Forebrain and hindbrain effects of ethanol on counterregulatory responses to hypoglycemia in conscious rats

Ethanol (OH) has been reported to blunt counterregulation and increase insulin sensitivity, thereby causing greater hypoglycemia in patients with diabetes mellitus. The aim of this study was to determine if fore- or hindbrain sensing of OH differentially affects autonomic and metabolic counterregulatory responses to hypoglycemia. Forty-one Sprague-Dawley rats received 5% OH or isotonic sodium chloride solution (or normal saline; SAL) infused peripherally or into the lateral (forebrain) or fourth cerebral ventricles (hindbrain) from time 0 to 120 minutes. From time 120 to 240 minutes, rats were exposed to a hyperinsulinemic (5 mU/[kg min]) hypoglycemic (2.9 +/- 0.1 mmol/L) clamp. The 4 groups of rats studied were as follows: SAL (n = 8), peripheral alcohol (POH) (n = 10), lateral ventricle alcohol (LVOH) (n = 12), and left ventricle alcohol (4VOH) (n = 11). After OH, basal levels of norepinephrine were lower in the POH and 4VOH groups (P < .05). Epinephrine and norepinephrine responses to hypoglycemia were significantly lower in POH, 4VOH, and LVOH vs SAL. However, the magnitude of blunting was significantly greater in POH and 4VOH vs LVOH. Other counterregulatory hormones and glucose kinetics were not significantly different among all groups during hypoglycemia. In summary, peripheral and central nervous system OH infusion blunted autonomic nervous system counterregulatory (epinephrine, norepinephrine) responses to subsequent hypoglycemia. The greater impact of 4VOH compared with LVOH administration suggests that OH exerts its effects to blunt autonomic nervous system counterregulatory responses during hypoglycemia primarily by actions on the hindbrain.