{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:29:43Z","timestamp":1791930583225,"version":"4.3.4"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1990,7]]},"abstract":"<jats:p>Islet amyloid polypeptide (IAPP), a putative polypeptide hormone, is a product of pancreatic beta-cells and the major constituent of the amyloid deposits seen mainly in islets of type 2 diabetic humans and diabetic cats. The connection between IAPP amyloid formation and diabetes is unknown, but a limited segment of the IAPP molecule, positions 20-29, seems responsible for the aggregation to fibrils. Differences in the amino acid sequence of this region probably determine whether or not islet amyloid can develop in a particular species. Amyloid fibril formation can be mimicked in vitro with the aid of synthetic peptides. With this technique we show that peptides corresponding to IAPP positions 20-29 of human and cat, species that develop IAPP-derived islet amyloid, form amyloid-like fibrils in vitro. The corresponding IAPP segment from three rodent species that do not develop IAPP-derived amyloid did not give rise to fibrils. Substitution of the human IAPP-(20-29) decapeptide with one or two amino acid residues from species without islet amyloid generally reduced the capacity to form fibrils. We conclude that the sequence Ala-Ile-Leu-Ser-Ser, corresponding to positions 25-29 of human IAPP, is strongly amyloidogenic and that a proline-for-serine substitution in position 28, as in several rodents, almost completely inhibits formation of amyloid fibrils.<\/jats:p>","DOI":"10.1073\/pnas.87.13.5036","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:22:10Z","timestamp":1149060130000},"page":"5036-5040","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":730,"title":["Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation."],"prefix":"10.1073","volume":"87","author":[{"given":"P","family":"Westermark","sequence":"first","affiliation":[{"name":"Department of Pathology I, University Hospital, Link\u00f6ping, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U","family":"Engstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Pathology I, University Hospital, Link\u00f6ping, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K H","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pathology I, University Hospital, Link\u00f6ping, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G T","family":"Westermark","sequence":"additional","affiliation":[{"name":"Department of Pathology I, University Hospital, Link\u00f6ping, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Betsholtz","sequence":"additional","affiliation":[{"name":"Department of Pathology I, University Hospital, Link\u00f6ping, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1990,7]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.87.13.5036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T12:58:43Z","timestamp":1649854723000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.87.13.5036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,7]]},"references-count":0,"journal-issue":{"issue":"13","published-print":{"date-parts":[[1990,7]]}},"alternative-id":["10.1073\/pnas.87.13.5036"],"URL":"https:\/\/doi.org\/10.1073\/pnas.87.13.5036","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,7]]},"assertion":[{"value":"1990-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}