This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The myocardium has the capacity to switch between free fatty acids and glucose as oxidative substrates, in response to changes in substrate supply, work demand, and local and systemic regulators. Disorders of metabolism, such as obesity and diabetes, are associated with increased rates of myocardial dysfunction, and it is possible that alterations in fuel selection underlie this relationship. Comparatively little is known about myocardial fuel selection in the basal state and in response to insulin in these disease states. The current proposal will test the hypothesis that the contribution of fatty acids to overall myocardial metabolism is increased in obese insulin resistant subjects, and that the capacity to switch to glucose metabolism under insulin stimulation is reduced. In the current protocol, we will perform positron emission tomography measurements of myocardial fatty acid oxidation, total oxidation, and tissue perfusion in lean and obese subjects. These studies will be performed under basal fasting conditions, and under steady state conditions of hyperinsulinemia. The resulting data will be used to support a future grant proposal which will explore these questions in more detail.
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