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Proc Natl Acad Sci U S A DOI:10.1073/pnas.1010018107

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

Publication TypeJournal Article
Year of Publication2010
AuthorsFomina-Yadlin, D, Kubicek, S, Walpita, D, Dančík, V, Hecksher-Sørensen, J, Bittker, JA, Sharifnia, T, Shamji, A, Clemons, PA, Wagner, BK, Schreiber, SL
JournalProc Natl Acad Sci U S A
Date Published2010 Aug 24
KeywordsAnimals, Cell Differentiation, Cell Line, Drug Evaluation, Preclinical, Gene Expression, Glucagon-Secreting Cells, Humans, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Mice, Molecular Structure, Protein Kinase Inhibitors, Quinolones, Ribosomal Protein S6 Kinases, RNA Interference, Tissue Culture Techniques

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.


Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID20696901
PubMed Central IDPMC2930573
Grant ListR37 GM038627 / GM / NIGMS NIH HHS / United States
DP2 DK083048 / DK / NIDDK NIH HHS / United States
R01 GM038627 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
GM38627 / GM / NIGMS NIH HHS / United States
RL1-HG004671 / HG / NHGRI NIH HHS / United States
DP2-DK083048 / DK / NIDDK NIH HHS / United States
RL1 HG004671 / HG / NHGRI NIH HHS / United States