Post-burn hepatic insulin resistance is associated with endoplasmic reticulum (ER) stress

Gerd G. Gauglitz, Stefanie Halder, Darren F. Boehning, Gabriela A. Kulp, David Herndon, José M. Barral, Marc G. Jeschke

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Insulin resistance with its associated hyperglycemias represents one significant contributor to mortality in burned patients. A variety of cellular stress-signaling pathways are activated as a consequence of burn. A key player in the cellular stress response is the endoplasmic reticulum (ER). Here, we investigated a possible role for ER-stress pathways in the progression of insulin function dysregulation postburn. Rats received a 60% total body surface area thermal injury, and a laparotomy was performed at 24, 72, and 192 h postburn. Liver was harvested before and 1 min after insulin injection (1 IU/kg) into the portal vein, and expression patterns of various proteins known to be involved in insulin and ER-stress signaling were determined by Western blotting. mRNA expression of glucose-6-phosphatase and glucokinase were determined by reverse-transcriptase-polymerase chain reaction and fasting serum glucose and insulin levels by standard enzymatic and enzyme-linked immunosorbent assay techniques, respectively. Insulin resistance indicated by increased glucose and insulin levels occurred starting 24 h postburn. Burn injury resulted in activation of ER stress pathways, reflected by significantly increased accumulation of phospho-PKR-like ER-kinase and phosphorylated inositol requiring enzyme 1, leading to an elevation of phospho-c-Jun N-terminal kinase and serine phosphorylation of insulin receptor substrate (IRS) 1 postburn. Insulin administration caused a significant increase in tyrosine phosphorylation of IRS-1, leading to activation of the phosphatidylinositol 3 kinase/Akt pathway in normal liver. Postburn tyrosine phosphorylation of IRS-1 was significantly impaired, associated with an inactivation of signaling molecules acting downstream of IRS-1, leading to significantly elevated transcription of glucose-6-phosphatase and significantly decreased mRNA expression of glucokinase. Activation of ER-stress signaling cascades may explain metabolic abnormalities involving insulin action after burn.

Original languageEnglish (US)
Pages (from-to)299-305
Number of pages7
JournalShock
Volume33
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

Endoplasmic Reticulum Stress
Burns
Insulin Resistance
Insulin Receptor Substrate Proteins
Insulin
Liver
Glucokinase
Glucose-6-Phosphatase
Phosphorylation
Endoplasmic Reticulum
Tyrosine
Immunosorbent Techniques
Phosphatidylinositol 3-Kinase
Glucose
Messenger RNA
JNK Mitogen-Activated Protein Kinases
Body Surface Area
Wounds and Injuries
Inositol
Portal Vein

Keywords

  • Burn injury
  • ER stress
  • Insulin resistance
  • Phosphatidylinositol 3 kinase/Akt

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Gauglitz, G. G., Halder, S., Boehning, D. F., Kulp, G. A., Herndon, D., Barral, J. M., & Jeschke, M. G. (2010). Post-burn hepatic insulin resistance is associated with endoplasmic reticulum (ER) stress. Shock, 33(3), 299-305. https://doi.org/10.1097/SHK.0b013e3181b2f439

Post-burn hepatic insulin resistance is associated with endoplasmic reticulum (ER) stress. / Gauglitz, Gerd G.; Halder, Stefanie; Boehning, Darren F.; Kulp, Gabriela A.; Herndon, David; Barral, José M.; Jeschke, Marc G.

In: Shock, Vol. 33, No. 3, 03.2010, p. 299-305.

Research output: Contribution to journalArticle

Gauglitz, GG, Halder, S, Boehning, DF, Kulp, GA, Herndon, D, Barral, JM & Jeschke, MG 2010, 'Post-burn hepatic insulin resistance is associated with endoplasmic reticulum (ER) stress', Shock, vol. 33, no. 3, pp. 299-305. https://doi.org/10.1097/SHK.0b013e3181b2f439
Gauglitz GG, Halder S, Boehning DF, Kulp GA, Herndon D, Barral JM et al. Post-burn hepatic insulin resistance is associated with endoplasmic reticulum (ER) stress. Shock. 2010 Mar;33(3):299-305. https://doi.org/10.1097/SHK.0b013e3181b2f439
Gauglitz, Gerd G. ; Halder, Stefanie ; Boehning, Darren F. ; Kulp, Gabriela A. ; Herndon, David ; Barral, José M. ; Jeschke, Marc G. / Post-burn hepatic insulin resistance is associated with endoplasmic reticulum (ER) stress. In: Shock. 2010 ; Vol. 33, No. 3. pp. 299-305.
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