EFFECTS OF CHOLECYSTOKININ AND GLUCAGON-LIKE PEPTIDE-1 ON THE SECRETION OF PANCREATIC-POLYPEPTIDE IN MICE

The gut hormones, cholecystokinin (CCK) and truncated glucagon-like pe ptide 1 (GLP-1(7-36)amide or GLP-1) both stimulate insulin secretion a nd affect glucagon secretion in mice, but their effects on the secreti on of other islet hormones have not been established in rodents. In th e present study, we have examined the influence of the C-terminal octa peptide of CCK, CCK-8, and GLP-1 on the secretion of pancreatic polype ptide (PP) in the mouse by the use of a radioimmunoassay for rodent PP . Mice were injected intravenously with CCK-8 (doses in the range of 0 .053-5.3 nmol/kg) or with GLP-1 (doses in the range of 1-32 nmol/kg) a nd blood was sampled at 2, 6 or 10 min after the injection. Controls w ere injected with saline. It was found that CCK-8 at 5.3 nmol/kg incre ases plasma levels of both PP and insulin when the sample was taken at 2 min, but not at 6 or 10 min, after injection. These effects were bl ocked by the selective CCKA-receptor antagonist, L-364,718 (2.4 mu mol /kg). GPL-1 increased plasma insulin levels at 32 nmol/kg at 2 and 6 m in after the injection, but plasma PP levels were unaltered. In conclu sion, this study, using a newly developed radioimmunoassay for PP in r odents, shows that CCK-8 but not GPL-1 stimulates PP secretion in mice at dose levels where both peptides stimulate insulin secretion. Furth ermore, PP secretion in response to CCK-8 showed a similarity with tha t of insulin in terms of dose- and time-response characteristics as we ll as sensitivity to CCKA-receptor antagonism.