title: Effect of hepatic denervation on peripheral insulin sensitivity in conscious dogs.
abstract: 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.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. genie.moore@mcmail.vanderbilt.edu
authors.forename: Mary Courtney
authors.initials: MC
authors.lastname: Moore
authors.forename: Shosuke
authors.initials: S
authors.lastname: Satake
authors.forename: Bryan
authors.initials: B
authors.lastname: Baranowski
authors.forename: Po-Shiuan
authors.initials: PS
authors.lastname: Hsieh
authors.forename: Doss W
authors.initials: DW
authors.lastname: Neal
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D003714:Denervation; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005943:Gluconeogenesis / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000097:blood; D006728:Hormones / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000294:innervation*; D008102:Liver Circulation / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology; D009424:Nervous System Physiological Phenomena; D011169:Portal Vein
chemical_list: D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007328:Insulin; D019344:Lactic Acid; D005947:Glucose; D000109:Acetylcholine; D005990:Glycerol