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 enzymes and blood hormone concentrations were determined in hemorrhagic hypotension-induced rats before and after resuscitation with lactated Ringer's. Northern blot analysis of total liver RNA after 30 min of hemorrhage showed control values for phospho-enolpyruvate carboxykinase and fructose-1,6-bisphosphatase mRNA, but significantly lower values for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (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 intracellular levels of fructose-6-phosphate and glucose-6-phosphate, and the results are consistent with a rapid activation of hepatic gluconeogenesis by the concomitant decrease in 6PF2K/FBPase and increase in Glu-6-Pase. Blood insulin levels were decreased during hemorrhage and with resuscitation, 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 insulin, which plays a dominant role in the regulation of these genes, was decreased during hemorrhage. It remains to be determined what factors are 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.
Maitra
S R
SR
Department of Emergency Medicine, University Medical Center, Stony Brook, NY 11794-8191, USA.
Gestring
M
M
el-Maghrabi
M R
MR
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D015870:Gene Expression; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D006019:Glycolysis; D007022:Hypotension / Q000201:enzymology* / Q000235:genetics* / Q000628:therapy; D007328:Insulin / Q000097:blood; D008099:Liver / Q000201:enzymology; D008297:Male; D025481:Phosphofructokinase-2; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000201:enzymology* / Q000235:genetics* / Q000628:therapy
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D005934:Glucagon; D017853:Phosphotransferases (Alcohol Group Acceptor); D025481:Phosphofructokinase-2; D010744:Phosphoric Monoester Hydrolases; D005952:Glucose-6-Phosphatase; D003345:Corticosterone