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The roles of aerobic exercise training and suppression IL-6 gene expression by RNA interference in the development of insulin resistance

机译:有氧运动训练和RNA干扰抑制IL-6基因表达在胰岛素抵抗形成中的作用

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Objective: To demonstrate the hypothesis that aerobic exercise training inhibits the development of insulin resistance through IL-6 and probe into the possible molecular mechanism about it. Methods: Rats were raised with high-fat diets for 8. weeks to develop insulin resistance, and glucose infusion rates (GIRs) were determined by hyperinsulinemic-euglycemic clamping to confirm the development of insulin resistance. Aerobic exercise training (the speed and duration time in the first week were respectively 16. m/min and 50. min, and speed increased 1. m/min and duration time increased 5. min every week following it) and/or IL-6shRNA plasmid injection (rats received IL-6shRNA injection via the tail vein every two weeks) were adopted during the development of insulin resistance. The serum IL-6, leptin, adiponectin, fasting blood glucose, fasting serum insulin, GIR, IL-6 gene expression levels, p-p38 in various tissues and p-STAT3/t-STAT3 ratio in the liver were measured. Results: Rats fed with high-fat diets for 8. weeks were developed insulin resistance and the IL-6mRNA levels of IL-6shRNA injection groups in various tissues were significantly lower than those of control group (P< 0.05), respectively. The development of insulin resistance in exercise rats significantly decreased, however, compared with that, the GIR of exercise rats injected by IL-6shRNA was lower (P< 0.05). The IL-6mRNA levels were highest in the fat tissue and lowest in the skeletal muscles in all the rats. The serum adiponectin levels decreased (P< 0.05) following the development of insulin resistance, and it increased (P< 0.05) when the rats were intervened by aerobic exercise training for 8. weeks at the same time. However, there were not significant differences when serum leptin concentrations were compared (P> 0.05). The p-p38 significantly increased in the rats fed with high-fat diets, however, p-p38 of the exercise high-fat diets rats in the liver and fat tissues significantly decreased than that (P< 0.05). The changes of p-p38 in exercise rats injected by IL-6shRNA were irregular. The activation of STAT3 in the liver significantly increased (P< 0.05) following the development of insulin resistance, and it decreased (P< 0.05) when the rats were intervened by aerobic exercise training for 8. weeks at the same time, and the gene silencing of IL-6 did not have effects on the activation of STAT3 in the liver (P> 0.05). Conclusions: In conclusion, aerobic exercise training prevented the development of insulin resistance through IL-6 to a certain degree. The gene expression and secretion of IL-6 could inhibit the development of insulin resistance. The mechanism of the effects were possibly related with elevating the levels of serum adiponectin, and/or inhibiting the activation of STAT3 in the liver and p38MAPK in the skeletal muscles, liver and fat tissues. ? 2012 Elsevier Ltd.
机译:目的:证明有氧运动训练通过IL-6抑制胰岛素抵抗的发展,并探讨其可能的分子机制。方法:高脂饮食饲养大鼠8周以发展胰岛素抵抗,并通过高胰岛素-正常血糖钳夹法测定葡萄糖输注速率(GIR),以确认胰岛素抵抗的发展。有氧运动训练(第一周的速度和持续时间分别为16. m / min和50. min,其后每周增加速度1. m / min,持续时间增加5. min)和/或IL-在胰岛素抵抗形成过程中采用了6shRNA质粒注射(大鼠每两周通过尾静脉注射IL-6shRNA注射)。测量血清IL-6,瘦素,脂联素,空腹血糖,空腹血清胰岛素,GIR,IL-6基因表达水平,各种组织中的p-p38和肝脏中的p-STAT3 / t-STAT3比。结果:高脂饮食喂养8周的大鼠出现胰岛素抵抗,各组织中IL-6shRNA注射组的IL-6mRNA水平分别显着低于对照组(P <0.05)。运动大鼠胰岛素抵抗的发展明显下降,但与之相比,IL-6shRNA注射的运动大鼠的GIR较低(P <0.05)。在所有大鼠中,IL-6mRNA水平在脂肪组织中最高,而在骨骼肌中最低。随着胰岛素抵抗的发展,血清脂联素水平降低(P <0.05),同时有氧运动训练干预8周后,血清脂联素水平升高(P <0.05)。但是,当比较血清瘦素浓度时,差异无统计学意义(P> 0.05)。饲喂高脂饮食的大鼠中p-p38显着升高,但是运动性高脂饮食大鼠在肝脏和脂肪组织中的p-p38显着降低(P <0.05)。用IL-6shRNA注射的运动大鼠中p-p38的变化是不规则的。随着胰岛素抵抗的发展,肝脏中STAT3的活化显着增加(P <0.05),同时有氧运动训练干预大鼠8周后,STAT3的活化降低(P <0.05),并且该基因IL-6沉默对肝脏中STAT3的激活没有影响(P> 0.05)。结论:总之,有氧运动训练在一定程度上阻止了通过IL-6引起的胰岛素抵抗。 IL-6的基因表达和分泌可以抑制胰岛素抵抗的发展。这种作用的机制可能与提高血清脂联素水平和/或抑制肝脏STAT3的活化以及抑制骨骼肌,肝脏和脂肪组织中的p38MAPK有关。 ? 2012爱思唯尔有限公司

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