依折麦布对db/db糖尿病小鼠胰岛自身胰岛素信号通路的影响-东南大学学报医学版

依折麦布对db/db糖尿病小鼠胰岛自身胰岛素信号通路的影响

单位：1. 南京军区南京总医院干部保健科, 江苏南京 210002;
2. 南京军区南京总医院心脏内科, 江苏南京 210002;
3. 南京军区南京总医院内分泌科, 江苏南京 210002

分类号：R587.1;R-33

出版年·卷·期（页码）：2014·33·第一期（54-58）

摘要：

目的：研究依折麦布对db/db糖尿病小鼠胰岛自身胰岛素信号通路的影响。方法：将40只8周龄db/db小鼠随机分为依折麦布组和db/db对照组，每组20只，分别予依折麦布10 mg·（kg·d）^-1和安慰剂灌胃。另设20只同周龄db/m小鼠，予安慰剂灌胃作为非糖尿病对照（db/m对照）组。每周监测体重、血糖，投药前及投药后6周测量生理及代谢指标，投药后6周后用蛋白质印迹法检测各组小鼠胰岛中蛋白酪氨酸磷酸酶1B（PTP1B）、葡萄糖转运子（GLUT-2）、葡萄糖激酶（GCK）表达的变化。结果：依折麦布组治疗6周后空腹血糖显著下降，同时总胆固醇及低密度脂蛋白胆固醇低于对照组（P<0.05）。依折麦布组治疗6周后与db/db对照组比较，PTP1B的表达水平明显下降（P<0.05），GLUT-2、GCK表达水平明显升高（P<0.05）。结论：依折麦布除降低血脂外，还可以改善db/db糖尿病小鼠胰岛自身胰岛素抵抗，促进胰岛素分泌，降低血糖。

Objective: To study the effect of ezetimibe on insulin signal pathway of B-cell in db/db mice and discuss its blood glucose lowering mechanism. Methods: 8-week-old db/db mice were randomized into ezetimibe 10 mg·(kg·d)^-1,or placebo. The age-matched nondiabetic littermates db/m mice were treated with placebo as the controls. Body weight and blood glucose were measured every week. After 6 weeks' treatment,physiological and metabolic parameters were measured. Western blotting method was adopted to detect PTP1B,GLUT-2 and GCK expressions of the B-cell in db/db mice. Results: Fasting blood glucose(FBG),total cholesterol(TC),low density lipoprotein cholesterol(LDLC) were lower in ezetimibe group than that in db/db group after 6 weeks' treatment.Western blotting method test revealed that the expressions of GLUT-2,GCK in ezetimibe group increased significantly compared to those of db/db group(P<0.05),however,the expression of PTP1B in ezetimibe group obviously decreased compared with db/db group(P<0.05). Conclusion: In addition to blood cholesterol lowing,ezetimibe also has beneficial effects on secretory function and insulin resistence of B-cell in db/db mice.

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