血管紧张素1-7对2型糖尿病大鼠胰岛素抵抗的影响及机制

Effects of angiotensin(1-7) on insulin resistance in type-2 diabetic rats and its mechanism

目的研究血管紧张素1-7[Ang-(1-7)]对2型糖尿病大鼠胰岛素抵抗的影响及机制。方法 36只8周龄健康雄性Wistar大鼠随机数字表法分为正常对照组、糖尿病对照组、Ang-(1-7)干预组。糖尿病对照组和Ang-(1-7)干预组以高脂高热量饮食喂养8周,一次性腹腔注射链脲佐菌素30 mg/kg,建立2型糖尿病大鼠模型。成模后,Ang-(1-7)干预组大鼠颈部皮下注射Ang-(1-7)300μg·kg-1·d-1,糖尿病对照组和正常对照组注射等体积的0.9%氯化钠注射液。干预8周,监测空腹血糖(FPG),检测血清空腹胰岛素(FINS)及AngⅡ含量,计算稳态模型胰岛素抵抗指数(HOMA-IR),用蛋白质印迹法检测大鼠附睾旁脂肪组织中葡萄糖转运蛋白4(GLUT4)的表达。结果与正常对照组相比,糖尿病对照组大鼠FPG显著升高,FINS减少了49.1%,AngⅡ含量、HOMA-IR分别增加了34.1%和84.6%(均P<0.05)。而Ang-(1-7)干预后与糖尿病对照组相比,FPG下降,FINS增加了32.9%,AngⅡ、HOMA-IR分别降低了14.3%和11.6%(均P<0.05)。糖尿病对照组大鼠GLUT4的表达量明显低于正常对照组,Ang-(1-7)干预后GLUT4表达量明显升高(P<0.05)。结论 Ang-(1-7)可通过增加脂肪组织中GLUT4的含量,改善胰岛素抵抗,从而发挥抗糖尿病作用。

Objective To investigate the effects of angiotensin （1-7） [Ang-（1-7）] on insulin resistance in type2 diabetic rats and its mechanism. Methods Thirty-six 8-week-old healthy male Wistar rats were randomly divided into the normal control group, diabetic control group and Ang-（1-7） intervention group. The diabetic control group and Ang-（1-7） intervention group were fed with high-fat and high-calorie diet for 8 weeks. The rat model of type2 diabetes was established by disposable intraperitoneal injection of 30mg/kg streptozotocin. After the establishment, the Ang-（1- 7） intervention group was injected with 300 μg·kg^-1·d^-1 Ang-（1-7） at the neck. The diabetic control group and normal control group were injected with the same volume of normal saline. After 8 weeks of intervention, the fasting plasma glucose （FPG） was monitored, serum fasting insulin （FINS） and Ang I1 content were measured, and the homeostasis model assessment of insulin resistance （HOMA-IR） index was calculated. The expression of glucose transporter 4 （GLUT4） in epididymal adipose tissues of the rats was determined by Western blotting. Results Compared with the normal control group, the FPG increased significantly, the FINS decreased 49.1%, and the Ang II content and HOMA-IR increased 34.1% and 84.6% in the diabetic control group （all P〈0.05）, respectively. Compared with the diabetic control group, the FPG decreased, FINS increased 32.9%, Ang I1 and HOMA-IR decreased 14.3% and 11.6% in the Ang-（1-7） intervention group, respectively （all P〈0.05）. The expression of GLUT4 in the diabetic control group was significantly lower than that in the normal control group, and the expression of GLUT4 significantly increased af- ter Ang- （1-7） intervention （P〈0.05）. Conclusion Ang-（1-7） can improve the insuhn resistance by increasing the content of GLUT4 in adipose tissues, and thus play an anti-diabetic effect.