摘要
目的探讨氯沙坦改善3T3-L1脂肪细胞胰岛素抵抗的主要作用机制。方法以地塞米松诱导3T3-L1脂肪细胞,建立胰岛素抵抗细胞模型,根据细胞模型添加干预药物的不同分为模型对照组(不添加任何药物)、氯沙坦组(分别给予1、10、100μmol/L氯沙坦干预48 h)和wortmannin+氯沙坦组,wortmannin+氯沙坦组以100 nmol/L的磷脂酰肌醇3激酶(PI3K)特异性抑制剂wortmannin预处理20 min后再加入100μmol/L氯沙坦干预48 h。观察脂肪细胞体积的变化,采用葡萄糖氧化酶法检测细胞培养上清液中葡萄糖的浓度,采用Western blotting分析脂肪细胞中PI3K和胰岛素受体底物1(IRS-1)的表达以及IRS-1丝氨酸磷酸化水平。结果与模型对照组比较,氯沙坦组脂肪细胞体积明显缩小(P<0.01),细胞培养上清液中葡萄糖的浓度显著降低(P<0.01),PI3K和IRS-1表达明显上升(P<0.01),IRS-1丝氨酸磷酸化水平显著下降(P<0.01)但可被wortmannin阻断。结论氯沙坦可使3T3-L1脂肪细胞胰岛素抵抗模型的细胞体积缩小,并增加细胞对葡萄糖的利用,其机制可能与PI3K信号通路有关。
Objective To investigate the main mechanism of losartan in treatment of insulin resistance in 3T3-L1 adipocytes. MethodsThe model of insulin resistance in 3T3-L1 adipocytes was induced by dexamethasone.Model control group（without treatment with any drug）,losartan group（treatment with 1 μmol/L,10 μmol/L and 100 μmol/L losartan for 48 h respectively） and wortmannin＋losartan group were divided.Adipocytes in wortmannin＋losartan group were pretreated with 100 nmol/L wortmannin,phosphatidylinositol 3-kinase（PI3K） inhibitor for 20 min,and were treated with 100 μmol/L losartan for 48 h.The size of adipocytes was observed,glucose oxidase method was employed to measure the glucose concentration in supernatant of culture fluid,and Western blotting was adopted to detect the expression of PI3K and insulin receptor substrate 1（IRS-1） and level of IRS-1 serine phosphorylation in adipocytes. ResultsCompared with model control group,the size of adipocytes significantly reduced（P0.01）,the glucose concentration in supernatant of culture fluid significantly decreased（P0.01）,the expression of PI3K and IRS-1 significantly increased（P0.01）.The level of IRS-1 serine phosphorylation significantly decreased compared with model control group（P0.01）,but the effect could be blocked by wortmannin. ConclusionLosartan could significantly decrease the cell size and increase the consumption of glucose in 3T3-L1 adipocytes with insulin resistance,and the mechanism might be associated with PI3K pathway.
出处
《上海交通大学学报（医学版）》
CAS
CSCD
北大核心
2011年第12期1702-1706,共5页
Journal of Shanghai Jiao tong University:Medical Science
基金
上海市宝山区科委基金(08-E-8)~~
