title: Important role of the hepatic vagus nerve in glucose uptake and production by the liver.
abstract: We examined the role of the hepatic vagus nerve in hepatic and peripheral glucose metabolism. To assess endogenous glucose production (EGP), hepatic uptake of first-pass glucose infused intraportally (HGU), and the metabolic clearance rate of glucose (MCR), rats were subjected to hepatic vagotomy (HV, n = 7) or sham operation (SH, n = 8), after 10 days, they were then subjected to a euglycemic-hyperinsulinemic clamp together with a portal glucose load in the 24-hour fasting state. Metabolic parameters were determined by the dual-tracer method using stable isotopes. During the experiment, [6,6-2H2]glucose was continuously infused into the peripheral vein. To maintain euglycemia (4.5 mmol/L), insulin (54 pmol x kg(-1) x min(-1)) and glucose were infused peripherally after the 90-minute tracer equilibration and 30-minute basal periods, and glucose containing 5% enriched [U-13C]glucose was infused intraportally (50 micromol x kg(-1) x min(-1)) for 120 minutes (clamp period). EGP was significantly higher in HV rats versus SH rats during the basal period (64.3 +/- 7.6 v 43.6 +/- 5.3 micromol x kg(-1) x min(-1), P < .005)) and was comparable to EGP in SH rats during the clamp period (9.3 +/- 21.5 v 1.1 +/- 11.7 micromol x kg(-1) x min(-1)). HGU was reduced in HV rats compared with SH rats during portal glucose infusion (5.9 +/- 2.4 v 10.1 +/- 3.2 micromol x kg(-1) x min(-1)). The MCR in HV rats was significantly higher than in SH rats in the basal period (11.0 +/- 2.0 v 7.9 +/- 0.8 mL x kg(-1) x min(-1), P < .01)) and was comparable to the MCR in SH rats during the clamp period (41.9 +/- 10.0 and 36.6 +/- 5.7 mL x kg(-1) x min(-1)). We conclude that innervation of the hepatic vagus nerve is important for the regulation of hepatic glucose production in the postabsorptive state and HGU in the postprandial state.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Matsuhisa
authors.forename: Y
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Shiba
authors.forename: I
authors.initials: I
authors.lastname: Nakahara
authors.forename: A
authors.initials: A
authors.lastname: Kuroda
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.forename: M
authors.initials: M
authors.lastname: Iida
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: Y
authors.initials: Y
authors.lastname: Kajimoto
authors.forename: M
authors.initials: M
authors.lastname: Kubota
authors.forename: M
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005227:Fatty Acids / Q000097:blood; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000294:innervation* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D006003:Glycogen; D005941:Glucokinase; D005947:Glucose