Mounier Catherine, Posner Barry I
BioMed, Department of Biological Science, University of Quebec in Montreal, 141 President Kennedy, Montreal, QC H2X 3Y7, Canada.
Can J Physiol Pharmacol. 2006 Jul;84(7):713-24. doi: 10.1139/y05-152.
Insulin, after binding to its receptor, regulates many cellular processes and the expression of several genes. For a subset of genes, insulin exerts a negative effect on transcription; for others, the effect is positive. Insulin controls gene transcription by modifying the binding of transcription factors on insulin-response elements or by regulating their transcriptional activities. Different insulin-signaling cascades have been characterized as mediating the insulin effect on gene transcription. In this review, we analyze recent data on the molecular mechanisms, mostly in the liver, through which insulin exerts its effect. We first focus on the key transcription factors (viz. Foxo, sterol-response-element-binding protein family (SREBP), and Sp1) involved in the regulation of gene transcription by insulin. We then present current information on the way insulin downregulates and upregulates gene transcription, using as examples of downregulation phosphoenolpyruvate carboxykinase (PEPCK) and insulin-like growth factor binding protein 1 (IGFBP-1) genes and of upregulation the fatty acid synthase and malic enzyme genes. The last part of the paper focuses on the signaling cascades activated by insulin in the liver, leading to the modulation of gene transcription.
胰岛素与其受体结合后，可调节多种细胞过程及多个基因的表达。对于一部分基因，胰岛素对转录起负向作用；对其他基因，则起正向作用。胰岛素通过改变转录因子与胰岛素反应元件的结合或调节其转录活性来控制基因转录。不同的胰岛素信号级联反应已被确定为介导胰岛素对基因转录的作用。在本综述中，我们分析了近期有关胰岛素发挥作用的分子机制的数据，主要是在肝脏中的机制。我们首先聚焦于参与胰岛素调节基因转录的关键转录因子（即叉头框蛋白O（Foxo）、固醇调节元件结合蛋白家族（SREBP）和特异性蛋白1（Sp1））。然后，我们以磷酸烯醇式丙酮酸羧激酶（PEPCK）和胰岛素样生长因子结合蛋白1（IGFBP - 1）基因的下调以及脂肪酸合酶和苹果酸酶基因的上调为例，介绍胰岛素下调和上调基因转录的当前信息。本文的最后一部分聚焦于胰岛素在肝脏中激活的信号级联反应，这些反应导致基因转录的调节。
