KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_43901D6BF91E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response.
Périodique
Cell reports
Auteur(s)
Rabhi N., Denechaud P.D., Gromada X., Hannou S.A., Zhang H., Rashid T., Salas E., Durand E., Sand O., Bonnefond A., Yengo L., Chavey C., Bonner C., Kerr-Conte J., Abderrahmani A., Auwerx J., Fajas L., Froguel P., Annicotte J.S.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
15
Numéro
5
Pages
1051-1061
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
The endoplasmic reticulum (ER) unfolded protein response (UPR(er)) pathway plays an important role in helping pancreatic β cells to adapt their cellular responses to environmental cues and metabolic stress. Although altered UPR(er) gene expression appears in rodent and human type 2 diabetic (T2D) islets, the underlying molecular mechanisms remain unknown. We show here that germline and β cell-specific disruption of the lysine acetyltransferase 2B (Kat2b) gene in mice leads to impaired insulin secretion and glucose intolerance. Genome-wide analysis of Kat2b-regulated genes and functional assays reveal a critical role for Kat2b in maintaining UPR(er) gene expression and subsequent β cell function. Importantly, Kat2b expression is decreased in mouse and human diabetic β cells and correlates with UPR(er) gene expression in normal human islets. In conclusion, Kat2b is a crucial transcriptional regulator for adaptive β cell function during metabolic stress by controlling UPR(er) and represents a promising target for T2D prevention and treatment.
Pubmed
Open Access
Oui
Création de la notice
10/06/2016 17:38
Dernière modification de la notice
20/08/2019 14:47
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