Impact of intraportal N[omega ]-nitro-L-arginine infusion on hepatic glucose metabolism in total parenteral nutrition-adapted dogs: Interaction with infection

Abstract

During chronic total parenteral nutrition (TPN), liver glucose uptake and lactate release are markedly elevated. However, in the presence of an infection, hepatic glucose uptake and lactate release are reduced. Glucose delivery (the product of liver blood flow and inflowing glucose concentration) is a major determinant of liver glucose uptake. Hepatic blood flow is increased during infection, and increased nitric oxide (NO) biosynthesis is thought to contribute to the increase. Our aim was to determine if the increase in liver blood flow served to limit the infection-induced decrease in hepatic glucose uptake and metabolism. Chronically catheterized conscious dogs received TPN for 5 days at a rate designed to match daily basal energy requirements. On the third day of TPN administration, a sterile (SHAM) or Escherichia coli (E. coli)-containing (INF) fibrin clot was implanted in the peritoneal cavity. Forty-two hours later, somatostatin was infused with intraportal replacement of insulin (10 [plusmn] 2 v 23 [plusmn] 2 [mu ]U/mL, SHAM v INF, respectively) and glucagon (22 [plusmn] 4 v 90 [plusmn] 8 pg/mL) to match concentrations observed in sham and infected animals. Tracer and arteriovenous difference techniques were used to assess hepatic glucose metabolism. Following a 120-minute basal sampling period, sham and infected animals received either intraportal saline or N[omega ]-nitro-L-arginine (L-NNA; 37 [mu ]g [middot] kg[minus ]1 [middot] min[minus ]1) infusion for 180 minutes. Isoglycemia (120 mg/dL) was maintained with a variable glucose infusion. In the infected group L-NNA infusion decreased hepatic arterial blood flow (23.3 [plusmn] 0.7 to 8.6 [plusmn] 0.5 mL [middot] kg[minus ]1 [middot] min[minus ]1), but not portal vein blood flow. Neither portal vein nor hepatic artery blood flow were altered by L-NNA infusion in the sham group. Hepatic glucose uptake and lactate metabolism were not altered by L-NNA infusion in either group. In summary, during infection, an increase in NO biosynthesis contributes to the increase in hepatic arterial blood flow, while it exerts no effect on hepatic glucose metabolism.