摘要
目的:研究胰高血糖素样肽-1(GLP-1)类似物利拉鲁肽对糖尿病前期小鼠胰岛功能的影响。方法:30只雄性C57BL/6J小鼠随机均分为正常饮食(WT)组、高脂饮食(WH)组、利拉鲁肽(LH)干预组,以RT-PCR检测胰岛素mRNA的表达,以TUNEL法检测胰岛细胞凋亡,以免疫组化法检测胰岛局部诱导型NO合酶(i NOS)及细胞内胰岛素水平等。结果:与WT组相比,WH组胰岛素表达减少,单位面积胰岛细胞凋亡计数明显增加,局部i NOS相对浓度增加(均P<0.01);与WH组比较,LH组胰岛素表达增加,胰岛凋亡细胞计数降低,局部i NOS相对浓度下降(均P<0.05)。结论:GLP-1类似物利拉鲁肽可以改善糖尿病前期小鼠胰岛功能,其机制可能与下调胰岛局部i NOS表达,减弱氧化应激对胰岛的损伤有关。
Objective To study the effect of glucagon-like peptide-1( GLP-1) analogue liraglutide on islet function in pre-diabetic mice. Methods Thirty male C57 BL/6 J mice were randomly divided into control( WT) group,high-fat diet( WH) group and high-fat diet plus liraglutide( LH) group. The expression of insulin mRNA was detected by RT-PCR,the apoptosis of islet cells was detected by TUNEL,and immunohistochemistry was used to determine local inducible NO synthase( i NOS) and intracellular insulin level. Results Compared with WT group,the expression of insulin in the islets of WH group was decreased,the amount of apoptotic cells in unit of islet was increased,and the relative of i NOS was increased( all P<0.01). Compared with WH group,the expression of insulin in LH group increased,the number of apoptotic cells decreased,and the relative concentration of i NOS decreased( P < 0. 05). Conclusion GLP-1 analogue liraglutide plays an important role in improving islet function in pre-diabetes mice.The mechanism may be related to down-regulation of islet local i NOS expression and attenuation of oxidative stress of islet.
引文
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