{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:52:04Z","timestamp":1790542324015,"version":"4.1.0"},"reference-count":35,"publisher":"Portland Press Ltd.","issue":"1","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":561,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,2,28]]},"abstract":"<jats:p>Insulin degrading enzyme (IDE) is believed to act as a junction point of Type 2 diabetes (T2D) and Alzheimer's disease (AD); however, the underlying mechanism was not completely clear yet. Transgenic APPSwe\/PS1 mice were used as the AD model and were treated with streptozocin\/streptozotocin (STZ) to develop a mixed mice model presenting both AD and T2D. Morris Water Maze (MWM) and recognition task were performed to trace the cognitive function. The detection of fasting plasma glucose (FPG) and plasma insulin concentration, and oral glucose tolerance test (OGTT) were used to trace the metabolism evolution. A\u03b240 and A\u03b242 were quantified by colorimetric ELISA kits. The mRNA or protein expression levels were determined by quantitative real-time RT-PCR and Western blotting analysis respectively. T2D contributes to the AD progress by accelerating and worsening spatial learning and recognition impairments. Metabolic parameters and glucose tolerance were significantly changed in the presence of the AD and T2D. The expression levels of IDE, PPAR\u03b3, and AMPK were down-regulated in mice with AD and T2D. PPAR\u03b3 activator rosiglitazone (RSZ) or AMPK activator AICAR increased the expression level of IDE and decreased A\u03b2 levels in mice with AD and T2D. RSZ or AICAR treatment also alleviated the spatial learning and recognition impairments in AD and T2D mice. Our results found that, in the mice with T2D and AD, the activators of PPAR\u03b3\/AMPK signaling pathway significantly increased the expression level of IDE, and decreased the accumulation of A\u03b240 and A\u03b242, as well as alleviated the spatial learning and recognition impairments.<\/jats:p>","DOI":"10.1042\/bsr20170862","type":"journal-article","created":{"date-parts":[[2017,12,9]],"date-time":"2017-12-09T01:45:20Z","timestamp":1512783920000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Insulin degrading enzyme contributes to the pathology in a mixed model of Type 2 diabetes and Alzheimer\u2019s disease: possible mechanisms of IDE in T2D and AD"],"prefix":"10.1042","volume":"38","author":[{"given":"Huajie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luolin","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of General Laboratory, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keshi","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First People\u2019s Hospital of Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,1,10]]},"reference":[{"key":"2021111618453881300_B1","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1016\/S0140-6736(02)11667-9","article-title":"The dementias","volume":"360","author":"Ritchie","year":"2002","journal-title":"Lancet"},{"key":"2021111618453881300_B2","first-page":"23","article-title":"Noncholinergic treatment options for Alzheimer\u2019s disease","volume":"64","author":"Sano","year":"2003","journal-title":"J. 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