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An IR cell model induced by glucosamine and a GDM mouse model induced by high\u2010fat and high\u2010sugar feeding were constructed. Cell viability was determined by a CCK\u20108 assay, and the presence of associated proteins was identified through western blotting, immunohistochemistry, and immunofluorescence techniques. Measurements of mouse body mass, fasting blood concentrationsglucose levels, fasting insulin, and oral glucose tolerance (OGTT) were obtained, and placental tissues were examined using HE and PAS staining. The findings revealed reduced expression of SIRT1 in the placental tissues of GDM patients, animals, and IR cell models. The overexpression of SIRT1 can significantly increase the glucose uptake capacity and viability of IR\u2010treated cells; increase the expression of p\u2010IRS1, p\u2010AKT, and GLUT4; and decrease the expression of GLUT1. Furthermore, SIRT1 diminished the expression of SOCS3 by hindering the phosphorylation and acetylation of STAT3, thereby improving IR. In the GDM mouse model, the overexpression of SIRT1 improved IR. Overall,SIRT1 reduces IR in trophoblast cells through the suppression of the STAT3\u2013SOCS3 signaling pathway, providing a new idea for clinical intervention in GDM.<\/jats:p>","DOI":"10.1096\/fj.202500520r","type":"journal-article","created":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T03:45:06Z","timestamp":1746848706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>SIRT1<\/scp>\n                    \u2010Mediated Regulation of\n                    <scp>STAT3<\/scp>\n                    \/\n                    <scp>SOCS3<\/scp>\n                    Inhibits Insulin Resistance in Trophoblast Cells and Improves Gestational Diabetes Mellitus"],"prefix":"10.1096","volume":"39","author":[{"given":"Ya","family":"Wen","sequence":"first","affiliation":[{"name":"Reproductive Genetics Department The First Affiliated Hospital of Kunming Medical University  Kunming 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