The role of Islet-1 in the endocrine pancreas: Lessons from pancreas specific Islet-1 deficient mice.

Recently, we have reported the LIM-homeodoman (HD) transcriptional regulator, Islet-1 (Isl-1) as a key regulator for pancreatic islets after the secondary transition and into early postnatal stages in mice. Previously, the role of Isl-1 had only been examined during early pancreas development in vivo and cell lines. These early studies concluded that Isl-1 is required for the differentiation of early endocrine cells, and hormone gene expression is regulated by Isl-1 in cell culture. However, it was not clear from these studies whether the regulation of hormone gene transcription by Isl-1 was a direct transcriptional event. In addition, the function of Isl-1 during the formation of principle hormone producing endocrine cells had not been investigated since Isl-1 null animals die prior to the formation of these cells. Using pancreas-specific inactivation of Isl-1 in mice, we have elucidated the role of Isl-1 during maturation, proliferation and survival of the endocrine pancreas after the secondary transition. We have also identified MafA, a potent Insulin gene regulator, as the first direct target of Isl-1 in β-cells.