Role of PDX-1 and MafA as a potential therapeutic target for diabetes

Abstract

Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, β-cell differentiation, and maintaining mature β-cell function. During pancreas development, PDX-1 expression is maintained in precursor cells, and later it becomes restricted to β-cells. In mature β-cells, PDX-1 regulates gene expression of various β-cell-related factors including insulin. Also, PDX-1 has potency to induce insulin-producing cells from non-β-cells in various tissues, 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 which functions as a potent activator of insulin gene transcription. During pancreas development, MafA expression is first detected at the beginning of the principal phase of insulin-producing cell production. Furthermore, 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 surrogate β-cells and could be a therapeutic target for diabetes.