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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
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.
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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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