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

Metabolism. 1999 Oct;48(10):1287-9. doi: 10.1016/s0026-0495(99)90269-x.

Abstract

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, we 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 release from the isolated pancreatic islets. VMH infusion of NE + 5-HT, but not of either neurotransmitter alone, produced a marked leftward shift in the dose-response curve of glucose-induced insulin release (twofold to sixfold increase at 5 to 7.5 mmol/L glucose v vehicle-treated animals). In addition, the islet responsiveness to 1 micromol/L NE and 10 micromol/L acetylcholine was abolished in these NE + 5-HT VMH-infused hamsters. These findings indicate that an increase of NE and 5-HT content in the VMH can induce dysregulation of islet insulin release in response to glucose and neurotransmitters. 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 dysfunction, which is one of the characteristics of type 2 diabetes.

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Glucose / pharmacology
  • In Vitro Techniques
  • Infusions, Parenteral
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Male
  • Mesocricetus
  • Norepinephrine / administration & dosage
  • Norepinephrine / pharmacology*
  • Serotonin / administration & dosage
  • Serotonin / pharmacology*
  • Ventromedial Hypothalamic Nucleus / drug effects
  • Ventromedial Hypothalamic Nucleus / physiology*

Substances

  • Insulin
  • Serotonin
  • Glucose
  • Acetylcholine
  • Norepinephrine