Mechanistic evaluation of the insulin response in H4IIE hepatoma cells: New endpoints for toxicity testing?
Mechanistic evaluation of the insulin response in H4IIE hepatoma cells: New endpoints for toxicity testing?
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DOI：
10.1016/j.toxlet.2012.05.016
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发表时间：
2012-07-20
影响因子：
3.5
通讯作者：
Blust, Ronny
中科院分区：
文献类型：
--
作者：
Hectors, Tine L. M.;Vanparys, Caroline;Blust, Ronny
为探讨大鼠肝癌细胞系H4IIE是否是研究肝脏胰岛素反应的生理学相关模型，以提示其在污染相关的胰岛素抵抗研究中的应用前景，本研究采用DNA微阵列分析、实时荧光定量PCR和流式细胞术细胞周期分析等方法，对H4IIE细胞胰岛素反应的相关性进行了评价。胰岛素剂量依赖性地刺激H4IIE生长，并且时间依赖性地改变已知的胰岛素应答基因：Fasn、Pck1和Irs2的表达。对暴露于胰岛素（100 nM）6 h和24 h的细胞进行的微阵列分析表明，与碳水化合物和脂质代谢相关的基因受到最深刻的影响，与体内肝脏胰岛素作用一致。由于碳水化合物和脂质代谢的变化在胰岛素抵抗的发病机制中是关键的，因此H4IIE细胞中生理相关胰岛素反应的存在要求进一步测试其在污染物驱动的胰岛素抵抗研究中的潜在用途。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
This study was designed to evaluate if the rat H4IIE hepatoma cell line is a physiologically relevant model to study hepatic insulin responses to hint at its prospective application in pollutant-related insulin resistance research.DNA microarray analysis, real-time PCR and flow cytometric cell cycle analysis were used to assess the relevance of the insulin response in H4IIE cells. Insulin dose dependently stimulated H4IIE growth and time dependently altered the expression of the known insulin responsive genes: Fasn, Pck1 and Irs2. Microarray analysis performed on cells exposed to insulin (100 nM) for 6 h and 24 h showed that genes related to carbohydrate and lipid metabolism were most profoundly afflicted, in accordance with in vivo hepatic insulin action. Since changes in carbohydrate and lipid metabolism are pivotal in the pathogenesis of insulin resistance, the presence of a physiological relevant insulin response in H4IIE cells pleads for further testing of its potential use in research on pollutant-driven insulin resistance. (C) 2012 Elsevier Ireland Ltd. All rights reserved.