Thorens B, Roduit R
Institute of Pharmacology and Toxicology, University of Lausanne, Switzerland.
Biochem Soc Trans. 1994 Aug;22(3):684-7. doi: 10.1042/bst0220684.
GLUT2 disappearance is a marker of the beta cell glucose-unresponsiveness associated with diabetes. Understanding the factor(s) leading to this dysfunction may shed light on pathogenesis of diabetes. Since the regulation of GLUT2 expression in diabetes can so far only be studied in in vivo experiments, we developed a novel experimental approach to study the genetic regulation of GLUT2 in diabetes. By encapsulating islets or cell lines in semi-permeable membranes, these cells can be exposed to the diabetic environment of rats or mice and can be retrieved for analysis of GLUT2 expression and for the change in the secretory response to glucose. Immunocytochemical analysis of transporter expression reveals changes in protein expression while transcriptional analysis of GLUT2 gene expression could be performed in cells transfected with promoter-reporter gene constructs. Using this last approach we hope to be able to characterize the promoter regions involved in the beta cell- and diabetes-specific regulation of GLUT2 expression and possibly to determine which factors are responsible for this regulation.
葡萄糖转运蛋白2（GLUT2）缺失是与糖尿病相关的β细胞葡萄糖无反应性的一个标志物。了解导致这种功能障碍的因素可能有助于揭示糖尿病的发病机制。由于目前只能在体内实验中研究糖尿病中GLUT2表达的调节，我们开发了一种新的实验方法来研究糖尿病中GLUT2的基因调控。通过将胰岛或细胞系封装在半透膜中，这些细胞可以暴露于大鼠或小鼠的糖尿病环境中，并可回收用于分析GLUT2表达以及对葡萄糖分泌反应的变化。转运蛋白表达的免疫细胞化学分析揭示了蛋白质表达的变化，而GLUT2基因表达的转录分析可以在转染了启动子-报告基因构建体的细胞中进行。使用最后这种方法，我们希望能够鉴定参与GLUT2表达的β细胞特异性和糖尿病特异性调节的启动子区域，并有可能确定哪些因素负责这种调节。
