{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:38:58Z","timestamp":1792251538807,"version":"4.4.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,7,9]]},"abstract":"<jats:p>The islet in non-insulin-dependent diabetes mellitus (NIDDM) is characterized by loss of beta cells and large local deposits of amyloid derived from the 37-amino acid protein, islet amyloid polypeptide (IAPP). We have hypothesized that IAPP amyloid forms intracellularly causing beta-cell destruction under conditions of high rates of expression. To test this we developed a homozygous transgenic mouse model with high rates of expression of human IAPP. Male transgenic mice spontaneously developed diabetes mellitus by 8 weeks of age, which was associated with selective beta-cell death and impaired insulin secretion. Small intra- and extracellular amorphous IAPP aggregates were present in islets of transgenic mice during the development of diabetes mellitus. However, IAPP derived amyloid deposits were found in only a minority of islets at approximately 20 weeks of age, notably after development of diabetes mellitus in male transgenic mice. Approximately 20% of female transgenic mice spontaneously developed diabetes mellitus at 30+ weeks of age, when beta-cell degeneration and both amorphous and amyloid deposits of IAPP were present. We conclude that overexpression of human IAPP causes beta-cell death, impaired insulin secretion, and diabetes mellitus. Large deposits of IAPP derived amyloid do not appear to be important in this cytotoxicity, but early, small amorphous intra- and extracellular aggregates of human IAPP were consistently present at the time of beta-cell death and therefore may be the most cytotoxic form of IAPP.<\/jats:p>","DOI":"10.1073\/pnas.93.14.7283","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:39Z","timestamp":1027679499000},"page":"7283-7288","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":303,"title":["Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide."],"prefix":"10.1073","volume":"93","author":[{"given":"J","family":"Janson","sequence":"first","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W C","family":"Soeller","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P C","family":"Roche","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R T","family":"Nelson","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Torchia","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D K","family":"Kreutter","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P C","family":"Butler","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,7,9]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.14.7283","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:38:19Z","timestamp":1649860699000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.14.7283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,7,9]]},"references-count":0,"journal-issue":{"issue":"14","published-print":{"date-parts":[[1996,7,9]]}},"alternative-id":["10.1073\/pnas.93.14.7283"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.14.7283","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,7,9]]},"assertion":[{"value":"1996-07-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}