PDX-1 and MafA Play a Crucial Role in Pancreatic β-Cell Differentiation and Maintenance of Mature β-Cell Function

Endocrine Journal

Taka-aki MATSUOKA¹  Toshihiko SHIRAIWA¹  Takeshi MIYATSUKA¹  Ken KATO¹  Dan KAWAMORI¹  Munehide MATSUHISA¹  Hideaki KANETO¹  Kaoru YAMAMOTO¹  Yoshimitsu YAMASAKI¹  Naoto KATAKAMI¹ 

[1] Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine

关键词: PDX-1;    MafA;    Pancreas development;    β-cell differentiation;    β-cell glucose toxicity;   

DOI  :  10.1507/endocrj.K07E-041

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(158)Cited-By(52)Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, β-cell differentiation, and maintenance of mature β-cell function. PDX-1 expression is maintained in pancreatic precursor cells during pancreas development but becomes restricted to β-cells in mature pancreas. In mature β-cells, PDX-1 transactivates the insulin and other genes involved in glucose sensing and metabolism such as GLUT2 and glucokinase. MafA is a recently isolated β-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. Furthermore, these transcription factors play an important role in induction of insulin-producing cells in various non-β-cells and thus could be therapeutic targets for diabetes. On the other hand, under diabetic conditions, expression and/or activities of PDX-1 and MafA in β-cells are reduced, which leads to suppression of insulin biosynthesis and secretion. It is likely that alteration of such transcription factors explains, at least in part, the molecular mechanism for β-cell glucose toxicity found in diabetes.

【 授权许可】

Unknown