酒精对大鼠胰岛素受体及底物-1基因表达影响

目的 研究慢性酒精摄入对雄性大鼠脂肪组织胰岛素受体(insulin receptor,IR)、胰岛素受体底物-1(insulin receptor substrate-1,IRS-1)mRNA表达的影响,探讨酒精与胰岛素敏感性的关系及相关分子机制.方法 清洁级雄性Wistar大鼠40只,按体重随机分为对照组和低、中、高酒精剂量组,每天分别给予0,0.8,1.6和2.4g/(kg·bw)的酒精灌胃.第19周末,断头处死大鼠,测定空腹血糖和血胰岛素,计算胰岛素抵抗指数(HOMA-IR).提取脂肪组织总RNA,通过半定量聚合酶链式反应方法测定IR、IRS-1mRNA表达水平.结果 与对照组相比,中、高剂量组空腹血糖(葡萄糖)浓度升高,差异有统计学意义(P<0.05);低、中剂量组胰岛素浓度升高,差异有统计学意义(P<0.05);各剂量组胰岛素抵抗指数(HOMA-IR)的升高差异均有统计学意义(P<0.05).低、中、高酒精剂量组IR、IRS-1mRNA表达水平分别为(0.588±0.039),(0.504±0.070);(2.678±0.031),(1.178±0.177);(0.761±0.137),(0.515±0.037).与对照组相比,各酒精剂量组IR、IRS-1mRNA表达水平均增加,差异有统计学意义(P<0.05).结论 慢性酒精摄入可以引起雄性大鼠胰岛素抵抗,酒精造成脂肪组织IR、IRS-1mRNA表达的改变可能是引起胰岛素抵抗的分子机制之一.

Effect of chronic ethanol intake on insulin receptor, insulin receptor subsrate.1 mRNA expression in rat adipose tissue

Objective To investigate the influence of chronic ethanol intake on insulin receptor(IR),insulin receptor substrate 21(IRS 21)mRNA exp ression in adipose tissue of rats and explore the possible molecular mechanism of the effect of alcohol on insulin sensitivity.Methods Fourty male Wistar rats were randomly divided into four groups on the basis of body weight:control group(C),low(L),moderate(M)and high alcohol group(H).The rats were adm in istrated with ethanol by gastric in tubation and the dose of each group was 0(control),0.8(L),1.6(M)and 2.4(H)g/kg·bw daily,respectively.Nineteen weeks later,serum was collected for testing of fasting plasm a glucose and insulin and HOM A-IR index of each group was calcu lated.Total adipose tissue RNA was extracted.The expression levels of IR,IRS-1 m RNA in adip ose tissue were detected by R T-PCR.Results Compared with the control group,the glucose concentration significantly increased in H ethanol group(P<0.05)and the insulin concentration significantly increased in L and Methanol groupd(P<0.05).HOMA-IR significantly increased in ethanol groups(P<0.05).IR,IRS21 mRNA exp ression remarkably increased in ethanol groups(P<0.05).Conclusion The study showed that chronic ethanol intake could induce insulin resistance.The increase of IR,IRS 21 mRNA exp ression in adiposetissue may be involved in the molecular mechanism of ethanol effects on insulin sensitivity.