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

Fomina-Yadlin, Dina; Kubicek, Stefan; Walpita, Deepika; Dancik, Vlado; Hecksher-Sørensen, Jacob; Bittker, Joshua A; Sharifnia, Tanaz; Shamji, Alykhan et al. · Proc Natl Acad Sci U S A · 2010

basic_science · Level V

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Abstract

High-content screening for small-molecule inducers of insulin expression identified the compound BRD7389, which caused alpha-cells to adopt several morphological and gene expression features of a beta-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 beta-cell-like state. BRD7389 also increases the endocrine cell content and function of donor human pancreatic islets in culture.

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