Analysis of thermal injury-induced insulin resistance in rodents. Implication of postreceptor mechanisms

Tsuneya Ikezu, Takashi Okamoto, Kazuyoshi Yonezawa, Ronald G. Tompkins, Jeevendra A.J. Martyn

Research output: Contribution to journalArticlepeer-review


Burn injury is associated with insulin resistance. The molecular basis of this resistance was investigated by examining insulin receptor signaling in rats after thermal injury. The impaired insulin-stimulated transport of [3H]2-deoxyglucose into soleus muscle strips confirmed the insulin resistance following burns. In vivo insulin-stimulated phosphoinositide 3- kinase activity, pivotal in translocation of GLUT4, was decreased in burns when assessed by its insulin receptor substrate-1 (IRS-1)-associated activity. Insulin-induced tyrosine kinase activity of insulin receptor (IR) and tyrosine phosphorylation of IRS-1 were also attenuated. Immunoprecipitated IR, however, appeared to have normal insulin-responsive kinase activity. Finally, immunoprecipitated IRS-1 was tested for its effect on partially purified recombinant IR and was found to inhibit its kinase activity. This inhibitory effect of IRS-1 was abolished by prior treatment of IRS-1 with alkaline phosphatase, indicating that burn injury-related hyperphosphorylation of IRS-1 is similar to that observed in TNFα-induced inhibition of IR signaling. All of these changes were observed in the absence of quantitative changes in IR, IRS-1, and phosphoinositide 3-kinase. Alterations in postreceptor insulin signaling, therefore, may be responsible for the insulin resistance after thermal injury.

Original languageEnglish (US)
Pages (from-to)25289-25295
Number of pages7
JournalJournal of Biological Chemistry
Issue number40
StatePublished - Oct 3 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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