A single episode of central glucoprivation reduces the adrenomedullary response to subsequent hypoglycemia in rats

Abstract

Hypoglycemia-associated autonomic failure (HAAF) is a complication of recurrent hypoglycemia in patients with diabetes. The present experiments were performed to study the contribution of brain glucose-sensitive structures to HAAF. In conscious rats, brain glucoprivation was elicited by injection of 2 deoxy- d-glucose (2-DG) into the third cerebral ventricle (intracerebroventricular, ICV), while controls received saline ICV. Two days after ICV injection, hormone responses to systemic hypoglycemic challenge were measured. The epinephrine response 60 min after insulin injection was reduced by 46% in rats treated with prior ICV 2-DG, relative to saline-treated controls (SAL: 10,050±970 pg/ml; 2-DG: 5590±880 pg/ml). Thus, the adrenomedullary response to sustained hypoglycemia is attenuated after prior brain glucoprivation induced by intracerebroventricular injection of 2-DG. These data support the hypothesis that the brain contributes to the loss of responsiveness to repeated hypoglycemia that may ultimately result in HAAF.