Significance of Ca2+, Rb+ fluxes, of cAMP and cGMP for the CCK8-modulated insulin release

Abstract In rat pancreatic islets the effects of cholecystokinin-8 (CCK 8 ) on glucose-mediated insulin release, 45 Ca 2+ net uptake, 45 Ca 2+ efflux, 86 Rb + efflux, cAMP- and cGMP levels were studied. In the presence of a substimulatory glucose concentration (3 mM) CCK 8 concentrations of up to 1 μM had no effect on insulin release, but CCK 8 at 10 nM potentiated the stimulatory effect of glucose (11.1 mM). 10 nM CCK 8 enhanced glucose-stimulated 45 Ca 2+ net uptake but was ineffective at substimulatory glucose levels. CCK 8 had no effect on cAMP and cGMP levels in the presence of 11.1 mM glucose. CCK 8 increased 86 Rb + (a measure of K + ) in the presence of both 3 and 11.1 mM glucose. This effect was abolished when Ca 2+ was omitted from the perifusion medium. CCK 8 did not alter glucose (11.1 mM)-stimulated 45 Ca 2+ efflux rate. These data indicate that (1) CCK 8 potentiates glucose-stimulated insulin secretion possibly via an effect on Ca 2+ uptake, 2) by affecting Ca 2+ uptake, CCK 8 enhances K + efflux, and 3) CCK 8 does not mediate its effect via cAMP or cGMP. With respect to 86 Rb + efflux the mechanism of CCK 8 action appears to be different from that of glucose. When the mechanism of CCK action on islets is compared with that on exocrine pancreas (data from others) there are similarities (importance of Ca 2+ uptake and non-importance of cAMP and cGMP).