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p43, a Truncated Form of Thyroid Hormone Receptor α, Regulates Maturation of Pancreatic β Cells

P43 is a truncated form of thyroid hormone receptor α localized in mitochondria, which stimulates mitochondrial respiratory chain activity. Previously, we showed that deletion of p43 led to reduction of pancreatic islet density and a loss of glucose-stimulated insulin secretion in adult mice. The pr...

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Autores principales: Blanchet, Emilie, Pessemesse, Laurence, Feillet-Coudray, Christine, Coudray, Charles, Cabello, Chantal, Bertrand-Gaday, Christelle, Casas, François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958131/
https://www.ncbi.nlm.nih.gov/pubmed/33801253
http://dx.doi.org/10.3390/ijms22052489
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author Blanchet, Emilie
Pessemesse, Laurence
Feillet-Coudray, Christine
Coudray, Charles
Cabello, Chantal
Bertrand-Gaday, Christelle
Casas, François
author_facet Blanchet, Emilie
Pessemesse, Laurence
Feillet-Coudray, Christine
Coudray, Charles
Cabello, Chantal
Bertrand-Gaday, Christelle
Casas, François
author_sort Blanchet, Emilie
collection PubMed
description P43 is a truncated form of thyroid hormone receptor α localized in mitochondria, which stimulates mitochondrial respiratory chain activity. Previously, we showed that deletion of p43 led to reduction of pancreatic islet density and a loss of glucose-stimulated insulin secretion in adult mice. The present study was designed to determine whether p43 was involved in the processes of β cell development and maturation. We used neonatal, juvenile, and adult p43-/- mice, and we analyzed the development of β cells in the pancreas. Here, we show that p43 deletion affected only slightly β cell proliferation during the postnatal period. However, we found a dramatic fall in p43-/- mice of MafA expression (V-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog A), a key transcription factor of beta-cell maturation. Analysis of the expression of antioxidant enzymes in pancreatic islet and 4-hydroxynonenal (4-HNE) (a specific marker of lipid peroxidation) staining revealed that oxidative stress occurred in mice lacking p43. Lastly, administration of antioxidants cocktail to p43-/- pregnant mice restored a normal islet density but failed to ensure an insulin secretion in response to glucose. Our findings demonstrated that p43 drives the maturation of β cells via its induction of transcription factor MafA during the critical postnatal window.
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spelling pubmed-79581312021-03-16 p43, a Truncated Form of Thyroid Hormone Receptor α, Regulates Maturation of Pancreatic β Cells Blanchet, Emilie Pessemesse, Laurence Feillet-Coudray, Christine Coudray, Charles Cabello, Chantal Bertrand-Gaday, Christelle Casas, François Int J Mol Sci Article P43 is a truncated form of thyroid hormone receptor α localized in mitochondria, which stimulates mitochondrial respiratory chain activity. Previously, we showed that deletion of p43 led to reduction of pancreatic islet density and a loss of glucose-stimulated insulin secretion in adult mice. The present study was designed to determine whether p43 was involved in the processes of β cell development and maturation. We used neonatal, juvenile, and adult p43-/- mice, and we analyzed the development of β cells in the pancreas. Here, we show that p43 deletion affected only slightly β cell proliferation during the postnatal period. However, we found a dramatic fall in p43-/- mice of MafA expression (V-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog A), a key transcription factor of beta-cell maturation. Analysis of the expression of antioxidant enzymes in pancreatic islet and 4-hydroxynonenal (4-HNE) (a specific marker of lipid peroxidation) staining revealed that oxidative stress occurred in mice lacking p43. Lastly, administration of antioxidants cocktail to p43-/- pregnant mice restored a normal islet density but failed to ensure an insulin secretion in response to glucose. Our findings demonstrated that p43 drives the maturation of β cells via its induction of transcription factor MafA during the critical postnatal window. MDPI 2021-03-02 /pmc/articles/PMC7958131/ /pubmed/33801253 http://dx.doi.org/10.3390/ijms22052489 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Blanchet, Emilie
Pessemesse, Laurence
Feillet-Coudray, Christine
Coudray, Charles
Cabello, Chantal
Bertrand-Gaday, Christelle
Casas, François
p43, a Truncated Form of Thyroid Hormone Receptor α, Regulates Maturation of Pancreatic β Cells
title p43, a Truncated Form of Thyroid Hormone Receptor α, Regulates Maturation of Pancreatic β Cells
title_full p43, a Truncated Form of Thyroid Hormone Receptor α, Regulates Maturation of Pancreatic β Cells
title_fullStr p43, a Truncated Form of Thyroid Hormone Receptor α, Regulates Maturation of Pancreatic β Cells
title_full_unstemmed p43, a Truncated Form of Thyroid Hormone Receptor α, Regulates Maturation of Pancreatic β Cells
title_short p43, a Truncated Form of Thyroid Hormone Receptor α, Regulates Maturation of Pancreatic β Cells
title_sort p43, a truncated form of thyroid hormone receptor α, regulates maturation of pancreatic β cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958131/
https://www.ncbi.nlm.nih.gov/pubmed/33801253
http://dx.doi.org/10.3390/ijms22052489
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