Cholecystokinin-33 potentiates and vasoactive intestinal polypeptide inhibits gastric inhibitory polypeptide--induced insulin secretion in the perfused rat pancreas.

Abstract

Gastric inhibitory polypeptide (GIP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) stimulate insulin secretion. In this study we investigated whether CCK-33 and VIP could influence the insulinogenic effect of simultaneously administered GIP and 6.7 mmol/l glucose in the perfused rat pancreas. We found that at 0.1 nmol/l, GIP markedly potentiated glucose-induced insulin release whereas CCK-33 and VIP had a weak stimulatory effect and only during the late phase. At this low dose level, CCK-33 potentiated but VIP inhibited the late phase of insulin release stimulated by glucose and GIP. At 1.0 nmol/l, GIP, CCK-33, and VIP markedly potentiated both phases of glucose-induced insulin secretion. At this dose level CCK-33 and GIP exerted additive stimulatory effects on the late phase of insulin release triggered by glucose. In contrast, 1.0 nmol/l VIP inhibited insulin secretion augmented by glucose and GIP. In summary 1) GIP, CCK-33 and VIP all potentiate glucose-induced insulin secretion from the perfused rat pancreas, and 2) CCK-33 potentiates and VIP inhibits GIP-induced insulin secretion. We suggest that interactions of this kind are of importance for the precise regulation of insulin secretion.