{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:58:44Z","timestamp":1782323924013,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Polyethylene glycol loxenatide (PEG\u2010Loxe) is applied in treating type 2 diabetes mellitus. Nevertheless, the effect and mechanism of PEG\u2010Loxe on lipid metabolism disorder and insulin resistance in type 2 diabetes mellitus are not fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Type 2 diabetes mellitus rats developed by high\u2010fat diet\/streptozotocin injection were treated with PEG\u2010Loxe (0.3 or 1\u2009mg\/kg). Insulin resistance was evaluated by fasting blood glucose (FBG), oral glucose tolerance test, fasting insulin, homeostasis model of assessment for insulin resistance and for insulin sensitivity. Immunohistochemistry, hematoxylin and eosin staining, and biochemistry measurements were performed to assess lipid metabolism. Inflammatory response and oxidative stress were assessed by inflammatory cytokines and reactive oxygen species. Genes\u2019 expressions were tested using RT\u2010qPCR, western blot, and in situ hybridization. Relationships of molecules were validated by pull\u2010down assay and RNA immunoprecipitation. mRNA stability was examined by actinomycin D assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High\u2010PEG\u2010Loxe decreased FBG and ameliorated glucose tolerance, hyperinsulinemia, and insulin resistance. Low\u2010PEG\u2010Loxe partly while high\u2010PEG\u2010Loxe apparently relieved hepatocyte injury, reduced lipase I, triglyceride, total cholesterol and leptin, and increased adiponectin in type 2 diabetes mellitus rats. PEG\u2010Loxe mitigated inflammatory response and oxidative stress. High\u2010PEG\u2010Loxe reduced RhoA and Rho\u2010associated coiled\u2010coil kinase 2 (ROCK2) in liver tissues of type 2 diabetes mellitus rats, while both doses of PEG\u2010Loxe decreased steroid receptor RNA activator (SRA). SRA overexpression reversed the protective functions of high\u2010PEG\u2010Loxe. SRA cooperated with cellular nucleic acid binding protein (CNBP) to enhance ROCK2 mRNA stability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>High\u2010PEG\u2010Loxe relieves insulin resistance and lipid metabolism disorder in type 2 diabetes mellitus through SRA\/CNBP\/ROCK2 axis. This research provides a molecular mechanism of PEG\u2010Loxe for treating type 2 diabetes mellitus.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.14373","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T12:45:18Z","timestamp":1733748318000},"page":"715-727","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Polyethylene glycol loxenatide modulates lipid metabolism and insulin resistance through <scp>lncRNA<\/scp> steroid receptor <scp>RNA<\/scp> activator\/cellular nucleic acid binding protein\/Rho\u2010associated coiled\u2010coil kinase 2 axis in type 2 diabetes mellitus"],"prefix":"10.1111","volume":"16","author":[{"given":"Zhuangsen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology Pingshan District People's Hospital of Shenzhen  Shenzhen Guangdong Province China"},{"name":"Department of Endocrinology Pingshan Hospital of Southern Medical 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