A small molecule inducer of β cell proliferation identified by high-throughput screening
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Glynne, Richard, Mcnamara, Peter, Laffitte, Bryan, Li, Jing, Wu, Tom, Jin, Qihui, Baaten, Janine, Cho, Charles, Kamireddy, Anwesh, Zhang, You-Qing, Harb, George, Filippi, Christophe, Shen, Weijun, Tremblay, Matthew, Deshmukh, Vishal, Wang, Weidong, Swoboda, Jonathan, Wu, Xu, Herman, Ann and Schultz, Peter (2013) A small molecule inducer of β cell proliferation identified by high-throughput screening. Journal of the American Chemical Society, 135 (5). pp. 1669-1672. ISSN 0002-7863
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.
| Item Type: | Article |
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| Date Deposited: | 13 Oct 2015 13:13 |
| Last Modified: | 13 Oct 2015 13:13 |
| URI: | https://oak.novartis.com/id/eprint/9363 |