title: ISL1 promotes pancreatic islet cell proliferation.
abstract: BACKGROUND
  Islet 1 (ISL1), a LIM-homeodomain transcription factor is essential for promoting pancreatic islets proliferation and maintaining endocrine cells survival in embryonic and postnatal pancreatic islets. However, how ISL1 exerts the role in adult islets is, to date, not clear.
  
  
  RESULTS
  Our results show that ISL1 expression was up-regulated at the mRNA level both in cultured pancreatic cells undergoing glucose oxidase stimulation as well in type 1 and type 2 diabetes mouse models. The knockdown of ISL1 expression increased the apoptosis level of HIT-T15 pancreatic islet cells. Using HIT-T15 and primary adult islet cells as cell models, we show that ISL1 promoted adult pancreatic islet cell proliferation with increased c-Myc and CyclinD1 transcription, while knockdown of ISL1 increased the proportion of cells in G(1) phase and decreased the proportion of cells in G(2)/M and S phases. Further investigation shows that ISL1 activated both c-Myc and CyclinD1 transcription through direct binding on their promoters.
  
  
  CONCLUSIONS
  ISL1 promoted adult pancreatic islet cell proliferation and probably by activating c-Myc and CyclinD1 transcription through direct binding on their promoters. Our findings extend the knowledge about the crucial role of ISL1 in maintaining mature islet cells homeostasis. Our results also provide insights into the new regulation relationships between ISL1 and other growth factors.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.forename: Weiping
authors.initials: W
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Yinan
authors.initials: Y
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Kangtao
authors.initials: K
authors.lastname: Ma
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D060850:LIM-Homeodomain Proteins; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D019938:Cyclin D1