Glucagon response to exercise is critical for accelerated hepatic glutamine metabolism and nitrogen disposal

The aim of this study was to determine the role of glucagon in hepatic glut amine (Gln) metabolism during exercise. Sampling (artery, portal vein, and hepatic vein) and infusion (vena cava) catheters and flow probes (portal ve in, hepatic artery) were implanted in anesthetized dogs. At least 16 days a fter surgery, an experiment, consisting of a 120-min equilibration period, a 30-min basal sampling period, and a 150-min exercise period, was performe d in these animals. [5-N-15] Gln was infused throughout experiments to meas ure gut and liver Gln kinetics and the incorporation of Gln amide nitrogen into urea. Somatostatin was infused throughout the study. Glucagon was infu sed at a basal rate until the beginning of exercise, when the rate was eith er 1) gradually increased to simulate the glucagon response to exercise (n = 5) or 2) unchanged to maintain basal glucagon (n 5 5). Insulin was infuse d during the equilibration and basal periods at rates designed to achieve s table euglycemia. The insulin infusion was reduced in both protocols to sim ulate the exercise-induced insulin decrement. These studies show that the e xercise-induced increase in glucagon is 1) essential for the increase in he patic Gln uptake and fractional extraction, 2) required for the full increm ent in ureagenesis, 3) required for the specific transfer of the Gln amide nitrogen to urea, and 4) unrelated to the increase in gut fractional Gln ex traction. These data show, by use of the physiological perturbation of exer cise, that glucagon is a physiological regulator of hepatic Gln metabolism in vivo.