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游离脂肪酸对肝脏氧化应激及胰岛素抵抗的影响 被引量:5

Effects of free fatty acid elevation on hepatic insulin resistance and hepatic oxidative stress
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摘要 目的:研究游离脂肪酸(FFA)慢性升高对肝脏胰岛素抵抗的影响,探讨氧化应激在其中的作用.方法:给Wistar大鼠分别静脉输注脂肪乳加肝素(IH组)和单纯输注生理盐水(SAL组)48h,在输注的最后2h,清醒状态下行高胰岛素-正血糖钳夹试验,观察延时输注脂肪乳导致的高FFA对葡萄糖利用率(葡萄糖输注率,GIR)的影响,并取肝组织测定羰基蛋白、肝细胞膜和细胞质PKC-δ的含量.结果:在高胰岛素-正血糖钳夹状态,IH输注组与SAL组比较,血清FFA增加4.3倍(P<0.001),羰基蛋白增加3.2倍,GIR下降58.6%(均P<0.001);48h的IH输注使肝细胞膜的PKC-δ/胞质PKC-δ比值增加4.0倍(P<0.001).结论:FFA慢性升高导致了肝脏GIR下降,葡萄糖的利用障碍,肝脏的PKC-δ向细胞膜转位增加,说明在慢性高FFA导致的肝脏胰岛素抵抗中,氧化应激反应起了重要的作用. AIM:To investigate the effects of long-term elevation of free fatty acids(FFA)on hepatic insulin resistance and hepatic oxidative stress. METHODS:A total of 32 Wistar rats were divided into two groups and given an intravenous infusion of intralipid plus heparin(IH)and saline (SAL),respectively.Two hours before the end of the infusion,a hyperinsulinemic-euglycemic clamp was performed to examine the ability of FFA to induce hepatic insulin resistance.After the clamp,liver tissue samples were taken to determine the protein carbonyl content by DNPH (2,4-dinitrophenylhydrazine)colorimetry and the content of protein kinase C-δby Western blot. RESULTS:Compared to SAL infusion,IH infu-sion resulted in an increase in plasma FFA level by 4.3 folds(P〈0.001),hepatic protein carbonyl content by 3.2 folds,and the membrane/cytosol ratio of PKC-δby 4.0 folds(P〈0.001). CONCLUSION:Long-term elevation of FFA induces elevation of hepatic protein carbonyl content,PKC-δtranslocation and insulin resistance, suggesting that PKC-δplays an important role in FFA-induced hepatic insulin resistance.
出处 《世界华人消化杂志》 CAS 北大核心 2009年第23期2405-2408,共4页 World Chinese Journal of Digestology
基金 辽宁省教育委员会基金资助项目 No20060999~~
关键词 游离脂肪酸 胰岛素抵抗 葡萄糖输注率 羰基蛋白 蛋白激酶C-δ Free fatty acids Insulin resistance Glucose infusion rate Protein carbonyl content Protein kinase C-δ
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