Small-molecule inducers of insulin expression in pancreatic alpha-cells
High-content screening for small-molecule inducers of insulin expression led to the identification of the compound BRD7389, which prompted alpha-cells to acquire multiple morphological and gene expression characteristics typical of a beta-cell state. Analysis of the assay performance profile suggests that kinase inhibition is the likely mechanism of action. Our data demonstrate that BRD7389 inhibits the RSK kinase family both biochemically and cellularly, and this inhibition appears to be linked to its ability to induce a beta-cell-like state. Additionally, BRD7389 enhances both the endocrine cell content and function of donor human pancreatic islets in culture.