C2C12 skeletal muscle cells exposure to phosphatidylcholine triggers IGF-1 like-responses

Cell Physiol Biochem. 2005;15(5):211-24. doi: 10.1159/000086408.


Glucose uptake by cells in response to stimulation with either IGF-1 or insulin is associated with the translocation of GLUT (glucose transporter) proteins from intracellular cytoplasmic compartments to the plasma membrane. In response to such stimulation, GLUT4 and GLUT1 translocation to the plasma membrane is triggered through an increase in their exocytosis involving phospholipase D (PLD) activation, disrupting the recycling of intracellular GLUT-containing vesicles between the plasma membrane and internal compartments. In skeletal muscle, insulin resistance is observed in association with an increase of dipalmitoyl-phosphatidylcholine, which is also known to interact with PLD. Based on evidence that the recycling process is important for GLUT translocation, we decided to address whether dipalmitoyl-phosphatidylcholine, a non-translocatable phospholipid known to alter the recycling of intracellular vesicles and to interact with PLD, can be involved in glucose metabolism. We show that an acute change in phospholipid composition, by addition of dipalmitoyl-phophatidylcholine, leads to GLUT1 translocation to the plasma membrane in conjunction to an increase of Akt and GSK3beta phosphorylation, which are sensitive to PI3K and PLD inhibitors. Moreover, we also show that long-term change in phospholipid composition disrupts both the IGF-1 signalling pathway and GLUT1 partitioning within the cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1,2-Dipalmitoylphosphatidylcholine / analysis
  • 1,2-Dipalmitoylphosphatidylcholine / pharmacology*
  • 1-Butanol / pharmacology
  • Animals
  • Cell Membrane / chemistry
  • Cells, Cultured
  • Choline / metabolism
  • Glucose Transporter Type 1
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor I / pharmacology
  • Mice
  • Monosaccharide Transport Proteins / metabolism*
  • Myoblasts, Skeletal / drug effects
  • Myoblasts, Skeletal / metabolism*
  • Peptides / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phospholipase D / metabolism
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Transport / drug effects
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Receptor, Insulin / metabolism


  • Glucose Transporter Type 1
  • Monosaccharide Transport Proteins
  • Peptides
  • Proto-Oncogene Proteins
  • Slc2a1 protein, mouse
  • 1,2-Dipalmitoylphosphatidylcholine
  • Insulin-Like Growth Factor I
  • 1-Butanol
  • Receptor, Insulin
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3
  • Phospholipase D
  • Choline
  • LY 295337