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

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.

SUBMITTER: Fomina-Yadlin D

PROVIDER: S-EPMC2930573 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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

Fomina-Yadlin Dina D Kubicek Stefan S Walpita Deepika D Dancik Vlado V Hecksher-Sørensen Jacob J Bittker Joshua A JA Sharifnia Tanaz T Shamji Alykhan A Clemons Paul A PA Wagner Bridget K BK Schreiber Stuart L SL

Proceedings of the National Academy of Sciences of the United States of America 20100809 34

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 cont ...[more]

PMID: 20696901

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