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

Abstract

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 the carotid bodies are involved in basal glucoregulation or the counterregulatory 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 implanted. Removal of carotid bodies was verified by the absence of a ventilatory response to NaCN. Experiments were performed in 18-h fasted conscious dogs and consisted of a tracer ([3-3 H]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 µU/ml) and clamp (40 µU/ml) insulin levels were similar in both 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 significantly different between the 2 groups in the basal state, but were reduced during the hypoglycemic clamp in CBR. Catecholamine levels were not significantly different between the 2 groups in the basal and hypoglycemic periods. The glucose infusion rate required to clamp glucose at 65 mg/dl was 2.5-fold greater in CBR compared with Sham T here is considerable uncertainty as to the site at which decrements in blood glucose are sensed. Sites in the brain (1), portal vein (2,3), liver (4), and pancreas (5) are all sensitive to blood glucose. Despite intensive investigation, however, the physiological role of these glucose-sensitive regions are highly controversial because no one site can completely explain the full counterregulatory response to hypoglycemia.We tested the hypothesis that the carotid bodies (or receptors near this site) are instrumental in detecting a decrement in blood glucose. This hypothesis was based on evidence that 1) the carotid bodies can detect glucose (6-8), 2) the carotid bodies have the "circuitry" to provide input to centers involved in glucoregulation (7-10), and 3) the carotid bodies have unique physiological characteristics making them potentially highly sensitive to changes in blood glucose content (high blood flow and metabolic rate per gram tissue) (11).To examine the role of the carotid bodies (or receptors anatomically near them), carotid body resected (CBR) conscious dogs or dogs having undergone a sham surgery (Sham) were studied in the basal state and during hyperinsulinemic, euglycemic, or hypoglycemic clamps. Isotope dilution methods were used to calculate glucose kinetics. RESEARCH DESIGN AND METHODSAnimal maintenance and surgical procedures. Mongrel dogs (n = 23, mean weight 25.1 ± 0.6 kg) of either sex that had been fed a standard...

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).…”

Glucose sensing and the pathogenesis of obesity and type 2 diabetes

“…Although not discussed here, there is evidence that glomus cells in the carotid body are also activated by hypoglycemia and may contribute to the overall control of counter-regulation. 59,60 The role of Glut2, glucokinase and the K ATP channel in the control of glucagon secretion has been investigated in several studies. Mice with inactivation of the Glut2 gene, and that express a transgenic glucose transporter in their pancreatic beta-cells to preserve normal glucose-stimulated insulin secretion (ripglut1;glut2 À/À mice), 61 display plasma glucagon levels in the fed state that are abnormally high.…”

Modulation of Food Intake by Glucose in Patients With Type 2 Diabetes

“…Hypothalamic glucose sensors are tightly linked with central nervous networks regulating energy homeostasis (14). Additional glucose sensors are localized in the portal vein (25,26) and carotid body (27,28), which via afferent fibers to the hypothalamus and other brain areas can likewise influence eating behavior. It is worth mentioning in this context that in a stepwise hypoglycemic clamp study, we have recently shown that even slightly lowering plasma glucose levels to 4.1 mmol/l in comparison to a level of 5.2 mmol/l increased feelings of hunger in healthy subjects (29).…”