Role of PDK1 in Skeletal Muscle Hypertrophy Induced by Exercise Load

Skeletal muscle mass is an important determinant of whole-body glucose disposal. We here show that mice (M-PDK1KO mice) with skeletal muscle–specific deficiency of 3'-phosphoinositide–dependent kinase 1 (PDK1), a key component of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, manifest a reduced skeletal muscle mass under the static condition as well as impairment of exercise load–induced muscle hypertrophy. Whereas exercise load-induced changes in gene expression were not affected, the phosphorylation of ribosomal protein S6 kinase (S6K) and S6 induced by exercise load was attenuated in skeletal muscle of M-PDK1KO mice, suggesting that PDK1 regulates muscle hypertrophy not through changes in gene expression but through stimulation of protein synthesis via the S6K-S6 axis. Total RNA was extracted from plantaris muscle of wild-type or mutant mice at 10 days after synergistic muscle ablation and was subjected to hybridization with the use of an Affymetrix Mouse Gene 2.0 ST Array (Affymetrix, Santa Clara, CA).