{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:56:18Z","timestamp":1790855778353,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T00:00:00Z","timestamp":1608768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771393"],"award-info":[{"award-number":["81771393"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Glucose hypometabolism is observed in epilepsy and promotes epileptogenesis. Glucose hypometabolism in epilepsy may be attributed to decreased neuronal glucose uptake, but its molecular mechanism remains unclear. Zinc\u2010\u03b12\u2010glycoprotein (ZAG) is related to glucose metabolism and is reported to suppress seizures. The anti\u2010epileptic effect of ZAG may be attributed to its regulation of neuronal glucose metabolism. This study explored the effect of ZAG on neuronal glucose uptake and its molecular mechanism via insulin\u2010like growth factor 1 receptor (IGF1R)\u2010regulated glucose transporter 3 (GLUT\u20103) expression. The ZAG level was modulated by lentivirus in primary culture neurons. Neuronal seizure models were induced by Mg<jats:sup>2+<\/jats:sup>\u2010free artificial cerebrospinal fluid. We assessed neuronal glucose uptake by the 2\u2010NBDG method and Glucose Uptake Colorimetric Assay Kit. IGF1R was activated by IGF1 and blocked by AXL1717. The expression and distribution of IGF1R and GLUT\u20103, together with IGF1R phosphorylation, were measured by western blot. The binding between ZAG and IGF1R was determined by coimmunoprecipitation. Neuronal glucose uptake and GLUT\u20103 expression were significantly decreased by seizure or ZAG knockdown, whereas ZAG over\u2010expression or IGF1 treatment reversed this decrease. The effect of ZAG on neuronal glucose uptake and GLUT\u20103 expression was blocked by AXL1717. ZAG increased IGF1R distribution and phosphorylation possibly by binding. Additionally, IGF1R increased GLUT\u20103 activity by increasing GLUT\u20103 expression. In epilepsy\/seizure, neuronal glucose uptake suppression may be attributed to a decrease in ZAG, which suppresses neuronal GLUT\u20103 expression by regulating the activity of IGF1R. ZAG, IGF1R, and GLUT\u20103 may be novel potential therapeutic targets of glucose hypometabolism in epilepsy and seizures.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15254-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15254","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T09:05:36Z","timestamp":1606813536000},"page":"695-709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Zinc\u2010\u03b12\u2010glycoprotein relieved seizure\u2010Induced neuronal glucose uptake impairment via insulin\u2010like growth factor 1 receptor\u2010regulated glucose transporter 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