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 i nduction of hepatic nitric oxide synthase within 3 hours. The response was maximal at 12 hours and was maintained over 18 hours. The inducti on of nitric oxide synthase correlated well with the increase in plasm a 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 flu x through phosphoenolpyruvate carboxykinase but not with alterations i n flux through either pyruvate kinase or 6-phosphofructo-1-kinase, sug gesting that a nitric oxide-induced inhibition of phosphoenolpyruvate carboxykinase may underlie the decreased glucose production in sepsis. (C) 1994 Academic Press, Inc.