Effects of the nitric oxide donor SIN-1 on net hepatic glucose uptake in the conscious dog

• Published in: American journal of physiology: endocrinology and metabolism 2008-02, Vol.294 (2), p.E300-E306
• Main Authors: An, Zhibo, DiCostanzo, Catherine A, Moore, Mary C, Edgerton, Dale S, Dardevet, Dominique P, Neal, Doss W, Cherrington, Alan D
• Format: Article
• Language: English
• Subjects: Animals; Blood Glucose - metabolism; Blood Pressure - drug effects; Carbon - metabolism; Dogs; Effectiveness studies; Fatty Acids, Nonesterified - metabolism; Glucagon - blood; Glucose; Glucose - metabolism; Glycerol - metabolism; Heart Rate - drug effects; Infusions, Intravenous; Insulin - blood; Lactic Acid - metabolism; Liver - drug effects; Liver - metabolism; Liver Circulation - drug effects; Molsidomine - administration & dosage; Molsidomine - analogs & derivatives; Molsidomine - pharmacology; Nitric oxide; Nitric Oxide Donors - administration & dosage; Nitric Oxide Donors - pharmacology; Portal Vein; Studies
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00380.2007

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee Submitted 18 June 2007 ; accepted in final form 19 November 2007 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 µmol·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 µg·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 µmol·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 µmol·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. 3-morpholinosydnominine; nitric oxide; net hepatic glucose uptake; hyperglycemia Address for reprint requests and other correspondence: Z. An, 702 Light Hall, Vanderbilt Univ. School of Medicine, Nashville, TN 37232-6015 (e-mail: zhibo.an{at}vanderbilt.edu )