ALTERATIONS IN HEPATIC 6-PHOSPHOFRUCTO-2-KINASE FRUCTOSE-2,6-BISPHOSPHATASE AND GLUCOSE-6-PHOSPHATASE GENE-EXPRESSION AFTER HEMORRHAGIC HYPOTENSION AND RESUSCITATION/

The mRNA abundance of several hepatic glycolytic and gluconeogenic enz ymes and blood hormone concentrations were determined in hemorrhagic h ypotension-induced rats before and after resuscitation with lactated R inger's. Northern blot analysis of total liver RNA after 30 min of hem orrhage showed control values for phospho-enolpyruvate carboxykinase a nd fructose-1,6-bisphosphatase mRNA, but significantly lower values fo r -phosphofructo-2-kinase/fructose-2,6-biphosphatase (6PF2K/FBPase) as well as 2.5-fold increases in glucose-6-phosphatase (Glu-6-Pase) mRNA . The latter finding is in agreement with the greatly reduced intracel lular revels of fructose-6-phosphate and glucose-6-phosphate, and the results are consistent with a rapid activation of hepatic gluconeogene sis by the concomitant decrease in 6PF2K/FBPase and increase in Glu-6- Pase. Blood insulin levels were decreased during hemorrhage and with r esuscitation, whereas glucocorticoids were increased 1.5-fold in both cases. Glucagon was unchanged during hemorrhage, but was reduced with resuscitation. Lactated Ringer's resuscitation seemed to affect 6PF2K/ FBPase only, which was restored to, and even exceeded, control values. In contrast, Glu-6-Pase mRNA was increased to fourfold control values . The increase in Glu-6-Pase and the decrease in 6PF2K/FBPase mRNA is probably at the level of altered transcriptional rates, because insuli n, which plays a dominant role in the regulation of these genes, was d ecreased during hemorrhage. it remains to be determined what factors a re causing further induction of Glu-6-Pase gene after lactated Ringer' s resuscitation when hepatic glucose metabolism seems to have reverted to the glycolytic mode.