Grizard J, Dardevet D, Balage M, Larbaud D, Sinaud S, Savary I, Grzelkowska K, Rochon C, Tauveron I, Obled C
Unité d'étude du métabolisme azoté, Inra centre de Clermont-Ferrand/Theix, Saint-Genès-Champanelle, France.
Reprod Nutr Dev. 1999 Jan-Feb;39(1):61-74. doi: 10.1051/rnd:19990104.
Insulin plays a major role in the regulation of skeletal muscle protein turnover but its mechanism of action is not fully understood, especially in vivo during catabolic states. These aspects are presently reviewed. Insulin inhibits the ATP-ubiquitin proteasome proteolytic pathway which is presumably the predominant pathway involved in the breakdown of muscle protein. Evidence of the ability of insulin to stimulate muscle protein synthesis in vivo was also presented. Many catabolic states in rats, e.g. streptozotocin diabetes, glucocorticoid excess or sepsis-induced cytokines, resulted in a decrease in insulin action on protein synthesis or degradation. The effect of catabolic factors would therefore be facilitated. In contrast, the antiproteolytic action of insulin was improved during hyperthyroidism in man and early lactation in goats. Excessive muscle protein breakdown should therefore be prevented. In other words, the anabolic hormone insulin partly controlled the 'catabolic drive'. Advances in the understanding of insulin signalling pathways and targets should provide information on the interactions between insulin action, muscle protein turnover and catabolic factors.
胰岛素在骨骼肌蛋白质周转的调节中起主要作用，但其作用机制尚未完全明确，尤其是在分解代谢状态下的体内情况。本文对这些方面进行了综述。胰岛素抑制ATP-泛素蛋白酶体蛋白水解途径，该途径可能是参与肌肉蛋白分解的主要途径。文中还给出了胰岛素在体内刺激肌肉蛋白合成能力的证据。大鼠的许多分解代谢状态，如链脲佐菌素诱导的糖尿病、糖皮质激素过量或脓毒症诱导的细胞因子，都会导致胰岛素对蛋白合成或降解的作用减弱。因此，分解代谢因子的作用会得到促进。相比之下，在人类甲状腺功能亢进和山羊泌乳早期，胰岛素的抗蛋白水解作用增强。因此，应防止肌肉蛋白过度分解。换句话说，合成代谢激素胰岛素部分控制了“分解代谢驱动力”。对胰岛素信号通路和靶点认识的进展应能提供有关胰岛素作用、肌肉蛋白周转和分解代谢因子之间相互作用的信息。
