Partial inhibition of nitric oxide synthesis in vivo does not inhibit glucose production in man

• Published in: Metabolism, clinical and experimental clinical and experimental, 2002-01, Vol.51 (1), p.57-64
• Main Authors: Sprangers, Fleur, Jellema, Wilbert T., Lopuha[auml ], Christa E., Endert, Erik, Ackermans, Mari[euml ]tte T., van Lieshout, Johannes J., van der Zee, Jaring S., Romijn, Johannes A., Sauerwein, Hans P.
• Format: Article
• Language: English
• Subjects: Adult; Antihypertensive agents; Arginine - blood; Biological and medical sciences; Carbohydrates; Cardiovascular system; Cross-Over Studies; Endocrine Glands - drug effects; Enzyme Inhibitors - blood; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Glucose - biosynthesis; Glucose - metabolism; Hemodynamics - drug effects; Humans; Infusions, Intravenous; Male; Medical sciences; Metabolisms and neurohumoral controls; Nitrates - blood; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; omega-N-Methylarginine - blood; omega-N-Methylarginine - pharmacology; Pharmacology. Drug treatments; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1053/meta.2002.28958

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 NG-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.