Cholecystokinin and gastric inhibitory polypeptide not glucagonotropic in dogs

The role of cholecystokinin (CCK) and gastric inhibitory polypeptide (GIP) as stimulators of glucagon secretion under physiologic conditions is uncertain. Previous studies have utilized CCK preparations now known to have been contaminated with GIP and possibly other gastrointestinal peptides. The present study was designed to determine if physiologic doses of highly purified (99%) CCK and GIP stimulate pancreatic glucagon release in the dog. Six adult, conscious, conditioned dogs weighing 20 to 25 kg each, were given intravenous infusions of CCK or GIP after an overnight fast. Peripheral blood, collected at time zero and thereafter at 15-min intervals for 120 min, was assayed for radioimmunoreactive GIP and glucagon (30K antisera). During the infusion of 200 and 400 ng/kg/hr of GIP, peak mean GIP concentrations of 678 ± 103 (SEM) and 1404 ± 171 pg/ml, respectively, were reached by 60 min. A 200 ng/kg intravenous bolus of GIP resulted in a peak mean serum GIP concentration of 2150 ± 275 pg/ml at 15 min. Peripheral mean basal glucagon concentrations of 48 ± 9 pg/ml did not change significantly during the GIP infusion or following the bolus infusion of GIP. CCK infused at 500 ng/kg/hr, a dose assumed to produce physiologic serum CCK concentrations, did not significantly change the mean basal glucagon level of 41 ± 1 pg/ml during the 120-min study period. We conclude that under the conditions of this study, neither CCK nor GIP are glucagonotropic in the dog.