{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:52:56Z","timestamp":1792691576518,"version":"4.5.0"},"reference-count":308,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>Islet amyloid polypeptide (IAPP), the main component of islet amyloid in type 2 diabetes and islet transplants, is now recognized as a contributor to beta cell dysfunction. Increasingly, evidence warrants its investigation in type 1 diabetes owing to both its immunomodulatory and metabolic actions. Autoreactive T cells to IAPP-derived epitopes have been described in humans, suggesting that IAPP is an islet autoantigen in type 1 diabetes. In addition, although aggregates of IAPP have not been implicated in type 1 diabetes, they are potent pro-inflammatory stimuli to innate immune cells, and thus, could influence autoimmunity. IAPP aggregates also occur rapidly in transplanted islets and likely contribute to islet transplant failure in type 1 diabetes through sterile inflammation. In addition, since type 1 diabetes is a disease of both insulin and IAPP deficiency, clinical trials have examined the potential benefits of IAPP replacement in type 1 diabetes with the injectable IAPP analogue, pramlintide. Pramlintide limits postprandial hyperglycemia by delaying gastric emptying and suppressing hyperglucagonemia, underlining the possible role of IAPP in postprandial glucose metabolism. Here, we review IAPP in the context of type 1 diabetes: from its potential involvement in type 1 diabetes pathogenesis, through its role in glucose metabolism and use of IAPP analogues as therapeutics, to its potential role in clinical islet transplant failure and considerations in this regard for future beta cell replacement strategies.<\/jats:p>","DOI":"10.1530\/jme-17-0138","type":"journal-article","created":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T20:45:13Z","timestamp":1517258713000},"page":"R57-R75","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":50,"title":["IAPP and type 1 diabetes: implications for immunity, metabolism and islet transplants"],"prefix":"10.1530","volume":"60","author":[{"given":"Heather C","family":"Denroche","sequence":"first","affiliation":[{"name":"1Department of Surgery, BC Children\u2019s Hospital, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Bruce","family":"Verchere","sequence":"additional","affiliation":[{"name":"1Department of Surgery, BC Children\u2019s Hospital, University of British Columbia, Vancouver, British Columbia, Canada"},{"name":"2Department of Pathology and Laboratory Medicine, BC Children\u2019s Hospital, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref1181","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/ni.2639","article-title":"CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation","volume":"14","year":"2013","journal-title":"Nature Immunology"},{"key":"ref2641","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/nbt.3033","article-title":"Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells","volume":"32","year":"2014","journal-title":"Nature Biotechnology"},{"key":"ref581","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1084\/jem.189.2.347","article-title":"The role of macrophages in T cell-mediated autoimmune diabetes in nonobese diabetic mice","volume":"189","year":"1999","journal-title":"Journal of Experimental Medicine"},{"key":"ref2461","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1172\/JCI31368","article-title":"Priming and effector dependence on insulin B:9-23 peptide in NOD islet autoimmunity","volume":"117","year":"2007","journal-title":"Journal of Clinical Investigation"},{"key":"ref941","first-page":"191","article-title":"Food intake and meal pattern in IAPP knockout mice with and without infusion of exogenous IAPP Scandinavian.","volume":"47","year":"2012","journal-title":"Journal of Gastroenterology"},{"key":"ref2171","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s001250050092","article-title":"Role of islet amyloid polypeptide secretion in insulin-resistant humans","volume":"37","year":"1994","journal-title":"Diabetologia"},{"key":"ref3051","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.2337\/dc07-2446","article-title":"Impaired hyperglycemia-induced delay in gastric emptying in patients with type 1 diabetes deficient for islet amyloid polypeptide","volume":"31","year":"2008","journal-title":"Diabetes Care"},{"key":"ref1311","first-page":"1721","article-title":"Simultaneous detection of circulating autoreactive CD8+ T-cells specific for different islet cell-associated epitopes using combinatorial MHC multimers","volume":"59","year":"2010","journal-title":"Blood"},{"key":"ref491","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1002\/jlb.58.5.526","article-title":"The amyloidogenic peptide human amylin augments the inflammatory activites of eosinophils","volume":"58","year":"1995","journal-title":"Journal of Leukocyte Biology"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1080\/01913120500323563","article-title":"Morphological and ultrastructural features of human islet grafts performed in diabetic nude mice","volume":"29","year":"2005","journal-title":"Ultrastructural Pathology"},{"key":"ref2691","first-page":"1570","article-title":"Disproportionately elevated proinsulin levels precede the onset of insulin-dependent diabetes mellitus in siblings with low first phase insulin responses. 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