PDX-1 and MafA in β-cell differentiation and dysfunction.

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