Pleiotropic Roles of PDX-1 in the Pancreas

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The Review of Diabetic Studies,2007,4,4,209-225.
Published:February 2008
Type:Review Article
Author(s) affiliations:

Hideaki Kaneto, Takeshi Miyatsuka, Dan Kawamori and Taka-aki Matsuoka

Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.


It is well known that pancreatic and duodenal homeobox factor-1 (PDX-1) plays a pleiotropic role in the pancreas. In the developing pancreas, PDX-1 is involved in both pancreas formation and β-cell differentiation. In mature β-cells, PDX-1 transactivates insulin and other β-cell-related genes such as GLUT2 and glucokinase. Furthermore, PDX-1 plays an important role in the induction of insulin-producing cells in various non-β-cells and is thereby a possible therapeutic target for diabetes. On the other hand, under diabetic conditions, expression and/or activity of PDX-1 in β-cells is reduced, which leads to suppression of insulin biosynthesis and secretion. It is likely that PDX-1 inactivation explains, at least in part, the molecular mechanism for β-cell glucose toxicity found in diabetes.