| First Author | Rabhi N | Year | 2016 |
| Journal | Cell Rep | Volume | 15 |
| Issue | 5 | Pages | 1051-1061 |
| PubMed ID | 27117420 | Mgi Jnum | J:235385 |
| Mgi Id | MGI:5796222 | Doi | 10.1016/j.celrep.2016.03.079 |
| Citation | Rabhi N, et al. (2016) KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response. Cell Rep 15(5):1051-61 |
| abstractText | The endoplasmic reticulum (ER) unfolded protein response (UPR(er)) pathway plays an important role in helping pancreatic beta 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 beta 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 beta cell function. Importantly, Kat2b expression is decreased in mouse and human diabetic beta cells and correlates with UPR(er) gene expression in normal human islets. In conclusion, Kat2b is a crucial transcriptional regulator for adaptive beta cell function during metabolic stress by controlling UPR(er) and represents a promising target for T2D prevention and treatment. |
