糖尿病基础研究

　　【摘要】 目的 观察二甲双胍对小鼠血清可溶性瘦素受体(sOB-R)水平的影响。 方法 健康雄性C57BL/6小鼠42只，随机分为正常饮食(CD)组及高脂饮食(HF)组，最后19只造模成功。对CD组及HF组分别予二甲双胍不同剂量灌胃及蒸馏水灌胃对照，1次/d，共15 d。采用ELISA测定小鼠血清sOB-R水平，Real-time PCR检测肝脏瘦素受体基因(OB-Rt)表达水平及在L02细胞上检测二甲双胍对OB-Rt水平的影响。结果 灌胃后，HF组FPG及胰岛素抵抗指数(HOMA-IR)较CD组降低、糖耐量改善，血清sOB-R水平较HF升高(P<0.05)。HF组肝脏OB-Rt mRNA表达水平均高于HF组(P<0.05);培养的L02细胞经二甲双胍(10 mM)处理后OB-Rt的mRNA表达水平较HF组升高(P<0.05)。结论 二甲双胍能剂量依赖性上调小鼠血清sOB-R水平，该作用可能是通过刺激肝脏OB-Rt基因表达实现的。

　　【关键词】二甲双胍;可溶性瘦素受体;胰岛素抵抗

　　【Abstract】Objective To observe the effect of metformin on soluble leptin receptor (sOB-R) level in the serum of C57BL/6 mice. Methods Healthy 42 male C57BL/6 mice were randomly divided and fed for 5 months with standard chow diet (CD group) or high-fat diet (HF group). Impaired glucose regulation was confirmed by measuring fasting glucose(FPG)，HOMA-IR and intraperitoneal glucose tolerance test (IPGTT). Metformin were then administrated to each group of mice once a day at lower [50 mg/(kg.d)]or higher [200 mg/(kg.d)]dose via gastric lavage for 15 days. Serum sOB-R level was determined by ELISA. Expression of leptin receptor gene was detected by real-time PCR in metformin-treated mice liver as well as cultured L02 hepatocyte. Results Compared to CD group, HF group mice showed significantly increased fasting blood glucose[(9.27±1.36)vs(6.87±0.15),P<0.05)]and impaired glucose tolerance (IGT). Metformin dose-dependently decreased fasting blood glucose, HOMA-IR and improved IGT in HF mice. Meanwhile, serum sOB-R levels statistically increased by metformin treatment in a dose-dependent manner[(23.92±0.00)vs(37.16±0.01)vs(57.94±0.01),P<0.05，P<0.01]。Furthermore, the mRNA of leptin recpetor significantly increased in metformin-treat mice liver as well as in cultured L02 cells. Conclusion Metformin dose-dependently upregulates serum sOB-R levels in mice likely due to increased liver leptin receptor gene expression which may contribute to improved blood glucose control.

　　【Key words】Metformin;Soluble leptin receptor;Insulin resistant