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Journal of Endocrinology (2009) 203, 365-374       DOI: 10.1677/JOE-09-0269
© 2009 Society for Endocrinology
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Age and tissue specific differences in the development of acute insulin resistance following injury

Lidong Zhai1 and Joseph L Messina1,2

1 Division of Molecular and Cellular Pathology, Department of Pathology, The University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, Alabama 35294-0019, USA
2 Veterans Affairs Medical Center, Birmingham, Alabama 35233, USA

(Correspondence should be addressed to J L Messina at Division of Molecular and Cellular Pathology, Department of Pathology, The University of Alabama at Birmingham; 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 min, 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 (~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.







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