{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:29:41Z","timestamp":1791930581667,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2006,7,17]],"date-time":"2006-07-17T00:00:00Z","timestamp":1153094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:p>Human amylin is a small fibrillogenic protein that is the major constituent of pancreatic islet amyloid, which occurs in most subjects with type 2 diabetes. There is evidence that it can elicit <jats:italic>in vitro<\/jats:italic> apoptosis in islet \u03b2\u2010cells, but the physical properties that underpin its cytotoxicity have not been clearly elucidated. Here we employed electron microscopy, thioflavin T fluorescence and CD spectroscopy to analyze amylin preparations whose cytotoxic potential was established by live\u2013dead assay in cultured \u03b2\u2010cells. Highly toxic amylin contained few preformed fibrils and initially showed little \u03b2\u2010sheet content, but underwent marked time\u2010dependent aggregation and \u03b2\u2010conformer formation following dissolution. By contrast, low\u2010toxicity amylin contained abundant preformed fibrils, and demonstrated high initial \u03b2\u2010sheet content but little propensity to aggregate further once dissolved. Thus, mature amylin fibrils are not toxic to \u03b2\u2010cells, and aggregates of fibrils such as occur in pancreatic islet amyloid <jats:italic>in vivo<\/jats:italic> are unlikely to contribute to \u03b2\u2010cell loss. Rather, the toxic molecular species is likely to comprise soluble oligomers with significant \u03b2\u2010sheet content. Attempts to find ways of protecting \u03b2\u2010cells from amylin\u2010mediated death might profitably focus on preventing the conformational change from random coil to \u03b2\u2010sheet.<\/jats:p>","DOI":"10.1111\/j.1742-4658.2006.05367.x","type":"journal-article","created":{"date-parts":[[2006,7,17]],"date-time":"2006-07-17T15:29:16Z","timestamp":1153150156000},"page":"3614-3624","source":"Crossref","is-referenced-by-count":202,"title":["The aggregation potential of human amylin determines its cytotoxicity towards islet \u03b2\u2010cells"],"prefix":"10.1111","volume":"273","author":[{"given":"Barbara","family":"Konarkowska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline F.","family":"Aitken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Kistler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth J. 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