AJP - Regulatory, Integrative and Comparative Physiology, Vol 273, Issue 5 1709-R1718, Copyright © 1997 by American Physiological Society
Sepsis-induced depression of rat glucose-6-phosphatase gene expression and activity
C. S. Deutschman, K. M. Andrejko, B. A. Haber, L. Bellin, E. Elenko, R. Harrison and R. Taub
Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.
Sepsis in rats decreases the hepatic expression of the gluconeogenic enzyme
glucose-6-phosphatase (G6Pase). The aim of this study was to investigate
the relationship among G6Pase transcription, mRNA, enzymatic activity, and
serum glucose levels at different intervals during mild or fulminant
sepsis. Both fulminant and mild sepsis immediately decreased hepatic G6Pase
mRNA levels. In mild sepsis, levels began to recover late in the time
course. Serum glucose levels were maintained in mild sepsis but decreased
markedly in fulminant sepsis. G6Pase transcription after fulminant sepsis
decreased and never recovered. A similar transcriptional decrease was noted
in mild sepsis, but some recovery occurred in this state. Histochemistry
after mild sepsis revealed a decrease in G6Pase protein and enzymatic
activity that paralleled transcription. These studies suggest that changes
in G6Pase transcription and activity are early markers for sepsis-induced
alterations in hepatic function. Mechanisms other than gene expression and
enzymatic activity serve to maintain glucose levels in mild sepsis, but in
the fulminant disorder, compensatory mechanisms fail and hypoglycemia
develops.
