{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T23:04:23Z","timestamp":1779923063350,"version":"3.53.1"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,10,23]],"date-time":"2014-10-23T00:00:00Z","timestamp":1414022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p>\n                    BACE2 (\u03b2\u2010site APP\u2010cleaving enzyme 2) is a protease localized in the brain, where it appears to play a role in the development of Alzheimer disease (AD). It is also found in the pancreas, although its biologic function is not fully known. Amyloidogenic diseases, including AD and type 2 diabetes mellitus (T2D), share the accumulation of abnormally folded and insoluble proteins that interfere with cell function. Islet amyloid polypeptide (IAPP) deposits are a key pathogenic feature of T2D. Within this context, we found by global gene expression profiling that BACE2 was up\u2010regulated in the rat pancreatic \u03b2\u2010cell line INS1E stably transfected with human\n                    <jats:italic>IAPP<\/jats:italic>\n                    gene (hIAPP\u2010INS1E). Glucose\u2010stimulated insulin secretion (GSIS) in hIAPP\u2010INS1E cells was 30% lower than in INS1E cells. Additionally, INS1E cells transfected with a transient overexpression of BACE2 showed a 60% decrease in proliferation, a 3\u2010fold increase in reactive oxygen species production, and a 25% reduction in GSIS compared to control cells. Remarkably, silencing of endogenous BACE2 in hIAPP\u2010INS1E cells resulted in a significant improvement in GSIS (3\u2010fold increase\n                    <jats:italic>vs.<\/jats:italic>\n                    untransfected cells), revealing the significant role of BACE2 expression in \u03b2\u2010cell function. Thus, BACE2 inhibition may be useful to recover insulin secretion in hIAPP\u2010INS1E defective cells and may be proposed as a therapeutic target for T2D.\u2010 Montane, J., Servitja, J.\u2010M., Novials, A. Inhibition of BACE2 counteracts hIAPP\u2010induced insulin secretory defects in pancreatic \u03b2\u2010cells. FASEB J. 29, 95\u2013104 (2015).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-255489","type":"journal-article","created":{"date-parts":[[2014,10,24]],"date-time":"2014-10-24T02:23:29Z","timestamp":1414117409000},"page":"95-104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Inhibition of BACE2 counteracts hIAPP\u2010induced insulin secretory defects in pancreatic \u03b2\u2010cells"],"prefix":"10.1096","volume":"29","author":[{"given":"Gema","family":"Alcarraz\u2010Viz\u00e1n","sequence":"first","affiliation":[{"name":"Diabetes and Obesity Research Laboratory Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Casini","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Laboratory Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Cadavez","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Laboratory Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montse","family":"Visa","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Laboratory Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Montane","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Laboratory Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan\u2010Marc","family":"Servitja","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Laboratory Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Novials","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Laboratory Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29103"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0405"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0240594"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00042.2009"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.1.102"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.39.5.634"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.42.10.1514"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-005-0007-2"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R800018200"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.08.035"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0037"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0178"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-1111-z"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5443.1255a"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3426com"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1385\/JMN:29:1:65","article-title":"Functional domains of the BACE1 and BACE2 promoters and mechanisms of transcriptional suppression of the BACE2 promoter in normal neuronal cells","volume":"29","author":"Lahiri D. 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