Small-molecule inducers of insulin expression in pancreatic alpha-cells.
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||
Proc Natl Acad Sci U S A
2010 Aug 24
|PubMed Central ID||
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