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
  • 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.