The Role of the Carotid Bodies in the Counter-Regulatory Response to Hypoglycemia

Although controversial, animal and tissue studies indicate that carotid bodies are sensitive to changes in glucose as well as in oxygen, thereby functioning as metabolic sensors. This study was designed to test the hypothesis that carotid bodies in humans participate in the counter-regulatory response to insulin-induced hypoglycemia. Dopamine and hyperoxia were used to suppress the carotid bodies' responsiveness in 16 normal subjects. Insulin and glucose infusions were used to clamp the plasma glucose in a step-wise decrease to 2.5 mmol/l over 4 hours while counter-regulatory hormones were measured. The hypoglycemic trajectories were similar under all three interventions (dopamine, hyperoxia and control), but the total glucose infused was significantly larger for hyperoxia than for dopamine. Cortisol and epinephrine both showed the expected increase with hypoglycemia, but there was no difference among interventions. Glucagon and norepinephrine levels were increased by dopamine, but only the normalized increase in glucagon was lower with dopamine and hyperoxia than control. The decrease in total glucose required for the dopamine experiments was most likely due to the higher baseline glucagon and norepinephrine levels. Hyperoxia did require more infused glucose, indicating some increased insulin sensitivity, but it was not clearly due to a decrease in cortisol or epinephrine responses. Thus, we did not find direct evidence of the carotid bodies' role in glucose homeostasis in humans.