Rabhi, NabilDenechaud, Pierre-DamienGromada, XavierHannou, Sarah AnissaZhang, HongboRashid, TalhaSalas, ElisabetDurand, EmmanuelleSand, OlivierBonnefond, AmélieYengo, LoicChavey, CarineBonner, CarolineKerr-Conte, JulieAbderrahmani, AmarAuwerx, JohanFajas, LluisFroguel, PhilippeAnnicotte, Jean-Sébastien2016-06-132016-06-132016-06-13201610.1016/j.celrep.2016.03.079https://infoscience.epfl.ch/handle/20.500.14299/126597WOS:000376164600015The 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.text::journal::journal article::research article