Review
| Rev Diabet Stud,
2007,
4(4):209-225 |
DOI 10.1900/RDS.2007.4.209 |
Pleiotropic Roles of PDX-1 in the Pancreas
Hideaki Kaneto, Takeshi Miyatsuka, Dan Kawamori, Taka-aki Matsuoka
Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Address correspondence to: Hideaki Kaneto, e-mail: kaneto@medone.med.osaka-u.ac.jp
Manuscript submitted January 28, 2008; resubmitted February 18, 2008; accepted February 29, 2008.
Keywords: diabetes, beta-cell differentiation, PDX-1, pancreas development, beta-cell glucose toxicity
Abstract
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.
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