title: C2C12 skeletal muscle cells exposure to phosphatidylcholine triggers IGF-1 like-responses.
abstract: 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.
authors.affiliation: Royal Veterinary College, Muscle Unit and Molecular Biology/VBS, Royal College Street, NW1 OTU London.
authors.forename: Cyril
authors.initials: C
authors.lastname: Rauch
authors.forename: Paul
authors.initials: P
authors.lastname: Loughna
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000032:analysis / Q000494:pharmacology*; D020001:1-Butanol / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D051272:Glucose Transporter Type 1; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin / Q000378:metabolism
chemical_list: D015060:1,2-Dipalmitoylphosphatidylcholine; D020001:1-Butanol; D002794:Choline; D051272:Glucose Transporter Type 1; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D007334:Insulin-Like Growth Factor I; D009004:Monosaccharide Transport Proteins; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D010739:Phospholipase D; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; C495678:Slc2a1 protein, mouse; C000605507:Gsk3b protein, mouse; C096018:LY 295337