Endocrinology, Vol 137, 4087-4094, Copyright © 1996 by Endocrine Society

ARTICLES

Phosphatidylinositol 3-kinase and p70 s6 kinase participate in the regulation of protein turnover in skeletal muscle by insulin and insulin-like growth factor I

D Dardevet, C Sornet, T Vary and J Grizard
Centre de Recherche en Nutrition Humaine et INRA, Unite d'Etude du Metabolisme Azote, Ceyrat, France.

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.

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