β-Cell-specific inactivation of the mouseIpf1/Pdx1 gene results in loss of the β-cell phenotype and maturity onset diabetes

Abstract

To study the late β-cell-specific function of the homeodomain protein IPF1/PDX1 we have generated mice in which theIpf1/Pdx1 gene has been disrupted specifically in β cells. These mice develop diabetes with age, and we show that IPF1/PDX1 is required for maintaining the β cell identity by positively regulating insulin and islet amyloid polypeptide expression and by repressing glucagon expression. We also provide evidence that IPF1/PDX1 regulates the expression of Glut2 in a dosage-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.