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Curr Med Chem. 2007;14(16):1745-52.

Crucial role of PDX-1 in pancreas development, beta-cell differentiation, and induction of surrogate beta-cells.

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  • 1Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. kaneto@medone.med.osaka-u.ac.jp

Abstract

Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, beta-cell differentiation, and maintaining mature beta-cell function. At an early stage of embryonic development, PDX-1 is initially expressed in the gut region when the foregut endoderm becomes committed to common pancreatic precursor cells. 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 transactivates the insulin gene and other genes involved in glucose sensing and metabolism, such as GLUT2 and glucokinase. 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, these transcription factors play a crucial role in inducing surrogate beta-cells from non-beta-cells and thus could be therapeutic targets for diabetes.

PMID:
17627512
[PubMed - indexed for MEDLINE]
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