利用高胰岛素正葡萄糖钳夹实验评估实验大鼠胰岛素抵抗异质性  

Evaluating heterogeneity of insulin resistance by hyperinsulinemic-euglycemic clamp test in rats

作　　者：朱云霞[1,2] 陆俊茜[1,2] 王琛[1,2] 贾伟平[1,2] 

机构地区：[1]上海交通大学附属第六人民医院内分泌代谢科 [2]上海交通大学糖尿病研究所上海市糖尿病重点实验室,200233

出　　处：《上海医学》2012年第1期27-31,共5页Shanghai Medical Journal

基　　金：国家自然科学基金(30971121);上海市科学技术委员会(08dj1400601)资助项目

摘　　要：目的通过高胰岛素正葡萄糖钳夹实验评估不同肥胖易感性大鼠的胰岛素抵抗状态。方法清洁级Sprague-Dawley大鼠30只,随机分为普食组(Chow组,10只)和高脂组(HF组,20只)。根据HF组喂养8周时的平均体重,将其进一步分为肥胖抵抗亚组(HF-OR亚组)和肥胖易感亚组(HF-OP亚组)。喂养8、16周时检测大鼠的血糖、血脂、胰岛素水平,并行口服糖耐量试验(OGTT)和胰岛素耐量实验(ITT);16周行高胰岛素正葡萄糖钳夹实验,测定肝脏脂质含量。结果整个实验周期中各组大鼠的空腹血糖、血清总胆固醇(TC)、三酰甘油(TG)水平的差异均无统计学意义(P值均>0.05),但第16周时HF-OP亚组的空腹血清胰岛素(FIns)显著高于Chow组(P<0.05),HF-OR亚组大鼠的肝脏TG和TC水平均显著高于Chow组(P值分别<0.05、0.01),HF-OP亚组大鼠的肝脏TC水平显著高于Chow组(P<0.01)。OGTT结果显示,与Chow组相比,HF-OP和HF-OR亚组第8、16周时的葡萄糖曲线下面积均显著增大(P值分别<0.05、0.01)。ITT结果表明,与Chow组相比,HF-OP亚组第8、16周时ITT血糖曲线下面积均有增大趋势,HF-OR亚组仅在第16周时有增大的趋势,但差异均无统计学意义(P值均>0.05)。高胰岛素正葡萄糖钳夹实验结果表明,与Chow组相比,HF-OP亚组葡萄糖输注率降低49.2%(P<0.05),HF-OR亚组仅降低25.9%(P>0.05)。结论高脂饮食致大鼠胰岛素敏感性的改变存在个体差异和时序性,肥胖抵抗大鼠可部分抵抗高脂饮食对胰岛素敏感性的损伤。Objective To evaluate insulin resistance in rats with diet-induced obesity by hyperinsulinemic-euglycemic clamp test. Methods Thirty Sprague-Dawley rats were randomly divided into chow group （normal diet, n = 10） and HF group （high fat diet, n = 20）. HF group was then further divided into 2 subgroups according to the mean weight at week 8; high fat-obesity prone （HF-OP） group and high fat-obesityresistant （HF-OR） group. At week 8 and 16, fasting blood glucose （FBG）, serum lipid profiles and fasting serum insulin were measured; oral glucose tolerance test （OGTT） and insulin resistance test （ITT） were conducted. At week 16, hepatic lipid content was detected and hyperinsulinemic-euglycemic clamp test was carried out. Results There were no significant differences in FBG, serum triglyeride （TG） and serum total cholesterol （TO） amongthe groups in the study （all P〉0. 05）. At week 16, fasting serum insulin and hepatic TC in HF-OP group and hepatic TG and TO in HF-OR group were significantly higher than those in chow group （ P〈0. 05, P〈0. 01 ）. Both HF-OP and HF-OR rats had impaired glucose tolerance as the area of OGTT curve （AUCg） was larger in HF group than that in chow group at week 8 and 16 （ P〈0. 05, P〈0. 01 ）. Compared with chow group, the area of ITT curve （AUOitt） tended to increase at both week 8 and week 16 in HF-OP group, and in HF-OR group only at week 16. But the differences had no statistical significance （all P 〉0.05）. Hyperinsulinemic-euglycemic clamp testshowed that glucose infusion rate （GIR） decreased by 49.2% in HF-OP rats （P〈0.05） whereas it was only decreased by 25.9 % in HF-OR rats （P〉0.05）. Conclusion There are time- and individual-differences in insulin sensitivity between obesity-prone and obesity-resistant rats induced by high fat diet. Decreased insulin sensitivity can be partly compensated in HF-OR rats. （Shanghai Med J, 2012, 35：27-31）

关 键 词：胰岛素抵抗异质性 高胰岛素正葡萄糖钳夹 高脂饮食 

分 类 号：R587[医药卫生—内分泌]