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糖皮质激素对衰老过程中胰岛素和胰岛素样生长因子-I调节的肌肉蛋白质代谢的影响。

Glucocorticoid effects on insulin- and IGF-I-regulated muscle protein metabolism during aging.

作者信息

Dardevet D, Sornet C, Savary I, Debras E, Patureau-Mirand P, Grizard J

机构信息

Unité d'Etude du Métabolisme Azoté, Institut National de la Recherche Agronomique, Ceyrat, France.

出版信息

J Endocrinol. 1998 Jan;156(1):83-9. doi: 10.1677/joe.0.1560083.

DOI:10.1677/joe.0.1560083
PMID:9496237
Abstract

This study was performed to assess the effect of glucocorticoids (dexamethasone) on insulin- and IGF-I-regulated muscle protein metabolism in adult and old rats. Muscle atrophy occurred more rapidly in old rats, and recovery of muscle mass was impaired when compared with adults. Muscle wasting resulted mainly from increased protein breakdown in adult rat but from depressed protein synthesis in the aged animal. Glucocorticoid treatment significantly decreased the stimulatory effect of insulin and IGF-I on muscle protein synthesis in adult rats by 25.9 and 58.1% respectively. In old rats, this effect was even greater, being 49.3 and 100% respectively. With regard to muscle proteolysis, glucocorticoids blunted the anti-proteolytic action of insulin and IGF-I in both age groups. During the recovery period, adult rats reversed the glucocorticoid-induced resistance of muscle protein metabolism within 3 days, at which time old rats still exhibited the decrease in insulin-regulated proteolysis. In conclusion, the higher sensitivity of old rat muscle to glucocorticoids may in part result from the greater modification of the effects of insulin and IGF-I on muscle protein metabolism. These responses to glucocorticoids in old rats may be associated with the emergence of muscle atrophy with advancing age.

摘要

本研究旨在评估糖皮质激素(地塞米松)对成年和老年大鼠胰岛素及胰岛素样生长因子-I(IGF-I)调节的肌肉蛋白质代谢的影响。与成年大鼠相比,老年大鼠的肌肉萎缩发生得更快,且肌肉质量的恢复受损。成年大鼠的肌肉消瘦主要源于蛋白质分解增加,而老年动物则源于蛋白质合成受抑制。糖皮质激素处理使成年大鼠中胰岛素和IGF-I对肌肉蛋白质合成的刺激作用分别显著降低了25.9%和58.1%。在老年大鼠中,这种作用甚至更大,分别为49.3%和100%。关于肌肉蛋白水解,糖皮质激素减弱了两个年龄组中胰岛素和IGF-I的抗蛋白水解作用。在恢复期,成年大鼠在3天内逆转了糖皮质激素诱导的肌肉蛋白质代谢抵抗,而此时老年大鼠仍表现出胰岛素调节的蛋白水解减少。总之,老年大鼠肌肉对糖皮质激素的更高敏感性可能部分源于胰岛素和IGF-I对肌肉蛋白质代谢的作用发生了更大改变。老年大鼠对糖皮质激素的这些反应可能与随着年龄增长肌肉萎缩的出现有关。

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