Effects of six cholecystokinin (CCK) fragments on insulin secretion in the mouse.
In a recent study it was demonstrated that the C-terminal octapeptide of cholecystokinin (CCK-26-33; often abbreviated CCK-8) and CCK-39 (= CCK--6-33) potently and with the same efficacy stimulated basal insulin secretion when injected intravenously to mice. In the present study, the effects of four other CCK fragments, CCK-30-33 (= CCK-4), CCK-1-33 (= CCK-33), CCK-1-21 (= CCK-21) and CCK-10-20, on basal and glucose-induced insulin secretion were studied. It was found that CCK-33 stimulated insulin secretion. At a dose level of 4.25 nmol/kg, plasma insulin concentrations were elevated by 58 +/- 7 microU/ml (P less than 0.001). On the contrary, neither CCK-4, nor CCK-21, nor CCK-10-20 displayed any effect on basal insulin secretion, not even at high dose levels. When injecting CCK-8, CCK-33 or CCK-39 at dose levels substimulatory on basal insulin secretion (0.53 nmol/kg), together with glucose, CCK-39 potentiated glucose-induced insulin secretion whereas CCK-8 and CCK-33 were without effects. In contrast, at the higher dose level of 5.3 nmol/kg, CCK-8, CCK-33, and CCK-39 all potentiated glucose-induced insulin secretion. The three other fragments, CCK-4, CCK-21, and CCK-10-20, were all without effects on glucose-induced insulin secretion. In conclusion, the potent stimulatory action on basal insulin secretion in the mouse exerted by various CCK fragments is confined to the C-terminal octapeptide (= CCK-8 or CCK-26-33).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology* / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D012844:Sincalide / Q000494:pharmacology; D013758:Tetragastrin / Q000494:pharmacology
D007328:Insulin; D010446:Peptide Fragments; D013758:Tetragastrin; C048641:cholecystokinin (10-20); C048640:cholecystokinin 21; D005749:Gastric Inhibitory Polypeptide; C032740:cholecystokinin 39; D002766:Cholecystokinin; D005947:Glucose; D012844:Sincalide