PPAR-α激动剂的胰岛素增敏作用及对解偶联蛋白基因表达的影响

Effect of peroxisome proliferator-activated receptors-α on improving insulin sensitivity and uncoupling proteins gene mRNA expression

目的观察非诺贝特对胰岛素抵抗大鼠(IR)模型的胰岛素增敏作用及对解偶联蛋白(UCPS)基因表达的影响方法应用高脂饮食制作IR大鼠模型,非诺贝特灌胃两周,以高胰岛素-正葡萄糖钳夹术评价胰岛素敏感性的变化,用半定量的逆转录-聚合酶链反应(RT-PCR)检测UCPs基因mRNA表达的改变结果高脂喂养IR大鼠肌肉UCP-3、肝脏UCP-2基因表达降低, 非诺贝特可以提高葡萄糖输注率GIR(15.30±4.37)与(9.89±3.28)mg·kg-1,显著降低血清三酰甘油(TG)(0.84±0.18)与(1.24±0.34)mmol·L-1(P<0.01);游离脂肪酸(FFA)(0.43±0.13)与(0.28±0.12)mmol·L-1(P<0.05),减少动物的体重增长, 可使肝脏内UCP-2基因mRNA表达增加62.8%,肌肉内UCP-3基因表达增加32.7%,对肌肉组织内UCP-2基因mRNA表达无影响。结论高脂喂养IR大鼠模型中,肌肉UCP-3,肝脏UCP-2基因表达降低;非诺贝特可改善IR,增强UCPs基因表达,它的减少体重和胰岛素增敏作用可能与此有关。

OBJECTIVE To explore the effect of fenofibrate, a ligand of peroxisome proliferator-activated receptors-α（ PPAR-α）, on improving insulin sensitivity and uncoupling proteins（UCPs） gene mRNA expression in high fat-fed rat model with insulin resistance.METHODS Fenofibrate was administrated （ 100 mg·kg^-1· d^-1 ） for two weeks in high fat-fed rat model with insulin resistance. The insulin sensitivity was evaluated by hyperinsulinemic euglycomic clamp. The UCPs mRNA in liver and muscle were measured using RT-PCR. RESULTS Fenofibrate treatment reduced significantly the level of serum triglycerides（TG） and free fat acid（FFA）, reduced body weight gain. It also increased glucose disposal rate, improved insulin sensitivity. Moreover, fenofibrate administration increased UCP-2 mRNA 62.8% in liver and increased UCP-3 mRNA 32.7% in muscle, whereas UCP-2 mRNA level in muscle did not changed significantly. CONCLUSION Fenofibrate reduced the level of serum TG and FFA, improved insulin sensitivity. The effect of improving sensitivity may involve in the overexpression of UCPs gene.