长期高脂饲养大鼠胰岛形态功能改变与外周胰岛素抵抗的关系  

Relationship between the morphological and functional alterations of pancreatic islets and peripheral insulin resistance in rats with long-term high-fat diet

作　　者：张贝[1] 袁莉[1] 曹玲玲[2] 邱海燕[1] 唐兆生[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院内分泌科 [2]江西九江市第一人民医院老干科

出　　处：《中华内分泌代谢杂志》2006年第5期467-471,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：湖北省自然科学基金项目(No.2005ABA158)

摘　　要：目的观察高脂高热量饲料长期饲养对大鼠胰岛形态功能的影响,探讨其与外周胰岛素抵抗的关系。方法8周龄雄性Wistar大鼠30只,分为正常对照组(NC,n=15)和高脂饲养组(HF,n=15),分别给予普通饲料和高脂高热量饲料饲养,采用高胰岛素-正常血糖钳夹技术测定外周胰岛素抵抗程度；以静脉胰岛素释放试验观察胰岛分泌功能；作胰岛素和胰高血糖素双重免疫组化染色,进行胰岛形态学及量化分析；RT-PCR观察胰岛素原mRNA水平的变化。结果HF组的葡萄糖输注率(GIR)显著低于NC组[(5．83±0．79)mg·kg^(-1)·min^(-1)vs(7．60±1．29)mg·kg^(-1)·min^(-1),P＜0．05]。胰岛的免疫组化结果显示HF组单个胰岛的体积增大[(15168±1327)μm^2 vs(6264±1840)μm^2,P＜0．01],β细胞相对于α细胞比率下降[(4．68±1．01)vs(11．84±3．82),P＜0．05],β细胞的胰岛素相对浓度降低[(-5．15±0．03) vs(-4．81±0．17),P＜0．01]。HF组胰岛素分泌高峰明显延迟至10min,NC组达峰时间为5min,HF组胰岛素曲线下面积在10～60min则显著增高[(152．51±34．53)mIU·L^(-1)·min^(-1)vs(86．40±21．21)mIU·L^(-1)·min^(-1),P＜0．01],60 min胰岛素仍在基础水平之上,胰岛素原mRNA差异无统计学意义。结论长期高脂高热量饮食不仅诱导出显著的胰岛素抵抗,胰岛的形态和功能已经出现了早期的损害,提示在2型糖尿病发生发展的前期阶段胰岛的代偿能力已经受损。Objective To investigate the effect of long-term high-fat diet on insulin resistance and the morphology and function of islets in rats and the relationship between them. Methods Thirty normal male Wistar rats （8 weeks old） were divided into two groups and fed either with normal chow （ NC, n = 15 ） , or high-caloric and high-fat diet （HF, n = 15 ）. Insulin resistance was assessed by euglycemic hyperinsulinemic clamp technique. The insulin secretory function of islets was evaluated by intravenous insulin releasing test. Morphological and quantitative analysis of pancreatic tissues was performed by double-label insulin and glucagon immunohistochemistry. Proinsulin mRNA was detected by RT-PCR. Results The glucose infusion rate （GIR） in HF rats was significantly lower than that in NC rats [ （ 5.83 ± 0.79 ） mg · kg^-1 · min^- 1 vs （7.60 ± 1.29 ） mg · kg^-1 · min^-1, p 〈 0.05 ]. Immunohistochemistry showed that HF rats had larger islet size [ （15 168 ± 1 327 ）μm^2 vs （6 264 ± 1 840 ）μm^2, P 〈 0.01 ] and significantly reduced insulin relative concentration of β cells [ （ - 5.15 ± 0.03 ） vs （ -4.81 ±0.17 ） , P 〈0.01 ] , as compared with NC rats. The islet relative β cell volume was decreased significantly （P 〈 0.01 ）, whereas the relative α cell volume was increased （P 〈 0.01 ）. So the ratio of β to α were lower in HF [ （4.68 ± 1.01 ） vs （ 11.84 ± 3.82 ） , P 〈 0.05 ]. The peak of insulin secretion in intravenous insulin releasing test in HF was at 10 min, whereas that in NC rats was at 5 min. AUC （area under curve） 10450 min of insulin in HF was higher than that in NC rats [ （ 152.51 ± 34.53 ） mIU · L^-1 ·min^-1 vs （ 86.40 ± 21.21 ） mIU · L^-1 ·min^-1 , P 〈 0. 01 ]. There was no difference in proinsulin mRNA levels between two groups. Conclusion Long-term high-caloric and high-fat diet results in early impairment of islet morphology and function, as well as significant insulin resistance, suggesting that the compensa

关 键 词：脂毒性 胰岛素抵抗 胰岛 免疫组织化学 逆转录聚合酶链反应 大鼠 Wistar 

分 类 号：R587.1[医药卫生—内分泌]