Bace2 Is a Beta-Cell-Enriched Protease that Regulates Pancreatic Beta-Cell Function and Mass

Decreased ? 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 ? cells. Mice with functionally inactive Bace2 and insulin-resistant mice treated with a newly identified Bace2 inhibitor both display augmented ? cell mass and improved control of glucose homeostasis due to increased insulin levels. These results implicate Bace2 in the control of ? cell maintenance and provide a rational strategy to inhibit this protease for the expansion of functional pancreatic ? cell mass.

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