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作 者:郭宁宁[1] 裴丽娜[1] 都健[1] 罗红飞[1] 刘佳[1] 林志楠[1] 张克莹[1]
机构地区:[1]中国医科大学附属第一医院内分泌科,辽宁沈阳110001
出 处:《中国现代医学杂志》2010年第23期3539-3542,3548,共5页China Journal of Modern Medicine
基 金:辽宁省教育厅科研项目计划(No:L2010597);辽宁省科学技术计划项目(No:2009225029)
摘 要:目的检测高脂饲料喂养大鼠的肝脏葡萄糖调节蛋白78(GRP78)mRNA的表达情况,探讨内质网应激与胰岛素抵抗之间的关系及GRP78在胰岛素抵抗发生机制中的作用。方法采用高脂饲料喂养建立胰岛素抵抗大鼠模型,30只雄性Wistar大鼠被随机分为基础饮食喂养组(NC,n=15)和高脂饮食喂养组(HF,n=15),分别喂养10周后,用正常血糖-高血浆胰岛素钳夹技术进行评估。应用Real Time PCR方法检测大鼠肝脏中GRP78 mRNA的表达。结果①高脂饲料组大鼠的葡萄糖输注率明显低于基础饲料组[GIR 60~120(0.90±0.15)vs(4.97±0.68)mg(/kg.min),P<0.01]。②高脂饲料组肝脏GRP78 mRNA的表达明显高于基础饲料组([1.13±0.50)vs(0.43±0.10,P<0.01]。③肝脏GRP78 mRNA表达与内脏脂肪占体质量的百分比(r=0.52,P=0.019)、总胆固醇(TC)(r=0.51,P=0.022)成正相关。结论高脂诱导的胰岛素抵抗大鼠肝脏中GRP78mRNA表达增加,表明大鼠肝脏发生内质网应激和未折叠蛋白反应。【Objective】 To detect the expression of glucose regulating protein 78(GRP78) mRNA in liver of high-fat diet fed rats,and to investigate the relationship between endoplasmic reticulum stress and insulin resistance,and the role of GRP78 in insulin resistance.【Methods】 Insulin resistance rat model was induced by high-fat diet feeding.Thirty male Wistar rats were randomly divided into two groups fed with either basic chow(NC,n =15) or high-fat diet(HF,n =15) for 10 weeks,then assessed by euglycemic-hyperinsulinemia clamp technique.The GRP78 mRNA expression was tested by real-time PCR.【Results】 ①The glucose infusion rate(GIR) in HF group significantly decreased compared with that in NC group [GIR60~120(0.90±0.15) mg/(kg·min) vs.(4.97±0.68) mg/(kg·min),P m0.01].②The GRP78 mRNA expression of liver in HF group was significantly increased in comparison with that in NC group [(1.13±0.50) vs.(0.43±0.10),PM 0.01].③The GRP78 mRNA expression of liver was positively correlated with the percentage of visceral fat in body weight(r =0.52,P =0.019)and total cholesterol(TC)(r =0.51,P =0.022).【Conclusion】 The increased expression of GRP78 mRNA in liver of insulin resistant rats shows that endoplasmic reticulum stress and unfolded protein response are provoked in liver of rats.
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