Endotoxin causes reciprocal changes in hepatic nitric oxide synthesis, gluconeogenesis, and flux through phosphoenolpyruvate carboxykinase.
Treatment of rats with bacterial endotoxin resulted in a significant induction of hepatic nitric oxide synthase within 3 hours. The response was maximal at 12 hours and was maintained over 18 hours. The induction of nitric oxide synthase correlated well with the increase in plasma nitrate plus nitrite concentrations and also with the inhibition of glucose synthesis in subsequently isolated hepatocytes. The decline in the rate of gluconeogenesis also correlated with an inhibition of flux through phosphoenolpyruvate carboxykinase but not with alterations in flux through either pyruvate kinase or 6-phosphofructo-1-kinase, suggesting that a nitric oxide-induced inhibition of phosphoenolpyruvate carboxykinase may underlie the decreased glucose production in sepsis.
Horton
R A
RA
School of Biological Sciences, University of Sussex, Brighton, U.K.
Knowles
R G
RG
Titheradge
M A
MA
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis; D000818:Animals; D001692:Biological Transport; D004731:Endotoxins / Q000494:pharmacology*; D004790:Enzyme Induction; D005943:Gluconeogenesis / Q000187:drug effects*; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D011770:Pyruvate Kinase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)