TNFalpha decreases gluconeogenesis in hepatocytes isolated from 10-day-old rats.
Gluconeogenesis decreases during septic shock, but its mechanism is not well known. Tumor necrosis factor alpha (TNF-alpha), which is a key cytokine in septic shock, can increase GLUT1 gene expression and glucose uptake in muscles and fatty tissues. TNF-alpha does not alter the metabolism of hepatocytes in which GLUT2 is the predominant glucose transporter. However, GLUT1 is the predominant glucose transporter in hepatocytes of 10-d-old rats. Thus, we hypothesized that TNF-alpha might increase glucose uptake and glycolysis in those cells, and decrease gluconeogenesis. In the present study, hepatocytes isolated from 10-d-old rats were incubated with TNF-alpha at the concentrations of 0, 0.98, 9.8, 98, and 980 ng/mL to evaluate TNF-alpha effects on gluconeogenesis and glucose uptake. TNF-alpha increased glucose uptake (41.1 +/- 8 to 114 +/- 21.4 micromol/10(6) cells at the concentration of 980 ng/mL of TNF-alpha) in a dose-dependent manner, and decreased gluconeogenesis (98.2 +/- 8.2 to 1.1 +/- 3.2 micromol/10(6) cells at the concentration of 980 ng/mL of TNF-alpha) in a dose-dependent manner. The decrease of glucokinase mRNA and GLUT1 mRNA abundance correlated with glucose uptake (r = 0.988 and 0.997, respectively), and the decrease of phosphoenolpyruvate carboxykinase mRNA abundance correlated with the decrease of gluconeogenesis (r = 0.972). The decrease of gluconeogenesis by TNF-alpha correlated with the increase of glucose uptake (r = -0.988). We concluded that TNF-alpha reciprocally suppressed gluconeogenesis in hepatocytes isolated from 10-d-old rats.
Department of Pediatrics, The Ronald McDonald Children's Hospital at Loyola, Loyola University of Chicago, Maywood, IL 60153, U.S.A. masakatsu@ameritech.net
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Goto
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Yoshioka
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Battelino
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Ravindranath
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Zeller
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D005941:Glucokinase / Q000235:genetics; D005943:Gluconeogenesis / Q000187:drug effects*; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D008070:Lipopolysaccharides; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D005941:Glucokinase; D019764:Phosphoenolpyruvate Carboxykinase (ATP)