Pleiotropic Roles of PDX-1 in the Pancreas.

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 beta-cell differentiation. In mature beta-cells, PDX-1 transactivates insulin and other beta-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-beta-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 beta-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 beta-cell glucose toxicity found in diabetes.