Augmented glucose use and pentose cycle activity in hepatic endothelial cells after in vivo endotoxemia.
Glucose use and pentose cycle activity were determined in freshly isolated rat hepatic endothelial cells 3 hr after an intravenous injection of Escherichia coli lipopolysaccharide (0.1 mg/kg body weight), by use of [1-14C]glucose, [6-14C]glucose and [2-3H]glucose. Lipopolysaccharide treatment in vivo increased glucose use fivefold, whereas glucose oxidation in the pentose cycle was elevated from 0.2 to 1.5 nmol/hr/10(7) cells. In vitro incubation of endothelial cells from saline- and lipopolysaccharide-treated animals in the presence of phorbol 12-myristate 13-acetate (10(-6) mol/L) increased pentose cycle activity twofold and eightfold, respectively. Phorbol 12-myristate 13-acetate caused only a 40% to 60% increase in glycolysis in both groups. Addition of t-butyl hydroperoxide (0.5 mmol/L), a substrate for glutathione peroxidase, caused a 24-fold and 16-fold increase in the glucose flux through the pentose cycle in cells from saline- and lipopolysaccharide-treated rats, respectively. Oxidation of glucose through the Krebs cycle was also increased several-fold after t-butyl hydroperoxide administration. Depletion of cellular glutathione by N-ethylmaleimide (0.1 mmol/L) inhibited the phorbol 12-myristate 13-acetate-induced or t-butyl hydroperoxide-induced increase in the pentose cycle activity with no marked effects on glycolysis. Diphenyleneiodonium (0.1 mmol/L), an inhibitor of superoxide and nitric oxide synthesis inhibited the phorbol 12-myristate 13-acetate-induced increased pentose cycle activity with no effects on the t-butyl hydroperoxide-induced response.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Spitzer
J J
JJ
D000704:Analysis of Variance; D000818:Animals; D002250:Carbon Radioisotopes; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D005033:Ethylmaleimide / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016877:Oxidants / Q000494:pharmacology; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D010545:Peroxides / Q000494:pharmacology; D011865:Radioisotope Dilution Technique; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium; D020122:tert-Butylhydroperoxide
D002250:Carbon Radioisotopes; D004731:Endotoxins; D008070:Lipopolysaccharides; D016877:Oxidants; D010545:Peroxides; D014316:Tritium; D020122:tert-Butylhydroperoxide; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D005033:Ethylmaleimide