Department of Medicine, University of Tennessee Health Science Center, Veterans Affairs Medical Center, Memphis, USA.
Horm Metab Res. 2010 Feb;42(2):115-21. doi: 10.1055/s-0029-1241834. Epub 2009 Dec 3.
Several studies suggest that TNF-alpha contributes to the development of insulin resistance (IR). We compared transcriptional profiles of rat H-411E liver cells exposed to insulin in the absence or presence of TNF-alpha. We identified 33 genes whose expression was altered by insulin, and then reversed by TNF-alpha. Twenty-six of these 33 genes created a single network centered around: insulin, TNF-alpha, p38-MAPK, TGFb1; SMAD and STAT1; and enzymes and cytokines involved in apoptosis (CASP3, GADD45B, IL2, TNF-alpha, etc.). We analyzed our data together with other data of gene expression in adipocytes and found a number of processes common to both, for example, cell death and inflammation; intercellular signaling and metabolism; G-Protein, IL-10 and PTEN signaling. Moreover, the two datasets combined generated a single molecular network that further identified PTEN (a phosphatase) as a unique new link between insulin signaling, IR, and apoptosis reflecting the pathophysiology of "metabolic syndrome".
多项研究表明 TNF-α 有助于胰岛素抵抗（IR）的发展。我们比较了在不存在或存在 TNF-α 的情况下，胰岛素对大鼠 H-411E 肝细胞转录谱的影响。我们确定了 33 个受胰岛素影响、随后被 TNF-α 逆转的表达发生改变的基因。这 33 个基因中的 26 个形成了一个以胰岛素、TNF-α、p38-MAPK、TGFb1；SMAD 和 STAT1；以及参与细胞凋亡的酶和细胞因子（CASP3、GADD45B、IL2、TNF-α 等）为中心的单一网络。我们将我们的数据与脂肪细胞中其他基因表达的数据一起进行分析，发现了许多两者共有的过程，例如细胞死亡和炎症；细胞间信号转导和代谢；G 蛋白、IL-10 和 PTEN 信号。此外，这两个数据集组合生成了一个单一的分子网络，该网络进一步确定了 PTEN（一种磷酸酶）作为胰岛素信号、IR 和细胞凋亡之间的独特新联系，反映了“代谢综合征”的病理生理学。
