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APPETITE, OBESITY AND METABOLISM

Dissociation of hypothalamic noradrenergic activity and sympathoadrenal responses to recurrent hypoglycemia

¹Department of Animal Sciences and ²Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801

Submitted 6 May 2002 ; accepted in final form 9 January 2004

This study evaluated whether attenuation of sympathoadrenal responses to recurrent hypoglycemia is mediated by diminished noradrenergic activity in the hypothalamus. Male Sprague-Dawley rats received either once daily insulin (1.0 units/kg) injections or an equal administration of saline for 3 days. Both groups received an administration of insulin on the fourth day, during which blood glucose and plasma catecholamines were determined, and extracellular norepinephrine (NE) in the ventromedial hypothalamus (VMH) or paraventricular hypothalamic nucleus (PVN) was monitored with microdialysis. The peak response of plasma epinephrine to insulin-induced hypoglycemia (nadir 3.2 mmol/l) was significantly reduced during the fourth hypoglycemic episode (774 ± 134 pg/ml) compared with the first episode (2,561 ± 410 pg/ml, P < 0.001). Baseline levels of extracellular NE were elevated 25% (P = 0.07) in the VMH and 46% (P = 0.03) in the PVN after multiple hypoglycemic episodes. There was no difference in noradrenergic activity during the first or fourth hypoglycemic episode in either brain area. The reduced sympathoadrenal output after recurrent hypoglycemia is likely postsynaptic from hypothalamic NE release or is mediated via a collateral pathway.

ventromedial hypothalamus; paraventricular nucleus; microdialysis; insulin; rats

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