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首页> 外文期刊>American Journal of Physiology >Effect of caloric restriction on mitochondrial reactive oxygen species production and bioenergetics: reversal by insulin.
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Effect of caloric restriction on mitochondrial reactive oxygen species production and bioenergetics: reversal by insulin.

机译：热量限制对线粒体活性氧产生和生物能的影响：胰岛素逆转。

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摘要

To gain insight into the antiaging mechanisms of caloric restriction (CR), mitochondria from liver tissue of male Brown Norway rats were used to study the effects of CR and insulin on mitochondrial reactive oxygen species production and bioenergetics. As assessed by hydrogen peroxide measurement, CR resulted in a decrease in the production rate of reactive oxygen species. This decrease was attributed to a decrease in protonmotive force in mitochondria from the CR animals. The decrease in protonmotive force resulted from an increase in proton leak activity and a concomitant decrease in substrate oxidation activity. Each of these effects of CR was reversed by subjecting CR animals to 2 wk of insulin treatment. To achieve continuous and stable insulin delivery, animals were placed under temporary halothane anesthesia and miniosmotic pumps were implanted subcutaneously. To gain further insight into how CR and insulin exerted its effects on mitochondrial bioenergetics, the effects of CR and insulin were quantified using modular metabolic control analysis. This analysis revealed that the effects of CR were transmitted through different reaction branches of the bioenergetic system, and insulin reversed the effects of CR by acting through the same branches. These results provide a plausible mechanism by which mitochondrial reactive oxygen species production is lowered by CR and a complete description of the effects of CR on mitochondrial bioenergetics. They also indicate that these changes may be due to lowered insulin concentrations and altered insulin signaling in the CR animal.
机译：为了深入了解热量限制（CR）的抗衰老机制，雄性Brown Norway大鼠肝脏组织中的线粒体用于研究CR和胰岛素对线粒体活性氧产生和生物能的影响。如通过过氧化氢测量所评估的，CR导致活性氧物质的生产率降低。该降低归因于来自CR动物的线粒体中质子动力的降低。质子动力的降低是由于质子泄漏活性的增加和底物氧化活性的随之降低引起的。通过对CR动物进行2周的胰岛素治疗，可以逆转CR的这些作用。为了实现连续和稳定的胰岛素输送，将动物置于暂时的氟烷麻醉下，并在皮下植入微渗透泵。为了进一步了解CR和胰岛素如何对线粒体生物能学发挥作用，使用模块化代谢控制分析对CR和胰岛素的作用进行了量化。该分析表明，CR的作用通过生物能系统的不同反应分支传播，胰岛素通过作用于相同的分支来逆转CR的作用。这些结果提供了通过CR降低线粒体活性氧产生的合理机制，并完整描述了CR对线粒体生物能学的影响。他们还表明这些变化可能是由于CR动物体内胰岛素浓度降低和胰岛素信号传导改变所致。

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