Partial inhibition of nitric oxide synthesis in vivo does not inhibit glucose production in man.
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.
Sprangers
Fleur
F
Department of Endocrinology and Metabolism, Metabolism Unit, Academic Medical Center, Amsterdam, The Netherlands.
Jellema
Wilbert T
WT
Lopuhaä
Christa E
CE
Endert
Erik
E
Ackermans
Mariëtte T
MT
Van Lieshout
Johannes J
JJ
Van Der Zee
Jaring S
JS
Romijn
Johannes A
JA
Sauerwein
Hans P
HP
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
D004791:Enzyme Inhibitors; D009566:Nitrates; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D005947:Glucose