title: Severe injury is associated with insulin resistance, endoplasmic reticulum stress response, and unfolded protein response.
abstract: OBJECTIVE
  We determined whether postburn hyperglycemia and insulin resistance are associated with endoplasmic reticulum (ER) stress/unfolded protein response (UPR) activation leading to impaired insulin receptor signaling.
  
  
  BACKGROUND
  Inflammation and cellular stress, hallmarks of severely burned and critically ill patients, have been causally linked to insulin resistance in type 2 diabetes via induction of ER stress and the UPR.
  
  
  METHODS
  Twenty severely burned pediatric patients were compared with 36 nonburned children. Clinical markers, protein, and GeneChip analysis were used to identify transcriptional changes in ER stress and UPR and insulin resistance-related signaling cascades in peripheral blood leukocytes, fat, and muscle at admission and up to 466 days postburn.
  
  
  RESULTS
  Burn-induced inflammatory and stress responses are accompanied by profound insulin resistance and hyperglycemia. Genomic and protein analysis revealed that burn injury was associated with alterations in the signaling pathways that affect insulin resistance, ER/sarcoplasmic reticulum stress, inflammation, and cell growth/apoptosis up to 466 days postburn.
  
  
  CONCLUSIONS
  Burn-induced insulin resistance is associated with persistent ER/sarcoplasmic reticulum stress/UPR and subsequent suppressed insulin receptor signaling over a prolonged period of time.
authors.affiliation: Ross Tilley Burn Centre, Sunnybrook Health Science Centre, Department of Surgery, Sunnybrook Research Institute, University of Toronto, Ontario, Canada. Marc.Jeschke@sunnybrook.ca
authors.forename: Marc G
authors.initials: MG
authors.lastname: Jeschke
authors.forename: Celeste C
authors.initials: CC
authors.lastname: Finnerty
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Juquan
authors.initials: J
authors.lastname: Song
authors.forename: Darren
authors.initials: D
authors.lastname: Boehning
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.forename: Henry V
authors.initials: HV
authors.lastname: Baker
authors.forename: Gerd G
authors.initials: GG
authors.lastname: Gauglitz
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002056:Burns / Q000150:complications / Q000378:metabolism*; D016022:Case-Control Studies; D002395:Catecholamines / Q000652:urine; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D006943:Hyperglycemia / Q000209:etiology* / Q000378:metabolism; D015151:Immunoblotting; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome / Q000378:metabolism; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D002395:Catecholamines; D016207:Cytokines; D007328:Insulin; D020543:Proteome; D006854:Hydrocortisone