Small-Molecule Inducer of β Cell Proliferation Identified by High-Throughput Screening

The identification of factors that promote beta cell proliferation could ultimately move type 1 diabetes treatment away from insulin injection therapy and toward a cure. We have performed high-throughput, cell-based screens using rodent beta cell lines to identify molecules that induce proliferation of beta cells. Herein we report the discovery and characterization of WS6, a novel small molecule that promotes beta cell proliferation in rodent and human primary islets. In the RIP-DTA mouse model of beta cell ablation, WS6 normalized blood glucose and induced concomitant increases in beta cell proliferation and beta cell number. Affinity pulldown and kinase profiling studies implicate Erb3 binding protein-1 and the I kappa B kinase pathway in the mechanism of action of WS6.