PDX-1 and MafA as Potential Therapeutic Targets for Diabetes

Abstract

Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development and β-cell differentiation, and functions as an activator of insulin gene transcription. MafA is a recently isolated β-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. PDX-1 and MafA play crucial roles in inducing insulin-producing cells from non- β-cells and could be therapeutic targets for diabetes. On the other hand, expression and/or activities of PDX-1 and MafA in β-cells are reduced under diabetic conditions. Alteration of such transcription factors leads to suppression of insulin biosynthesis and secretion and thus explains, at least in part, the molecular mechanism for β-cell glucose toxicity. Keywords: pancreas development, bHLH transcription factor, maturity-onset diabetes of the young (MODY), insulin gene, PDX-1-VP16 fusion protein