title: Over-expression of NYGGF4 (PID1) inhibits glucose transport in skeletal myotubes by blocking the IRS1/PI3K/AKT insulin pathway.
abstract: BACKGROUND
  Defects in insulin-stimulated glucose uptake in muscle are the important early events in the pathogenesis of insulin resistance. NYGGF4 (also named PID1) is a recently discovered gene which is suggested to be associated with obesity-associated insulin resistance. In this study, we aimed to investigate the effects of NYGGF4 on glucose uptake and insulin signaling in rat skeletal muscle cells.
  
  
  METHODS
  Rat L6 myoblasts were transfected with either an empty vector or an NYGGF4-expressing vector and induced to differentiate into mature L6 skeletal myotubes. Glucose uptake was determined by measuring uptake of 2-deoxy-d-[(3)H] glucose. Immunoblotting was performed to detect the translocation of insulin-sensitive glucose transporter 4 (GLUT4). Immunoblotting was also used to measure phosphorylation and total protein levels of the insulin signaling proteins including insulin receptor (IR), insulin receptor substrate 1 (IRS1), Akt, extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38, and c-Jun-N-terminal kinase (JNK).
  
  
  RESULTS
  NYGGF4 over-expression in L6 skeletal myotubes reduced insulin-stimulated glucose uptake and impaired insulin-stimulated GLUT4 translocation. It also diminished insulin-stimulated tyrosine phosphorylation of IRS1 and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, p38, or JNK.
  
  
  CONCLUSIONS
  Over-expression of NYGGF4 inhibits glucose transport in skeletal myotubes by blocking the IRS1/PI3K/AKT insulin pathway. These observations highlight the potential role of NYGGF4 in glucose homeostasis and the development of insulin resistance in obesity.
authors.affiliation: Department of Pediatrics, Second affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: W L
authors.initials: WL
authors.lastname: Wu
authors.forename: W H
authors.initials: WH
authors.lastname: Gan
authors.forename: M L
authors.initials: ML
authors.lastname: Tong
authors.forename: X L
authors.initials: XL
authors.lastname: Li
authors.forename: J Z
authors.initials: JZ
authors.lastname: Dai
authors.forename: C M
authors.initials: CM
authors.lastname: Zhang
authors.forename: X R
authors.initials: XR
authors.lastname: Guo
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D005947:Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D019869:Phosphatidylinositol 3-Kinases; D011506:Proteins; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; C558580:Pid1 protein, rat