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

• DOI: 10.1016/j.celrep.2016.03.079
• Publication Date: 2016-04-30T21:08:29Z
• Authors: Nabil Rabhi; Pierre-Damien Den...; Xavier Gromada; Sarah Anissa Hannou; Hongbo Zhang; Talha Rashid; Elisabet Salas; Emmanuelle Durand; Olivier Sand; Amélie Bonnefond; Loic Yengo; Carine Chavey; Caroline Bonner; Julie Kerr-Conte; Amar Abderrahmani; Johan Auwerx; Lluis Fajas; Philippe Froguel; Jean-Sébastien An...
• Keywords: Pancreatic Islets

The endoplasmic reticulum (ER) unfolded protein response (UPR(er)) pathway plays an important role in helping pancreatic β cells to adapt their cellular responses environmental cues and metabolic stress. Although altered UPR(er) gene expression appears rodent human type 2 diabetic (T2D) islets, the underlying molecular mechanisms remain unknown. We show here that germline cell-specific disruption of lysine acetyltransferase 2B (Kat2b) mice leads impaired insulin secretion glucose intolerance. Genome-wide analysis Kat2b-regulated genes functional assays reveal a critical for Kat2b maintaining subsequent cell function. Importantly, is decreased mouse correlates with normal islets. In conclusion, crucial transcriptional regulator adaptive function during stress by controlling represents promising target T2D prevention treatment.