Evidence that carotid bodies play an important role in glucoregulation in vivo

The carotid bodies are sensitive to glucose in vitro and can be stimulated to cause hyperglycemia in vivo. The aim of this study was to determine if t he carotid bodies are involved in basal glucoregulation or the counterregul atory response to an insulin-induced decrement in arterial glucose in vivo. Dogs were surgically prepared >16 days before the experiment, The carotid bodies and their associated nerves were removed (carotid body resected [CBR ]) or left intact (Sham), and infusion and sampling catheters were implante d. Removal of carotid bodies was verified by the absence of a ventilatory r esponse to NaCN. Experiments were performed in 18-h fasted conscious dogs a nd consisted of a tracer ([3-H-3]glucose) equilibration period (-120 to -40 min), a basal period (-40 to 0 min), and an insulin infusion (1 mU . kg(-1 ) min(-1)) period (0-150 min) during which glucose was infused as needed to clamp at mildly hypoglycemic (65 mg/dl) or euglycemic (105 mg/dl) levels. Basal (8 mu U/ml) and clamp (40 mu U/ml) insulin levels were similar in bot h groups, Basal arterial glucagon was reduced in CBR compared with Sham (30 +/- 2 vs. 40 +/- 2 pg/ml) and remained reduced in CBR during hypoglycemia (peak levels of 36 +/- 3 vs. 52 +/- 7 pg/ml), Cortisol levels were not sign ificantly different between the 2 groups in the basal state, but were reduc ed during the hypoglycemic clamp in CBR, Catecholamine levels were not sign ificantly different between the 2 groups in the basal and hypoglycemic peri ods. The glucose infusion rate required to clamp glucose at 65 mg/dl was 2. 5-fold greater in CBR compared with Sham (4.0 +/- 0,4 vs. 1.6 +/- 0.4 mg kg (-1) min(-1)). Basal endogenous glucose appearance (R-a) was equal in CBR a nd Sham (2.5 +/- 0.1 vs, 2.5 +/- 0.2 mg, kg(-1) min(-1)). During the hypogl ycemic clamp, insulin suppressed R-a in CBR but not Sham (1.1 +/- 0.2 vs. 2 .5 +/- 0.2 mg kg(-1) min(-1) during the last 30 min of the clamp), reflecti ng impaired counterregulation, Glucose disappearance (R-d) in the basal sta te was similar in CBR and Sham, whereas it was elevated in CBR during the h ypoglycemic clamp ( 4.8 +/- 0.1 vs. 3.9 +/- 0.1 mg . kg(-1) min(-1) during the last 30 min of clamp). R-d was also evevatd in euglycemic clamp studies , indicating an effect of carotid body resection independent of hypoglycemi a. There were no other measured systematic endocrine or metabolic effects o f carotid body resection during euglycemic clamps. In conclusion, we found that the carotid bodies (or receptors anatomically close by) play an import ant role in the insulin-induced counterregulatory response to mild hypoglyc emia.