Krapivner Sergey, Popov Sergej, Chernogubova Ekaterina, Hellénius Mai-Lis, Fisher Rachel M, Hamsten Anders, van't Hooft Ferdinand M
Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska University Hospital, Stockholm, Sweden.
J Clin Endocrinol Metab. 2008 May;93(5):1995-2001. doi: 10.1210/jc.2007-1850. Epub 2008 Mar 4.
Insulin-induced genes (INSIGs) encode proteins that block proteolytic activation of sterol regulatory element-binding proteins, transcription factors that regulate lipogenic enzymes, and adipocyte differentiation.
Here, we analyzed the relative significance of INSIG1 and INSIG2 in human liver and adipocyte metabolism, and defined a novel, functional polymorphism in the promoter of INSIG2 associated with body mass index.
Variations in gene expression of different human tissues, of hepatoma cells exposed to INSIG1 and INSIG2 gene silencing probes, and of differentiating 3T3-L1 adipocytes were determined by real-time quantitative PCR. The functional significance of a novel polymorphism in the promoter of INSIG2 was analyzed using in vitro methods and gene expression analysis of human adipose tissue, whereas the phenotype associated with this polymorphism was studied in two cohorts of middle-aged men.
Gene expression analysis of 17 human tissues demonstrated that INSIG1 is highly expressed in the liver, whereas INSIG2 is ubiquitously expressed. Gene silencing experiments confirmed that INSIG1, but not INSIG2, regulates the expression of sterol regulatory element-binding proteins target genes in human hepatoma cells. In contrast, adipocyte differentiation of 3T3-L1 cells was associated with a 13-fold increase in expression of INSIG2. Significant relationships between the INSIG2-102G/A polymorphism and body mass index were observed in two cohorts of middle-aged men (ANOVA P = 0.017 and 0.044, respectively). In vitro studies and analysis of allele-specific expression in human adipose tissue substantiated the functional significance of the INSIG2-102G/A polymorphism.
INSIG2 is involved in adipocyte metabolism and body weight regulation.
胰岛素诱导基因（INSIGs）编码的蛋白质可阻断固醇调节元件结合蛋白的蛋白水解激活，固醇调节元件结合蛋白是调节脂肪生成酶和脂肪细胞分化的转录因子。
在此，我们分析了INSIG1和INSIG2在人类肝脏和脂肪细胞代谢中的相对重要性，并确定了INSIG2启动子中与体重指数相关的一种新型功能性多态性。
通过实时定量PCR测定不同人类组织、暴露于INSIG1和INSIG2基因沉默探针的肝癌细胞以及分化中的3T3-L1脂肪细胞的基因表达变化。使用体外方法和人类脂肪组织的基因表达分析来分析INSIG2启动子中新型多态性的功能意义，而在两组中年男性中研究与这种多态性相关的表型。
对17种人类组织的基因表达分析表明，INSIG1在肝脏中高度表达，而INSIG2广泛表达。基因沉默实验证实，INSIG1而非INSIG2调节人类肝癌细胞中固醇调节元件结合蛋白靶基因的表达。相反，3T3-L1细胞的脂肪细胞分化与INSIG2表达增加13倍有关。在两组中年男性中观察到INSIG2 - 102G/A多态性与体重指数之间存在显著关系（方差分析P值分别为0.017和0.044）。体外研究和人类脂肪组织中等位基因特异性表达分析证实了INSIG2 - 102G/A多态性的功能意义。
INSIG2参与脂肪细胞代谢和体重调节。
