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)