Small-molecule inducers of insulin expression in pancreatic α-cells

被引：66

作者：

Fomina-Yadlin, Dina ^{[1
,2
,3
]}

Kubicek, Stefan ^{[1
,2
]}

Walpita, Deepika ^{[2
]}

Dancik, Vlado ^{[2
,4
]}

Hecksher-Sorensen, Jacob ^{[2
]}

Bittker, Joshua A. ^{[2
]}

Sharifnia, Tanaz ^{[2
,5
]}

Shamji, Alykhan ^{[2
]}

Clemons, Paul A. ^{[2
]}

Wagner, Bridget K. ^{[2
]}

Schreiber, Stuart L. ^{[1
,2
,6
]}

机构：

[1] Harvard & Massachusetts Inst Technol, Howard Hughes Med Inst, Cambridge, MA 02142 USA

[2] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA 02142 USA

[3] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[4] Slovak Acad Sci, Math Inst, Kosice 04001, Slovakia

[5] Harvard Univ, Sch Med, Dept Biol & Biomed Sci, Boston, MA 02115 USA

[6] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 34期

基金：

美国国家卫生研究院;

关键词：

BRD7389; pancreatic islets; Rsk kinase; transdifferentiation; beta cells; BETA-CELLS; IN-VIVO; RSK; INHIBITORS;

D O I：

10.1073/pnas.1010018107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：15099 / 15104

页数：6

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