Chemoreceptors in the carotid bodies sense arterial oxygen tension and regulate respiration. Isolated carotid body glomus cells also sense glucose, and animal studies have shown the carotid bodies play a role in the counterregulatory response to hypoglycaemia. Thus, we hypothesized that glucose infusion rate would be augmented and neuro-hormonal counterregulation blunted during hypoglycaemia when the carotid bodies were desensitized by hyperoxia. Seven healthy adults (four male, three female) underwent two 180 min hyperinsulinaemic (2 mU (kg fat-free mass (FFM))-1 min-1), hypoglycaemic (3.33 mmol l-1) clamps 1 week apart, randomized to either normoxia (arterial 111 ± 6.3 mmHg) or hyperoxia (345 ± 80.6 mmHg) (P < 0.05). Plasma glucose concentrations were similar during normoxia and hyperoxia at baseline (5.52 ± 0.15 vs. 5.55 ± 0.13 μmol ml-1) and during the clamp (3.4 ± 0.05 vs. 3.3 ± 0.05 μmol ml-1). The glucose infusion rate was 44.2 ± 3.5% higher (P < 0.01) during hyperoxia than normoxia at steady state during the clamp (28.2 ± 0.15 vs. 42.7 ± 0.65 μmol (kg FFM)-1 min-1; P < 0.01). Area under the curve values (expressed as percentage normoxia response) for counterregulatory hormones during hypoglycaemia were significantly suppressed by hyperoxia (noradrenaline 50.7 ± 5.2%, adrenaline 62.6 ± 3.3%, cortisol 63.2 ± 2.1%, growth hormone 53.1 ± 2.7%, glucagon 48.6 ± 2.1%, all P < 0.05 vs. normoxia). These data support the idea that the carotid bodies respond to glucose and play a role in the counterregulatory response to hypoglycaemia in humans. Chemoreceptors in the carotid bodies sense arterial oxygen tension and regulate respiration. Isolated carotid body glomus cells also sense low glucose. Animal studies have shown that the carotid bodies play a role in the counterregulatory response to hypoglycaemia. Using hyperoxia to desensitize the carotid bodies, we tested the role of the carotid bodies in hypoglycaemic counterregulation in humans. The glucose infusion rate during hypoglycaemic clamp was significantly augmented with hyperoxia versus normoxia. Counterregulatory hormones (noradrenaline, adrenaline, cortisol, growth hormone and glucagon) were significantly suppressed during hypoglycaemia with hyperoxia. These data support the idea that the carotid bodies respond to low glucose and support a novel role in mediating the counterregulatory response to hypoglycaemia in humans. Altered carotid body sensing/control of blood glucose might also have implications for clinical conditions associated with altered regulation of blood glucose including sleep apnoea, Type II diabetes and also hypoglycaemia unawareness in Type I diabetes.
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