title: Double stranded viral RNA induces inflammation and insulin resistance in skeletal muscle from pregnant women in vitro.
abstract: OBJECTIVE
  Maternal peripheral insulin resistance and increased inflammation are two features of pregnancies complicated by pre-existing maternal obesity and gestational diabetes mellitus (GDM). There is now increasing evidence that activation of Toll-like receptor (TLR) signalling pathways by viral products may play a role in the pathophysiology of diabetes. Thus, the aim of this study was to assess the effect of the TLR3 ligand and viral dsRNA analogue polyinosinic polycytidilic acid (poly(I:C)) on inflammation and the insulin signalling pathway in skeletal muscle from pregnant women.
  
  
  METHODS
  Human skeletal muscle tissue explants were performed to determine the effect of poly(I:C) on the expression and secretion of markers of inflammation, and the insulin signalling pathway and glucose uptake.
  
  
  RESULTS
  Poly(I:C) significantly increased the expression of a number of inflammatory markers in skeletal muscle from pregnant women. Specifically, there was an increase in the expression and/or secretion of the pro-inflammatory cytokines TNF-α, and IL-6 and the pro-inflammatory chemokines IL-8 and MCP-1. These effect of poly(I:C) appear to mediated via a number of signalling molecules including the pro-inflammatory transcription factor NF-κB, and the serine threonine kinases GSK3 and AMPKα. Additionally, poly(I:C) decreased insulin stimulated GLUT-4 expression and glucose uptake in skeletal muscle from pregnant women.
  
  
  CONCLUSIONS
  The in vitro data presented in this study suggests that viral infection may contribute to the pathophysiology of pregnancies complicated by pre-existing maternal obesity and/or GDM. It should be noted that the in vitro studies cannot be directly used to infer the same outcomes in the intact subject.
authors.affiliation: Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia. Electronic address: mlappas@unimelb.edu.au.
authors.forename: Martha
authors.initials: M
authors.lastname: Lappas
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000328:Adult; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000235:genetics; D016640:Diabetes, Gestational / Q000378:metabolism*; D005260:Female; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology*; D011247:Pregnancy; D012313:RNA / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D051275:Glucose Transporter Type 4; D015850:Interleukin-6; D016209:Interleukin-8; C495692:SLC2A4 protein, human; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; D011070:Poly I-C
keywords: Inflammation; Insulin resistance; Pro-inflammatory cytokines; Skeletal muscle; Viral infection