title: Chronic ventromedial hypothalamic infusion of norepinephrine and serotonin promotes insulin resistance and glucose intolerance.
abstract: The ventromedial hypothalamus (VMH) is involved in the regulation of peripheral metabolism. We and others have shown that activities, or extracellular metabolites of norepinephrine (NE) and serotonin (5-HT) are elevated in the VMH of both genetically and seasonally insulin-resistant and glucose-intolerant animals. This study examined whether chronic increases in VMH NE and 5-HT concentration of normal animals might lead to insulin-resistant and glucose-intolerant conditions in hamsters. Euinsulinemic, glucose-tolerant hamsters were infused continuously for 5 weeks into the right VMH with either vehicle, NE (5 or 25 nmol/h), 5-HT (2.5 nmol/h), or NE (5 or 25 nmol/h) plus 5-HT (2.5 nmol/h) through osmotic minipumps. Compared to vehicle, NE (25 nmol/h) significantly increased the glucose total area under the curve (TAUC) by 32% during glucose tolerance tests (GTT) conducted after 5 weeks' infusion. 5-HT alone significantly increased the GTT insulin TAUC (131%) and basal plasma insulin level (116%) but not glucose TAUC. NE (5 nmol/h) plus 5-HT infusion significantly increased insulin TAUC (129%) and basal plasma insulin (120%), whereas NE (25 nmol/h) plus 5-HT infusion significantly increased both the GTT glucose and insulin TAUC (43 and 113%, respectively), as well as basal plasma insulin level (158%), relative to vehicle infusion. Our findings demonstrate for the first time the differential and, more importantly, interactive effects of increased VMH NE and 5-HT in producing hyperinsulinemia, insulin resistance and glucose intolerance.
authors.affiliation: Ergo Science Corp., Charlestown, Mass., USA. sluo@ergo.com
authors.forename: S
authors.initials: S
authors.lastname: Luo
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.forename: A H
authors.initials: AH
authors.lastname: Cincotta
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D006224:Cricetinae; D005951:Glucose Tolerance Test; D006946:Hyperinsulinism / Q000139:chemically induced; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008647:Mesocricetus; D009638:Norepinephrine / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*; D013566:Sympathomimetics / Q000494:pharmacology*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013566:Sympathomimetics; D012701:Serotonin; D009638:Norepinephrine