MECHANISMS OF THE STIMULATION OF INSULIN RELEASE BY OXYTOCIN IN NORMAL MOUSE ISLETS

Oxytocin (OT) produced a dose-dependent increase in somatostatin, glucagon and insulin release by isolated mouse islets. A small effect on somatostatin release was observed with 0.1 nM-OT, but 1-10 nM-OT was required to affect A- and B-cells significantly. The effects of OT on somatostatin and glucagon release were similar in the presence of 3 mM- and 10 mM-glucose. No change in insulin release was produced by OT in 3 mM-glucose, but a stimulation was still observed in the presence of a maximally effective concentration of glucose (30 mM). The increase in insulin release produced by OT (in 15 mM-glucose) was accompanied by small accelerations of Rb-86 and Ca-45 efflux from islet cells. Omission of extracellular Ca2+ accentuated the effect of OT on Rb-86 efflux, attenuated that on Ca-45 efflux, and abolished that on release. OT never inhibited Rb-86 efflux. It did not affect the resting potential of B-cells, but slightly increased the Ca2+-dependent electrical activity induced by 15 mM-glucose. OT did not affect cyclic AMP levels, but increased inositol phosphate levels in islet cells. It is suggested that the amplification of glucose-induced insulin release that OT produces is due to a stimulation of phosphoinositide metabolism, and presumably an activation of protein kinase C, rather than to change in cyclic AMP levels or a direct action on the membrane potential. Since OT is present in the pancreas, it is possible that it exerts a neuropeptidergic control of the islet function.