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

Esterházy, Daria; Stützer, Ina; Wang, Haiyan; Rechsteiner, Markus P; Beauchamp, Jeremy; Döbeli, Heinz; Hilpert, Hans; Matile, Hugues; Prummer, Michael; Schmidt, Alexander; Lieske, Nora; Boehm, Bernhard; Marselli, Lorella; Bosco, Domenico; Kerr-Conte, Julie; Aebersold, Ruedi; Spinas, Giatgen Andreia; Moch, Holger; Migliorini, Cristiano; Stoffel, Markus

doi:10.1016/j.cmet.2011.06.018

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Title		Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass
Authors		Esterházy, Daria Stützer, Ina Wang, Haiyan Rechsteiner, Markus P Beauchamp, Jeremy Döbeli, Heinz Hilpert, Hans Matile, Hugues Prummer, Michael Schmidt, Alexander Lieske, Nora Boehm, Bernhard Marselli, Lorella Bosco, Domenico Kerr-Conte, Julie Aebersold, Ruedi Spinas, Giatgen Andreia Moch, Holger Migliorini, Cristiano Stoffel, Markus show all authors [1 - 20]
Published in		Cell metabolism. 2011, vol. 14, no. 3, p. 365-77
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.
Keywords		Adolescent — Amino Acid Sequence — Amyloid Precursor Protein Secretases/antagonists & inhibitors/genetics/metabolism — Animals — Aspartic Acid Endopeptidases/antagonists & inhibitors/genetics/metabolism — Blood Glucose/analysis — Cells, Cultured — Diabetes Mellitus, Type 2/drug therapy/genetics/metabolism — Enzyme Inhibitors/pharmacology — Female — Gene Silencing/drug effects — Humans — Insulin/metabolism/pharmacology — Insulin Resistance — Insulin-Secreting Cells/cytology/drug effects/metabolism — Membrane Glycoproteins/antagonists & inhibitors/genetics/metabolism — Mice — Mice, Inbred C57BL — Middle Aged — Molecular Sequence Data — Plasmids — RNA, Small Interfering/pharmacology — Reverse Transcriptase Polymerase Chain Reaction — Signal Transduction/genetics — Species Specificity — Substrate Specificity — Transfection
Identifiers		DOI: 10.1016/j.cmet.2011.06.018 PMID: 21907142
Full text		Article (Published version) (1.1 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de chirurgie
Research groups		Cultures cellulaires et transplantations (519) La transplantation d'îlots de Langerhans (623)
Citation (ISO format)		ESTERHÁZY, Daria et al. Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass. In: Cell metabolism, 2011, vol. 14, n° 3, p. 365-77. doi: 10.1016/j.cmet.2011.06.018 https://archive-ouverte.unige.ch/unige:25023