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Proceedings of the National Academy of Sciences of the United States of America 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, Dancik, V, Hecksher-Sørensen, J, Bittker, JA, Sharifnia, T, Shamji, A, Clemons, PA, Wagner, BK, Schreiber, SL
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue34
Pages15099-104
Date Published2010/08/24
ISSN0027-8424
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.

URLhttp://www.pnas.org/cgi/pmidlookup?view=long&pmid=20696901
DOI10.1073/pnas.1010018107
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/20696901?dopt=Abstract