Effects of cholecystokinin, gastric inhibitory polypeptide, and secretin on insulin and glucagon secretion in rats.

Pure porcine cholecystokinin-33 [the triacontatriapeptide form of cholecystokinin (CCK-33)], gastric inhibitory polypeptide (GIP), and secretin were infused in rats in doses of 1, 10 and 1000 pmol/kg . min. The peptides were administered alone or in combination with glucose (40 mg/kg . min) or arginine (50 mg/kg . min). In the basal state, CCK-33 and GIP produced significant hypoglycemia at all concentrations used, although they elevated insulin levels only at the highest dose. Secretin had no effect. CCK-33 at a dose of 1 pmol/kg . min enhanced the secretion of insulin induced by glucose or arginine. These effects were more pronounced when higher doses of CCK-33 were administered. GIP at a dose of 1 pmol/kg . min had no effect on insulin release. Higher doses of GIP significantly potentiated insulin release stimulated by glucose or arginine. Secretin (100 pmol/kg . min) had no clear-cut effect on glucose-induced insulin secretion, but it slightly enhanced arginine-induced secretion. All hormones investigated, at all doses used, significantly stimulated the arginine-induced secretion of glucagon. We conclude that CCK-33 is a potent stimulatory factor of glucose- and arginine-induced insulin secretion and should therefore be taken into consideration as an incretin candidate. In addition, CCK-33 and GIP modulate glucose homeostasis by affecting glucagon release.