title: The role of Islet-1 in the endocrine pancreas: Lessons from pancreas specific Islet-1 deficient mice.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Institute of Diabetes for Diabetes, Obesity and Metabolism, USA. catheril@mail.med.upenn.edu
authors.forename: Catherine Lee
authors.initials: CL
authors.lastname: May
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics; D010179:Pancreas / Q000196:embryology / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors
chemical_list: D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1