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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Rabhi N,Denechaud PD,Gromada X,Hannou SA,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 JSdoi
10.1016/j.celrep.2016.03.079subject
Has Abstractpub_date
2016-05-03 00:00:00pages
1051-1061issue
5issn
2211-1247pii
S2211-1247(16)30368-0journal_volume
15pub_type
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