Fed levels of amino acids are required for the somatotropin-induced increase in muscle protein synthesis

Am J Physiol Endocrinol Metab. 2008 Oct;295(4):E876-83. doi: 10.1152/ajpendo.90423.2008. Epub 2008 Aug 5.


Chronic somatotropin (pST) treatment in pigs increases muscle protein synthesis and circulating insulin, a known promoter of protein synthesis. Previously, we showed that the pST-mediated rise in insulin could not account for the pST-induced increase in muscle protein synthesis when amino acids were maintained at fasting levels. This study aimed to determine whether the pST-induced increase in insulin promotes skeletal muscle protein synthesis when amino acids are provided at fed levels and whether the response is associated with enhanced translation initiation factor activation. Growing pigs were treated with pST (0 or 180 microg x kg(-1) x day(-1)) for 7 days, and then pancreatic-glucose-amino acid clamps were performed. Amino acids were raised to fed levels in the presence of either fasted or fed insulin concentrations; glucose was maintained at fasting throughout. Muscle protein synthesis was increased by pST treatment and by amino acids (with or without insulin) (P<0.001). In pST-treated pigs, fed, but not fasting, amino acid concentrations further increased muscle protein synthesis rates irrespective of insulin level (P<0.02). Fed amino acids, with or without raised insulin concentrations, increased the phosphorylation of S6 kinase (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1), decreased inactive 4EBP1.eIF4E complex association, and increased active eIF4E.eIF4G complex formation (P<0.02). pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of muscle protein synthesis requires fed amino acid levels, but not fed insulin levels. However, under the current conditions, the response to amino acids is not mediated by the activation of translation initiation factors that regulate mRNA binding to the ribosomal complex.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acids / pharmacology*
  • Animals
  • Blotting, Western
  • Body Weight / physiology
  • Eukaryotic Initiation Factor-4E / biosynthesis
  • Eukaryotic Initiation Factor-4E / genetics
  • Female
  • Glucose / metabolism
  • Growth Hormone / pharmacology*
  • Hormones / blood
  • Kinetics
  • Muscle Proteins / biosynthesis*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism*
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Protein Kinases / physiology
  • Ribosomal Protein S6 Kinases / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Swine
  • TOR Serine-Threonine Kinases


  • Amino Acids
  • Eukaryotic Initiation Factor-4E
  • Hormones
  • Muscle Proteins
  • Growth Hormone
  • Protein Kinases
  • Ribosomal Protein S6 Kinases
  • TOR Serine-Threonine Kinases
  • Glucose