{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:36:55Z","timestamp":1792571815907,"version":"4.5.0"},"reference-count":0,"publisher":"American Diabetes Association","issue":"5","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,5,1]]},"abstract":"<jats:p>We have previously shown that hemizygous transgenic mice expressing human islet amyloid polypeptide (hIAPP) in pancreatic beta-cells have no diabetic phenotype, whereas in the homozygous state, they developed severe, early-onset hyperglycemia associated with impaired insulin secretion and beta-cell death. We investigated the possibility that when the hemizygous mice are crossed onto an obese, insulin-resistant strain such as agouti viable yellow (A(vy)\/a), they would exhibit a phenotype more akin to human type 2 diabetes. The hIAPP-expressing A(vy) males (TG-Y) displayed fasting hyperglycemia at 90 days of age and by 1 year progressed to severe hyperglycemia relative to their nontransgenic counterparts. Plasma insulin concentrations and pancreatic insulin content dropped 10- to 20-fold, suggesting severe impairment of beta-cell function. Histopathological findings revealed beta-cell degeneration and loss consistent with the drop in the plasma insulin concentration. In addition, large deposits of IAPP amyloid were present in TG-Y islets. We conclude that in transgenic mice expressing hIAPP, insulin resistance can induce overt, slow-onset diabetes associated with islet amyloid and decreased beta-cell mass.<\/jats:p>","DOI":"10.2337\/diabetes.47.5.743","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"743-750","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":117,"title":["Islet amyloid-associated diabetes in obese A(vy)\/a mice expressing human islet amyloid polypeptide."],"prefix":"10.2337","volume":"47","author":[{"given":"W C","family":"Soeller","sequence":"first","affiliation":[{"name":"Department of Molecular Sciences, Central Research Division, Pfizer, Groton, Connecticut 06340, USA. soellerwc@pfizer.com"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Janson","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Central Research Division, Pfizer, Groton, Connecticut 06340, USA. soellerwc@pfizer.com"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S E","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Central Research Division, Pfizer, Groton, Connecticut 06340, USA. soellerwc@pfizer.com"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J C","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Central Research Division, Pfizer, Groton, Connecticut 06340, USA. soellerwc@pfizer.com"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M D","family":"Carty","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Central Research Division, Pfizer, Groton, Connecticut 06340, USA. soellerwc@pfizer.com"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R W","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Central Research Division, Pfizer, Groton, Connecticut 06340, USA. soellerwc@pfizer.com"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D K","family":"Kreutter","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Central Research Division, Pfizer, Groton, Connecticut 06340, USA. soellerwc@pfizer.com"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P C","family":"Butler","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Central Research Division, Pfizer, Groton, Connecticut 06340, USA. soellerwc@pfizer.com"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/47\/5\/743\/363342\/9588445.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/47\/5\/743\/363342\/9588445.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:44:52Z","timestamp":1667407492000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/47\/5\/743\/9459\/Islet-amyloid-associated-diabetes-in-obese-A-vy-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,5,1]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1998,5,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diabetes.47.5.743","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,5,1]]}}}