Desbuquois B, Tozzo E, Collinet M, Lopez S, Bortoli S, Amessou M
I.N.S.E.R.M. Unité 30, Hôpital Necker Enfants-Malades, Paris.
Ann Endocrinol (Paris). 1993;54(6):373-84.
The insulin receptor is a membrane macromolecule whose expression on the cell surface is essential for cell sensitivity to insulin. Current knowledge on the regulation of expression of the insulin receptor and its gene in human and animal cells is presented. Although ubiquitously distributed, the insulin receptor and its messenger RNA (mRNA) are mainly expressed in metabolically active cells such as hepatocytes and adipocytes. Two receptor isoforms, generated by alternative splicing of exon 11, have been identified. Isoform B (exon 11+) predominates in liver and adipocytes, and isoform A (exon 11-) in brain, spleen and leukocytes. In vivo and in several cell models, the expression of the insulin receptor and/or its mRNA is under positive regulation by glucocorticoid hormones and negative regulation by insulin. Glucocorticoid hormones stimulate receptor gene transcription and receptor protein synthesis. Insulin stimulates receptor protein degradation and, in certain cell types, decreases receptor mRNA level. Vanadate (an insulinomimetic agent) corrects, in vivo, the hyperexpression of the liver receptor observed in experimental insulinopenic diabetes, but its effects on receptor expression in vitro are complex and vary with the cell type. In vivo the insulin receptor and/or its mRNA are expressed early in fetal development with a high level, in liver, of isoform A. Maximal expression is reached at the end of gestation and then decreases after birth. In several cell models, receptor protein and/or mRNA expression is affected by cell growth and/or differentiation. Several cis- and trans-acting factors regulating the expression of the human insulin receptor gene and its response to glucocorticoid hormones have been identified.
胰岛素受体是一种膜大分子，其在细胞表面的表达对于细胞对胰岛素的敏感性至关重要。本文介绍了目前关于人和动物细胞中胰岛素受体及其基因表达调控的知识。尽管胰岛素受体及其信使核糖核酸（mRNA）广泛分布，但主要在代谢活跃的细胞如肝细胞和脂肪细胞中表达。已鉴定出由外显子11选择性剪接产生的两种受体亚型。B亚型（外显子11+）在肝脏和脂肪细胞中占主导，A亚型（外显子11-）在脑、脾脏和白细胞中占主导。在体内和几种细胞模型中，胰岛素受体和/或其mRNA的表达受糖皮质激素的正调控和胰岛素的负调控。糖皮质激素刺激受体基因转录和受体蛋白合成。胰岛素刺激受体蛋白降解，并且在某些细胞类型中降低受体mRNA水平。钒酸盐（一种胰岛素模拟剂）在体内可纠正实验性胰岛素缺乏糖尿病中观察到的肝脏受体过度表达，但其在体外对受体表达的影响复杂且因细胞类型而异。在体内，胰岛素受体和/或其mRNA在胎儿发育早期高水平表达，在肝脏中以A亚型为主。在妊娠末期达到最大表达，然后在出生后下降。在几种细胞模型中，受体蛋白和/或mRNA表达受细胞生长和/或分化的影响。已鉴定出几种调节人胰岛素受体基因表达及其对糖皮质激素反应的顺式和反式作用因子。
