Long-term infusion of norepinephrine plus serotonin into the ventromedial hypothalamus impairs pancreatic islet function

To examine the possibility of a cause-effect relationship between enhanced monoamine content in the ventromedial hypothalamus ([VMH] a characteristic of hyperinsulinemic and insulin-resistant animals) and islet dysfunction, w e infused norepinephrine ([NE] 25 nmol/h) and/or serotonin ([5-HT] 2.5 nmol /h) into the VMH of normal hamsters for 5 weeks and then examined insulin r elease from the isolated pancreatic islets. VMH infusion of NE + 5-HT, but not of either neurotransmitter alone, produced a marked leftward shift in t he dose-response curve of glucose-induced insulin release (twofold to sixfo ld increase at 5 to 7.5 mmol/L glucose v vehicle-treated animals). In addit ion, the islet responsiveness to 1 mu mol/L NE and 10 mu mol/L acetylcholin e was abolished in these NE + 5-HT VMH-infused hamsters. These findings ind icate that an increase of NE and 5-HT content in the VMH can induce dysregu lation of islet insulin release in response to glucose and neurotransmitter s. Inasmuch as VMH NE and 5-HT levels are elevated in hyperinsulinemic and insulin-resistant animals, the present findings suggest that an endogenous increase in these hypothalamic monoamines may contribute to islet dysfuncti on, which is one of the characteristics of type 2 diabetes. Copyright (C) 1 999 by W.B. Saunders Company.