利拉鲁肽对胰岛素抵抗大鼠模型胰腺11β-羟甾脱氢酶1表达的影响

摘要

Objective To observe the effect of liraglutide on the expression of 11beta-hydroxysteroid dehydrogenases Type 1 (11β-HSD1), its cooperative enzyme H6PD and glucocorticoid receptor (GR) in the pancreas of insulin resistant (IR) rats. Methods Forty rats were randomly divided into five groups, normal control group, liraglutide group, food-restricted group, saline group and carbenoxolone group. IR model was established in the latter four groups by being fed with 10％ (w/ v) fructose for 10 weeks. Liraglutide, food restriction, saline and carbenoxolone were given in liraglutide group, food-restricted group, saline group and carbenoxolone group, respectively, for 4 weeks. Body weight and diet were recorded every 3 days. Food-restricted group were fed according to the diet of liraglutide group. At the end of the experiment, weight gain were recorded and triglyceride (TG), fasting insulin (FIns) and fructosamine were assayed. The mRNA and protein levels of pancreatic 11β-HSD1, H6PD and GR were assayed by qPCR and Western blot, respectively. Results Compared with normal control group, serum FIns, TG and weitht gain were significantly increased in the other 4 groups. Compared with saline group, after 4 week-treatment, serum FIns, TG and weight gain were significantly lower in liraglutide group, while the protein levels of pancreatic 11β-HSD1, H6PD and GR were significantly reduced (P ＜ 0. 05). There was no significant difference in 11β-HSD1, H6PD or GR mRNA among the 4 IR groups. Conclusion Liraglutide can improve hyperinsulinemia, hypertriglyceridemia and weight gain in IR rats, and reduce the protein expression of 11β-HSD1, H6PD and GR in the pancreas of IR rats.%目的 探讨利拉鲁肽对胰岛素抵抗(IR) 模型大鼠的胰腺糖皮质激素活化酶11β-羟甾脱氢酶1 (11β-HSD1) 与其相关酶己糖6磷酸脱氢酶(H6PD) 和糖皮质激素受体(GR) 表达的影响.方法 40只大鼠随机分成空白对照组、利拉鲁肽组、饮食限制组、生理盐水组和生胃酮组,其中后4组先予10％ 果糖溶液造IR 模型,然后各组继续果糖喂养并分别予皮下注射利拉鲁肽、生理盐水、饮食限制和生胃酮(非选择性11β-HSD 抑制剂) 灌胃干预,连续4周.每3 d记录大鼠体重、饮水和摄食量,饮食限制组根据利拉鲁肽组给予相应的饮食量.实验结束后比较体重增长比、空腹胰岛素(FIns) 、三酰甘油(TG) 和果糖胺,并分别通过荧光定量PCR 和Western blot法检测胰腺11β-HSD1、H6PD、和GR 的mRNA 和蛋白表达.结果 10％ 果糖溶液喂养10周后IR 模型各组与空白对照组相比,大鼠血清TG、FPG 和FIns均升高,胰岛素敏感指数(ISI) 降低(PFPG ＜ 0. 05,PTG、PFIns、PISI等均＜ 0. 01) ,体重差异无统计学意义.对IR 模型各组干预4周后,与生理盐水组相比,利拉鲁肽组FIns、TG 和体重增长比均降低,11β-HSD1、H6PD 和GR 蛋白表达均减少(均P ＜ 0. 01);饮食限制组和生胃酮组虽然TG、体重增长比降低(均P ＜ 0. 01) 和FIns降低(P饮食限制组＜ 0. 01,P生胃酮组＞ 0. 05) ,但是11β-HSD1、H6PD 和GR 蛋白表达均无明显改变.IR 模型各组比较mRNA 表达均无显著变化.结论 利拉鲁肽可改善IR 大鼠模型高FIns血症、高TG 血症和体重增长,同时减少该模型胰腺11β-HSD1、H6PD和GR 的蛋白表达.