2. Academic Validation
  3. Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass

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

  • Cell Metab. 2011 Sep 7;14(3):365-77. doi: 10.1016/j.cmet.2011.06.018.
Daria Esterházy 1,  Ina Stützer,  Haiyan Wang,  Markus P Rechsteiner,  Jeremy Beauchamp,  Heinz Döbeli,  Hans Hilpert,  Hugues Matile,  Michael Prummer,  Alexander Schmidt,  Nora Lieske,  Bernhard Boehm,  Lorella Marselli,  Domenico Bosco,  Julie Kerr-Conte,  Ruedi Aebersold,  Giatgen Andreia Spinas,  Holger Moch,  Cristiano Migliorini,  Markus Stoffel
Affiliations

Affiliation

  • 1 Institute of Molecular Systems Biology, ETH Zurich, Zurich 8093, Switzerland.
PMID: 21907142 DOI: 10.1016/j.cmet.2011.06.018
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.

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