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青钱柳多糖调节胰岛和肝脏葡萄糖转运蛋白4转位干预2型糖尿病大鼠的作用机制

Effect and Mechanism of Cyclocarya paliurus (Batal.) lljinskaja Polysaccharides on Type2 Diabetic Rats by Regulating GLUT4 Translocation in Islet and Liver
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摘要 目的 观察青钱柳多糖调节胰岛和肝脏葡萄糖转运蛋白4(GLUT4)转位改善2型糖尿病(T2DM)大鼠外周胰岛抵抗的作用。方法 建立T2DM大鼠模型(给予高脂饲料后注射链脲佐菌素35 mg·kg^(-1)),将造模成功的大鼠随机分为模型对照组,青钱柳多糖提取物小、大剂量组(5,10 g·kg^(-1))和盐酸二甲双胍组(0.25 g·kg^(-1)),每组9只,给药8周。测定空腹血糖、血脂变化;苏木精-伊红染色法观察胰岛和肝脏病理形态的改变;免疫组化法观察胰岛磷酸化磷酯酰肌醇3激酶(p-PI3K)、磷酸化丝氨酸苏氨酸蛋白激酶1(p-Akt1)、GLUT4蛋白的表达;免疫荧光观察肝脏和胰岛GLUT4转位。结果 与模型对照组比较,青钱柳多糖提取物小、大剂量组和盐酸二甲双胍组大鼠胰岛和肝脏结构较完整,血糖下降(P<0.05),高密度脂蛋白升高(P<0.05),胰岛p-PI3K、p-Akt1、GLUT4蛋白表达升高(P<0.05),肝脏和胰岛GLUT4转位增强(P<0.05)。结论 青钱柳多糖可调节T2DM大鼠糖脂紊乱,其机制可能是增强胰岛p-PI3K、p-Akt1、GLUT4蛋白的表达,促进肝脏和胰岛GLUT4转位,从而调节外周胰岛抵抗。 Objective To investigate the effect of Cyclocarya paliurus(Batal.)lljinskaja polysaccharides on insulin resistance in type 2 diabetic rats by regulating glucose transporter 4(GLUT4)translocation in islet and liver.Methods High-fat diet combined with low-dose streptozotocin(35 mg·kg^(-1))to induce type 2 diabetes model,all the rats were randomly divided into model control group,Cyclocarya paliurus polysaccharides groups(5,10 g·kg^(-1))and metformin group(0.25 g·kg^(-1)),and treated for eight weeks(n=9 in each group).Fasting glucose and lipid were determined.Histopathology of rat islet and liver were observed by hematoxylin and eosin staining.Protein expressions of phosphorylated phosphoinositide-3-kinase(p-PI3K),phosphorylated serine-threonine kinase 1(p-Akt1),and GLUT4 in islet were measured by immunohistochemistry staining.GLUT4 translocation in the islet and liver was detected by immunofluorescence.Results Compared with the model control group,the Cyclocarya paliurus polysaccharides group and metformin group had declined fasting glucose levels and increased high-density lipoprotein(P<0.05).The structure of the islets and liver was relatively complete.The content of p-PI3K,p-Akt1 and GLUT4 in the islet increased(P<0.05).GLUT4 translocation in the liver and islet enhanced(P<0.05).Conclusions Cyclocarya paliurus polysaccharides alleviate glucose and lipid metabolism disorders.The mechanism may lay in it activating protein expressions of p-PI3K,p-Akt1,and GLUT4 in islet cells.GLUT4 translocation to the islet and liver cell membrane are increased to regulate peripheral islet resistance.
作者 刘海云 石淼婷 骆欣怡 孙敏燕 徐晨曦 陈鲲翰 王晓敏 舒任庚 LIU Haiyun;SHI Miaoting;LUO Xinyi;SUN Minyan;XU Chenxi;CHEN Kunhan;WANG Xiaomin;SHU Rengeng(School of Tradition Chinese Medicine,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)
出处 《医药导报》 CAS 北大核心 2024年第1期13-19,共7页 Herald of Medicine
基金 国家自然科学基金资助项目(20162002) 江西中医药大学创新创业项目(2022104、2023091)。
关键词 青钱柳多糖 葡萄糖转运蛋白4转位 外周胰岛素抵抗 2型糖尿病 Cyclocarya Paliurus(Batal.)lljinskaja polysaccharides Glucose transporter 4 translocation Peripheral islet resistance Type 2 diabetic
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