title: Effects of the nitric oxide donor SIN-1 on net hepatic glucose uptake in the conscious dog.
abstract: To determine the role of nitric oxide in regulating net hepatic glucose uptake (NHGU) in vivo, studies were performed on three groups of 42-h-fasted conscious dogs using a nitric oxide donor [3-morpholinosydnonimine (SIN-1)]. The experimental period was divided into period 1 (0-90 min) and period 2 (P2; 90-240 min). At 0 min, somatostatin was infused peripherally, and insulin (4-fold basal) and glucagon (basal) were given intraportally. Glucose was delivered intraportally (22.2 mumol.kg(-1).min(-1)) and peripherally (as needed) to increase the hepatic glucose load twofold basal. At 90 min, an infusion of SIN-1 (4 mug.kg(-1).min(-1)) was started in a peripheral vein (PeSin-1, n = 10) or the portal vein (PoSin-1, n = 12) while the control group received saline (SAL, n = 8). Both peripheral and portal infusion of SIN-1, unlike saline, significantly reduced systolic and diastolic blood pressure. Heart rate rose in PeSin-1 and PoSin-1 (96 +/- 5 to 120 +/- 10 and 88 +/- 6 to 107 +/- 5 beats/min, respectively, P < 0.05) but did not change in response to saline. NHGU during P2 was 31.0 +/- 2.4 and 29.9 +/- 2.0 mumol.kg(-1).min(-1) in SAL and PeSin-1, respectively but was 23.7 +/- 1.7 in PoSin-1 (P < 0.05). Net hepatic carbon retention during P2 was significantly lower in PoSin-1 than SAL or PeSin-1 (21.4 +/- 1.2 vs. 27.1 +/- 1.5 and 26.1 +/- 1.0 mumol.kg(-1).min(-1)). Nonhepatic glucose uptake did not change in response to saline or SIN-1 infusion. In conclusion, portal but not peripheral infusion of the nitric oxide donor SIN-1 inhibited NHGU.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA. zhibo.an@vanderbilt.edu
authors.forename: Zhibo
authors.initials: Z
authors.lastname: An
authors.forename: Catherine A
authors.initials: CA
authors.lastname: DiCostanzo
authors.forename: Mary C
authors.initials: MC
authors.lastname: Moore
authors.forename: Dale S
authors.initials: DS
authors.lastname: Edgerton
authors.forename: Dominique P
authors.initials: DP
authors.lastname: Dardevet
authors.forename: Doss W
authors.initials: DW
authors.lastname: Neal
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002244:Carbon / Q000378:metabolism; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects; D008981:Molsidomine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D011169:Portal Vein
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020030:Nitric Oxide Donors; D019344:Lactic Acid; C002385:linsidomine; D002244:Carbon; D005934:Glucagon; D008981:Molsidomine; D005947:Glucose; D005990:Glycerol