Norepinephrine-Stimulated Glutamate Release in the Ventromedial Hypothalamus Is Important to Enhance the Counterregulatory Response during Hypoglycemia

We previously showed that norepinephrine acts through β2-adrenergic receptors to stimulate the release of glutamate in the ventromedial hypothalamus (VMH) and the secretion of counter-regulatory hormones under basal non-stimulated conditions. The current study investigates the importance of this interaction during hypoglycemia and more specifically, whether norepinephrine is an absolute requirement for glutamate secretion in the VMH in response to hypoglycemia and/or whether glutamate neurons respond to hypoglycemia independent of this input. To address this question, we locally delivered the β2-adrenergic receptor blocker, ICI-118,551, into the VMH and evaluated glutamate release in the VMH using microdialysis, as well as its effects on the counter-regulatory hormone responses during a hypoglycemic clamp. These responses were compared to control animals given artificial extracellular fluid. Our data shows that β2-adrenergic receptor blockade reduced VMH glutamate levels, and this was accompanied by a 38% reduction in plasma epinephrine secretion during hypoglycemia (P<0.05 vs Control). Our data suggest that during hypoglycemia, noradrenergic inputs may help drive the release of neurotransmitter glutamate in the VMH that in turn, enhances the release of counter-regulatory hormones. Disclosure I. E. Nelson: None. D. A. Appadurai: None. C. Uzo: None. O. Chan: None.