{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:17:38Z","timestamp":1792498658157,"version":"4.5.0"},"reference-count":39,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:p>The islet in type 2 diabetes is characterized by an \u223c60% \u03b2-cell deficit, increased \u03b2-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). Human IAPP (hIAPP) but not rodent IAPP (rIAPP) forms toxic oligomers and amyloid fibrils in an aqueous environment. We previously reported that overexpression of hIAPP in transgenic rats triggered endoplasmic reticulum (ER) stress-induced apoptosis in \u03b2-cells. In the present study, we sought to establish whether the cytotoxic effects of hIAPP depend on its propensity to oligomerize, rather than as a consequence of protein overexpression. To accomplish this, we established a novel homozygous mouse model overexpressing rIAPP at a comparable expression rate and, on the same background, as a homozygous transgenic hIAPP mouse model previously reported to develop diabetes associated with \u03b2-cell loss. We report that by 10 wk of age hIAPP mice develop diabetes with a deficit in \u03b2-cell mass due to increased \u03b2-cell apoptosis. The rIAPP transgenic mice counterparts do not develop diabetes or have decreased \u03b2-cell mass. Both rIAPP and hIAPP transgenic mice have increased expression of BiP, but only hIAPP transgenic mice have elevated ER stress markers (X-box-binding protein-1, nuclear localized CCAAT\/enhancer binding-protein homologous protein, active caspase-12, and accumulation of ubiquitinated proteins). These findings indicate that the \u03b2-cell toxic effects of hIAPP depend on the propensity of IAPP to aggregate, but not on the consequence of protein overexpression.<\/jats:p>","DOI":"10.1152\/ajpendo.00318.2007","type":"journal-article","created":{"date-parts":[[2007,10,3]],"date-time":"2007-10-03T00:28:55Z","timestamp":1191371335000},"page":"E1656-E1662","source":"Crossref","is-referenced-by-count":123,"title":["Induction of endoplasmic reticulum stress-induced \u03b2-cell apoptosis and accumulation of polyubiquitinated proteins by human islet amyloid polypeptide"],"prefix":"10.1152","volume":"293","author":[{"given":"Chang-jiang","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena","family":"Haataja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Gurlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuju","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter C.","family":"Soeller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.6.1509"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.1.102"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.9.2304"},{"key":"R4","unstructured":"Butler PC.Islet Amyloid and Its Potential Role in the Pathogenesis of Type II Diabetes Mellitus.Philadelphia, PA: Lippincott, William, and Wilkins, 1996."},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0178"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.8.1094"},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Couce M, O'Brien TD, Moran A, Roche PC, Butler PC.Diabetes mellitus in cystic fibrosis is characterized by islet amyloidosis.J Clin Endocrinol Metab81: 1267\u20131272, 1996.","DOI":"10.1210\/jc.81.3.1267"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500997200"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000192103.24796.42"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.07.052"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.2.455"},{"key":"R12","doi-asserted-by":"crossref","unstructured":"Hishikawa N, Hashizume Y, Yoshida M, Sobue G.Clinical and neuropathological correlates of Lewy body disease.Acta Neuropathol (Berl)105: 341\u2013350, 2003.","DOI":"10.1007\/s00401-002-0651-4"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.3.424"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051175"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0197"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.3.491"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.14.7283"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079469"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Kloppel G, Lohr M, Habich K, Oberholzer M, Heitz PU.Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited.Surv Synth Pathol Res4: 110\u2013125, 1985.","DOI":"10.1159\/000156969"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05367.x"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1038\/418291a"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0590-z"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1579"},{"key":"R24","doi-asserted-by":"crossref","unstructured":"Lo D, Burkly LC, Widera G, Cowing C, Flavell RA, Palmiter RD, Brinster RL.Diabetes and tolerance in transgenic mice expressing class ii MHC molecules in pancreatic beta cells.Cell53: 159\u2013168, 1998.","DOI":"10.1016\/0092-8674(88)90497-7"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.2337\/db05-1672"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00082.2006"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.4.1988"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1126\/science.3029875"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1038\/47513"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.2337\/diab.43.2.329"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1177\/030098589303000401"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502685200"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.7.1701"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2002.196"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.5.743"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1999.276.1.E19"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl081"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308244200"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00894-7"}],"container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpendo.00318.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:28:22Z","timestamp":1587947302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpendo.00318.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,12]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2007,12]]}},"alternative-id":["10.1152\/ajpendo.00318.2007"],"URL":"https:\/\/doi.org\/10.1152\/ajpendo.00318.2007","relation":{},"ISSN":["0193-1849","1522-1555"],"issn-type":[{"value":"0193-1849","type":"print"},{"value":"1522-1555","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,12]]}}}