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胰岛素治疗对糖尿病大鼠骨骼肌脂肪酸转运相关蛋白表达影响的研究

来自:中国糖尿病杂志  编辑:汤孙寅焱 毕艳 孙婧|点击数:|2013-04-02

  ·糖尿病基础研究·

  胰岛素治疗对糖尿病大鼠骨骼肌脂肪酸转运相关蛋白表达影响的研究

  汤孙寅焱 毕艳 孙婧 杨慧杰 陈莹莹 朱大龙

  【摘要】 目的 探讨胰岛素干预治疗对骨骼肌细胞内脂肪酸转运蛋白表达的影响。 方法 建立高脂喂养联合小剂量STZ诱导的糖尿病SD大鼠模型,在血糖升高后3 d开始给予中效胰岛素或格列齐特治疗3周,血糖控制目标随机血糖<8 mmol/L。通过Western blot检测骨骼肌细胞内脂蛋白脂酶(LPL),脂肪酸转位酶(FAT)、脂肪酸转运蛋白1(FATP-1),及肉毒碱棕榈酰转移酶1(CPT-1)蛋白表达水平。 结果 与NC组比较,糖尿病大鼠骨骼肌细胞内LPL蛋白表达上调30%,胰岛素和格列齐特治疗下调了LPL蛋白表达;糖尿病大鼠骨骼肌细胞内CPT-1和FAT蛋白分别下调了45%和47%,胰岛素和格列齐特治疗分别上调了FAT蛋白表达31%和26%,胰岛素治疗同时上调了CPT-1蛋白表达57.5%;FATP-1和FABP蛋白表达在各组间无变化。 结论 胰岛素治疗改善了细胞内脂肪酸转运及线粒体氧化,可能是骨骼肌细胞内脂质沉积减少的机制之一。

  【关键词】 胰岛素;糖尿病;肌, 骨骼;脂肪酸转运蛋白质类

  Effect of early insulin therapy on fatty acid transporters in skeletal muscle of diabetic rats TANGSUN Yin-yan, BI Yan,SUN Jing, et al. Department of endocrinology, Drum Tower Hospital affiliated to Medical School, Nanjing University, Nanjing 210008, China

  Corresponding author: BI Yan, E-mail: biyan@nju.edu.cn

  【Abstract】Objective To investigate the effect of insulin treatment on fatty acid transporters in skeletal muscles of diabetic rats. Methods High fat diet and low dose streptozotocin (STZ) induced diabetic rats were given NPH insulin or gliclazide for 3 weeks initiated on the 3rd day after STZ injection as treatment. The target of controlled blood glucose was to <8mmol/L. Lipoprotein lipase (LPL), fatty acid translocase (FAT), fatty acid transport protein 1 (FATP1), fatty acid binding protein (FABP), carnitine palmitoyltransferase 1 (CPT-1) in skeletal muscle of diabetic rats were assayed by Western blot. Results Compared to normal rats, LPL protein in untreated diabetic rats was 30% higher, which was significantly decreased by insulin and gliclazide treatment. CPT-1 and FAT protein levels were decreased by 45% and 47% respectively in untreated diabetic rats, of which FAT was increased by 31% and 26% due to insulin and gliclazide treatment, and CPT-1 expression was increased by 57.5% owing to insulin treatment. Insulin and gliclazide failed to affect FATP1 and FABP protein expressions. Conclusions Insulin exerted its anti-lipo toxicityeffect in skeletal muscle of diabetic rats potentially through amelioration of impaired fatty acid transportation and mitochondrial dysfunction.

  【Key Words】 Insulin; Diabetes mellitus; Muscle, Skeleton; Fatty acid transporter proteins

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