Dardevet D, Sornet C, Vary T, Grizard J
Centre de Recherche en Nutrition Humaine et INRA, Unité d'Etude du Métabolisme Azoté, Ceyrat, France.
Endocrinology. 1996 Oct;137(10):4087-94. doi: 10.1210/endo.137.10.8828461.
This study was designed to evaluate the role of phosphatidylinositol (PI3) kinase, p70 S6 kinase (p70S6K), and mitogen-activated protein (MAP) kinase in the regulation of muscle protein metabolism by insulin and insulin-like growth factor I (IGF-I). Wortmannin and LY294002 (inhibitors of P13 kinase) both abolished the stimulation of protein synthesis by insulin or IGF-I in epitrochlearis muscle incubated in vitro. LY294002 also totally reversed the antiproteolytic action of these hormones. Although p70S6K activation by insulin and IGF-I may be mediated by PI3 kinase in epitrochlearis muscle, the specific inhibition of this kinase by rapamycin caused only partial (25%) inhibition of the stimulation of protein synthesis by these two hormones. Rapamycin had no effect on proteolysis. Finally, insulin or IGF-I did not stimulate MAP kinase activity at any of the times tested (2-25 min), suggesting that this protein kinase was not directly involved in the regulation of muscle protein metabolism. These observations provide evidence that PI3 kinase and p70S6K, but not MAP kinase, play a role in the regulation of muscle protein turnover by insulin or IGF-I.
本研究旨在评估磷脂酰肌醇-3（PI3）激酶、p70核糖体蛋白S6激酶（p70S6K）和丝裂原活化蛋白（MAP）激酶在胰岛素和胰岛素样生长因子I（IGF-I）对肌肉蛋白质代谢调节中的作用。渥曼青霉素和LY294002（PI3激酶抑制剂）均消除了胰岛素或IGF-I对体外孵育的肱三头肌蛋白质合成的刺激作用。LY294002还完全逆转了这些激素的抗蛋白水解作用。尽管在肱三头肌中胰岛素和IGF-I对p70S6K的激活可能由PI3激酶介导，但雷帕霉素对该激酶的特异性抑制仅部分（25%）抑制了这两种激素对蛋白质合成的刺激作用。雷帕霉素对蛋白水解无影响。最后，在任何测试时间（2 - 25分钟），胰岛素或IGF-I均未刺激MAP激酶活性，这表明该蛋白激酶不直接参与肌肉蛋白质代谢的调节。这些观察结果提供了证据，表明PI3激酶和p70S6K而非MAP激酶在胰岛素或IGF-I对肌肉蛋白质周转的调节中发挥作用。
