title: Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and 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.
authors: Institute of Molecular Systems Biology, ETH Zurich, Zurich 8093, Switzerland.
authors: Daria
authors: D
authors: Esterházy
authors: Ina
authors: I
authors: Stützer
authors: Haiyan
authors: H
authors: Wang
authors: Markus P
authors: MP
authors: Rechsteiner
authors: Jeremy
authors: J
authors: Beauchamp
authors: Heinz
authors: H
authors: Döbeli
authors: Hans
authors: H
authors: Hilpert
authors: Hugues
authors: H
authors: Matile
authors: Michael
authors: M
authors: Prummer
authors: Alexander
authors: A
authors: Schmidt
authors: Nora
authors: N
authors: Lieske
authors: Bernhard
authors: B
authors: Boehm
authors: Lorella
authors: L
authors: Marselli
authors: Domenico
authors: D
authors: Bosco
authors: Julie
authors: J
authors: Kerr-Conte
authors: Ruedi
authors: R
authors: Aebersold
authors: Giatgen Andreia
authors: GA
authors: Spinas
authors: Holger
authors: H
authors: Moch
authors: Cristiano
authors: C
authors: Migliorini
authors: Markus
authors: M
authors: Stoffel
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008969:Molecular Sequence Data; D010957:Plasmids; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D013045:Species Specificity; D013379:Substrate Specificity; D014162:Transfection
chemical_list: C509285:Bace2 protein, mouse; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C504407:Tmem27 protein, mouse; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases