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

Abstract : P43 is a truncated form of thyroid hormone receptor alpha 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 beta cell development and maturation. We used neonatal, juvenile, and adult p43-/- mice, and we analyzed the development of beta cells in the pancreas. Here, we show that p43 deletion affected only slightly beta 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 beta cells via its induction of transcription factor MafA during the critical postnatal window.
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https://hal.inrae.fr/hal-03184462
Contributor : Christelle Raynaud <>
Submitted on : Tuesday, May 25, 2021 - 4:00:23 PM
Last modification on : Thursday, May 27, 2021 - 11:01:59 AM

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Emilie Blanchet, Laurence Pessemesse, Christine Feillet-Coudray, Charles Coudray, Chantal Cabello, et al.. p43, a Truncated Form of Thyroid Hormone Receptor α, Regulates Maturation of Pancreatic β Cells. International Journal of Molecular Sciences, MDPI, 2021, 22 (5), ⟨10.3390/ijms22052489⟩. ⟨hal-03184462⟩

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