PDX-1 and MafA: Key Transcription Factors in Pancreas

Abstract

Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, β-cell differentiation and in maintaining normal β-cell function by regulating several β-cell-related genes including insulin. PDX-1 has potency to induce insulin-producing cells in non β-cells in various tissues such as pancreas and liver and PDX-1-VP16 fusion protein more efficiently induces insulin-producing cells, especially in the presence of NeuroD or Ngn3. MafA is a recently isolated β-cell-specific transcription factor and functions as a potent transactivator for the insulin gene. MafA markedly enhances insulin gene promoter activity and ameliorates glucose tolerance in diabetic mice, especially in the presence of PDX-1 and NeuroD. Taken together, PDX-1 and MafA play a crucial role in inducing insulin-producing cells and could be a therapeutic target for diabetes.