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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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2489 |
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| author | Emilie Blanchet Laurence Pessemesse Christine Feillet-Coudray Charles Coudray Chantal Cabello Christelle Bertrand-Gaday François Casas |
| author_facet | Emilie Blanchet Laurence Pessemesse Christine Feillet-Coudray Charles Coudray Chantal Cabello Christelle Bertrand-Gaday François Casas |
| author_sort | Emilie Blanchet |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T06:01:06Z |
| format | Article |
| id | doaj.art-480ed97829f7401f9513c993e08dd3c6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T06:01:06Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-480ed97829f7401f9513c993e08dd3c62023-12-03T12:09:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01225248910.3390/ijms22052489p43, a Truncated Form of Thyroid Hormone Receptor α, Regulates Maturation of Pancreatic β CellsEmilie Blanchet0Laurence Pessemesse1Christine Feillet-Coudray2Charles Coudray3Chantal Cabello4Christelle Bertrand-Gaday5François Casas6DMEM (Dynamique du Muscle et Métabolisme), INRAE, University Montpellier, 34060 Montpellier, FranceDMEM (Dynamique du Muscle et Métabolisme), INRAE, University Montpellier, 34060 Montpellier, FranceDMEM (Dynamique du Muscle et Métabolisme), INRAE, University Montpellier, 34060 Montpellier, FranceDMEM (Dynamique du Muscle et Métabolisme), INRAE, University Montpellier, 34060 Montpellier, FranceDMEM (Dynamique du Muscle et Métabolisme), INRAE, University Montpellier, 34060 Montpellier, FranceDMEM (Dynamique du Muscle et Métabolisme), INRAE, University Montpellier, 34060 Montpellier, FranceDMEM (Dynamique du Muscle et Métabolisme), INRAE, University Montpellier, 34060 Montpellier, FranceP43 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.https://www.mdpi.com/1422-0067/22/5/2489thyroid hormonep43mitochondriabeta-cellsinsulinMafA |
| spellingShingle | Emilie Blanchet Laurence Pessemesse Christine Feillet-Coudray Charles Coudray Chantal Cabello Christelle Bertrand-Gaday François Casas p43, a Truncated Form of Thyroid Hormone Receptor α, Regulates Maturation of Pancreatic β Cells International Journal of Molecular Sciences thyroid hormone p43 mitochondria beta-cells insulin MafA |
| 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 | thyroid hormone p43 mitochondria beta-cells insulin MafA |
| url | https://www.mdpi.com/1422-0067/22/5/2489 |
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