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MafA and MafB Regulate Genes Critical to β-Cells in a Unique Temporal Manner

OBJECTIVE: Several transcription factors are essential to pancreatic islet β-cell development, proliferation, and activity, including MafA and MafB. However, MafA and MafB are distinct from others in regard to temporal and islet cell expression pattern, with β-cells affected by MafB only during deve...

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Autores principales: Artner, Isabella, Hang, Yan, Mazur, Magdalena, Yamamoto, Tsunehiko, Guo, Min, Lindner, Jill, Magnuson, Mark A., Stein, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279542/
https://www.ncbi.nlm.nih.gov/pubmed/20627934
http://dx.doi.org/10.2337/db10-0190
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author Artner, Isabella
Hang, Yan
Mazur, Magdalena
Yamamoto, Tsunehiko
Guo, Min
Lindner, Jill
Magnuson, Mark A.
Stein, Roland
author_facet Artner, Isabella
Hang, Yan
Mazur, Magdalena
Yamamoto, Tsunehiko
Guo, Min
Lindner, Jill
Magnuson, Mark A.
Stein, Roland
author_sort Artner, Isabella
collection PubMed
description OBJECTIVE: Several transcription factors are essential to pancreatic islet β-cell development, proliferation, and activity, including MafA and MafB. However, MafA and MafB are distinct from others in regard to temporal and islet cell expression pattern, with β-cells affected by MafB only during development and exclusively by MafA in the adult. Our aim was to define the functional relationship between these closely related activators to the β-cell. RESEARCH DESIGN AND METHODS: The distribution of MafA and MafB in the β-cell population was determined immunohistochemically at various developmental and perinatal stages in mice. To identify genes regulated by MafB, microarray profiling was performed on wild-type and MafB(−/−) pancreata at embryonic day 18.5, with candidates evaluated by quantitative RT-PCR and in situ hybridization. The potential role of MafA in the expression of verified targets was next analyzed in adult islets of a pancreas-wide MafA mutant (termed MafA(ΔPanc)). RESULTS: MafB was produced in a larger fraction of β-cells than MafA during development and found to regulate potential effectors of glucose sensing, hormone processing, vesicle formation, and insulin secretion. Notably, expression from many of these genes was compromised in MafA(ΔPanc) islets, suggesting that MafA is required to sustain expression in adults. CONCLUSIONS: Our results provide insight into the sequential manner by which MafA and MafB regulate islet β-cell formation and maturation.
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spelling pubmed-32795422012-02-16 MafA and MafB Regulate Genes Critical to β-Cells in a Unique Temporal Manner Artner, Isabella Hang, Yan Mazur, Magdalena Yamamoto, Tsunehiko Guo, Min Lindner, Jill Magnuson, Mark A. Stein, Roland Diabetes Islet Studies OBJECTIVE: Several transcription factors are essential to pancreatic islet β-cell development, proliferation, and activity, including MafA and MafB. However, MafA and MafB are distinct from others in regard to temporal and islet cell expression pattern, with β-cells affected by MafB only during development and exclusively by MafA in the adult. Our aim was to define the functional relationship between these closely related activators to the β-cell. RESEARCH DESIGN AND METHODS: The distribution of MafA and MafB in the β-cell population was determined immunohistochemically at various developmental and perinatal stages in mice. To identify genes regulated by MafB, microarray profiling was performed on wild-type and MafB(−/−) pancreata at embryonic day 18.5, with candidates evaluated by quantitative RT-PCR and in situ hybridization. The potential role of MafA in the expression of verified targets was next analyzed in adult islets of a pancreas-wide MafA mutant (termed MafA(ΔPanc)). RESULTS: MafB was produced in a larger fraction of β-cells than MafA during development and found to regulate potential effectors of glucose sensing, hormone processing, vesicle formation, and insulin secretion. Notably, expression from many of these genes was compromised in MafA(ΔPanc) islets, suggesting that MafA is required to sustain expression in adults. CONCLUSIONS: Our results provide insight into the sequential manner by which MafA and MafB regulate islet β-cell formation and maturation. American Diabetes Association 2010-10 2010-07-13 /pmc/articles/PMC3279542/ /pubmed/20627934 http://dx.doi.org/10.2337/db10-0190 Text en © 2010 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 Islet Studies
Artner, Isabella
Hang, Yan
Mazur, Magdalena
Yamamoto, Tsunehiko
Guo, Min
Lindner, Jill
Magnuson, Mark A.
Stein, Roland
MafA and MafB Regulate Genes Critical to β-Cells in a Unique Temporal Manner
title MafA and MafB Regulate Genes Critical to β-Cells in a Unique Temporal Manner
title_full MafA and MafB Regulate Genes Critical to β-Cells in a Unique Temporal Manner
title_fullStr MafA and MafB Regulate Genes Critical to β-Cells in a Unique Temporal Manner
title_full_unstemmed MafA and MafB Regulate Genes Critical to β-Cells in a Unique Temporal Manner
title_short MafA and MafB Regulate Genes Critical to β-Cells in a Unique Temporal Manner
title_sort mafa and mafb regulate genes critical to β-cells in a unique temporal manner
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279542/
https://www.ncbi.nlm.nih.gov/pubmed/20627934
http://dx.doi.org/10.2337/db10-0190
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