Glucagon regulates hepatic inducible nitric oxide synthesis in vivo.
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.
Harbrecht
Brian G
BG
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. harbrechtbg@msx.upmc.edu
Perpetua
Michelle
M
Fulmer
Melissa
M
Zhang
Baochun
B
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
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