title: Glucagon regulates hepatic inducible nitric oxide synthesis in vivo.
abstract: The inducible nitric oxide synthase (iNOS) is stimulated to produce large quantities of nitric oxide (NO) by proinflammatory stimuli, hemorrhagic shock, and a variety of cytokines. We have previously shown that cAMP profoundly inhibits hepatocyte iNOS expression in vitro. In this study, we tested whether glucagon, a hormone that increases cAMP in hepatocytes, could regulate hepatic iNOS expression and activity in vivo. Rats were injected intraperitoneally with lipopolysaccharide (LPS, 10 mg/kg) and treated with either saline or glucagon (500 microg/kg i.p.). Plasma and liver tissue were obtained 6 and 24 h after LPS. LPS induced increased iNOS mRNA, iNOS protein, and plasma levels of nitrite/nitrate that were all significantly decreased by glucagon treatment. The reduction in iNOS expression produced by glucagon was associated with a reduction in plasma AST and LDH levels, suggesting decreased LPS-induced hepatic injury. These data suggest that glucagon may participate in the in vivo regulation of hepatic iNOS expression after proinflammatory stimuli.
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. harbrechtbg@msx.upmc.edu
authors.forename: Brian G
authors.initials: BG
authors.lastname: Harbrecht
authors.forename: Michelle
authors.initials: M
authors.lastname: Perpetua
authors.forename: Melissa
authors.initials: M
authors.lastname: Fulmer
authors.forename: Baochun
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D012965:Sodium Chloride; D012313:RNA; D005934:Glucagon; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001219:Aspartate Aminotransferases; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose