| Severe Injury Is Associated With Insulin Resistance, Endoplasmic Reticulum Stress Response, and Unfolded Protein Response. | |
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MedLine Citation:
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PMID: 22241293 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. CONCLUSION:: 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. |
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Authors:
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Marc G Jeschke; Celeste C Finnerty; David N Herndon; Juquan Song; Darren Boehning; Ronald G Tompkins; Henry V Baker; Gerd G Gauglitz |
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Publication Detail:
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Type: JOURNAL ARTICLE |
Journal Detail:
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Title: Annals of surgery Volume: 255 ISSN: 1528-1140 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-1-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372354 Medline TA: Ann Surg Country: - |
Other Details:
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Languages: ENG Pagination: 370-378 Citation Subset: - |
Affiliation:
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*Ross Tilley Burn Centre, Sunnybrook Health Science Centre, Department of Surgery, Sunnybrook Research Institute, University of Toronto, Ontario, Canada; †Shriners Hospitals for Children, Galveston, TX; Departments of ‡Surgery; §Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX; ¶Department of Surgery, Massachusetts General Hospital, Shriners Hospital for Children, and Harvard Medical School, Harvard University, Boston, MA; ‖Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL; **Department of Dermatology and Allergology, Ludwig-Maximilian-University Munich, Frauenlobstrasse, Munich, Germany. |
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