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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...

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Autores principales: Mazur, Magdalena A., Winkler, Marcus, Ganić, Elvira, Colberg, Jesper K., Johansson, Jenny K., Bennet, Hedvig, Fex, Malin, Nuber, Ulrike A., Artner, Isabella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
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.
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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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