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Microphthalmia Transcription Factor Regulates Pancreatic β-Cell Function
Precise regulation of β-cell function is crucial for maintaining blood glucose homeostasis. Pax6 is an essential regulator of β-cell–specific factors like insulin and Glut2. Studies in the developing eye suggest that Pax6 interacts with Mitf to regulate pigment cell differentiation. Here, we show th...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717881/ https://www.ncbi.nlm.nih.gov/pubmed/23610061 http://dx.doi.org/10.2337/db12-1464 |
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author | Mazur, Magdalena A. Winkler, Marcus Ganić, Elvira Colberg, Jesper K. Johansson, Jenny K. Bennet, Hedvig Fex, Malin Nuber, Ulrike A. Artner, Isabella |
author_facet | Mazur, Magdalena A. Winkler, Marcus Ganić, Elvira Colberg, Jesper K. Johansson, Jenny K. Bennet, Hedvig Fex, Malin Nuber, Ulrike A. Artner, Isabella |
author_sort | Mazur, Magdalena A. |
collection | PubMed |
description | Precise regulation of β-cell function is crucial for maintaining blood glucose homeostasis. Pax6 is an essential regulator of β-cell–specific factors like insulin and Glut2. Studies in the developing eye suggest that Pax6 interacts with Mitf to regulate pigment cell differentiation. Here, we show that Mitf, like Pax6, is expressed in all pancreatic endocrine cells during mouse postnatal development and in the adult islet. A Mitf loss-of-function mutation results in improved glucose tolerance and enhanced insulin secretion but no increase in β-cell mass in adult mice. Mutant β-cells secrete more insulin in response to glucose than wild-type cells, suggesting that Mitf is involved in regulating β-cell function. In fact, the transcription of genes critical for maintaining glucose homeostasis (insulin and Glut2) and β-cell formation and function (Pax4 and Pax6) is significantly upregulated in Mitf mutant islets. The increased Pax6 expression may cause the improved β-cell function observed in Mitf mutant animals, as it activates insulin and Glut2 transcription. Chromatin immunoprecipitation analysis shows that Mitf binds to Pax4 and Pax6 regulatory regions, suggesting that Mitf represses their transcription in wild-type β-cells. We demonstrate that Mitf directly regulates Pax6 transcription and controls β-cell function. |
format | Online Article Text |
id | pubmed-3717881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-37178812014-08-01 Microphthalmia Transcription Factor Regulates Pancreatic β-Cell Function Mazur, Magdalena A. Winkler, Marcus Ganić, Elvira Colberg, Jesper K. Johansson, Jenny K. Bennet, Hedvig Fex, Malin Nuber, Ulrike A. Artner, Isabella Diabetes Original Research Precise regulation of β-cell function is crucial for maintaining blood glucose homeostasis. Pax6 is an essential regulator of β-cell–specific factors like insulin and Glut2. Studies in the developing eye suggest that Pax6 interacts with Mitf to regulate pigment cell differentiation. Here, we show that Mitf, like Pax6, is expressed in all pancreatic endocrine cells during mouse postnatal development and in the adult islet. A Mitf loss-of-function mutation results in improved glucose tolerance and enhanced insulin secretion but no increase in β-cell mass in adult mice. Mutant β-cells secrete more insulin in response to glucose than wild-type cells, suggesting that Mitf is involved in regulating β-cell function. In fact, the transcription of genes critical for maintaining glucose homeostasis (insulin and Glut2) and β-cell formation and function (Pax4 and Pax6) is significantly upregulated in Mitf mutant islets. The increased Pax6 expression may cause the improved β-cell function observed in Mitf mutant animals, as it activates insulin and Glut2 transcription. Chromatin immunoprecipitation analysis shows that Mitf binds to Pax4 and Pax6 regulatory regions, suggesting that Mitf represses their transcription in wild-type β-cells. We demonstrate that Mitf directly regulates Pax6 transcription and controls β-cell function. American Diabetes Association 2013-08 2013-07-17 /pmc/articles/PMC3717881/ /pubmed/23610061 http://dx.doi.org/10.2337/db12-1464 Text en © 2013 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 Research Mazur, Magdalena A. Winkler, Marcus Ganić, Elvira Colberg, Jesper K. Johansson, Jenny K. Bennet, Hedvig Fex, Malin Nuber, Ulrike A. Artner, Isabella Microphthalmia Transcription Factor Regulates Pancreatic β-Cell Function |
title | Microphthalmia Transcription Factor Regulates Pancreatic β-Cell Function |
title_full | Microphthalmia Transcription Factor Regulates Pancreatic β-Cell Function |
title_fullStr | Microphthalmia Transcription Factor Regulates Pancreatic β-Cell Function |
title_full_unstemmed | Microphthalmia Transcription Factor Regulates Pancreatic β-Cell Function |
title_short | Microphthalmia Transcription Factor Regulates Pancreatic β-Cell Function |
title_sort | microphthalmia transcription factor regulates pancreatic β-cell function |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717881/ https://www.ncbi.nlm.nih.gov/pubmed/23610061 http://dx.doi.org/10.2337/db12-1464 |
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