Glutathione Regulates The Transcriptional Activation Of Insulin Gene Expression In Pancreatic Beta-Cells

Dysfunction of islet beta -cells seen in type 1 and type 2 diabetes has been in part shown to be ascribed to oxidative cellular damage evoked by the factors including cytokine and hyperglycemia, Free radical scavenge system in beta -cells appears to play an important role in intracellular contents of glutathione (GSH), a major reducing component. MIN6 cells stably transfected with ribozyme gene which cleaves GSH mRNA were established in which intracellular GSH content. Transient transfection with luciferase reporter gene driven by 1.9 kbp preproinsulin gene 5' region was carried out. The data showed that luciferase activity was increased about 8 times in ribozyme-transfected MIN6 cells as compared to that in untransfected cells. The present study demonstrated that the intracellular content of GSH may play a crucial role in determining insulin gene promoter activity, indicating that alteration of redox state in pancreatic beta -cells may be involved in insulin biosynthesis.