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Diabetic rats were treated with nerolidol (25\u00a0mg\/kg BW) for 28\u00a0days. Results showed that nerolidol treatment significantly reduced ( p &lt; 0.05) the level of elevated glucose, glycosylated hemoglobin and improved ( p &lt; 0.05) the body weight and insulin level. Nerolidol also considerably improved ( p &lt; 0.05) the carbohydrate metabolic enzyme activities and increased the glycogen storage in the liver of diabetic rats. Increased serum triglycerides, total cholesterol (C), low-density lipoproteins-C and very low-density lipoproteins-C levels were significantly lowered ( p &lt; 0.05), while reduction of serum high-density lipoprotein-C was alleviated after administration of nerolidol. In addition, nerolidol attenuated oxidative stress markers by significantly increasing ( p &lt; 0.05) the levels of superoxide dismutase, catalase, reduced glutathione, and lowering ( p &lt; 0.05) the level of thiobarbituric acid reactive substances, and lipid hydroperoxide. Similarly, nerolidol showed its pharmacological effects against hepatic markers via restoring ( p &lt; 0.05) the alleviated level of alanine transaminase, aspartate aminotransferase, and alkaline phosphatase. Finally, it improved insulin-dependent glucose transport in skeletal muscle by enhancing and activating glucose transporter protein-4. These findings confirmed the antidiabetic potential of nerolidol in type 2 diabetic rats. This may be related to a high antioxidant capacity, the restoration of plasma insulin and lipid levels, and the activation of insulin signaling in STZ\/HFD-induced diabetic rats.<\/jats:p>","DOI":"10.1177\/09603271221126487","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T10:44:28Z","timestamp":1664361868000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Antidiabetic effects of nerolidol through promoting insulin receptor signaling in high-fat diet and low dose streptozotocin-induced type 2 diabetic rats"],"prefix":"10.1177","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7294-978X","authenticated-orcid":false,"given":"Nengmei","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Haimen People\u2019s Hospital, Nantong, 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