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

Esterházy, Daria
Stützer, Ina
Rechsteiner, Markus P
Beauchamp, Jeremy
Döbeli, Heinz
Hilpert, Hans
Matile, Hugues
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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 AdolescentAmino Acid SequenceAmyloid Precursor Protein Secretases/antagonists & inhibitors/genetics/metabolismAnimalsAspartic Acid Endopeptidases/antagonists & inhibitors/genetics/metabolismBlood Glucose/analysisCells, CulturedDiabetes Mellitus, Type 2/drug therapy/genetics/metabolismEnzyme Inhibitors/pharmacologyFemaleGene Silencing/drug effectsHumansInsulin/metabolism/pharmacologyInsulin ResistanceInsulin-Secreting Cells/cytology/drug effects/metabolismMembrane Glycoproteins/antagonists & inhibitors/genetics/metabolismMiceMice, Inbred C57BLMiddle AgedMolecular Sequence DataPlasmidsRNA, Small Interfering/pharmacologyReverse Transcriptase Polymerase Chain ReactionSignal Transduction/geneticsSpecies SpecificitySubstrate SpecificityTransfection
PMID: 21907142
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Research groups Cultures cellulaires et transplantations (519)
La transplantation d'îlots de Langerhans (623)
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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

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Deposited on : 2013-01-07

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