Author/Editor		Goto, Masakatsu; Yoshioka, Toyokazu; Battelino, Tadej; Ravindranath, Thyyar; Zeller, Patrick W
Title		TNFalpha decreases gluconeogenesis in hepatocytes isolated from 10-day-old rats
Type		članek
Source		Pediatr Res
Vol. and No.		Letnik 49, št. 4
Publication year		2001
Volume		str. 552-7
Language		eng
Abstract		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 ?mol/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 ?mol/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.
Descriptors		TUMOR NECROSIS FACTOR GLUCONEOGENESIS LIVER SALMONELLA ENTERITIDIS ENDOTOXINS RATS, SPRAGUE-DAWLEY RNA, RIBOSOMAL, 28S RNA, MESSENGER GLUCOSE GLUCOKINASE CELLS, CULTURED PHOSPHOENOLPYRUVATE CARBOXYKINASES BLOTTING, NORTHERN