ALTERED LEVELS OF MESSENGER-RNA ENCODING ENZYMES OF HEPATIC GLUCOSE-METABOLISM IN SEPTIC RATS

We investigated whether the multiple pathophysiological signals genera ted in a peritonitis septic model alter the mRNA levels of glycolytic and gluconeogenic enzymes, and whether these alterations are associate d with glucose dyshomeostasis. Rats were sham-operated in the control group, and peritonitis sepsis was produced by a 1 cm cecal incision in the septic group. At 2, 4, and 6 hr post-surgery, total cellular RNAs were isolated from livers, and Northern blots performed to measure mR NA levels of aldolase B (ADL), lactate dehydrogenase (LDH), pyruvate k inase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and glucokinase (GK). Hepatic PEPCK enzymatic activity was measured by condensing (CO 2)-C-14 with phosphoenolpyruvate (PEP) to form malate. Serum glucose c oncentrations were also measured. We found the following: At 2 hr of p eritonitis sepsis, serum glucose concentrations, mRNA levels of all en zymes, and PEPCK enzymatic activity increased over control levels. At 4 hr of peritonitis sepsis, serum glucose concentrations and mRNA leve ls of GK and PK continued to increase; mRNA levels of all other enzyme s, as well as PEPCK enzymatic activity decreased to or below control l evels. At 6 hr of peritonitis sepsis, serum glucose concentrations, mR NA levels of all enzymes, and PEPCK enzymatic activity decreased to or below control levels. We concluded that sepsis affects mRNA levels of glycolytic and gluconeogenic enzymes at the transcriptional level, an d that these alterations are associated with glucose dyshomeostasis. ( C) 1993 Wiley-Liss, Inc.