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

  • Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15099-104. doi: 10.1073/pnas.1010018107.
Dina Fomina-Yadlin  1 ,  Stefan Kubicek ,  Deepika Walpita ,  Vlado Dancik ,  Jacob Hecksher-Sørensen ,  Joshua A Bittker ,  Tanaz Sharifnia ,  Alykhan Shamji ,  Paul A Clemons ,  Bridget K Wagner ,  Stuart L Schreiber
Affiliations
  • 1. Howard Hughes Medical Institute, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142.
PMID: 20696901 DOI: 10.1073/pnas.1010018107
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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