Reactive XXXX species have a causal role in multiple forms of insulin resistance.

@entity6 @entity39 @entity5 @entity28 @entity26 @entity19 @entity619 @entity413
Insulin resistance is a cardinal feature of type 2 @entity6 and is characteristic of a wide range of other clinical and experimental settings. Little is known about why insulin resistance occurs in so many contexts. Do the various insults that trigger insulin resistance act through a common mechanism? Or, as has been suggested, do they use distinct cellular pathways? Here we report a genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine @entity5 - @entity39 factor-alpha and the other with the glucocorticoid @entity619 . Gene expression analysis suggests that reactive @entity26 species (ROS) levels are increased in both models, and we confirmed this through measures of cellular redox state. ROS have previously been proposed to be involved in insulin resistance, although evidence for a causal role has been scant. We tested this hypothesis in cell culture using six treatments designed to alter ROS levels, including two small molecules and four transgenes; all ameliorated insulin resistance to varying degrees. One of these treatments was tested in @entity28 , insulin-resistant @entity19 and was shown to improve insulin sensitivity and @entity413 homeostasis. Together, our findings suggest that increased ROS levels are an important trigger for insulin resistance in numerous settings.
