BETA-CELL-SPECIFIC INACTIVATION OF THE MOUSE IPF1 PDX1 GENE RESULTS IN LOSS OF THE BETA-CELL PHENOTYPE AND MATURITY-ONSET DIABETES/

To study the late beta-cell-specific function of the homeodomain prote in IPF1/PDX1 we have generated mice in which the Ipf1/Pdx1 gene has be en disrupted specifically in beta cells. These mice develop diabetes w ith age, and we show that IPF1/PDX1 is required for maintaining the be ta cell identity by positively regulating insulin and islet amyloid po lypeptide expression and by repressing glucagon expression. We also pr ovide evidence that IPF1/PDX1 regulates the expression of Glut2 in a d osage-dependent manner suggesting that lowered IPF1/ PDX1 activity may contribute to the development of type II diabetes by causing impaired expression of both Glut2 and insulin.