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


Esterházy, D; Stützer, I; Wang, H; Rechsteiner, M P; Beauchamp, J; Döbeli, H; Hilpert, H; Matile, H; Prummer, M; Schmidt, A; Lieske, N; Boehm, B; Marselli, L; Bosco, D; Kerr-Conte, J; Aebersold, R; Spinas, G A; Moch, H; Migliorini, C; Stoffel, M (2011). Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass. Cell Metabolism, 14(3):365-377.

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.

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2011
Deposited On:04 Jan 2012 10:19
Last Modified:05 Apr 2016 15:14
Publisher:Elsevier
ISSN:1550-4131
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.cmet.2011.06.018
PubMed ID:21907142

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