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Islet-1 is Required for the Maturation, Proliferation, and Survival of the Endocrine Pancreas
OBJECTIVE: The generation of mature cell types during pancreatic development depends on the expression of many regulatory and signaling proteins. In this study, we tested the hypothesis that the transcriptional regulator Islet-1 (Isl-1), whose expression is first detected in the mesenchyme and epith...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731519/ https://www.ncbi.nlm.nih.gov/pubmed/19502415 http://dx.doi.org/10.2337/db08-0987 |
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author | Du, Aiping Hunter, Chad S. Murray, Johanna Noble, Daniel Cai, Chen-Leng Evans, Sylvia M. Stein, Roland May, Catherine Lee |
author_facet | Du, Aiping Hunter, Chad S. Murray, Johanna Noble, Daniel Cai, Chen-Leng Evans, Sylvia M. Stein, Roland May, Catherine Lee |
author_sort | Du, Aiping |
collection | PubMed |
description | OBJECTIVE: The generation of mature cell types during pancreatic development depends on the expression of many regulatory and signaling proteins. In this study, we tested the hypothesis that the transcriptional regulator Islet-1 (Isl-1), whose expression is first detected in the mesenchyme and epithelium of the developing pancreas and is later restricted to mature islet cells, is involved in the terminal differentiation of islet cells and maintenance of islet mass. RESEARCH DESIGN AND METHODS: To investigate the role of Isl-1 in the pancreatic epithelium during the secondary transition, Isl-1 was conditionally and specifically deleted from embryonic day 13.5 onward using Cre/LoxP technology. RESULTS: Isl-1–deficient endocrine precursors failed to mature into functional islet cells. The postnatal expansion of endocrine cell mass was impaired, and consequently Isl-1 deficient mice were diabetic. In addition, MafA, a potent regulator of the Insulin gene and β-cell function, was identified as a direct transcriptional target of Isl-1. CONCLUSIONS: These results demonstrate the requirement for Isl-1 in the maturation, proliferation, and survival of the second wave of hormone-producing islet cells. |
format | Text |
id | pubmed-2731519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-27315192010-09-01 Islet-1 is Required for the Maturation, Proliferation, and Survival of the Endocrine Pancreas Du, Aiping Hunter, Chad S. Murray, Johanna Noble, Daniel Cai, Chen-Leng Evans, Sylvia M. Stein, Roland May, Catherine Lee Diabetes Original Article OBJECTIVE: The generation of mature cell types during pancreatic development depends on the expression of many regulatory and signaling proteins. In this study, we tested the hypothesis that the transcriptional regulator Islet-1 (Isl-1), whose expression is first detected in the mesenchyme and epithelium of the developing pancreas and is later restricted to mature islet cells, is involved in the terminal differentiation of islet cells and maintenance of islet mass. RESEARCH DESIGN AND METHODS: To investigate the role of Isl-1 in the pancreatic epithelium during the secondary transition, Isl-1 was conditionally and specifically deleted from embryonic day 13.5 onward using Cre/LoxP technology. RESULTS: Isl-1–deficient endocrine precursors failed to mature into functional islet cells. The postnatal expansion of endocrine cell mass was impaired, and consequently Isl-1 deficient mice were diabetic. In addition, MafA, a potent regulator of the Insulin gene and β-cell function, was identified as a direct transcriptional target of Isl-1. CONCLUSIONS: These results demonstrate the requirement for Isl-1 in the maturation, proliferation, and survival of the second wave of hormone-producing islet cells. American Diabetes Association 2009-09 2009-06-05 /pmc/articles/PMC2731519/ /pubmed/19502415 http://dx.doi.org/10.2337/db08-0987 Text en © 2009 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Article Du, Aiping Hunter, Chad S. Murray, Johanna Noble, Daniel Cai, Chen-Leng Evans, Sylvia M. Stein, Roland May, Catherine Lee Islet-1 is Required for the Maturation, Proliferation, and Survival of the Endocrine Pancreas |
title | Islet-1 is Required for the Maturation, Proliferation, and Survival of the Endocrine Pancreas |
title_full | Islet-1 is Required for the Maturation, Proliferation, and Survival of the Endocrine Pancreas |
title_fullStr | Islet-1 is Required for the Maturation, Proliferation, and Survival of the Endocrine Pancreas |
title_full_unstemmed | Islet-1 is Required for the Maturation, Proliferation, and Survival of the Endocrine Pancreas |
title_short | Islet-1 is Required for the Maturation, Proliferation, and Survival of the Endocrine Pancreas |
title_sort | islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731519/ https://www.ncbi.nlm.nih.gov/pubmed/19502415 http://dx.doi.org/10.2337/db08-0987 |
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