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, 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.
Liang
Y
Y
Pre-clinical Research Laboratory, Ergo Science, Charlestown, MA 02129, USA.
Luo
S
S
Cincotta
A H
AH
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007263:Infusions, Parenteral; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*
D007328:Insulin; D012701:Serotonin; D005947:Glucose; D000109:Acetylcholine; D009638:Norepinephrine