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目的研究脂肪组织磷酸烯丙醇羧激酶(PEPCK)与高脂饲养大鼠的胰岛素抵抗的关系及罗格列酮对其的影响。方法将8周龄雄性SD大鼠,分为两组短期组(8周,33只)和长期组(28周,30只)。每组各包括正常饲养组(正常组,11只、10只),高脂组(11只、10只)和罗格列酮组(11只、10只)。饲养至实验终点时取空腹血测血游离脂肪酸(FFA)和甘油三酯。采用正常血糖高胰岛素钳方法及组织对3H-2-脱氧葡萄糖(2-DG)的摄取能力测定各组的胰岛素敏感性,用逆转录-聚合酶链反应(RT-PCR)方法分析脂肪PEPCK mRNA表达的变化。结果与正常组比较,长期高脂饲养使甘油三酯增加32%(P<0.05)。短期高脂饲养组葡萄糖输注速率(GIR)下降51%(P<0.01);长期高脂饲养组肝脏、肌肉和脂肪组织2-DG摄取率分别下降了42%、36%和48%(P<0.01),短期及长期高脂饲养组脂肪组织PEPCK mRNA含量没有改变。与高脂组比较,罗格列酮干预短期组和长期组的FFA分别低125%和49%(P<0.05);甘油三酯分别下降54.0%和23%(P<0.01);短期干预组GIR增加了150%(P<0.01);而长期干预组肝脏、肌肉和脂肪组织2-DG摄取率分别高39%、66%和66%(均P<0.01);同时短期及长期罗格列酮干预使大鼠脂肪组织PEPCK mRNA含量分别增加165%和43%(P<0.05)。结论噻唑烷二酮类药物通过诱导脂肪组织PEPCK表达,增加脂肪酸再酯化,降低循环FFA,可能与改善胰岛素敏感性有关。
Objective To investigate the relationship between adipose tissue phospholipid-carbinol kinase (PEPCK) and insulin resistance in high fat diet rats and the effect of rosiglitazone on it. Methods 8-week-old male Sprague Dawley rats were divided into two groups: short-term group (8 weeks, 33 animals) and long-term group (28 weeks, 30 animals). Each group included normal feeding group (n = 11, n = 10), high fat group (n = 11) and rosiglitazone group (n = 11). Fed to the end of the experiment, fasting blood was taken to measure free fatty acids (FFA) and triglycerides. The insulin sensitivity of each group was determined by the method of hyperglycemic insulin clamp and the tissue uptake of 3H-2-deoxyglucose (2-DG). PEPCK mRNA was analyzed by RT-PCR Changes in expression. Results Compared with the normal group, long-term high fat diet increased triglycerides by 32% (P <0.05). The glucose uptake rate (GIR) in short-term high fat diet group decreased by 51% (P <0.01). The uptake of 2-DG in liver, muscle and adipose tissue decreased by 42%, 36% and 48% <0.01). The content of PEPCK mRNA in adipose tissue in short-term and long-term high fat diet group did not change. Compared with the high-fat group, the FFA of rosiglitazone-treated group was 125% and 49% lower than that of the long-term group (P <0.05), triglyceride decreased 54.0% and 23% GIR increased by 150% (P <0.01), while the 2-DG uptake of liver, muscle and adipose tissue was 39%, 66% and 66% higher in the long-term intervention group Ketone intervention increased PEPCK mRNA content in rat adipose tissue by 165% and 43%, respectively (P <0.05). Conclusion Thiazolidinediones may be related to the improvement of insulin sensitivity by inducing PEPCK expression in adipose tissue, increasing fatty acid reesterification and decreasing circulating FFA.