Cholecystokinin-33 potentiates and vasoactive intestinal polypeptide inhibits gastric inhibitory polypeptide--induced insulin secretion in the perfused rat pancreas.
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.
Sandberg
E
E
Department of Endocrinology, Karolinska Institute, Stockholm, Sweden.
Ahrén
B
B
Tendler
D
D
Efendic
S
S
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D004347:Drug Interactions; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D007328:Insulin; D010446:Peptide Fragments; C049614:cholecystokinin 33 (10-20); D014660:Vasoactive Intestinal Peptide; D005749:Gastric Inhibitory Polypeptide; D002766:Cholecystokinin; D005947:Glucose