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Thyroid Hormone Promotes Postnatal Rat Pancreatic β-Cell Development and Glucose-Responsive Insulin Secretion Through MAFA
Neonatal β cells do not secrete glucose-responsive insulin and are considered immature. We previously showed the transcription factor MAFA is key for the functional maturation of β cells, but the physiological regulators of this process are unknown. Here we show that postnatal rat β cells express 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/PMC3636623/ https://www.ncbi.nlm.nih.gov/pubmed/23305647 http://dx.doi.org/10.2337/db12-0849 |
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author | Aguayo-Mazzucato, Cristina Zavacki, Ann Marie Marinelarena, Alejandra Hollister-Lock, Jennifer El Khattabi, Ilham Marsili, Alessandro Weir, Gordon C. Sharma, Arun Larsen, P. Reed Bonner-Weir, Susan |
author_facet | Aguayo-Mazzucato, Cristina Zavacki, Ann Marie Marinelarena, Alejandra Hollister-Lock, Jennifer El Khattabi, Ilham Marsili, Alessandro Weir, Gordon C. Sharma, Arun Larsen, P. Reed Bonner-Weir, Susan |
author_sort | Aguayo-Mazzucato, Cristina |
collection | PubMed |
description | Neonatal β cells do not secrete glucose-responsive insulin and are considered immature. We previously showed the transcription factor MAFA is key for the functional maturation of β cells, but the physiological regulators of this process are unknown. Here we show that postnatal rat β cells express thyroid hormone (TH) receptor isoforms and deiodinases in an age-dependent pattern as glucose responsiveness develops. In vivo neonatal triiodothyronine supplementation and TH inhibition, respectively, accelerated and delayed metabolic development. In vitro exposure of immature islets to triiodothyronine enhanced the expression of Mafa, the secretion of glucose-responsive insulin, and the proportion of responsive cells, all of which are effects that were abolished in the presence of dominant-negative Mafa. Using chromatin immunoprecipitation and electrophoretic mobility shift assay, we show that TH has a direct receptor-ligand interaction with the Mafa promoter and, using a luciferase reporter, that this interaction was functional. Thus, TH can be considered a physiological regulator of functional maturation of β cells via its induction of Mafa. |
format | Online Article Text |
id | pubmed-3636623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-36366232014-05-01 Thyroid Hormone Promotes Postnatal Rat Pancreatic β-Cell Development and Glucose-Responsive Insulin Secretion Through MAFA Aguayo-Mazzucato, Cristina Zavacki, Ann Marie Marinelarena, Alejandra Hollister-Lock, Jennifer El Khattabi, Ilham Marsili, Alessandro Weir, Gordon C. Sharma, Arun Larsen, P. Reed Bonner-Weir, Susan Diabetes Original Research Neonatal β cells do not secrete glucose-responsive insulin and are considered immature. We previously showed the transcription factor MAFA is key for the functional maturation of β cells, but the physiological regulators of this process are unknown. Here we show that postnatal rat β cells express thyroid hormone (TH) receptor isoforms and deiodinases in an age-dependent pattern as glucose responsiveness develops. In vivo neonatal triiodothyronine supplementation and TH inhibition, respectively, accelerated and delayed metabolic development. In vitro exposure of immature islets to triiodothyronine enhanced the expression of Mafa, the secretion of glucose-responsive insulin, and the proportion of responsive cells, all of which are effects that were abolished in the presence of dominant-negative Mafa. Using chromatin immunoprecipitation and electrophoretic mobility shift assay, we show that TH has a direct receptor-ligand interaction with the Mafa promoter and, using a luciferase reporter, that this interaction was functional. Thus, TH can be considered a physiological regulator of functional maturation of β cells via its induction of Mafa. American Diabetes Association 2013-05 2013-04-16 /pmc/articles/PMC3636623/ /pubmed/23305647 http://dx.doi.org/10.2337/db12-0849 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 Aguayo-Mazzucato, Cristina Zavacki, Ann Marie Marinelarena, Alejandra Hollister-Lock, Jennifer El Khattabi, Ilham Marsili, Alessandro Weir, Gordon C. Sharma, Arun Larsen, P. Reed Bonner-Weir, Susan Thyroid Hormone Promotes Postnatal Rat Pancreatic β-Cell Development and Glucose-Responsive Insulin Secretion Through MAFA |
title | Thyroid Hormone Promotes Postnatal Rat Pancreatic β-Cell Development and Glucose-Responsive Insulin Secretion Through MAFA |
title_full | Thyroid Hormone Promotes Postnatal Rat Pancreatic β-Cell Development and Glucose-Responsive Insulin Secretion Through MAFA |
title_fullStr | Thyroid Hormone Promotes Postnatal Rat Pancreatic β-Cell Development and Glucose-Responsive Insulin Secretion Through MAFA |
title_full_unstemmed | Thyroid Hormone Promotes Postnatal Rat Pancreatic β-Cell Development and Glucose-Responsive Insulin Secretion Through MAFA |
title_short | Thyroid Hormone Promotes Postnatal Rat Pancreatic β-Cell Development and Glucose-Responsive Insulin Secretion Through MAFA |
title_sort | thyroid hormone promotes postnatal rat pancreatic β-cell development and glucose-responsive insulin secretion through mafa |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636623/ https://www.ncbi.nlm.nih.gov/pubmed/23305647 http://dx.doi.org/10.2337/db12-0849 |
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