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Small-Molecule Inducer of β Cell Proliferation Identified by High-Throughput Screening
- Source :
- Journal of the American Chemical Society. 135:1669-1672
- Publication Year :
- 2013
- Publisher :
- American Chemical Society (ACS), 2013.
-
Abstract
- The identification of factors that promote β cell proliferation could ultimately move type 1 diabetes treatment away from insulin injection therapy and toward a cure. We have performed high-throughput, cell-based screens using rodent β cell lines to identify molecules that induce proliferation of β cells. Herein we report the discovery and characterization of WS6, a novel small molecule that promotes β cell proliferation in rodent and human primary islets. In the RIP-DTA mouse model of β cell ablation, WS6 normalized blood glucose and induced concomitant increases in β cell proliferation and β cell number. Affinity pulldown and kinase profiling studies implicate Erb3 binding protein-1 and the IκB kinase pathway in the mechanism of action of WS6.
- Subjects :
- Cell
Drug Evaluation, Preclinical
IκB kinase
Biochemistry
Catalysis
Cell Line
Islets of Langerhans
Mice
Structure-Activity Relationship
Colloid and Surface Chemistry
medicine
Animals
Humans
Urea
Inducer
Cell Proliferation
Dose-Response Relationship, Drug
Molecular Structure
Kinase
Cell growth
Chemistry
General Chemistry
Small molecule
Molecular biology
High-Throughput Screening Assays
Molecular Weight
medicine.anatomical_structure
Mechanism of action
Cell culture
medicine.symptom
Subjects
Details
- ISSN :
- 15205126 and 00027863
- Volume :
- 135
- Database :
- OpenAIRE
- Journal :
- Journal of the American Chemical Society
- Accession number :
- edsair.doi.dedup.....75bd49122d522040efaa9a74797d00bd