Department of Chemistry, 10550 North Torrey Pines Road, The Scripps Research Institute, La Jolla, California 92037, United States.
J Am Chem Soc. 2013 Feb 6;135(5):1669-72. doi: 10.1021/ja309304m. Epub 2013 Jan 25.
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.
确定促进β细胞增殖的因素最终可能使 1 型糖尿病的治疗方法从胰岛素注射治疗转向治愈。我们使用啮齿动物β细胞系进行了高通量、基于细胞的筛选，以鉴定诱导β细胞增殖的分子。在此，我们报告了 WS6 的发现和特性，WS6 是一种新型的小分子，可促进啮齿动物和人原代胰岛中的β细胞增殖。在 RIP-DTA 小鼠β细胞消融模型中，WS6 使血糖正常化，并同时诱导β细胞增殖和β细胞数量增加。亲和下拉和激酶谱分析研究表明，Erb3 结合蛋白-1 和 IκB 激酶途径参与了 WS6 的作用机制。
