JCI table of contents, March 9, 2006

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How sweet it is: scientists find cellular link between insulin resistance and heart disease

Insulin resistance (IR) is a metabolic disorder in which the body does not respond to the insulin produced by the pancreas, typically resulting in elevated blood sugar levels and diabetes. Importantly, individuals with diabetes also have a significantly higher risk of developing cardiovascular disease (CVD), even after accounting for risk factors such as elevated cholesterol levels and high blood pressure. Now, in a study appearing online on March 9 in advance of print publication in the April issue of the Journal of Clinical Investigation, Michael Brownlee and colleagues at Albert Einstein College of Medicine in New York show a link between the metabolism of lipids called free fatty acids (FFAs) and a tissue damaging oxidant called "superoxide." The researchers measured the effects of FFA metabolism in cells from the aortas of cows, when the cells were treated with a high sugar solution to mimic the events that occur in the blood vessels during insulin resistance and diabetes. The authors found that the cells metabolized FFAs, which led to increased production of superoxide and the activation of a variety of inflammatory signals previously implicated in highblood-sugarinduced vascular damage. In addition, the authors also found that two important antiatherogenic enzymes, prostacyclin synthase and eNOS, were inactivated, suggesting that insulin resistance and high blood sugar can directly damage the cells of blood vessels, contributing to heart disease. The researchers also examined mouse and rat animal models of insulin resistance

Contact: Brooke Grindlinger
Journal of Clinical Investigation

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