Hepatocyte nitric oxide biosynthesis inhibits glucose output and competes with urea synthesis for L-arginine.
Inflammatory stimulation of the liver is known to induce nitric oxide (NO) biosynthesis. NO can interfere with the activity of a number of enzymes important to cellular metabolism. This study was carried out to investigate the influence of NO on rat hepatocyte glucose output and urea production. Induction of NO synthesis by incubation with a combination of cytokines and lipopolysaccharide led to a 48.8 +/- 2.4% inhibition of glucose output and to a 45.0 +/- 6.4% suppression of urea production. Inhibition of NO synthesis with NG-monomethyl-L-arginine was able to totally prevent these effects. High concentrations of L-arginine overcame the inhibition of urea production caused by endogenous NO synthesis. Exposure of HC to NO donors resulted in a concentration-dependent inhibition of glucose output, without having any effect on urea production. Hepatocellular glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity was also found to be inhibited by endogenously produced NO (33.5 +/- 5.2%), as well as by exogenously applied NO. However, an exact correlation between GAPDH activity and glucose output could not be established. These data indicate that NO biosynthesis may contribute to the development of hepatic dysfunction in chronic sepsis.
Department of Surgery, Technical University of Munich, Germany.
J
J
Stadler
D
D
Barton
H
H
Beil-Moeller
S
S
Diekmann
C
C
Hierholzer
W
W
Erhard
C D
CD
Heidecke
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D005947:Glucose / Q000037:antagonists & inhibitors*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014508:Urea / Q000037:antagonists & inhibitors* / Q000378:metabolism
D009569:Nitric Oxide; D014508:Urea; D001120:Arginine; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D005947:Glucose