{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:26:24Z","timestamp":1789986384436,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T00:00:00Z","timestamp":1488153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP\u2010126204"],"award-info":[{"award-number":["MOP\u2010126204"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2017,5]]},"abstract":"\n Aims<\/jats:title>\n \n Islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to \u03b2\u2010cell failure in type 2 diabetes, cultured and transplanted islets. We previously showed that biosynthetic hIAPP aggregates induce \u03b2\u2010cell Fas upregulation and activation of the Fas apoptotic pathway. We used cultured human and hIAPP\u2010expressing mouse islets to investigate: (1) the role of interleukin\u20101\u03b2 (\n IL<\/jats:styled-content>\n \u20101\u03b2) in amyloid\u2010induced\n F<\/jats:styled-content>\n as upregulation; and (2) the effects of\n IL<\/jats:styled-content>\n \u20101\u03b2\u2010induced \u03b2\u2010cell dysfunction on pro\u2010islet amyloid polypeptide (\n proIAPP<\/jats:styled-content>\n ) processing and amyloid formation.\n <\/jats:p>\n <\/jats:sec>\n \n Research Design and Methods<\/jats:title>\n \n Human and h\n \n IAPP<\/jats:styled-content>\n <\/jats:italic>\n \u2010expressing mouse islets were cultured to form amyloid without or with the\n IL<\/jats:styled-content>\n \u20101 receptor antagonist (\n IL<\/jats:styled-content>\n \u20101\n Ra<\/jats:styled-content>\n ) anakinra, in the presence or absence of recombinant\n IL<\/jats:styled-content>\n \u20101\u03b2. Human islets in which amyloid formation was prevented (amyloid inhibitor or Ad\u2010proh\n IAPP<\/jats:italic>\n \u2010siRNA) were cultured similarly. \u03b2\u2010cell function, apoptosis,\n F<\/jats:styled-content>\n as expression, caspase\u20108 activation, islet\n IL<\/jats:styled-content>\n \u20101\u03b2, \u03b2\u2010cell area, \u03b2\u2010\/\u03b1\u2010cell ratio, amyloid formation, and (pro)\n IAPP<\/jats:styled-content>\n forms were assessed.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n hIAPP<\/jats:styled-content>\n aggregates were found to increase\n IL<\/jats:styled-content>\n \u20101\u03b2 levels in cultured human islets that correlated with \u03b2\u2010cell\n F<\/jats:styled-content>\n as upregulation, caspase\u20108 activation and apoptosis, all of which were reduced by\n IL\u20101Ra<\/jats:styled-content>\n treatment or prevention of amyloid formation. Moreover,\n IL\u20101Ra<\/jats:styled-content>\n improved culture\u2010induced \u03b2\u2010cell dysfunction and restored impaired\n proIAPP<\/jats:styled-content>\n processing, leading to lower amyloid formation.\n IL<\/jats:styled-content>\n \u20101\u03b2 treatment potentiated impaired\n proIAPP<\/jats:styled-content>\n processing and increased amyloid formation in cultured human and h\n \n IAPP<\/jats:styled-content>\n <\/jats:italic>\n \u2010expressing mouse islets, which were prevented by\n IL\u20101Ra<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n IL\u20101\u03b2 plays a dual role by: (1) mediating amyloid\u2010induced Fas upregulation and \u03b2\u2010cell apoptosis; (2) inducing impaired\n proIAPP<\/jats:styled-content>\n processing thereby potentiating amyloid formation. Blocking\n IL<\/jats:styled-content>\n \u20101\u03b2 may provide a new strategy to preserve \u03b2 cells in conditions associated with islet amyloid formation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.12873","type":"journal-article","created":{"date-parts":[[2017,1,6]],"date-time":"2017-01-06T02:24:18Z","timestamp":1483669458000},"page":"682-694","source":"Crossref","is-referenced-by-count":42,"title":["Dual role of interleukin\u20101\u03b2 in islet amyloid formation and its \u03b2\u2010cell toxicity:\n I<\/scp>\n mplications for type 2 diabetes and islet transplantation"],"prefix":"10.1111","volume":"19","author":[{"given":"Yoo Jin","family":"Park","sequence":"first","affiliation":[{"name":"Department of Surgery, Faculty of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth L.","family":"Warnock","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziliang","family":"Ao","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nooshin","family":"Safikhan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Meloche","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Asadi","sequence":"additional","affiliation":[{"name":"Department of Cellular and Physiological Sciences, Faculty of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Kieffer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine University of British Columbia Vancouver British Columbia Canada"},{"name":"Department of Cellular and Physiological Sciences, Faculty of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1903-5257","authenticated-orcid":false,"given":"Lucy","family":"Marzban","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1326"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62154-6"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00042.2009"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.02.036"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0485"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2451-2"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-3152-1"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0802893"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909024107"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0037"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090532"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0197"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-1255-x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500997200"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3CP53345J"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008423200"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.631697"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0522"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2010.111"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71981"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69866"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810087106"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2925"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4275"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0b013e32833bf6dc"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200215318"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0396"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0543"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0305683101"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0863"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3447-x"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3304-y"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6438"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/db05-1566"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.7.2117"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2802-z"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1935"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(97)00039-2"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1650"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11729"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.12873","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.12873","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:21:13Z","timestamp":1761862873000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.12873"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,27]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1111\/dom.12873"],"URL":"https:\/\/doi.org\/10.1111\/dom.12873","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,27]]}}}