title: Partial inhibition of nitric oxide synthesis in vivo does not inhibit glucose production in man.
abstract: 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.
authors.affiliation: Department of Endocrinology and Metabolism, Metabolism Unit, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Fleur
authors.initials: F
authors.lastname: Sprangers
authors.forename: Wilbert T
authors.initials: WT
authors.lastname: Jellema
authors.forename: Christa E
authors.initials: CE
authors.lastname: Lopuhaä
authors.forename: Erik
authors.initials: E
authors.lastname: Endert
authors.forename: Mariëtte T
authors.initials: MT
authors.lastname: Ackermans
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Van Lieshout
authors.forename: Jaring S
authors.initials: JS
authors.lastname: Van Der Zee
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Hans P
authors.initials: HP
authors.lastname: Sauerwein
mesh_terms: D000328:Adult; D001120:Arginine / Q000097:blood; D018592:Cross-Over Studies; D004702:Endocrine Glands / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000097:blood / Q000494:pharmacology; D005947:Glucose / Q000096:biosynthesis* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019323:omega-N-Methylarginine / Q000097:blood / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D009566:Nitrates; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D005947:Glucose