{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:12:53Z","timestamp":1777396373150,"version":"3.51.4"},"reference-count":64,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T00:00:00Z","timestamp":1589328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2020,6,15]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Abnormally hyperphosphorylated tau is the major protein of neurofibrillary tangles in Alzheimer\u2019s disease. Insulin activates PI3K-AKT signaling and regulates tau phosphorylation. Impaired brain insulin signaling is involved in Alzheimer\u2019s disease pathogenesis. However, the effect of peripheral insulin on tau phosphorylation is controversial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>In the present study, we determined the effect of peripheral insulin administration on tau phosphorylation in brain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We intraperitoneally injected a super physiological dose of insulin to mice and analyzed PI3K-AKT signaling and tau phosphorylation in brains by western blots.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We found that peripherally administered insulin activated the PI3K-AKT signaling pathway immediately in the liver, but not in the brain. Tau phosphorylation in the mouse brain was found to be first decreased (15\u200amin) and then increased (30\u200amin and 60\u200amin) after peripheral insulin administration and these changes correlated inversely with body temperature and the level of brain protein O-GlcNAcylation. Maintaining body temperature of mice post peripheral insulin administration prevented the insulin\/hypoglycemia-induced tau hyperphosphorylation after peripheral insulin administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These findings suggest that peripheral insulin can induce tau hyperphosphorylation through both hypothermia and downregulation of brain protein O-GlcNAcylation during hypoglycemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-200147","type":"journal-article","created":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T13:03:13Z","timestamp":1589547793000},"page":"1377-1390","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Effect of Peripheral Insulin Administration on Phosphorylation of Tau in the Brain"],"prefix":"10.1177","volume":"75","author":[{"given":"Yanli","family":"Jiang","sequence":"first","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education of China, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China"},{"name":"Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longfei","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education of China, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China"},{"name":"Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Ling","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranran","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Xin","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalid","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of 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