title: Liraglutide enhances glucose transporter 4 translocation via regulation of AMP-activated protein kinase signaling pathways in mouse skeletal muscle cells.
abstract: OBJECTIVE
  Liraglutide is an anti-diabetic drug and human glucagon-like peptide-1 (GLP-1) analog that primarily functions in the pancreas. However, its extra-pancreatic functions are not clear. Skeletal muscle tissue is an important determinant of blood glucose and cells take in approximately 80% of dietary glucose via glucose transporter 4 (GLUT4) on the plasma membrane. Insulin and muscle contraction are two physiological stimuli of GLUT4 translocation to the cell membrane from intracellular storage compartments, but the signaling mechanisms that mediate these processes are different. AMP-activated protein kinase (AMPK) and Akt are the key signal molecules mediating the effects of muscle contraction and insulin, respectively, on GLUT4 translocation. Here, we investigate the effect of liraglutide on GLUT4 translocation and the roles of AMPK and Akt in this mechanism in skeletal muscle cells by stably expressing GLUT4myc with an exofacial myc-epitope C(2)C(12)-GLUT4myc.
  
  
  METHODS
  The cell surface GLUT4myc levels were determined by an antibody-coupled colorimetric assay. The phosphorylation levels of AMPK, Akt, AS160, TBC1D1, and GLUT4 were determined by western blotting. The cAMP levels were measured by an ELISA kit. siRNA was transfected with Lipofectamine 2000. Analysis of variance (ANOVA) was used for data analysis.
  
  
  RESULTS
  Liraglutide stimulated GLUT4 translocation in C(2)C(12)-GLUT4myc myotubes. Liraglutide increased the intracellular cAMP levels and the phosphorylation of AMPK, AS160, and TBC1D1. Akt phosphorylation and GLUT4 expression were not affected. Inhibition of AMPK by siRNA or Compound C reduced liraglutide-induced GLUT4 translocation.
  
  
  CONCLUSIONS
  Our results suggest that liraglutide may induce GLUT4 translocation by activation of AMPK in muscle cells.
authors: Department of Immunology, Key Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Tianjin Medical University, Tianjin, 300070 China; Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors: Zhu
authors: Z
authors: Li
authors: Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors: Chang-Lin
authors: CL
authors: Ni
authors: Department of Immunology, Key Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Tianjin Medical University, Tianjin, 300070 China.
authors: Zhi
authors: Z
authors: Yao
authors: Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China. Electronic address: xfx22081@vip.163.com.
authors: Li-Ming
authors: LM
authors: Chen
authors: Department of Immunology, Key Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Tianjin Medical University, Tianjin, 300070 China; Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China. Electronic address: wniu@tijmu.edu.cn.
authors: Wen-Yan
authors: WY
authors: Niu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D000069450:Liraglutide; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; C495693:Slc2a4 protein, mouse; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; Glucagon-like peptide 1; Glucose transporter 4; Translocation