上海交通大学学报（医学版）

›› 2012, Vol. 32 ›› Issue (1): 48-.doi: 10.3969/j.issn.1674-8115.2012.01.009

• 论著（基础研究） • 上一篇    下一篇

两种高脂血症小鼠模型糖代谢及靶组织胰岛素敏感性研究

白洁菲, 章 瑶, 苏布德格日乐, 李圣贤, 黄 融, 刘 伟, 胡耀敏   

  1. 上海交通大学 医学院附属仁济医院内分泌代谢病科, 上海 200127
  • 出版日期:2012-01-28 发布日期:2012-01-29
  • 通讯作者: 胡耀敏, 电子信箱: amin99@163.com。
  • 作者简介:白洁菲（1985—）, 女, 硕士生；电子信箱: baijf1985@126.com。
  • 基金资助:

    国家自然科学基金（81170758, 30670988）；仁济医院科研培育基金（RJPY10-004）;上海高校选拔培养优秀青年教师科研专项基金（jdy09018）

Research of glucose metabolism and tissue-targeted insulin sensitivity in two mouse models of hyperlipidemia

BAI Jie-fei, ZHANG Yao, SU Budegerile, LI Sheng-xian, HUANG Rong, LIU Wei, HU Yao-min   

  1. Department of Endocrinology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
  • Online:2012-01-28 Published:2012-01-29
  • Supported by:

    National Natural Science Foundation of China, 81170758, 30670988；Foundation from Renji Hospital, RJPY10-004；Excellent Young College Teachers Training Foundation of Shanghai, jdy09018

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摘要：

目的 观察高三酰甘油血症和高胆固醇血症小鼠的糖代谢及靶组织（肝脏和骨骼肌）胰岛素敏感性的变化。方法 采用普通饲料喂养小鼠（对照组，n=8）、脂蛋白脂酶基因敲除杂合子小鼠（LPL+/-）（高三酰甘油血症组，n=8）和高脂饲料喂养小鼠（高胆固醇血症组，n=8）作为实验对象。测量各组小鼠的体质量；检测血清三酰甘油（TG）、胆固醇（TC）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、血糖浓度和空腹胰岛素水平，计算稳态模型胰岛素抵抗指数（HOMA-IR）和胰岛素敏感指数（ISI）；Western blotting检测肝脏和骨骼肌组织在胰岛素刺激后Akt473位丝氨酸磷酸化水平（p-Aktser473的相对表达量）的变化。结果 高三酰甘油血症组血清TG浓度显著高于对照组和高胆固醇血症组（P<0.05），高胆固醇血症组血清TC浓度显著高于对照组和高三酰甘油血症组（P<0.05）。与对照组比较，高三酰甘油血症组血糖浓度、空腹胰岛素水平和HOMA-IR有增高趋势，ISI则有所降低，但差异均无统计学意义（P>0.05）；与对照组和高三酰甘油血症组比较，高胆固醇血症组血糖浓度、空腹胰岛素水平和HOMA-IR显著升高，而ISI明显下降（均P<0.05）。高三酰甘油血症组和高胆固醇组肝脏和骨骼肌组织经胰岛素刺激后的p-Aktser473相对表达量及其升高倍数显著低于对照组（P<0.05）；在高胆固醇组，肝脏组织p-Aktser473相对表达量的升高倍数显著低于高三酰甘油血症组，骨骼肌组织在胰岛素刺激后的p-Aktser473相对表达量明显高于高三酰甘油血症组（P<0.05）。结论 高三酰甘油血症和高胆固醇血症均伴有靶组织胰岛素敏感性受损，其中高脂喂养小鼠出现高胆固醇血症时伴有更明显的糖代谢紊乱。

关键词: 高脂血症, 高三酰甘油血症, 高胆固醇血症, 胰岛素敏感性, 糖尿病

Abstract:

Objective To observe the change of glucose metabolism and tissue-targeted (liver and skeletal muscle) insulin sensitivity in mice with hypertriglyceridemia or hypercholesterolemia. Methods Mice fed with normal diet (control group, n=8), lipoprotein lipase gene knockout heterozygous mice (LPL+/-) (hypertriglyceridemia group, n=8) and mice fed with high-fat diet (hypercholesterolemia group, n=8) were selected. Body weight of each group of mice was measured, serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), blood glucose and fasting insulin were detected, homeostasis model assessment of insulin resistance(HOMA-IR) and insulin sensitivity index (ISI) were calculated, and the change of phosphorylation of serine of Akt473 after insulin stimulation (relative expression of p-Aktser473) in liver and skeletal muscle tissues was determined by Western blotting. Results Serum TG in hypertriglyceridemia group was significantly higher than those in control group and hypercholesterolemia group (P<0.05), and serum TC in hypercholesterolemia group was significantly higher than those in control group and hypertriglyceridemia group (P<0.05). Blood glucose, fasting insulin and HOMA-IR were higher, and ISI was lower in hypertriglyceridemia group than in control group, while there was no significant difference in these parameters between two groups (P>0.05). Blood glucose, fasting insulin and HOMA-IR were significantly higher, and ISI was significantly lower in hypercholesterolemia group than in control group and hypertriglyceridemia group (P<0.05). The relative expression of p-Aktser473 and times of increase in relative expression in liver and skeletal muscle tissues after insulin stimulation in hypertriglyceridemia group and hypercholesterolemia group were significantly lower than those in control group (P<0.05). The increase in relative expression of p-Aktser473 in liver tissues in hypercholesterolemia group was significantly lower than that in hypertriglyceridemia group (P<0.05), and the relative expression of p-Aktser473 in skeletal muscle tissues after insulin stimulation in hypercholesterolemia group was significantly higher than that in hypertriglyceridemia group (P<0.05). Conclusion Mice with hypertriglyceridemia or hypercholesteremia have impaired tissue-targeted insulin sensitivity, and those with hypercholesteremia fed with high-fat diet have more significantly impaired glucose metabolism.

Key words: hyperlipidemia, hypertriglyceridemia, hypercholesteremia, insulin sensitivity, diabetes