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Research suggests how steroids cause diabetes and hypertension; liver plays critical role

St. Louis, July 17, 2003 -- Steroids called glucocorticoids are critical for treating diseases such as asthma, arthritis and pain syndromes, but they also can trigger diabetes and hypertension. Research at Washington University School of Medicine in St. Louis now shows why these commonly used drugs have such dangerous side effects.

The team found that a protein called peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is critical in this process and that the liver plays a key role. The findings help explain the high incidence of diabetes and hypertension in obese individuals, a group that normally produces significantly more glucocorticoids than people of average weight.

"Glucocorticoids are very effective for treating many diseases," says first author Carlos Bernal-Mizrachi, M.D., instructor of medicine. "If we can understand the mechanisms by which these drugs cause side effects like diabetes and hypertension, we may be able to intervene and prevent these disorders in people who are taking steroids and in people who are obese."

The study appears online and in the August issue of the journal Nature Medicine. Bernal-Mizrachi led the study, in collaboration with Clay F. Semenkovich, M.D., professor of medicine and of cell biology and physiology and director of the Division of Endocrinology, Metabolism and Lipid Research, and Daniel P. Kelly, M.D., professor of medicine, of molecular biology and pharmacology and of pediatrics and director of the Center for Cardiovascular research.

Hypertension (persistent high blood pressure) and diabetes (chronic insulin deficiency) both are related to insulin-resistance, in which the body does not properly respond to insulin.

PPAR-alpha is found in the liver, kidney, muscles, blood vessels and other organs. Since it is activated by fatty acids and since glucocorticoids alter fatty acid processing, Bernal-Mizrachi and his colleagues hypothesized that the two may act together to pro
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Contact: Gila Z. Reckess
reckessg@msnotes.wustl.edu
314-286-0109
Washington University School of Medicine
17-Jul-2003


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