title: Hyperinsulinemia increases norepinephrine metabolism in the ventromedial hypothalamus of rats.
abstract: Numerous studies have implicated increased ventromedial hypothalamic (VMH) norepinephrine (NE) activity as a contributing factor to the obese, hyperinsulinemic, glucose intolerant condition. However, factors contributing to the increased VMH NE activity remain unknown. This study therefore investigated in normal rats the effect of a hyperinsulinemic-euglycemic clamp on VMH monoamine turnover and utilization via simultaneous VMH microdialysis to establish a role for hyperinsulinemia in the stimulation of VMH NE activity. Within 20 min of initiation of the hyperinsulinemic-euglycemic clamp, VMH extracellular methoxyhydroxy phenylglycol (metabolite of NE) level increased by 54% and remained approximately at this level for the 100 min duration of the clamp relative to control values (p<0.05). Hyperinsulinemia did not affect VMH dopamine or serotonin metabolism. Subsequent establishment of a hyperinsulinemic-hypoglycemic camp did not alter the VMH monoamine metabolism profile relative to the hyperinsulinemic-euglycemic clamp. Infusion of saline (as control) in a separate group of rats over the entire clamp period induced no changes in any monoamine metabolic profile relative to baseline. Hyperinsulinemia can feedback to stimulate VMH NE activity and, as a result, may contribute to the initiation and/or perpetuation of the obese, hyperinsulinemic, glucose-intolerant state.
authors.affiliation: Ergo Science Corp., North Andover, MA 01845, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Cincotta
authors.forename: S
authors.initials: S
authors.lastname: Luo
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D006946:Hyperinsulinism / Q000097:blood*; D007328:Insulin / Q000097:blood; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism*; D014851:Wakefulness / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D009638:Norepinephrine; D006719:Homovanillic Acid