Effect of hepatic denervation on peripheral insulin sensitivity in conscious dogs

We tested the hypothesis that the loss of hepatic nerves decreases peripheral insulin sensitivity. Surgical hepatic denervation (DN) was performed in 22 dogs approximately 16 days before study; 7 dogs (Sham-Sal) had a sham procedure. A euglycemic hyperinsulinemic (1 mU x kg(-1) x min(-1); arterial insulin 35 +/- 1 microU/ml in all dogs) clamp was performed in conscious dogs. From 0 to 90 min of the clamp, all dogs received the same treatment; then the DN dogs were divided into three groups. From 90 to 180 min, DN-PeA (n = 7) and DN-PoA (n = 7) groups received acetylcholine 2.5 microg x kg(-1) x min(-1) via peripheral or portal vein, respectively, and DN-Sal (n = 8) received no acetylcholine. During 150-180 min, the Sham-Sal, DN-Sal, DN-PeA, and DN-PoA groups exhibited glucose infusion rates of 12.4 +/- 0.8, 9.3 +/- 0.8 (P < 0.05 vs. Sham-Sal), 9.1 +/- 0.1 (P < 0.05 vs. Sham-Sal), and 12.7 +/- 1.6 mg. kg(-1) x min(-1); nonhepatic glucose uptakes of 11.5 +/- 0.9, 8.9 +/- 0.7 (P < 0.05 vs. Sham-Sal), 8.6 +/- 0.9 (P < 0.05 vs. Sham-Sal), and 11.9 +/- 1.7 mg. kg(-1). min(-1); net hindlimb glucose uptakes of 18.4 +/- 2.1, 13.7 +/- 1.1 (P < 0.05 vs. Sham-Sal), 17.5 +/- 1.9, and 16.7 +/- 3.2 mg/min; and glucose utilization rates of 14.4 +/- 1.4, 10.4 +/- 0.8 (P < 0.05 vs. Sham-Sal), 9.8 +/- 0.9 (P < 0.05 vs. Sham-Sal), and 13.6 +/- 1.8 mg. kg(-1) x min(-1), respectively. DN caused peripheral insulin resistance, and intraportal but not peripheral acetylcholine restored insulin sensitivity.