Insulin promoter factor-1 controls several aspects of beta-cell identity.

Abstract

In the adult pancreas, the � -cells sense glucose and control blood glucose levels by secreting active insulin. To address the role of IPF- 1 in the adult � -cell, we previously generated transgenic mice in which the IPF-1 gene has been disrupted specifically in the � -cells using the CRE-lox system. This model revealed that IPF-1 was required to maintain correct hormone expression in the � -cell and to maintain high levels of expression of Glut2, the key component in the glucose-sensing machinery (5). More recent work has shown that in these mice, the expression of the proinsulin pro- cessing enzymes PC1/3 and PC2 are also affected, leading to par- tially processed insulin being stored and subsequently secreted from the � -cells. All together, these results show that IPF-1 is nec- essary to maintain glucose homeostasis by controlling several aspects of � -cell identity, because aberrant IPF-1 expression leads to � -cell dysfunction and consequently type 2 diabetes. We believe that these approaches will generate data that will expand our understanding of the intrinsic regulatory molecules that act upstream and downstream of IPF-1 dur- ing pancreatic development and in the adult � -cell. We hope this knowledge will contribute to the development of improved diabetes therapies.