海地瓜岩藻多糖硫酸酯促进胰岛素抵抗小鼠肝糖原合成及作用机制  

EFFECTS OF FUCOIDAN ISOLATED FROM ACAUDINA MOLPADIOIDES ON HEPATIC GLYCOGEN SYNTHESIS IN INSULIN RESISTANT MICE AND ITS MECHANISM

作　　者：田迎樱 胡世伟[1] 李兆杰[1] 王玉明[1] 薛长湖[1] 

机构地区：[1]中国海洋大学食品科学与工程学院,青岛266003

出　　处：《营养学报》2015年第4期376-383,共8页Acta Nutrimenta Sinica

基　　金：国家自然科学基金(No.31371876;31471684);海洋公益性行业科研专项(No.201105029)

摘　　要：目的研究海地瓜岩藻聚糖硫酸酯(Fucoidan isolated from Acaudina molpadioides,Am-FUC)对胰岛素抵抗小鼠肝糖原合成的影响。方法以高脂高糖饲料饲喂雄性C57BL/6J小鼠,建立胰岛素抵抗小鼠模型。模型小鼠饲喂Am-FUC 19w后,检测其空腹血糖、葡萄糖耐受性、胰岛素水平、肝糖原含量及糖代谢关键酶活力。采用q RT-PCR法进一步研究小鼠肝糖原合成通路PKB/GSK-3β中关键基因m RNA表达。结果 Am-FUC能显著降低模型小鼠空腹血糖水平,改善葡萄糖耐受量,提高肝糖原含量;增加肝脏中己糖激酶(hexokinase,HK)和丙酮酸激酶(pyruvate kinase,PK)等糖原合成相关酶活力,降低糖原磷酸化酶(glycogen phosphorylase,GP)和葡萄糖-6-磷酸酶(glucose-6-phosphatase,G6Pase)等糖异生关键酶活力;显著上调肝脏中IR(insulin receptor,)、IRS-2(insulin receptor substrate-2)、PI3K(phosphatidylinositol 3-hydroxy kinase,)、AKT(Protein Kinase B,)、GS(glycogen synthase)的m RNA及磷酸化蛋白的表达,抑制糖原合成负调节基因GSK-3β(glycogen synthase kinase-3β)的m RNA及磷酸化蛋白的表达。结论 Am-FUC能显著促进模型小鼠合成肝糖原,改善胰岛素抵抗,其作用机制与调控肝脏中糖代谢关键酶活力及PI3K/AKT/GSK-3β糖原合成通路有关。ObjectiveThis study investigated the effects of fucoidan fromAcaudina molpadioides （Am-FUC） on hepatic glycogen synthesis in insulin resistant mice.Method The insulin resistant model was established by feeding male C57BL/6J mice with and high-fat and high-sucrose diet consecutively. After 19 w of feeding, fasting blood glucose level, glucose tolerance, serum insulin level, hepatic glycogen content, and key hepatic enzymatic activities related to glucose metabolism were determined. The pivotal genes, such as phosphatidylinositol 3-hydroxy kinase（PI3K）, protein kinase B （AKT）, and glycogen synthase kinase-3β （GSK-3β） mRNA and phosphorylated protein expressions of AKTKT/GSK-3β signaling pathway in the liver of insulin resistant mice were further investigated by qRT-PCR and Western bloting method. Results：Am-FUC significantly decreased body weight, adipose tissue weight, alleviated fasting blood glucose level, improved glucose tolerance and hepatic glycogen content, enhanced glycogen synthesis-related enzymes activities, such as hexokinase （HK） and pyruvate kinase （PK）, reduced gluconeogenesis key enzyme, glycogen phosphorylase （GP） and glucose -6-phosphatase （G6Pase） activities in insulin resistant mice. Am-FUC also markedly up-regulated insulin receptor （ IR） ,insulin receptor substrate-2 （IRS-2）,phosphatidylinositol 3-hydroxy kinase （PI3K）,protein kinase B （AKT） and glycogen synthase （GS） mRNA and phosphorylated protein expression levels,while down-regulated GSK-3β mRNA and phosphorylated protein expression levels, which were negatively correlated to glycogen synthesis, in the liver. Conclusion Am-FUC may have a role in the promotion of hepatic glycogen synthesis and ameliorate insulin resistancevia regulating hepatic glucose metabolism key enzymes activities and PI3K/AKT/GSK-3β signaling pathway.

关 键 词：海地瓜 岩藻聚糖硫酸酯 肝糖原 糖代谢关键酶 PI3K、PKB、GSK-3β 

分 类 号：R151[医药卫生—营养与食品卫生学]