酒精对大鼠胰岛素受体及底物-1基因表达影响

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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。 Objective To investigate the effects of chronic alcohol intake on the mRNA expression of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) in adipose tissue of male rats and to explore the relationship between alcohol and insulin sensitivity Sexual relations and related molecular mechanisms. Methods Forty clean male Wistar rats were randomly divided into control group and low, middle and high alcohol groups according to body weight. Groups of 0, 0.8, 1.6 and 2.4 g / (kg.bw) At the end of the 19th week, rats were killed by decapitation, fasting blood glucose and blood insulin were measured, and insulin resistance index (HOMA-IR) was calculated. The total RNA of adipose tissue was extracted and the expression of IR and IRS-1 mRNA was determined by semi-quantitative polymerase chain reaction. Results Compared with the control group, the fasting blood glucose (glucose) concentrations in the middle and high dose groups were significantly increased (P <0.05), and the insulin concentrations in the low and middle dose groups were significantly increased (P < 0.05). The difference of HOMA-IR in each dose group was statistically significant (P <0.05). The mRNA expression levels of IR and IRS-1 in the low, middle and high alcohol groups were (0.588 ± 0.039) and (0.504 ± 0.070), (2.678 ± 0.031) and (1.178 ± 0.177), (0.761 ± 0.137) and 0.037). Compared with the control group, the levels of IR and IRS-1 mRNA in each dose group increased significantly (P <0.05). Conclusion Chronic alcohol intake may induce insulin resistance in male rats. Alteration of IR and IRS-1 mRNA expression in adipose tissue caused by alcohol may be one of the molecular mechanisms that cause insulin resistance.
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