title: Over-expression of LYRM1 inhibits glucose transport in rat skeletal muscles via attenuated phosphorylation of PI3K (p85) and Akt.
abstract: To explore the effect of LYRM1 over-expression on basal and insulin-stimulated glucose uptake in rat skeletal muscle cells, and to understand the underlying mechanisms, Rat myoblasts (L6) transfected with either an empty expression vector (pcDNA3.1Myc/His B) or a LYRM1 expression vector were differentiated into myotubes. Glucose uptake was determined by measuring 2-deoxy-D-[(3)H] glucose uptake into L6 myotubes. Western blotting was performed to assess the translocation of insulin-sensitive glucose transporter 4 (GLUT4). It was also used to measure the phosphorylation and total protein contents of insulin-signaling proteins, such as the insulin receptor (IR), insulin receptor substrate (IRS)-1, phosphatidylinositol-3-kinase (PI3K) p85, Akt, ERK1/2, P38, and JNK. LYRM1 over-expression in L6 myotubes reduced insulin-stimulated glucose uptake and impaired insulin-stimulated GLUT4 translocation. It also diminished insulin-stimulated tyrosine phosphorylation of IRS-1, PI3K (p85), and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, P38, and JNK. LYRM1 regulates the function of IRS-1, PI3K, and Akt, and decreases GLUT4 translocation and glucose uptake in response to insulin. These observations highlight the potential role of LYRM1 in glucose homeostasis and possibly in the pathophysiology of type 2 diabetes related to obesity.
authors.affiliation: Department of Pediatrics, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Chunzhao
authors.initials: C
authors.lastname: Kou
authors.forename: Xinguo
authors.initials: X
authors.lastname: Cao
authors.forename: Dani
authors.initials: D
authors.lastname: Qin
authors.forename: Chenbo
authors.initials: C
authors.lastname: Ji
authors.forename: Jingai
authors.initials: J
authors.lastname: Zhu
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhang
authors.forename: Chun
authors.initials: C
authors.lastname: Zhu
authors.forename: Chunlin
authors.initials: C
authors.lastname: Gao
authors.forename: Ronghua
authors.initials: R
authors.lastname: Chen
authors.forename: Xirong
authors.initials: X
authors.lastname: Guo
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D015153:Blotting, Western; D002460:Cell Line; D003847:Deoxyglucose / Q000378:metabolism*; D015536:Down-Regulation; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000201:enzymology*; D032448:Myoblasts, Skeletal / Q000201:enzymology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C495694:Slc2a4 protein, rat; D003847:Deoxyglucose; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt