Putative hypothalamic glucoreceptors play no essential role in the response to moderate hypoglycemia

The response to insulin-induced hypoglycemia includes increased plasma levels of glucagon, epinephrine, norepinephrine, cortisol, and growth hormone. This integrated response is thought to be mediated via sympathetic afferent pathways emanating from the ventromedial hypothalamus. However, the precise loci of the receptors that sense glucopenia are not known. In this study, we investigated the importance of putative forebrain glucoreceptors to the systemic response to hypoglycemia. Three protocols were performed. Protocol 1: the systemic response was observed in conscious dogs to hypoglycemia induced by infusion of insulin at a high rate (150 mU/min). Protocol 2: the effect of concomitant bilateral, intracarotid glucose infusion on the response to intravenous insulin was examined. Intracarotid glucose infusion rates were chosen to yield central euglycemia in the face of systemic hypoglycemia. Protocol 3: as a control for protocol 2, glucose was infused at low rates into the systemic circulation, yielding hypoglycemia in both central and systemic blood. When insulin was infused at 150 mU/min, without glucose replacement (protocol 1; N = 6), plasma insulin increased from 14 +/- 3 to 335 +/- 35 microU/ml at 60 min (P less than 0.001). Glucose fell from basal (104 +/- 3 mg/dl) to 38 +/- 3 mg/dl (P less than 0.001). Significant increases were observed in epinephrine (basal, B: 63 +/- 8; steady state, SS: 1762 +/- 582 pg/ml; P less than 0.007), norepinephrine (B: 209 +/- 33, SS: 650 +/- 133 pg/ml; P less than 0.01), and glucagon (B: 256 +/- 35, SS: 467 +/- 35 pg/ml; P less than 0.03). In addition, endogenous glucose production (Ra) increased from 72 +/- 4 to 108 +/- 9 mg/min (P less than 0.02) despite frank hyperinsulinemia. Infusion glucose into the carotid arteries at 204 +/- 10 mg/min (protocol 2; N = 7) during a 4-h systemic insulin infusion was sufficient to prevent jugular hypoglycemia [jugular glucose, Gj, B: 100 +/- 3, SS (90-160 min): 101 +/- 3 mg/dl; P greater than 0.70], but not peripheral hypoglycemia (Gp, B: 102 +/- 2, SS: 55 +/- 3 mg/dl; P less than 0.001). Despite carotid glucose replacement, counterregulatory responses were still observed in epinephrine (B: 98 +/- 14, SS: 466 +/- 127 pg/ml; P less than 0.04) and norepinephrine (B: 213 +/- 19, SS: 474 +/- 133 pg/ml; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)