标题：Dioscin attenuates high-fat diet-induced insulin resistance of adipose tissue through the IRS-1/PI3K/Akt signaling pathway
作者：Li, Haijuan; Yu, Lianzhi; Zhao, Changsheng
作者机构：[Li, Haijuan] Qingdao Univ, Affiliated Yantai Yuhuangding Hosp, Dept Clin Nutr, Yantai 264000, Shandong, Peoples R China.; [Yu, Lianzhi] Qingdao Uni 更多
通讯作者地址：[Zhao, CS]Shandong Univ, Hosp 2, Dept Nutr, 247 Beiyuan Ave, Jinan 250033, Shandong, Peoples R China.
来源：MOLECULAR MEDICINE REPORTS
关键词：dioscin; insulin tolerance; high-fat diet; insulin receptor substrate 1;; phosphoinositide 3-kinase; protein kinase B pathway
摘要：Insulin resistance, as a common metabolic disorder, may be caused by diet-induced obesity. The aim of the present study is to investigate the effects of dioscin on regulating insulin resistance of adipose tissue induced by a high-fat diet (HFD). An animal model was established successfully using C57BL/6J mice with high-fat feeding, followed by treatment with 5, 10 and 20 mg/kg dioscin through gavage for 18 weeks, and randomly divided into a control group, a HFD model group and a dioscin group treated with 5, 10 and 20 mg/kg/day dioscin for 12 weeks. Histopathological changes in adipose tissues were examined using hematoxylin and eosin staining. Biochemical parameters of the serum were also monitored, including glucose, insulin, total triglyceride, homeostasis model assessment of insulin resistance (HOMA-IR) and adipose insulin resistance (Adipo-IR) levels. Expression of the mRNA and associated proteins of the insulin receptor substrate 1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathways were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. HOMA-IR and Adipo-IR values of mice fed with a HFD were significantly higher compared with those in the control group (P<0.01). However, dioscin administration significantly decreased HOMA-IR and Adipo-IR values in a dose-dependent manner (P<0.05), suggesting the effects of dioscin on attenuating insulin resistance. RT-qPCR results indicated that the associated genes of the IRS-1/PI3K/Akt pathway were significantly downregulated by HFD compared with the control group (P<0.05), while dioscin significantly increased the expression of those genes compared with the control group (P<0.05). Similarly, the significant increase in phosphorylated (p-)IRS-1/IRS-1 (P<0.05) and p-Akt/Akt (P<0.05) values were substantially reversed by dioscin treatment. Dioscin pronouncedly mitigated insulin resistance in adipose tissues through the IRS-1/PI3K/Akt pathway and has potential to be used as a novel therapeutic agent for the therapy of HFD-induced insulin resistance in adipose tissue.