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Augmented glucose use and pentose cycle activity in hepatic endothelial cells after in vivo endotoxemia

✍ Scribed by Zoltán Spolarics; John J. Spitzer


Book ID
102852199
Publisher
John Wiley and Sons
Year
1993
Tongue
English
Weight
698 KB
Volume
17
Category
Article
ISSN
0270-9139

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✦ Synopsis


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 glucose and [2-3Hlglucose. Lipopolysaccharide treatment in uiuo increased glucose use fivefold, whereas glucose oxidation in the pentose cycle was elevated from 0.2 to 1.5 nmol/hr/lO' cells. In vitro incubation of endothelial cells from saline-and lipopolysaccharide-treated animals in the presence of phorbol12-myristate 13-acetate ( 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 mmolb), a substrate for gluathione peroxidase, caused a 24fold 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 mmo1L) inhibited the phorbol 12-myristate 13-acetateinduced or t-butyl hydroperoxide-induced increase in the pentose cycle activity with no marked effects on glycolysis. Diphenyleneiodonium (0.1 mmolL), 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. Endothelial cells from control animals treated with either 12-myristate 13-acetate or t-butyl hydroperoxide in the presence of exogenous glucose 20 mmol/L showed a similar increase in glycolysis but less increase in the pentose cycle activity as found after lipopolysaccharide treatment in the presence of glucose 5 mmol/L. This finding suggests that glucose-&phosphate dehydrogenase or pathways dependent on pentose cycle intermediates became upregulated after lipopolysaccharide administration. The lipopolysaccharide-