| First Author | Sekiya M | Year | 2023 |
| Journal | Cell Rep | Pages | 112914 |
| PubMed ID | 37557182 | Mgi Jnum | J:338980 |
| Mgi Id | MGI:7517252 | Doi | 10.1016/j.celrep.2023.112914 |
| Citation | Sekiya M, et al. (2023) Loss of CtBP2 may be a mechanistic link between metabolic derangements and progressive impairment of pancreatic beta cell function. Cell Rep :112914 |
| abstractText | The adaptive increase in insulin secretion in early stages of obesity serves as a safeguard mechanism to maintain glucose homeostasis that cannot be sustained, and the eventual decompensation of beta cells is a key event in the pathogenesis of diabetes. Here we describe a crucial system orchestrated by a transcriptional cofactor CtBP2. In cultured beta cells, insulin gene expression is coactivated by CtBP2. Global genomic mapping of CtBP2 binding sites identifies a key interaction between CtBP2 and NEUROD1 through which CtBP2 decompacts chromatin in the insulin gene promoter. CtBP2 expression is diminished in pancreatic islets in multiple mouse models of obesity, as well as human obesity. Pancreatic beta cell-specific CtBP2-deficient mice manifest glucose intolerance with impaired insulin secretion. Our transcriptome analysis highlights an essential role of CtBP2 in the maintenance of beta cell integrity. This system provides clues to the molecular basis in obesity and may be targetable to develop therapeutic approaches. |
