Small-molecule inducers of insulin expression in pancreatic α-cells.

High-content screening for small-molecule inducers of insulin expression identified the compound BRD7389, which caused α-cells to adopt several morphological and gene expression features of a β-cell state. Assay-performance profile analysis suggests kinase inhibition as a mechanism of action, and we show that biochemical and cellular inhibition of the RSK kinase family by BRD7389 is likely related to its ability induce a β-cell-like state. 8RD7389 also increases the endocrine cell content and function of donor human pancreatic islets in culture. [ABSTRACT FROM AUTHOR]