In the liver, paracrine interaction between Kupffer cells and hepatocytes influences glucose metabolism. In vitro in rats, nitric oxide (NO), a paracrine mediator, inhibits several pathways of hepatic glucose production. The role of NO on glucose production has not been studied in vivo in humans. Glucose production was measured during N(G)-monomethyl-L-arginine, monoacetate salt (L-NMMA) infusion, an inhibitor of NO synthesis in vivo, in 6 healthy men fasting 23 hours in a saline-controlled crossover study. During L-NMMA infusion, NO output decreased 40% to 50%, peripheral vascular resistance increased approximately 22%, and cardiac output (CO) decreased approximately 14%. The decrease in glucose production was not different between L-NMMA and saline. Glucose concentration, substrate supply, and glucoregulatory hormone concentrations were not different; epinephrine was lower with L-NMMA. A 40% to 50% inhibition of NO synthesis in vivo in humans does not affect glucose production during short-term fasting. The hypothesis that NO is an important modulator of basal glucose production in healthy humans in vivo should therefore be rejected.
Copyright 2002 by W.B. Saunders Company