Influence of peri-arterial hepatic denervation on the glycemic response to exercise in rats

Abstract

Exercise is known to increase hepatic glucose production. Previous studies have suggested that the sympathetic nerves only marginally contribute to this process. This study examined whether increased catecholamine response or increased adrenoceptor sensitivity might have affected previous results showing no effect of hepatic denervation on the increased hepatic glucose production during exercise. Hepatic sympathetic denervated rats, sham-operated rats and control rats were forced to swim against a counter current for 15 minutes. Denervations and sham operations were performed 9 days prior to swimming. The results show that denervation did not affect the changes in levels of blood glucose, plasma FFA, and catecholamines before, during and after swimming. Furthermore, hepatic adrenoceptor sensitivity was not altered in denervated rats, since intravenous infusions of epinephrine (20 ng/min) and norepinephrine (50 ng/min) similarly changed blood glucose and plasma FFA levels in liver-denervated, sham-operated and control rats. Thus, the increase in blood glucose levels during intravenous infusion of epinephrine and norepinephrine in the respective groups was 1.2 ± 0.3 and 1.0 ± 0.3 mmol/l (liver-denervated rats), 1.6 ± 0.4 and 0.7 ± 0.3 mmol/l (sham-operated rats) and 1.3 ± 0.3 and 0.8 ± 0.3 mmol/l (control rats), respectively. After adrenodemedullation, however, the rise of glucose levels during swimming in liver-denervated and control rats was completely abolished. Thus, the glucose response to swimming with and without adrenodemullation was 0.1 ± 0.4 and 1.7 ± 0.4 mmol/l in liver-denervated rats ( P < 0.01) and −0.2 ± 0.4 and 2.2 ± 0.2 mmol/l in control rats ( P < 0.001), respectively. The study therefore suggests that the peri-arterial hepatic nerves have a negligible influence on the glycemic response to exercise in rats. Instead, the glycemic response seems to be mediated mainly by the adrenal medulla.