Journal
DIABETES RESEARCH AND CLINICAL PRACTICE
Volume 77, Issue -, Pages S127-S137Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.diabres.2007.01.046
Keywords
PDX-1; MafA; transcription factor; insulin gene; surrogate beta-cells
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Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, beta-cell differentiation, and maintaining mature beta-cell function. During pancreas development, PDX-1 expression is maintained in precursor cells, and later it becomes restricted to beta-cells. In mature beta-cells, PDX-1 regulates gene expression of various beta-cell-related factors including insulin. Also, PDX-1 has potency to induce insulin-producing cells from non-p-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 beta-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 P-cells and could be a therapeutic target for diabetes. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
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