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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-09-0269v1 203/3/365    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhai, L. Articles by Messina, J. Search for Related Content PubMed PubMed Citation Articles by Zhai, L. Articles by Messina, J.

L Zhai, Pathology, University of Alabama at Birmingham, Birmingham, United States
J Messina, Pathology, University of Alabama at Birmingham, Birmingham, 35294-0019, United States

Correspondence: Joseph Messina, Email: messinaj{at}uab.edu

Injuries, hemorrhage, sepsis, burn, and critical illnesses all induce insulin resistance, and insulin resistance is strongly associated with advancing age. However, the effect of age on injury-induced insulin resistance is not well studied. We performed surgical trauma in male rats of three different ages (3-, 6- and 10-weeks old). Rats were either hemorrhaged to a mean arterial pressure of 35-40 mmHg and subsequently maintained at that pressure for up to 90 minutes, or maintained without hemorrhage as controls. Results indicate that insulin-induced intracellular signaling was diminished in liver and skeletal muscle of 6- and 10-week old rats following trauma and hemorrhage. In even younger rats, immediately post-weaning (approximately 3 weeks of age), insulin signaling was lost in liver, but not in skeletal muscle. Glucocorticoids can play a role in the chronic development of insulin resistance. Our results demonstrate that corticosterone levels were increased in 6- and 10-week old animals following hemorrhage, but little change was measured in 3-week old animals. Blockade of glucocorticoid synthesis prevented the development of insulin resistance in skeletal muscle, but not in liver of 6- and 10-week old rats. Moreover, skeletal muscle glucocorticoid receptor levels increased dramatically between 3 and 6 weeks of age. These results indicate that trauma and hemorrhage-induced hepatic insulin resistance occurs at all ages tested. However, there is no development of insulin resistance following trauma and hemorrhage in skeletal muscle of post-weaning rats. In skeletal muscle of 6- and 10-week old rats, inhibition of glucocorticoid levels prevents the development of insulin resistance.