{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:51:29Z","timestamp":1791863489956,"version":"4.3.4"},"reference-count":29,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Immunopathol Pharmacol"],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:p>Recent findings revealed that type 2 diabetes mellitus (T2D) is a chronic inflammatory disease and an islet amyloid polypeptide (IAPP)\/amylin, is deposited within pancreatic islets. IAPP\/amylin has been reported to activate NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in infiltrated macrophages. NLRP3, an intracellular pattern recognition receptor, has been shown to recognize pathogens and\/or metabolites and complexes with the adopter protein apoptosis-associated speck-like protein containing a caspase-recruitment domain ASC to form a huge complex, called an inflammasome, an interleukin (IL)-1\u03b2-processing platform. Although reactive oxygen species (ROS) were reported to be involved in activation of NLRP3 inflammasome, we were hypothesized that IAPP could directly activate NLRP3 inflammasome, leading to islets \u03b2-cell death. We analyzed expression of the inflammasome components ASC, NLRP3, caspase-1, IL-1\u03b2, IAPP\/amylin, and insulin immunohistochemically in Langerhans\u2019 islets of autopsy cases. The initial event of NLRP3 inflammasome activation was assessed using a cell-free system consisting of NLRP3 and ASC with the amplified luminescent proximity homogeneous assay. IAPP\/amylin deposition in Langerhans\u2019 islets was detected and significantly correlated with expressions of IL-1\u03b2\u2003and ASC. IAPP\/amylin directly interacted with NLRP3 and initiated an interaction between NLRP3 and ASC in a cell-free system. The deposition of IAPP\/amylin in \u03b2-cells of Langerhans\u2019 islets may act together with the expression level of an inflammasome component, ASC, to regulate IL-1\u03b2 processing, and directly lead to the dysfunction of \u03b2-cells. The interaction between IAPP\/amylin and NLRP3 could be an attractive drug target to avoid both inflammation and\u2003\u03b2-cell death for T2D therapy.<\/jats:p>","DOI":"10.1177\/2058738418788749","type":"journal-article","created":{"date-parts":[[2018,7,17]],"date-time":"2018-07-17T07:23:35Z","timestamp":1531812215000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":35,"title":["IAPP\/amylin deposition, which is correlated with expressions of ASC and IL-1\u03b2 in \u03b2-cells of Langerhans\u2019 islets, directly initiates NLRP3 inflammasome activation"],"prefix":"10.1177","volume":"32","author":[{"given":"Shinnosuke","family":"Morikawa","sequence":"first","affiliation":[{"name":"Department of Pathology, Proteo-Science Center and Graduate School of Medicine, Ehime University, Toon, 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