A time study of hepatic glycolytic intermediates in endotoxemic and septic rats and mice

A time study was conducted on three key glycolytic intermediates in endotoxemic rat liver to determine which metabolite showed the earliest concentration changes. Glucose-6-phosphate (G6P) was found to be significantly decreased one hour after IV injection of endotoxin, whereas phosphoenolpyruvate (PEP) and fructose-1,6-diphosphate (FDP) were unaltered until three hours. In rat peritonitis produced by cecal incision, liver biopsy at five hours again revealed that only G6P levels were significantly influenced by the septic challenge. In a similar murine peritonitis model, which permitted longer survival times, analysis of liver samples at 12 and 18 hours supported the conclusion that G6P was the metabolite that responded first or most consistently to endotoxin and sepsis. Later changes in FDP and PEP appear to be secondary events. It is postulated that endotoxin may have a direct or indirect action on G6P regulating enzymes. Since rational therapy for septic shock must combat early changes, it would seem that measures that restore G6P levels might prevent the disturbed carbohydrate metabolism that characterizes late and severe sepsis.