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Small-molecule inducers of insulin expression in pancreatic alpha-cells.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2010 Aug 24; Vol. 107 (34), pp. 15099-104. Date of Electronic Publication: 2010 Aug 09. - Publication Year :
- 2010
-
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.
- Subjects :
- Animals
Cell Differentiation drug effects
Cell Line
Drug Evaluation, Preclinical
Gene Expression drug effects
Glucagon-Secreting Cells cytology
Humans
Insulin-Secreting Cells cytology
Insulin-Secreting Cells drug effects
Insulin-Secreting Cells metabolism
Islets of Langerhans drug effects
Islets of Langerhans metabolism
Mice
Molecular Structure
Protein Kinase Inhibitors chemistry
Quinolones chemistry
RNA Interference
Ribosomal Protein S6 Kinases antagonists & inhibitors
Ribosomal Protein S6 Kinases genetics
Tissue Culture Techniques
Glucagon-Secreting Cells drug effects
Glucagon-Secreting Cells metabolism
Insulin biosynthesis
Protein Kinase Inhibitors pharmacology
Quinolones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 107
- Issue :
- 34
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 20696901
- Full Text :
- https://doi.org/10.1073/pnas.1010018107