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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
Volume107
Issue34
Pages15099-104
Date Published2010 Aug 24
ISSN1091-6490
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
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.

DOI10.1073/pnas.1010018107
Pubmed

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

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