectively, displayed different influences on insulin release. CCK-39 potentiated glucose- as well as carbachol-induced insulin secretion, whereas it did not influence L-IPNA-induced insulin release. An equimolar dose of CCK-8, on the contrary, had no apparent effect on either glucose-, carbachol-, or L-IPNA-induced insulin release. This observation indicates that stimulated insulin release is influenced by amino acid sequences other than those of the C-terminal octapeptide in CCK-39 and that the response of the stimulated insulin-secreting cells to CCK-39 is dependent on the nature of the secretagogue.
D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology* / Q000031:analogs & derivatives; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D012844:Sincalide
D001286:Atropine Derivatives; D007328:Insulin; D010446:Peptide Fragments; C032740:cholecystokinin 39; C006649:methylatropine; D002217:Carbachol; D002766:Cholecystokinin; D011433:Propranolol; D005947:Glucose; D007545:Isoproterenol; D012844:Sincalide