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Am J Physiol Endocrinol Metab 292: E654-E667, 2007. First published October 31, 2006; doi:10.1152/ajpendo.00453.2006
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INVITED REVIEW

Glucocorticoids produce whole body insulin resistance with changes in cardiac metabolism

Dake Qi and Brian Rodrigues

Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada

Insulin resistance is viewed as an insufficiency in insulin action, with glucocorticoids being recognized to play a key role in its pathogenesis. With insulin resistance, metabolism in multiple organ systems such as skeletal muscle, liver, and adipose tissue is altered. These metabolic alterations are widely believed to be important factors in the morbidity and mortality of cardiovascular disease. More importantly, clinical and experimental studies have established that metabolic abnormalities in the heart per se also play a crucial role in the development of heart failure. Following glucocorticoids, glucose utilization is compromised in the heart. This attenuated glucose metabolism is associated with altered fatty acid supply, composition, and utilization. In the heart, elevated fatty acid use has been implicated in a number of metabolic, morphological, and mechanical changes and, more recently, in "lipotoxicity". In the present article, we review the action of glucocorticoids, their role in insulin resistance, and their influence in modulating peripheral and cardiac metabolism and heart disease.

dexamethasone; fatty acid; glucose; lipoprotein lipase; pyruvate dehydrogenase kinase



Address for reprint requests and other correspondence: B. Rodrigues, Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The Univ. of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3 (e-mail: rodrigue{at}interchange.ubc.ca)




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