Pleiotropic Roles of PDX-1 in the Pancreas
Hideaki Kaneto, Takeshi Miyatsuka, Dan Kawamori, Taka-aki MatsuokaDepartment 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.
Keywordsdiabetes · beta-cell differentiation · PDX-1 · pancreas development · beta-cell glucose toxicity,.
Rev Diabet Stud