KAT2B is required for pancreatic beta cell adaptation to metabolic stress by controlling the unfolded protein response

Rabhi, Nabil, Denechaud, Pierre-Damien, Gromada, Xavier, Hannou, Sarah Anissa, Zhang, Hongbo, Rashid, Talha, Salas, Elisabet, Durand, Emmanuelle, Sand, Olivier, Bonnefond, Amelie, Yengo, Loic, Chavey, Carine, Bonner, Caroline, Kerr-Conte, Julie, Abderrahmani, Amar, Auwerx, Johan, Fajas, Lluis, Froguel, Philippe and Annicotte, Jean-Sebastien (2016) KAT2B is required for pancreatic beta cell adaptation to metabolic stress by controlling the unfolded protein response. Cell Reports, 15 5: 1051-1061. doi:10.1016/j.celrep.2016.03.079


Author Rabhi, Nabil
Denechaud, Pierre-Damien
Gromada, Xavier
Hannou, Sarah Anissa
Zhang, Hongbo
Rashid, Talha
Salas, Elisabet
Durand, Emmanuelle
Sand, Olivier
Bonnefond, Amelie
Yengo, Loic
Chavey, Carine
Bonner, Caroline
Kerr-Conte, Julie
Abderrahmani, Amar
Auwerx, Johan
Fajas, Lluis
Froguel, Philippe
Annicotte, Jean-Sebastien
Title KAT2B is required for pancreatic beta cell adaptation to metabolic stress by controlling the unfolded protein response
Journal name Cell Reports   Check publisher's open access policy
ISSN 2211-1247
Publication date 2016-05-03
Sub-type Article (original research)
DOI 10.1016/j.celrep.2016.03.079
Open Access Status DOI
Volume 15
Issue 5
Start page 1051
End page 1061
Total pages 11
Place of publication New York, NY, United States
Publisher Elsevier
Collection year 2017
Language eng
Formatted abstract
The endoplasmic reticulum (ER) unfolded protein response (UPRer) pathway plays an important role in helping pancreatic β cells to adapt their cellular responses to environmental cues and metabolic stress. Although altered UPRer 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 UPRer gene expression and subsequent β cell function. Importantly, Kat2b expression is decreased in mouse and human diabetic β cells and correlates with UPRer gene expression in normal human islets. In conclusion, Kat2b is a crucial transcriptional regulator for adaptive β cell function during metabolic stress by controlling UPRer and represents a promising target for T2D prevention and treatment. 
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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