Role of carotid bodies in control of the neuroendocrine response to exercise

Abstract

This study was aimed at assessing the role of carotid body function in neuroendocrine and glucoregulatory responses to exercise. The carotid bodies and associated nerves were removed (CBR, n = 6) or left intact (Sham, n = 6) in anesthetized dogs >16 days before experiments, and infusion and sampling catheters were implanted. Conscious dogs were studied at rest and during 150 min of exercise. Isotopic dilution was used to assess glucose production (R(a)) and disappearance (R(d)). Arterial glucagon was reduced in CBR compared with Sham at rest (29 +/- 3 vs. 47 +/- 3 pg/ml). During exercise, glucagon increased more in Sham than in CBR (47 +/- 9 vs. 15 +/- 2 pg/ml). Cortisol and epinephrine levels were similar in the two groups at rest and during exercise. Basal norepinephrine was similar in CBR and Sham. During exercise, norepinephrine increased by 432 +/- 124 pg/ml in Sham, but by only 201 +/- 28 pg/ml in CBR. Basal arterial plasma glucose was 108 +/- 2 and 105 +/- 2 mg/dl in CBR and Sham, respectively. Arterial glucose dropped by 10 +/- 3 mg/dl at onset of exercise in CBR (P < 0.01) but was unchanged in Sham (decrease of 3 +/- 2 mg/dl, not significant). Basal glucose kinetics were equal in Sham and CBR. At onset of exercise, R(a) and R(d) were transiently uncoupled in CBR (i.e., R(d) > R(a)) but were closely matched in Sham. In steady-state exercise, R(a) and R(d) were closely matched in both groups. Insulin was equal in the basal period and decreased similarly during exercise. These studies suggest that input from the carotid bodies, or receptors anatomically close to them, 1) is important in control of basal glucagon and the exercise-induced increment in glucagon, 2) is involved in the sympathetic response to exercise, and 3) participates in the non-steady-state coupling of R(a) to R(d), but 4) is not essential to glucoregulation during sustained exercise.

Prevention of Overt Hypoglycemia During Exercise

“…Studies have shown that resection of the carotid bodies slightly reduced the epinephrine response and significantly attenuated the R a response to modest hypoglycemia (31). Other studies from our laboratory suggest that these receptors may play a role in neuroendocrine regulation during exercise (32). Therefore, regulatory mechanisms associated with the carotid bodies may be a factor.…”

Mechanisms of Low-Glucose Sensitivity in Carotid Body Glomus Cells

“…The glucosesensing role of the CB was suggested by reports that anesthetized animals show a rapid increase in the output of hepatic glucose after infusion of the CB region with sodium cyanide (15,16) or alterations of carbohydrate metabolism in acute hypoxia (17). In addition, it was known that the counterregulatory response to insulininduced mild hypoglycemia (8) or the neurosecretory response in exercise (9) in dogs was impaired after resection of the carotid body and surrounding tissues. It has also been hypothesized that CB dysfunction could be one of the factors underlying type 2 diabetes (18).…”

Four grams of glucose

“…This was based on demonstrations that carotid bodies 1) sense glucose (2,3,51), 2) project afferent nerves to brain regions involved in glucoregulation (1), and 3) have unique characteristics (i.e., high blood flow and high metabolic rate) that make them highly sensitive to blood composition (66). Comparison of carotid body resected and sham-operated dogs (50) suggested that the carotid bodies or sensors close by are involved in arterial glucagon and sympathetic nerve responses to exercise. Carotid bodies, however, were not essential to glucose homeostasis during sustained exercise, indicating that compensatory mechanisms come into play in the carotid body resected dog.…”