Blockade of the renin-angiotensin system improves insulin receptor signaling and insulin-stimulated skeletal muscle glucose transport in burn injury

Sherry O. Kasper, Erin E. Phillips, Scott M. Castle, Brian Daley, Blaine Enderson, Michael Karlstad

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Burn injury is associated with a decline in glucose utilization and insulin sensitivity due to alterations in postreceptor insulin signaling pathways. We have reported that blockade of the renin-angiotensin system with losartan, an angiotensin II type 1 (AT1) receptor blocker, improves whole body insulin sensitivity and glucose metabolism after burn injury. This study examines whether losartan improves insulin signaling pathways and insulin-stimulated glucose transport in skeletal muscle in burn-injured rats. Rats were injured by a 30% full-skin-thickness scalding burn and treated with losartan or placebo for 3 days after burn. Insulin signaling pathways were investigated in rectus abdominus muscle taken before and 90 s after intraportal insulin injection (10 U•kg). Insulin-stimulated insulin receptor substrate 1-associated phosphatidylinositol 3-kinase and plasma membrane-associated GLUT4 transporter were substantially increased with losartan treatment in burn-injured animals (59% above sham). Serine phosphorylated AKT/PKB was decreased with burn injury, and this decrease was attenuated with losartan treatment. In a separate group of rats, the effect of insulin on 2-deoxyglucose transport was significantly impaired in burned as compared with sham soleus muscles, in vitro; however, treatment of burned rats with losartan completely abolished the reduction of insulin-stimulated 2-deoxyglucose transport. These findings demonstrate a cross talk between the AT1 and insulin receptor that negatively modulates insulin receptor signaling and suggest a potential role of renin-angiotensin system blockade as a therapeutic strategy for enhancing insulin sensitivity in skeletal muscle and improving whole-body glucose homeostasis in burn injury.

Original languageEnglish (US)
Pages (from-to)80-85
Number of pages6
JournalShock
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2011

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Insulin Receptor
Renin-Angiotensin System
Losartan
Skeletal Muscle
Insulin
Glucose
Wounds and Injuries
Insulin Resistance
Deoxyglucose
Burns
Phosphatidylinositol 3-Kinase
Angiotensin II Type 1 Receptor Blockers
Insulin Receptor Substrate Proteins
Rectus Abdominis
Angiotensin Type 1 Receptor
Therapeutics
Serine
Homeostasis
Placebos
Cell Membrane

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Blockade of the renin-angiotensin system improves insulin receptor signaling and insulin-stimulated skeletal muscle glucose transport in burn injury. / Kasper, Sherry O.; Phillips, Erin E.; Castle, Scott M.; Daley, Brian; Enderson, Blaine; Karlstad, Michael.

In: Shock, Vol. 35, No. 1, 01.01.2011, p. 80-85.

Research output: Contribution to journalArticle

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