高脂饮食所致胰岛素抵抗小鼠心肌胰岛素受体底物1的改变  

Effect of high fat diet on the expression of insulin receptor substrate 1 in the heart of Kunming mice with insulin resistance

作　　者：毛拓华[1] 李竞[1] 高凌[1] 唐其柱[2] 

机构地区：[1]武汉大学人民医院内分泌科,430060 [2]武汉大学人民医院心内科,430060

出　　处：《中华实验外科杂志》2016年第2期429-431,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金（81470516、81571376）

摘　　要：目的探讨在高脂饮食导致的外周胰岛素抵抗存在的情况下，心肌胰岛素信号传导通路中的关键信号分子胰岛素受体底物1（IRS1）的改变及其机制。方法将20只雄性昆明小鼠随机分为对照组（ND组）10只及胰岛素抵抗组（IR组）10只，ND组给予普通饲料，IR组给予高脂饲料。16周时称量体质量、检测空腹血糖和空腹胰岛素，计算稳态模型胰岛素抵抗指数（HOMA-IR），用Western blot的方法检测心肌组织磷酸化c-jun氨基末端激酶（p-JNK）及307位丝氨酸磷酸化的IRS1（p-IRS1）的表达，用免疫组织化学染色的方法检测心肌组织活化的核因子-κB（NF—κB）的表达。结果ND组小鼠的体质量、空腹血糖、空腹胰岛素、HOMA—IR分别为（53．45±3．97）g、（5．60±0．63）mmol／L、（8．36±1．66）mU／L、2．06±0．35，IR组小鼠分别为（61．70±4．47）g、（7．44±0．68）mmol／L、（9．61±1．33）mU／L、3．16±0．36，IR组小鼠的体质量、空腹血糖、空腹胰岛素和HOMA—IR均高于ND组（P〈0．05）；ND组小鼠p-IRS1、p-JNK的表达水平和NF—κB的阳性细胞率分别为0．32±0．26、0．17±0．40、（11．17±6．75）％，IR组小鼠分别为0．77±0．23、0．68±0．12、（56．45±4．02）％，与ND组小鼠比较，IR组小鼠心肌p-IRS1蛋白水平明显上升（P〈0．05），IR组心肌活化的NF—κB和p-JNK表达比ND组显著增加（P〈0．01）。结论高脂饮食可成功诱导外周胰岛素抵抗小鼠模型，高脂饮食可能通过JNK和NF—κB通路引起IRS1丝氨酸磷酸化增加，进而导致心肌的胰岛素传导信号通路异常。Objective To determine the effect of high fat diet on the expression of insulin receptor substrate 1 （IRS1） in the heart of Kuming mice with insulin resistance （IR）. Methods Twenty male Knnming mice were randomly divided into normal diet （ND） group （n = 10） and IR group （n = 10）. The mice in ND group were fed on routine diet, and those in IR group on high fat diet. After 16 weeks, the body weight, fasting glucose and fasting insulin were detected. Homeostasis model assessment for insulin resistance （HOMA - IR） was calculated. The phosphorylation levels of c - 3UN N - terminal kinase （ p - JNK） and IRS1 （ p - IRS1 ） in the heart were measured by Western blotting. The activation of nuclear factor - KB （ NF - KB） in the heart was detected by immunohistochemistry. Results The body weight, fasting glucose , fasting insulin and HOMA - IR in ND group were （53.45± 3.97） g, （5.60 ± 0. 63） mmol/L, （8.36 ± 1. 66） mU/L, and 2. 06 ±0. 35, and those in IR group were （61.70 ±4.47） g, （7.44 ±0. 68） mmol/L, （9. 61 ± 1.33） mU/L, and 3.16 ± 0. 36, respectively. As compared with ND group, the body weight, fasting glucose, fasting insulin and HOMA - IR were significantly increased in IR group （P 〈 0. 05）. The protein levels of p - IRS1 （ Set 307） and p - JNK and the NF - κB positive cells in ND group were 0. 32± 0. 26, 0. 17 ± 0.40, and （ 11.17 ±6. 75） %, and those in IR group were 0. 77 ±0. 23, 0. 68 ±0. 12, and （56.45±4. 02） % respectively. As compared with ND group, the Ser307 phos- phorylation level of IRS - 1 was increased in IR group （ P 〈 0.05 ）. The levels of p - JNK and activated forms of NF - KB in IR group were markedly increased by high fat diet when compared to those in ND group （ P 〈 0. 01 ）. Conclusion The high fat diet t^d mice developed peripheral insulin resistance characterized by an increase in HOMA - IR. High fat diet caused the activation of JNK and NF - KB in cardiac tissue, and upregulated Ser307 phosphoryl

关 键 词：胰岛素抵抗 高脂饮食 心肌 胰岛素受体底物1 

分 类 号：R587.1[医药卫生—内分泌]