长期酒精摄入对雄性大鼠胰岛素敏感性及肝脏IR、IRS-1、IRS-2 mRNA表达的影响

目的从基因表达水平探讨长期酒精摄入影响肝脏胰岛素敏感性的分子机制。方法清洁级Wistar雄性大鼠40只,随机分为对照组和低、中、高剂量酒精组,每天摄入酒精剂量分别为0、0·8、1·6和2·4g/kg bw。给予酒精19周后,测定空腹血糖、血胰岛素,计算胰岛素抵抗指数(HOMA-IR)。提取肝脏总RNA,通过RT-PCR测定胰岛素受体(IR)、胰岛素受体底物1(IRS-1)、胰岛素受体底物2(IRS-2)的mRNA表达水平。结果与对照组相比,高剂量组血糖升高(P<0·05);各剂量组血胰岛素浓度均升高,低、中剂量组升高有显著性差异(P<0·05);各剂量组HOMA-IR均显著高于对照组(P<0·05)。各剂量组IR mRNA表达均降低;IRS-1及IRS-2mRNA表达在低、中剂量组升高,高剂量组降低。结论长期过量酒精摄入可以引起雄性大鼠胰岛素抵抗,肝脏IR、IRS-1、IRS-2mRNA表达降低是酒精影响胰岛素敏感性的分子机制之一。

Influence of chronic ethanol intake insulin sensitivity and IR, IRS-1, IRS-2 mRNA expression of liver in male rats

ObjectiveTo investigate the effect of ethanol intake on the insulin sensitivity of hepatic tissue in male rats and explores its possible molecular mechanisms.Methods Wister rats were administrated ethanol at a dose of 0 (control), 0.8 (low ethanol, L), 1.6 (medium ethanol, M) and 2.4 g/kg (high ethanol, H) daily, respectively. Each group had ten males. Nineteen weeks later, serum was collected for testing of fasting plasma glucose and insulin. Total liver RNA was extracted. The expression levels of IR, IRS-1, IRS-2 mRNA in hepatic tissue were detected by RT-PCR.Results Compared with the control group, the glucose concentration significantly increased in H ethanol groups (P<0.05), the insulin concentration significantly increased in L and M ethanol groups (P<0.05), HOMA-IR significantly increased in every ethanol group (P<0.05). IR mRNA expression remarkably decreased in every ethanol group. IRS-1, IRS-2 mRNA expression increased in L and M ethanol groups but decreased in H ethanol group. Conclusion The present study showed that ethanol abuse could induce to insulin resistance. The decreased of IR, IRS-1, IRS-2 mRNA expression of liver may be involved in the molecular mechanism of the effects of ethanol on insulin insensitivity.