Glucose deprivation promotes activation of mTOR signaling pathway and protein synthesis in rat skeletal muscle cells

Pflugers Arch. 2015 Jun;467(6):1357-66. doi: 10.1007/s00424-014-1583-2. Epub 2014 Jul 31.

Abstract

Signaling through mammalian target of rapamycin (mTOR) has been shown to play a central role in the regulation of skeletal muscle growth induced by a wide range of stimuli either mechanical or metabolic, such as growth factors and amino acids. Here, we demonstrate that mTOR and its downstream target, the ribosomal S6 kinase (p70(S6K)), are activated in L6 myocytes by a short-term glucose deprivation. Such response is specific of skeletal muscle and is likely responsible for the increased rate of protein synthesis and expression of the muscle-specific proteins during recovery from glucose deprivation. Nitric oxide and phosphatidylinositol-3-kinase (PI3K) are upstream positive regulators of mTOR since their pharmacological inhibition prevents the activation of p70(S6K) in response to glucose deprivation. We therefore propose a model of response to a brief period of glucose deprivation that may occur in skeletal muscle cells during resistance exercise and that may lead to protein accretion when blood flow recovers and all nutrients are again available.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Glucose / deficiency*
  • Glucose / metabolism
  • HEK293 Cells
  • Humans
  • Muscle Contraction
  • Myoblasts, Skeletal / metabolism*
  • Myoblasts, Skeletal / physiology
  • Nitric Oxide / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Biosynthesis*
  • Rats
  • Ribosomal Protein S6 Kinases / metabolism
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Nitric Oxide
  • Phosphatidylinositol 3-Kinases
  • TOR Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases
  • Glucose