{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T04:24:15Z","timestamp":1775535855372,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T00:00:00Z","timestamp":1408406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001518","name":"Maurice and Phyllis Paykel Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001518","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001511","name":"Auckland Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001511","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001537","name":"University of Auckland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:p>\n                    The aggregation of human amylin (hA) to form cytotoxic structures has been closely associated with the causation of type 2 diabetes. We sought to advance understanding of how altered expression and aggregation of hA might link \u03b2\u2010cell degeneration with diabetes onset and progression, by comparing phenotypes between homozygous and hemizygous hA\u2010transgenic mice. The homozygous mice displayed elevated islet hA that correlated positively with measures of oligomer formation (\n                    <jats:italic>r<\/jats:italic>\n                    =0.91;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.0001). They also developed hyperinsulinemia with transient insulin resistance during the prediabetes stage and then underwent rapid \u03b2\u2010cell loss, culminating in severe juvenile\u2010onset diabetes. The prediabetes stage was prolonged in the hemizygous mice, wherein \u03b2\u2010cell dysfunction and extensive oligomer formation occurred in adulthood at a much later stage, when hA levels were lower (\n                    <jats:italic>r<\/jats:italic>\n                    = \u20130.60;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.0001). This is the first report to show that hA\u2010evoked diabetes is associated with age, insulin resistance, progressive islet dysfunction, and \u03b2\u2010cell apoptosis, which interact variably to cause the different diabetes syndromes. The various levels of hA elevation cause different extents of oligomer formation in the disease stages, thus eliciting early\u2010 or adult\u2010onset diabetes syndromes, reminiscent of type 1 and 2 diabetes, respectively. Thus, the hA\u2010evoked diabetes phenotypes differ substantively according to degree of amylin overproduction. These findings are relevant to the understanding of the pathogenesis and the development of experimental therapeutics for diabetes.\u2014Zhang, S., Liu, H., Chuang, C. L., Li, X., Au, M., Zhang, L., Phillips, A. R. J., Scott, D. W., Cooper, G.J. S. The pathogenic mechanism of diabetes varies with the degree of overexpression and oligomerization of human amylin in the pancreatic islet \u03b2 cells. FASEB J. 28, 5083\u20135096 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-251744","type":"journal-article","created":{"date-parts":[[2014,8,20]],"date-time":"2014-08-20T04:57:04Z","timestamp":1408510624000},"page":"5083-5096","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["The pathogenic mechanism of diabetes varies with the degree of overexpression and oligomerization of human amylin in the pancreatic islet \u03b2 cells"],"prefix":"10.1096","volume":"28","author":[{"given":"Shaoping","family":"Zhang","sequence":"first","affiliation":[{"name":"The School of Biological Sciences Faculty of Science University of Auckland Auckland New Zealand"},{"name":"The Maurice Wilkins Centre for Molecular BioDiscovery Faculty of Science University of Auckland Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"The School of Biological Sciences Faculty of Science University of Auckland Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia Lin","family":"Chuang","sequence":"additional","affiliation":[{"name":"The School of Biological Sciences Faculty of Science University of Auckland Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoling","family":"Li","sequence":"additional","affiliation":[{"name":"The School of Biological Sciences Faculty of Science University of Auckland Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie","family":"Au","sequence":"additional","affiliation":[{"name":"The School of Biological Sciences Faculty of Science University of Auckland Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"The School of Biological Sciences Faculty of Science University of Auckland Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony R. 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