Ghrelin改善果糖诱导大鼠胰岛素抵抗的机制研究

Role of ghrelin in ameliorating insulin resistance in fructose-fed rats and its mechanism

32只雄性SD大鼠分为止常对照组（n=16）和果糖组（n=16），分别予以正常饮水和10％果糖4周，2绀再分别以生理盐水和50nmol／kg胃促生长素（Ghrelin）干预6周（每组n=8），测定空腹血糖、血脂和胰岛素等牛化指标，RT—PCR检测大鼠骨骼肌胰岛素受体（Ins—R）mRNA表达水平，Western印迹法检测胰岛素受体底物1（IRS-1）的磷酸化水平。结果显示，高果糖组大鼠血浆胰岛素浓度和稳态模型评估的胰岛素抵抗指数（HOMA—IR）均较正常对照组明显升高[（13．1±3．6对9．0±1．5）μU／ml，P〈0．05；2．78±0．14对1．81±0．13，P〈0．01）]，而高果糖喂养的大鼠经Ghrelin干预后胰岛素水平[（9．6±2．5）μU／ml，P〈0．05]和HOMA—IR（1．96±0．12，P〈0．01）明显降低，骨骼肌lns—RmRNA表达和IRS—1磷酸化水平明显升高（P〈0．01），提示Ghrelin可能通过恢复骨骼肌Ins—R和受体后功能．改善胰岛素抵抗。

Thirty-two male Sprague-Dawley rats were divided into control group （ u = 16） and fructose group （ n = 16 ） fed with 10% fructose solution. After 4 weeks, the rats of two groups were treated with saline and 50 nmol/kg ghrelin for 6 weeks, respectively （ each group n = 8 ）. Fasting plasma glucose, insulin, and blood lipid profile were measured. Insulin reeeptor （Ins-R） mRNA expression in muscle was detected by RT-PCR. The phosphorylation of insulin receptor substrate-1 （ IRS-1 ） was measured by Western blot. The results showed that insulin level and homeostasis model assessment for insulin resistance index （HOMA-IR） in fructose group were higher than those in contrnl group [ （ 13.1 ± 3.6 μs 9.0 ± 1.5 ） μU/ml, P〈0.05 ;2.78 ±0. 14 vs 1.81 ± 0. 13, P〈0.01 ） ] After ghrelin treatment, plasma insulin concentration [ （9.6 ±2.5 ）μU/mL, P〈0.05 ] and HOMA-IR （ 1.96 ± 0. 12, P〈0.01 ） significantly decreased, along with increased lns-R mRNA and 1RS-I phosphorylation in skeletal muscle （P 〈 0.01 ）. These results suggest that ghrelin can ameliorate insulin resistance in fructose-fed rats by restoring Ins-R function.