Severe injury is associated with insulin resistance, endoplasmic reticulum stress response, and unfolded protein response

Marc G. Jeschke, Celeste Finnerty, David Herndon, Juquan Song, Darren Boehning, Ronald G. Tompkins, Henry V. Baker, Gerd G. Gauglitz

Research output: Contribution to journalArticle

59 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Pages (from-to)370-378
Number of pages9
JournalAnnals of Surgery
Volume255
Issue number2
DOIs
StatePublished - Feb 2012

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Unfolded Protein Response
Endoplasmic Reticulum Stress
Heat-Shock Proteins
Insulin Resistance
Wounds and Injuries
Insulin Receptor
Sarcoplasmic Reticulum
Burns
Hyperglycemia
Endoplasmic Reticulum
Inflammation
Critical Illness
Type 2 Diabetes Mellitus
Proteins
Leukocytes
Biomarkers
Fats
Pediatrics
Apoptosis
Muscles

ASJC Scopus subject areas

  • Surgery

Cite this

Severe injury is associated with insulin resistance, endoplasmic reticulum stress response, and unfolded protein response. / Jeschke, Marc G.; Finnerty, Celeste; Herndon, David; Song, Juquan; Boehning, Darren; Tompkins, Ronald G.; Baker, Henry V.; Gauglitz, Gerd G.

In: Annals of Surgery, Vol. 255, No. 2, 02.2012, p. 370-378.

Research output: Contribution to journalArticle

Jeschke, Marc G. ; Finnerty, Celeste ; Herndon, David ; Song, Juquan ; Boehning, Darren ; Tompkins, Ronald G. ; Baker, Henry V. ; Gauglitz, Gerd G. / Severe injury is associated with insulin resistance, endoplasmic reticulum stress response, and unfolded protein response. In: Annals of Surgery. 2012 ; Vol. 255, No. 2. pp. 370-378.
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