Hepatic denervation does not significantly change the response of the liver to glucagon in conscious dogs

Abstract

In view of the increasing frequency of liver transplantation, and the importance of glucagon in the minute-to-minute regulation of glucose production, we assessed the effect of hepatic denervation on the liver's response to a physiological rise in glucagon in 18-h fasted dogs. Before study (2 wk), the dogs underwent liver denervation (DN; n = 6) or sham operation (SH; n = 5). Endogenous insulin and glucagon secretion were inhibited using somatostatin, and the two hormones were replaced intraportally in basal amounts. After the control period the glucagon infusion rate was tripled for 3 h. Glucagon increased from 41 +/- 8 to 128 +/- 8 and 54 +/- 4 to 129 +/- 9 pg/ml in SH and DN, respectively (P < 0.05), causing tracer-determined glucose production to increase from 2.5 +/- 0.1 to 4.9 +/- 0.5 and 2.3 +/- 0.1 to 5.8 +/- 0.8 mg.kg-1.min-1 by 15 min, respectively (P < 0.05). Glucose clearance fell slightly during glucagon infusion in DN, causing a somewhat greater increase in the plasma glucose level (to 175 +/- 15 vs. 207 +/- 20 mg/dl). The changes in gluconeogenic efficiency increased 65-90% in both groups (P < 0.05). In conclusion, denervation of the liver failed to significantly alter the metabolic response of that organ to a half-maximally effective increment in the plasma glucagon level.