Tumor necrosis factor-alpha-induced insulin resistance in adipocytes.
Tumor necrosis factor-alpha-induced insulin resistance in adipocytes.
复制标题
肿瘤坏死因子-α 诱导脂肪细胞胰岛素抵抗。
DOI：
10.1046/j.1525-1373.2000.22318.x
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Pekala,PH
中科院分区：
文献类型：
--
作者：
Qi,C;Pekala,PH
最近研究胰岛素抵抗与肥胖和非胰岛素依赖型糖尿病的发生之间的联系与肿瘤坏死因子-α（TNF-α）作为中心介质的参与一致。在胰岛素抵抗性肥胖小鼠模型中，已证明循环中TNF-α的中和可恢复胰岛素介导的葡萄糖摄取。脂肪组织已被证明是合成TNF-α的位点，肥胖程度与合成水平直接相关。对肥胖人类患者进行的研究已经证明了TNF-α水平、肥胖程度以及观察到的高胰岛素血症水平之间的相关性。细胞培养中的机制研究表明，TNF-α通过调节胰岛素应答性葡萄糖转运蛋白的合成以及通过干扰胰岛素信号传导而使细胞产生胰岛素抵抗。本文将讨论这些问题，并向读者介绍TNF-α的分子方面，其受体以及TNF-α启动的信号级联反应，这是必要的，以了解这种细胞因子在脂肪组织代谢的调节功能。
Recent studies examining the link between insulin resistance and the development of obesity and noninsulin-dependent diabetes mellitus are consistent with the involvement of tumor necrosis factor-α (TNF-α) as a central mediator. In insulin resistant obese mouse models, neutralization of TNF-α in circulation has been demonstrated to restore insulin-mediated glucose uptake. Adipose tissue has been shown to be a site for synthesis of TNF-α, with the degree of adiposity directly correlated with the level of synthesis. Studies conducted on obese human patients have demonstrated a correlation between levels of TNF-α, the extent of obesity, as well as the level of hyperinsulinemia observed. Mechanistic studies in cell culture have suggested that TNF-α functions to render cells insulin resistant through regulation of the synthesis of the insulin responsive glucose transporter as well as through interference with insulin signaling. This review will address these issues and additionally introduce the reader to the molecular aspects of TNF-α, its receptors as well as TNF-α-initiated signaling cascades, that are necessary to understand the function of this cytokine in the regulation of adipose tissue metabolism.