Leucine and insulin activate p70 S6 kinase through different pathways in human skeletal muscle.
Amino acids and insulin have anabolic effects in skeletal muscle, but the mechanisms are poorly understood. To test the hypothesis that leucine and insulin stimulate translation initiation in human skeletal muscle by phosphorylating 70-kDa ribosomal protein S6 kinase (p70(S6k)), we infused healthy adults with leucine alone (n = 6), insulin alone (n = 6), or both leucine and insulin (n = 6) for 2 h. p70(S6k) and protein kinase B (PKB) serine(473) phosphorylation were measured in vastus lateralis muscles. Plasma leucine increased from approximately 116 to 343 micromol/l during the leucine-alone and leucine + insulin infusions. Plasma insulin increased to approximately 400 pmol/l during the insulin-alone and leucine + insulin infusions and was unchanged during the leucine-alone infusion. Phosphorylation of p70(S6k) increased 4-fold in response to leucine alone, 8-fold in response to insulin alone, and 18-fold after the leucine + insulin infusion. Insulin-alone and leucine + insulin infusions increased PKB phosphorylation, but leucine alone had no effect. These results show that physiological concentrations of leucine and insulin activate a key mediator of protein synthesis in human skeletal muscle. They suggest that leucine stimulates protein synthesis through a nutrient signaling mechanism independent of insulin, raising the possibility that administration of branched-chain amino acids may improve protein synthesis in insulin-resistant states.
Greiwe
J S
JS
Department of Medicine, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Kwon
G
G
McDaniel
M L
ML
Semenkovich
C F
CF
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000097:blood / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D011518:Proto-Oncogene Proteins; D010768:Phosphoserine; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D007930:Leucine