Department of Physiological Sciences, State University of Londrina, Londrina, PR 86051-990, Brazil.
Mol Cell Biochem. 2013 Mar;375(1-2):89-96. doi: 10.1007/s11010-012-1531-4. Epub 2012 Dec 9.
Tumor necrosis factor α (TNFα) is a cytokine involved in many metabolic responses in both normal and pathological states. Considering that the effects of TNFα on hepatic gluconeogenesis are inconclusive, we investigated the influence of this cytokine in gluconeogenesis from various glucose precursors. TNFα (10 μg/kg) was intravenously injected in rats; 6 h later, gluconeogenesis from alanine, lactate, glutamine, glycerol, and several related metabolic parameters were evaluated in situ perfused liver. TNFα reduced the hepatic glucose production (p < 0.001), increased the pyruvate production (p < 0.01), and had no effect on the lactate and urea production from alanine. TNFα also reduced the glucose production (p < 0.01), but had no effect on the pyruvate production from lactate. In addition, TNFα did not alter the hepatic glucose production from glutamine nor from glycerol. It can be concluded that the TNFα inhibited hepatic gluconeogenesis from alanine and lactate, which enter in gluconeogenic pathway before the pyruvate carboxylase step, but not from glutamine and glycerol, which enter in this pathway after the pyruvate carboxylase step, suggesting an important role of this metabolic step in the changes mediated by TNFα.
肿瘤坏死因子 α（TNFα）是一种参与正常和病理状态下多种代谢反应的细胞因子。考虑到 TNFα 对肝糖异生的影响尚无定论，我们研究了这种细胞因子对各种葡萄糖前体的糖异生的影响。将 TNFα（10μg/kg）静脉注射到大鼠体内；6 小时后，在原位灌流肝脏中评估 TNFα 对丙氨酸、乳酸、谷氨酰胺、甘油和几种相关代谢参数的糖异生作用。TNFα 降低了肝葡萄糖生成（p<0.001），增加了丙酮酸生成（p<0.01），但对丙氨酸生成的乳酸和尿素没有影响。TNFα 还降低了乳酸来源的葡萄糖生成（p<0.01），但对丙酮酸来源的乳酸生成没有影响。此外，TNFα 对谷氨酰胺和甘油来源的肝葡萄糖生成没有影响。可以得出结论，TNFα 抑制了丙氨酸和乳酸来源的肝糖异生，这两种物质在丙酮酸羧化酶步骤之前进入糖异生途径，但不抑制谷氨酰胺和甘油来源的肝糖异生，这两种物质在丙酮酸羧化酶步骤之后进入该途径，表明该代谢步骤在 TNFα 介导的变化中起着重要作用。
