{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:11:40Z","timestamp":1791295900633,"version":"4.1.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Islets from patients with type 2 diabetes exhibit \u03b2 cell dysfunction, amyloid deposition, macrophage infiltration, and increased expression of proinflammatory cytokines and chemokines. We sought to determine whether human islet amyloid polypeptide (hIAPP), the main component of islet amyloid, might contribute to islet inflammation by recruiting and activating macrophages. Early aggregates of hIAPP, but not nonamyloidogenic rodent islet amyloid polypeptide, caused release of CCL2 and CXCL1 by islets and induced secretion of TNF-\u03b1, IL-1\u03b1, IL-1\u03b2, CCL2, CCL3, CXCL1, CXCL2, and CXCL10 by C57BL\/6 bone marrow-derived macrophages. hIAPP-induced TNF-\u03b1 secretion was markedly diminished in MyD88-, but not TLR2- or TLR4-deficient macrophages, and in cells treated with the IL-1R antagonist (IL-1Ra) anakinra. To determine the significance of IL-1 signaling in hIAPP-induced pancreatic islet dysfunction, islets from wild-type or hIAPP-expressing transgenic mice were transplanted into diabetic NOD\/SCID recipients implanted with mini-osmotic pumps containing IL-1Ra (50 mg\/kg\/d) or saline. IL-1Ra significantly improved the impairment in glucose tolerance observed in recipients of transgenic grafts 8 wk following transplantation. Islet grafts expressing hIAPP contained amyloid deposits in close association with F4\/80-expressing macrophages. Transgenic grafts contained 50% more macrophages than wild-type grafts, an effect that was inhibited by IL-1Ra. Our results suggest that hIAPP-induced islet chemokine secretion promotes macrophage recruitment and that IL-1R\/MyD88, but not TLR2 or TLR4 signaling is required for maximal macrophage responsiveness to prefibrillar hIAPP. These data raise the possibility that islet amyloid-induced inflammation contributes to \u03b2 cell dysfunction in type 2 diabetes and islet transplantation.<\/jats:p>","DOI":"10.4049\/jimmunol.1002854","type":"journal-article","created":{"date-parts":[[2011,8,4]],"date-time":"2011-08-04T07:02:30Z","timestamp":1312441350000},"page":"2755-2765","source":"Crossref","is-referenced-by-count":172,"title":["IL-1 Blockade Attenuates Islet Amyloid Polypeptide-Induced Proinflammatory Cytokine Release and Pancreatic Islet Graft Dysfunction"],"prefix":"10.1093","volume":"187","author":[{"given":"Clara","family":"Westwell-Roper","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia , Vancouver, British Columbia, Canada V5Z 4H4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek L","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia , Vancouver, British Columbia, Canada V5Z 4H4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Soukhatcheva","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia , Vancouver, British Columbia, Canada V5Z 4H4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn J","family":"Potter","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia , Vancouver, British Columbia, Canada V5Z 4H4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"van Rooijen","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Vrije Universiteit Medical Center , 1081 BT Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan A","family":"Ehses","sequence":"additional","affiliation":[{"name":"Department of Surgery, Child and Family Research Institute, University of British Columbia , Vancouver, British Columbia, Canada V5Z 4H4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Bruce","family":"Verchere","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia , Vancouver, British Columbia, Canada V5Z 4H4"},{"name":"Department of Surgery, Child and Family Research Institute, University of British Columbia , Vancouver, British Columbia, Canada V5Z 4H4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,9,1]]},"reference":[{"key":"2025032410304097800_r1","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/nature05482","article-title":"Mechanisms linking obesity to insulin resistance and type 2 diabetes","volume":"444","author":"Kahn","year":"2006","journal-title":"Nature"},{"key":"2025032410304097800_r2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2337\/diabetes.52.1.102","article-title":"Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes","volume":"52","author":"Butler","year":"2003","journal-title":"Diabetes"},{"key":"2025032410304097800_r3","doi-asserted-by":"crossref","first-page":"4065","DOI":"10.1210\/jc.2008-0396","article-title":"Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta-cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation","volume":"93","author":"B\u00f6ni-Schnetzler","year":"2008","journal-title":"J. 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