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

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State: Public
Version: Final published version
Serval ID
serval:BIB_43901D6BF91E
Type
Article: article from journal or magazin.
Collection
Publications
Title
KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response.
Journal
Cell reports
Author(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)
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
15
Number
5
Pages
1051-1061
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
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
Yes
Create date
10/06/2016 17:38
Last modification date
20/08/2019 14:47
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