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Cell Metab. 2011 Sep 7;14(3):365-77. doi: 10.1016/j.cmet.2011.06.018.

Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass.

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  • 1Institute of Molecular Systems Biology, ETH Zurich, Zurich 8093, Switzerland.

Abstract

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

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