Effect of conditional deletion of Bmal1 in pancreatic ß-cells in modulating transcriptional islet response to STZ-mediated pro-inflammatory injury

The circadian clock plays a vital role in modulating the cellular immune response. However, its role in mediating pro-inflammatory diabetogenic ß-cell injury remains largely unexplored. Our studies demonstrate that conditional deletion of Bmal1 in mouse ß-cells was shown to impair the ability of ß-cells to recover from streptozotocin-mediated pro-inflammatory injury in vivo, leading to ß-cell failure and the development of diabetes. Our study suggests that the ß-cell circadian clock mediates ß-cell response and recovery from pro-inflammatory injury common to the pathogenesis of diabetes mellitus. Overall design: Control & ß-Bmal1-/- mice were given submaximal dose of streptozotocin (STZ) or citrate buffer vehicle (VEH) and pancreatic islets were isolated at 24 h and 4 wk post STZ/ VEH injection.