ScienceDaily (June 18, 2007) — Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and is strongly associated with obesity, according to a new study.  Gerald Shulman and colleagues from Yale University Medical School report that overexpression of uncoupling protein 3 (UCP3) in the skeletal muscle of mice is able to protect against the development of high-fat diet-induced insulin resistance.

Uncoupling proteins act to convert stored fat into thermal energy. In the current study the authors began by showing that mice fed a high-fat diet were markedly insulin resistant, a result of defects in insulin signaling in skeletal muscle and liver. In contrast, mice overexpressing UCP3 in skeletal muscle experienced increased whole body energy expenditure and were completely protected against fat-induced defects in insulin signaling and action in these tissues.

They went on to delineate the events at the cellular levels that underlie this protective mechanism and suggest that some of these cellular events may serve as excellent therapeutic targets for the treatment of type 2 diabetes.

Reference: Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance, Online  June 14, published in July print issue of the Journal of Clinical Investigation.

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