大果白刺通过PI3K/AKT信号通路改善2型糖尿病小鼠胰岛抵抗

    Improvement Effect of Insulin Resistance of Nitraria Roborowskii Kom in Type 2 Diabetic Mice via PI3K/AKT Signaling Pathway

    • 摘要:
      目的 探究大果白刺95%乙醇提取物(NRK-C)对2型糖尿病(type 2diabetes mellitus,T2DM)小鼠的降血糖作用及其可能机制。
      方法 通过高脂饮食(high-fat diet,HFD)联合6次腹腔注射35 mg·kg-1链脲佐菌素(streptozotocin,STZ)诱导T2DM小鼠模型,对(T2DM)小鼠体质量、脏器指标、血糖水平、血清生化指标以及采用HE/PAS染色技术对肝组织病理切片进行分析,探究NRK-C对T2DM小鼠的降血糖作用。进一步采用蛋白质印迹和免疫荧光检测测定NRK-C对关键信号蛋白的调节作用。
      结果 NRK-C给药7周后空腹血糖水平显著降低。此外,NRK-C还能显著改善糖尿病小鼠的葡萄糖耐量、肝糖原水平和血脂水平(总胆固醇、甘油三酯、低密度脂蛋白和高密度脂蛋白),显著降低糖尿病小鼠的胰岛素抵抗,在治疗糖尿病方面发挥重要作用。进一步的机制研究表明,NRK-C干预后磷酸化PI3K表达上调,p-GSK3β表达上调,表明NRK-C可能通过调节PI3K/AKT信号通路发挥潜在的治疗糖尿病作用。
      结论 所有这些结果都表明NRK-C可能改善T2DM,并具有作为辅助治疗的潜力。

       

      Abstract:
      OBJECTIVE To explore hypoglycemic effect of 95% ethanol fraction of Nitraria roborowskii Kom(NRK-C) and its possible mechanism evaluated in the type 2 diabetes mellitus(T2DM) mice.
      METHODS  The body weight, organ indices, blood glucose levels, serum biochemical indexes, as well as HE/PAS histopathological section were all analyzed to assess the hypoglycemic effect of NRK-C in T2DM mice induced by a high-fat diet(HFD) combined with six intraperitoneal injections of 35 mg·kg-1 of streptozotocin(STZ). The Western blotting and immunofluorescence were further applied to determine the regulatory effect of NRK-C on key signaling proteins.
      RESULTS The fasting blood glucose levels were significantly reduced after 7 weeks of administration of NRK-C. In addition, NRK-C could also significantly improve glucose tolerance, hepatic glycogen levels, and lipid levels(total cholesterol, triglyceride, low density lipoprotein and high density lipoprotein), and significantly reduced insulin resistance of diabetic mice, which played an important role in the antidiabetic effects. Further mechanism research demonstrated that phosphorylated PI3K expression was up-regulated and p-GSK3β expression was up-regulated after NRK-C intervention, indicating that NRK-C might exert a potential antidiabetic effect by modulating the PI3K/AKT signaling pathway.
      CONCLUSION All these results suggested that NRK-C might improve T2DM and had the potential to be used as an adjunctive therapy.

       

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