Cholecystokinin (CCK8) regulates glucagon, insulin, and somatostatin secretion from isolated rat pancreatic islets: interaction with glucose.

Abstract

The effect of CCK8 on glucagon, insulin and somatostatin release and its interaction with glucose was studied in freshly isolated rat pancreatic islets. While glucose alone inhibited glucagon secretion [half-maximal effect (EC50) = 4.6 mM], glucose in the presence of 10 nM CCK8 increased glucagon release (EC50 = 6.9 mM). This effect of CCK8 was dose-dependent at 11.1 mM glucose (EC50 = 1.0 nM). The dose-response curve for glucose on insulin secretion was shifted to the left by 10 nM CCK8; the EC50 of glucose was 11.6 and 9.3 mM in the absence and presence of CCK8, respectively. Glucose alone enhanced somatostatin release; this glucose-induced release was further increased by 10 nM CCK8. Our data indicate that first, CCK8 is able to reverse the inhibitory effect of glucose on glucagon secretion, second, CCK8 sensitizes the beta cell to the insulinotropic effect of glucose, and third, CCK8 enhances the effect of glucose on somatostatin release.