非诺贝特改善老年高脂喂养C57小鼠胰岛β细胞功能及其作用机制研究

发布时间：2018-02-11 13:14

本文关键词： 非诺贝特老年高脂喂养C小鼠 β细胞功能钙离子　出处：《中国临床药理学杂志》2015年10期 　论文类型：期刊论文

【摘要】：目的考察非诺贝特对老年高脂喂养C57(Aged-C57)小鼠胰岛β细胞功能的影响并探讨可能的作用机制。方法老年高脂喂养C57小鼠(n=28),随机分为老年动物模型组和非诺贝特组(100 mg·kg-1d-1),连续灌胃给药8周。另取正常雄性C57小鼠14只,作为正常组。考察其对血糖、血脂、胰岛素敏感性及β细胞功能的影响。结果非诺贝特给药约5周,可显著改善Aged-C57小鼠胰岛素耐量血糖-时间曲线下面积(P0.01);给药7周,能显著降低Aged-C57小鼠的空腹血糖(P0.01)及空腹血胰岛素水平(P0.05);亦可显著降低其血清三酰甘油水平(P0.05);非诺贝特可显著增加高血糖钳夹葡萄糖刺激后5min和10 min的胰岛素分泌(P0.01,P0.05),增加稳态葡萄糖输注速率(P0.05);非诺贝特可明增加其胰腺中Ca2+含量(P0.05)及胰腺线粒体ATPase活性(P0.01);与模型组相比,非诺贝特可显著上调胰腺中胰岛素合成和信号通路中INS1、PDX1、IRS2和PKB的mRNA表达水平(P0.01),显著上调钙离子释放相关蛋白RYR3及SERCA2的基因表达水平(P0.001,P0.01)。结论长期给予非诺贝特显著改善老年高脂喂养C57(Aged-C57)小鼠的糖脂代谢紊乱状态,其作用机制可能与通过上调胰腺PDX1、INS1及细胞钙库Ca2+释放相关因子的表达有关。
[Abstract]:Objective to investigate the effect of fenofibrate on the function of islet 尾 cells in aged C57Aged-C57mice and to explore the possible mechanism. Methods the aged C57 mice were randomly divided into aged animal model group and fenofibrate group (100 mg 路kg ~ (-1) d ~ (-1)). For 8 weeks, 14 normal male C57 mice were taken. As a normal group, the effects of fenofibrate on blood glucose, blood lipids, insulin sensitivity and 尾 -cell function were investigated. Results fenofibrate administration for about 5 weeks significantly improved the area under the insulin tolerance glycemic time curve in Aged-C57 mice (P 0.01), and administered it for 7 weeks. It can significantly decrease fasting blood glucose (P0.01) and fasting serum insulin level (P0.05N) and serum triglyceride level (P0.05N) in Aged-C57 mice. Fenofibrate can significantly increase insulin secretion at 5 minutes and 10 min after hyperglycemic clamp glucose stimulation. In comparison with the model group, the stable glucose infusion rate (P0.05) and the content of Ca2 in the pancreas (P0.05) and the activity of mitochondrial ATPase in the pancreas were increased by P0.01 (P0.05), and compared with the model group, compared with the model group, the content of Ca2 in the pancreas and the activity of mitochondrial ATPase in the pancreatic mitochondria were increased. Fenofibrate could significantly upregulate insulin synthesis in pancreas and mRNA expression level of PKB and IRS2 in the signal pathway of INS1PDX1, and significantly up-regulate the gene expression level of Ca2 + releasing related protein RYR3 and SERCA2. Conclusion fenofibrate can be significantly modified by fenofibrate for a long time. The disorder of glucose and lipid metabolism in C57 + Aged-C57 mice. The mechanism may be related to the up-regulation of the expression of PDX1-INS1 and Ca2 release in the calcium pool of the pancreas.
【作者单位】：中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室;
【基金】：国家科技重大新药创制、重大专项基金资助项目(2012ZX09301002-004)
【分类号】：R965

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