PDX-1 functions as a master factor in the pancreas

Abstract

Various pancreatic transcription factors are involved in pancreas development and β-cell differentiation. Among them, pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development and β-cell differentiation, and maintaining mature β-cell function. MafA is a recently isolated β-cell-specific transcription factor and functions as a potent activator of insulin gene transcription. These pancreatic transcription factors also play a crucial role in inducing surrogate β-cells from non- β-cells and thus could be therapeutic targets for diabetes. On the other hand, under diabetic conditions, expression and/or activities of PDX-1 and MafA in β-cells are reduced, which leads to suppression of insulin biosynthesis and secretion. Thus, it is likely that alteration of such transcription factors explains, at least in part, the molecular mechanism for β-cell glucose toxicity found in diabetes.