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.

The effects of gastric inhibitory polypeptide (GIP) on insulin secretion as well as on the intra-islet accumulation of [3H]cyclic AMP were investigated in isolated pancreatic islets of the rat. In the presence of 6.7 mmol/l of glucose, 3.0 and 30 nmol/l of GIP induced both insulin and [3H]cyclic AMP responses, while lower and higher concentrations of the peptide were ineffective. A coupling of the two parameters was also found with regard to interaction between glucose and GIP. Thus while 30 nmol/l of GIP was stimulatory together with 6.7, 16.7 or 33.3 mmol/l of glucose, the peptide stimulated neither insulin release, nor the accumulation of [3H]cyclic AMP in the presence of a low concentration of glucose (3.3 mmol/l).

Novel intestinal polypeptide YY (PYY) and pancreatic polypeptide (PP) were infused in fed anaesthetized rats. The peptides (10 and 100 pmol/kg X min) were administered during 30 min, alone, together with glucose or together with arginine. Plasma concentrations of glucose, insulin and glucagon were measured. At the dose of 10 pmol/kg X min the peptides had no effect. PP at the dose of 100 pmol/kg X min slightly augmented basal, but had no effect on stimulated insulin and glucagon release. PYY at the dose of 100 pmol/kg X min was without effect on basal insulin and glucagon levels and on glucose-induced insulin release, but exerted an inhibitory effect on arginine-induced secretion of both insulin and glucagon. It is unlikely that PYY and PP can affect secretion of insulin and glucagon via blood circulation. The potential capability of high doses of PP to affect insulin and glucagon secretion suggests that this peptide may exert direct (paracrine) effects on the pancreatic A- and B-cells.

No abstract

Pure porcine vasoactive intestinal polypeptide (VIP) and porcine intestinal heptacosapeptide (PHI) were infused in fed rats in doses of 1, 10, and 100 pmol/kg . min. The peptides were administered alone or together with glucose (40 mg/kg . min) or arginine (50 mg/kg . min). In the basal state, VIP at a dose of 1 pmol/kg . min and PHI at a dose of 10 pmol/kg . min produced a slight but significant hypoglycemia, whereas 100 pmol/kg . min VIP and PHI had a hyperglycemic effect. VIP at a dose of 10 and 100 pmol/kg . min enhanced the glucose-induced secretion of insulin. PHI exerted such an effect only when administered at the highest dose. When arginine was present as a secretagogue, 10 pmol/kg . min of both VIP and PHI potentiated secretion of insulin and glucagon and elevated the prevailing hyperglycemia. In conclusion, when given as a constant infusion in rats, both PHI and VIP exert a direct hypoglycemic effect and modulate the influence of glucose and arginine on insulin and glucagon secretion. It is as yet unclear to what extent these findings reflect normal physiological events.