Institute of Molecular Systems Biology, ETH Zurich, Zurich 8093, Switzerland.
Cell Metab. 2011 Sep 7;14(3):365-77. doi: 10.1016/j.cmet.2011.06.018.
Decreased β cell mass and function are hallmarks of type 2 diabetes. Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human β cells. Mice with functionally inactive Bace2 and insulin-resistant mice treated with a newly identified Bace2 inhibitor both display augmented β cell mass and improved control of glucose homeostasis due to increased insulin levels. These results implicate Bace2 in the control of β cell maintenance and provide a rational strategy to inhibit this protease for the expansion of functional pancreatic β cell mass.
β 细胞数量和功能的减少是 2 型糖尿病的特征。在这里，我们通过 siRNA 筛选鉴定出 β 位淀粉样前体蛋白裂解酶 2（Bace2）是鼠和人 β 细胞中促增殖的质膜蛋白 Tmem27 的脱落酶。功能失活的 Bace2 小鼠和用新鉴定的 Bace2 抑制剂治疗的胰岛素抵抗小鼠都表现出 β 细胞数量增加和葡萄糖稳态控制改善，这是由于胰岛素水平升高所致。这些结果表明 Bace2 参与了 β 细胞的维持控制，并提供了一种抑制这种蛋白酶的合理策略，以扩大功能性胰腺 β 细胞的数量。
