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...

The effects of the exercise-induced rise in glucagon were studied during 2.5 h of treadmill exercise in 18-h fasted dogs. Five dogs were studied during paired experiments in which pancreatic hormones were clamped at basal levels during a control period (using somatostatin and intraportal hormone replacement), then altered during exercise to stimulate the normal exercise-induced fall in insulin, while glucagon was 1) increased to mimic its normal exercise-induced rise (SG) and 2) maintained at a basal level (BG). Six additional dogs were studied as described with saline infusion alone (C). Gluconeogenesis (GNG) and glucose production (Ra) were measured using tracers [( 3-3H]glucose and [U-14C]alanine) and arteriovenous differences. Glucose fell slightly during exercise in C and was infused in SG and BG so as to mimic the response in C. Glucagon rose from 60 +/- 3 and 74 +/- 5 pg/ml to 118 +/- 14 and 122 +/- 17 pg/ml with exercise in C and SG and was unchanged from basal in BG (67 +/- 6 pg/ml). In C, SG, and BG, insulin fell during exercise by 5 +/- 1, 6 +/- 1, and 6 +/- 1 microU/ml. Ra rose from 3.3 +/- 0.2 and 3.0 +/- 0.2 mg.kg-1.min-1 to 8.6 +/- 0.8 and 9.5 +/- 1.5 mg.kg-1.min-1 with exercise in C and SG, but from only 3.0 +/- 0.2 to 5.5 +/- 0.8 mg.kg-1.min-1 in BG. GNG increased by 248 +/- 38 and 183 +/- 75% with exercise in C and SG but by only 56 +/- 21% in BG. Intrahepatic gluconeogenic efficiency was also enhanced by the rise in glucagon increasing by 338 +/- 55 and 198 +/- 52% in C and SG but by only 54 +/- 46% in BG. The rise in hepatic fractional alanine extraction was 0.38 +/- 0.04 and 0.33 +/- 0.04 during exercise in C and SG and only 0.08 +/- 0.06 in BG. Ra was increased beyond that which could be explained by effects on GNG alone, hence hepatic glycogenolysis must have also been enhanced by the rise in glucagon. In conclusion, in the dog, the exercise-induced rise in glucagon 1) controls approximately 65% of the increase in Ra, 2) increases hepatic glycogenolysis and GNG, and 3) enhances GNG by stimulating precursor extraction by the liver and precursor conversion to glucose within the liver.

Exercise leads to marked increases in muscle insulin sensitivity and glucose effectiveness. Oral glucose tolerance immediately after exercise is generally not improved. The hypothesis tested by these experiments is that after exercise the increased muscle glucose uptake during an intestinal glucose load is counterbalanced by an increase in the efficiency with which glucose enters the circulation and that this occurs due to an increase in intestinal glucose absorption or decrease in hepatic glucose disposal.

To examine the role of the exercise-induced fall in insulin, dogs were studied during 150 min of treadmill exercise alone (C) or with insulin clamped at basal levels by an intraportal infusion so as to prevent the normal fall in its concentration (IC). To counteract the suppressive effect of insulin on glucagon release, glucagon was replaced intraportally in a separate group of dogs in which insulin levels were clamped (IC + G). In all dogs, catheters were placed in an artery and in the portal and hepatic veins for sampling and in the vena cava and the portal vein for infusion purposes. Glucose production (Ra) and gluconeogenesis were assessed with isotope and arteriovenous difference techniques. In C, insulin fell 5 +/- 2 microU/ml by the end of exercise and was unchanged in IC (delta 0 +/- 2 microU/ml) and IC + G (delta 0 +/- 1 microU/ml). Glucagon rose 54 +/- 11 pg/ml with exercise in C and was unchanged in IC (delta - 4 +/- 11 pg/ml), and normal increments were restored in IC + G (delta 55 +/- 10 pg/ml). Catecholamines and cortisol rose similarly in all groups. Ra increased by an average of 4.0 +/- 0.4, 0.9 +/- 0.3, and 1.8 +/- 0.4 mg.kg-1.min-1 during exercise in C, IC, and IC + G, respectively. Gluconeogenesis from alanine rose by 212 +/- 34, 91 +/- 39, and 184 +/- 47% with exercise in C, IC, and IC + G.(ABSTRACT TRUNCATED AT 250 WORDS)

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