Interaction of gastric inhibitory polypeptide (GIP) and cholecystokinin (CCK-8) with basal and stimulated insulin secretion in mice.
The interaction of GIP and CCK-8 with basal insulin secretion and with insulin release induced by glucose or by the beta-adrenoceptor agonist L-isopropylnoradrenaline (L-IPNA) was studied in mice. GIP and CCK-8, when injected in threshold doses not affecting basal insulin secretion, did markedly enhance basal insulin release when given simultaneously. Maximal doses of the two peptides, on the other hand, did not potentiate each other's action, but displayed a pure additive effect on insulin secretion. Insulin release induced by a half-maximal dose of glucose was slightly potentiated by the threshold dose of GIP and markedly potentiated by the maximal dose i.e. the effect was greater than the algebraic sum of the individual actions. CCK-8 was without potentiating effect at both dose levels. The combination of GIP and CCK-8 did not display the potentiating effect of GIP alone on glucose-stimulated insulin release. However, an additive action was observed at both dose levels. Insulin release stimulated by a half-maximal dose of L-IPNA was not affected by either GIP or CCK-8 at the threshold doses. The combination of the two peptides and L-IPNA, however, displayed a lower response than that expected from an additive effect. Similarly, at the high dose level of the peptides, the combination of GIP plus CCK-8 and L-IPNA as well as CCK-8 alone plus L-IPNA displayed a lower insulin response than that expected from an additive effect. GIP alone plus L-IPNA gave the expected additive effect. The results show that interactions between different gastrointestinal polypeptides with insulin release may greatly change the expected effect exerted by any individually tested peptide, and that the action of the peptides on stimulated insulin secretion is highly dependent on the nature of the secretagogue. Such complex interactions must be borne in mind in the search for the incretin factor(s).
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002766:Cholecystokinin / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D005768:Gastrointestinal Hormones; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D002766:Cholecystokinin; D005947:Glucose; D007545:Isoproterenol