EFFECT OF LIVER DENERVATION ON GLUCOSE-PRODUCTION DURING RUNNING IN GUINEA-PIGS

Activity in sympathetic liver nerves has been proposed to be important for glucose production in exercising humans. However, liver denervation does not influence the exercise-induced increase in glucose production in the rat and dog. These species have a poor sympathetic liver innervation in contrast to the rich innervation in humans. The effect of liver denervation on glucose production during exercise was therefore studied in the guinea pig, a species with a rich sympathetic hepatic innervation comparable to that of humans. Guinea pigs were selectively liver denervated (n = 9) or sham operated (n = 8) and instrumented with a carotid and a jugular catheter. One week later they ran on a treadmill at 32 m/min for 20 min. Glucose turnover was evaluated by a primed constant-rate intravenous infusion of [3-H-3]glucose. Arterial blood was sampled for analysis of hormones and metabolites. At rest, liver-denervated guinea pigs had lower glucose turnover and plasma concentrations of glucose, glycerol, and cortisol than control animals. During running, the increase in hepatic glucose production was similar in the two groups (4.1 +/- 0.8 vs. 3.8 +/- 0.7 mu mol.min(-1).100 g(-1) in control animals) and so were hepatic (247 +/- 25 vs. 246 +/- 45 mmol glucose units/kg wet wt in control animals) and muscle glycogen concentrations at the end of exercise. Exercise-induced increases were also similar in the two groups for epinephrine (1.9 +/- 0.3 vs. 1.6 +/- 0.2 nM in control animals), norepinephrine (13.0 +/- 1.9 vs. 11.1 +/- 2.3 nM in control animals), cortisol [0.41 +/- 0.03 vs. 0.57 +/- 0.08 mu M in control animals (P = 0.09)], and glycerol [47 +/- 7 vs. 70 +/- 12 mu M in control animals (P = 0.103)]. In conclusion, sympathetic liver nerve activity is not a prerequisite for the exercise-induced increase in glucose production in the guinea pig.