| First Author | Rakshit K | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 11 | Pages | 111179 |
| PubMed ID | 39524327 | Mgi Jnum | J:358364 |
| Mgi Id | MGI:7781008 | Doi | 10.1016/j.isci.2024.111179 |
| Citation | Rakshit K, et al. (2024) Core circadian transcription factor Bmal1 mediates beta cell response and recovery from pro-inflammatory injury. iScience 27(11):111179 |
| abstractText | The circadian clock plays a vital role in modulating the cellular immune response. However, its role in mediating pro-inflammatory diabetogenic beta cell injury remains largely unexplored. Our studies demonstrate that the exposure of beta cells to IL-1beta-mediated inflammation alters genome-wide DNA binding of core circadian transcription factors BMAL1:CLOCK enriched for genomic sites important for cellular response to inflammation. Correspondingly, conditional deletion of Bmal1 in mouse beta cells was shown to impair the ability of beta cells to recover from streptozotocin-mediated pro-inflammatory injury in vivo, leading to beta cell failure and the development of diabetes. Further data integration analysis revealed that the beta cell circadian clock orchestrates the recovery from pro-inflammatory injury by regulating transcriptional responses to oxidative stress, DNA damage, and nuclear factor kappaB(NF-kappaB)-driven inflammation. Our study suggests that the beta cell circadian clock mediates beta cell response and recovery from pro-inflammatory injury common to the pathogenesis of diabetes mellitus. |
