Insulin attenuates the systemic inflammatory response in endotoxemic rats
Insulin attenuates the systemic inflammatory response in endotoxemic rats
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DOI：
10.1210/en.2004-0592
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发表时间：
2004-09-01
期刊：
影响因子：
4.8
通讯作者：
Einspanier, R
中科院分区：
文献类型：
--
作者：
Jeschke, MG;Klein, D;Einspanier, R
胰岛素可降低危重患者的死亡率，预防感染和脓毒症的发生。胰岛素改善存活率的分子和细胞机制尚未确定。本研究的目的是确定胰岛素对内毒素血症时炎症反应的影响。内毒素血症大鼠随机分为两组，分别接受生理盐水或胰岛素。测定胰岛素对肝脏信号转录因子mRNA表达、促炎和炎性细胞因子mRNA和蛋白浓度的影响。胰岛素给药没有改变葡萄糖或电解质水平，但显著降低了促炎信号转录因子[CCAAT/增强子结合蛋白-β、信号转导和转录激活因子-3和-5、RANTES（受激活调节，正常T细胞表达和分泌）]和肝脏中的细胞因子表达以及IL-1 β、IL-6、巨噬细胞炎症因子和TNF α的血清水平。与对照组相比，胰岛素给药进一步降低了血清中的高迁移率族1蛋白。此外，胰岛素增加了肝脏中IL-2、IL-4和IL-10的血清水平;以及细胞因子信号传导的肝脏抑制因子-3 mRNA的表达。胰岛素通过减少促炎级联反应和增加炎症级联反应来调节炎症反应。由于胰岛素治疗患者和对照组之间的葡萄糖和电解质水平没有差异，因此我们假设这些作用是胰岛素的直接调节机制，而不是通过调节葡萄糖或电解质代谢间接产生的。
Insulin decreases the mortality and prevents the incidence of infection and sepsis in critically ill patients. The molecular and cellular mechanisms by which insulin improves survival have not been defined. The purpose of the present study was to determine the effect of insulin on the inflammatory reaction during endotoxemia. Endotoxemic rats were randomly divided into two groups to receive either saline or insulin. The effects of insulin on hepatic signal transcription factor mRNA expression, proinflammatory and antiinflammatory cytokine mRNA and protein concentration were determined. Insulin administration did not change glucose or electrolyte levels, but significantly decreased proinflammatory signal transcription factors [CCAAT/enhancer-binding protein-beta, signal transducer and activator of transcription-3 and-5, RANTES (regulated on activation, normal T cell expressed and secreted)] and cytokine expression in the liver and serum levels of IL-1beta, IL-6, macrophage inflammatory factor, and TNFalpha. Insulin administration further decreased high mobility group 1 protein in the serum compared with controls. In addition, insulin increased antiinflammatory cytokine expression in the liver; serum levels of IL-2, IL-4, and IL-10; and hepatic suppressor of cytokine signaling-3 mRNA expression. Insulin modulates the inflammatory response by decreasing the proinflammatory and increasing the antiinflammatory cascade. Because glucose and electrolyte levels did not differ between insulin-treated patients and controls, we hypothesize that the effects are direct antiinflammatory mechanisms of insulin, rather than indirect, through modulation of glucose or electrolyte metabolism.