Insulin secretion from ob/ob mouse pancreatic islets: effects of neurotransmitters.

Effects of glucose, acetylcholine, and norepinephrine on insulin secretion from pancreatic islets of 8- to 9-wk-old female genetically obese (ob/ob) and lean mice were determined. The ob/ob islets were 60% larger in diameter than lean mouse islets, secreted fourfold more insulin in response to glucose, and secreted insulin at lower glucose concentrations than lean islets. In the presence of 15 mM glucose, ob/ob islets showed an 8-fold greater absolute increase in insulin secretion in response to acetylcholine and a 12-fold greater absolute decrease in insulin secretion in response to norepinephrine inhibition compared with lean islets. In the presence of 5 mM glucose, acetylcholine increased insulin secretion by threefold from ob/ob islets with no effect on lean islets. When both ob/ob and lean islets were stimulated by glucose to equivalent levels of insulin secretion, acetylcholine potentiated glucose-induced insulin secretion equally in ob/ob and lean islets. Enhanced glucose-induced responsiveness of ob/ob islets thus can explain the greater acetylcholine potentiation of insulin secretion and probably the greater norepinephrine inhibition of insulin secretion in ob/ob islets compared with lean islets. These data are consistent with the hypotheses that the major alteration in ob/ob mouse islets is in glucose sensitivity and responsiveness, which subsequently increases ob/ob islet susceptibility to neural regulation of insulin secretion.