Hyperinsulinemia increases norepinephrine metabolism in the ventromedial hypothalamus of rats

Numerous studies have implicated increased ventromedial hypothalamic (VMH) norepinephrine (NE) activity as a contributing factor to the obese, hyperin sulinemic, glucose intolerant condition. However, factors contributing to t he increased VMH NE activity remain unknown. This study therefore investiga ted in normal rats the effect of a hyperinsulinemic-euglycemic clamp on VMH monoamine turnover and utilization via simultaneous VMH microdialysis to e stablish 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 increase d 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 no t affect VMH dopamine or serotonin metabolism. Subsequent establishment of a hyperinsulinemic-hypoglycemic clamp did not alter the VMH monoamine metab olism profile relative to the hyperinsulinemic-euglycemic clamp. Infusion o f saline (as control) in a separate group of rats over the entire clamp per iod induced no changes in any monoamine metabolic profile relative to basel ine. Hyperinsulinemia can feedback to stimulate VMH NE activity and, as a r esult, may contribute to the initiation and/or perpetuation of the obese, h yperinsulinemic, glucose-intolerant state. NeuroReport 11:383-387 (C) 2000 Lippincott Williams & Wilkins.