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 peptide 1 (GLP-1(7-36)amide or GLP-1) both stimulate insulin secretion and affect glucagon secretion in mice, but their effects on the secretion of other islet hormones have not been established in rodents. In the present study, we have examined the influence of the C-terminal octapeptide of CCK, CCK-8, and GLP-1 on the secretion of pancreatic polypeptide (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) and blood was sampled at 2, 6 or 10 min after the injection. Controls were injected with saline. It was found that CCK-8 at 5.3 nmol/kg increases 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 blocked by the selective CCKA-receptor antagonist, L-364,718 (2.4 micromol/kg). GPL-1 increased plasma insulin levels at 32 nmol/kg at 2 and 6 min after the injection, but plasma PP levels were unaltered. In conclusion, this study, using a newly developed radioimmunoassay for PP in rodents, shows that CCK-8 but not GPL-1 stimulated PP secretion in mice at dose levels where both peptides stimulate insulin secretion. Furthermore, PP secretion in response to CCK-8 showed a similarity with that of insulin in terms of dose- and time-response characteristics as well as sensitivity to CCKA-receptor antagonism.