胰岛素通过脂联素受体2/过氧化酶增殖物激活受体-α通路改善2型糖尿病大鼠的肝脏脂质沉积  

Insulin treatment can improve hepatic lipid accumulation in rats with type 2 diabetes through adiponectin receptor 2/peroxisome proliferator-activated receptor-α signaling pathway

作　　者：张雷[1] 梁华[1] 严晋华[1] 徐芬[1] 毕艳[1] 孙卫平[1] 翁建平[1] 

机构地区：[1]中山大学附属第三医院内分泌科,广州510630

出　　处：《中华糖尿病杂志》2011年第3期236-240,共5页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：国家自然科学基金资助项目（30900506）;国家重点基础研究发展计划973资助项目（2006CB503902）

摘　　要：目的 探讨脂联素受体2（AdipoR2）/过氧化酶增殖物激活受体-α（PPAR-α）通路在胰岛素对2型糖尿病大鼠肝脏脂质沉积中的作用.方法使用高脂饮食诱导联合链脲佐菌素（STZ）处理的2型糖尿病大鼠模型.8周龄雄性清洁级SD大鼠42只,适应性喂养1周后,按随机数字表法分为3组：正常对照组（予常规饮食,n=12）、糖尿病组[予高脂饮食（脂肪占热卡的56%）联合STZ处理,成模后不予干预,n=15]、胰岛素组（在糖尿病成模后即开始为期3周的NPH胰岛素治疗,n=15）.干预结束后,处死大鼠,留取血清及肝脏组织.用ELISA法检测血清脂联素水平,Western blot法和（或）实时 PCR方法检测肝脏组织中AdipoR2/PPAR-α通路相关因子的表达水平.多组定量资料之间的比较用方差分析,两两比较用最小差异显著性分析（LSD法）.结果 （1）糖尿病组大鼠血清脂联素水平为（0.27±0.09）μg/L,较对照组（0.55±0.16）μg/L下降了51.5% （P〉0.05）,而胰岛素组为（1.54±0.24 ）μg/L（与糖尿病组比较,P〈0.01）;（2）糖尿病组肝脏AdipoR2 mRNA和蛋白的表达分别为0.70±0.30 和0.72±0.12,均较正常对照组（0.38±0.02 和0.49±0.05）的表达升高,而胰岛素组其表达降低[分别为mRNA （0.27±0.09）和蛋白（0.42±0.09）],差异均具有统计学意义（P〈0.05）;（3）糖尿病组肝脏PPAR-α mRNA和蛋白的表达水平分别为0.60±0.20和0.19±0.04,均较正常对照组的表达（2.70±1.50 和0.43±0.18）明显下降,而胰岛素组分别为mRNA（1.30±0.40）和蛋白（0.27±0.07）.结论 胰岛素干预可以通过作用于AdipoR2/PPAR-α通路增强肝脏脂肪酸氧化来改善2型糖尿病大鼠肝脏的脂质沉积.Objective To investigate the effect of insulin treatment on adiponectin receptor 2（AdipoR2）/peroxisome proliferator-activated receptor-α（PPAR-α） signaling pathway of high-fat-fed/streptozotocin-treated diabetic rats. Methods High-fat-diet and streptozotocin-treated type 2 diabetic SD rats were used in our experiment. Briefly, 42 male SD rats were randomly grouped into normal controls （NC, n=12） and high-fat-fed group （n=30, 56% fat in calorie） after one week′s acclimatization. The normal controls were given normal diet. The diabetic rats were induced by high-fat-diet and streptozotocin injection. The insulin group （INS, n=15） were given NPH insulin injection after the diagnosis of diabetes mellitus for 3 weeks. At the end, the rats were sacrificed and serum samples and liver tissues were collected and stored at -80 ℃. We used rat adiponectin ELISA kit to detect fasting serum adiponectin level. Realtime PCR and Western blott were performed to determine the expression of molecular effectors involved in AdipoR2/ PPAR-α pathway. ANOVA or LSD test were used for data analysis. Results The expressions of serum adiponectin detected by rat adiponectin ELISA kit in NC, DM and INS groups were （0.55±0.16）, （0.27±0.09） and （1.54±0.24） μg/L respectively, that was to say, lower fasting adiponectin level was found in diabetic rats than that in NC rats which could be ameliorated by insulin treatment. The expression of AdipoR2 mRNA was 0.70±0.30 and protein level was 0.72±0.12 in diabetic rats that were up-regulated compared with the controls （0.38±0.02 for mRNA and 0.49±0.05 for protein） and decreased after insulin treatment （0.27±0.09 for mRNA and 0.42±0.09 for protein）. In diabetic rats, both mRNA and protein levels of hepatic PPAR-α were much lower （0.60±0.20 and 0.19±0.04, respectively） than those in the controls （2.70±1.50 and 0.43±0.18, respectively） （P〈0.05）, while elevated after insulin treatment （1.30±0.40 and 0.27±0.07, respectively）.Concl

关 键 词：糖尿病 2型 胰岛素 脂联素 过氧化物酶体增殖物激活受体-Α 

分 类 号：R587.1[医药卫生—内分泌]