This project will take advantage of the techniques developed in old Project 1 to quantify glucose oxidative and fatty acid metabolism in the rodent. The project will utilize both rat (ZDF Zucker) and mouse models (MHC-PPAR or MCK-PPAR) of diabetes to evaluate in these well controlled models, the differences in metabolic profile between diabetic animals and normal controls as well as the effect of the therapies being utilized in humans in the instrumentation project. An important advantage of the animal model is the ability to evaluate the impact that genetic changes have on cardiac metabolism and other tissues resulting from these therapies. This project will also utilize animal models to validate the radiopharmaceuticals being developed in Project 1. The project will, therefore, interact with both other projects. The radiopharmaceuticals for the metabolism studies will be produced in the cyclotron/radiochemistry core and this project will take advantage of the advances in microPET technology being carried out in the instrumentation core. This project will address the general hypothesis that rodent models of cardiac disease in conjunction with microPET and microCT imaging can be used to evaluate metabolic changes in the disease as well as changes caused by drug therapies. To this aim we will evaluate three models of diabetes and selected therapies.
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