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

Proc Natl Acad Sci U S A

Authors	Dina Fomina-Yadlin Stefan Kubicek Deepika Walpita Vlado Dančík Jacob Hecksher-Sørensen Joshua Bittker Tanaz Sharifnia Alykhan Shamji Paul Clemons Bridget Wagner Stuart Schreiber
Keywords	Animals Humans Mice Cell Differentiation Cell Line RNA Interference Gene Expression Insulin Insulin-Secreting Cells Protein Kinase Inhibitors Molecular Structure Drug Evaluation, Preclinical Islets of Langerhans Glucagon-Secreting Cells Quinolones Ribosomal Protein S6 Kinases 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.
Year of Publication	2010
Journal	Proc Natl Acad Sci U S A
Volume	107
Issue	34
Pages	15099-104
Date Published	2010 Aug 24
ISSN	1091-6490
DOI	10.1073/pnas.1010018107
PubMed ID	20696901
PubMed Central ID	PMC2930573
Links	Google Scholar DOI PubMed
Grant list	R37 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