Reactive oxygen species and insulin-resistant cardiomyopathy.

1. The prevalence of insulin resistance has increased markedly in the past decade and is known to be associated with cardiovascular risk. Evidence of an insulin-resistant cardiomyopathy, independent of pressure or volume loading influences, is now emerging. 2. Cardiac oxidative stress is often observed coincident with insulin resistance and there is accumulating evidence that reactive oxygen species (ROS) mediate deleterious effects in the insulin-resistant heart. It is established that ROS modification of signalling proteins can adversely modulate cellular processes, leading to cardiac growth remodelling and dysfunction. The mechanisms of ROS-induced damage in insulin-resistant cardiomyopathy are yet to be fully elucidated. 3. A number of different animal models have been used to study cardiac insulin resistance, including high-sugar dietary interventions, genetically modified diabetic mice and streptozotocin-induced diabetes. Mechanistic studies manipulating cardiac anti-oxidant levels, either endogenously or exogenously, in these models have demonstrated a role for ROS in the cardiac manifestations associated with insulin resistance. 4. The present review summarizes the cardiac-specific characteristics of insulin resistance, the features of cardiac metabolism relevant to ROS generation and ROS-mediated cardiomyocyte damage pathways. In vivo studies in which a combination of genetic and environmental variables have been manipulated are considered. These studies provide particular insights into the induction and suppression of insulin-resistant cardiomyopathy.