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

摘要

First published November 20, 2007; doi:10.1152/ajpendo.00380.2007.-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 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) (4mug-kg-min~(-1)) was started in a peripheral vein (PeSin-l,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-l 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.