Division of Endocrinology, Metabolism and Diabetes, and Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84112. Objective: Fatty acid (FA)-induced mitochondrial uncoupling and oxidative stress have been proposed to reduce cardiac efficiency and contribute to cardiac dysfunction in type 2 diabetes. We hypothesized that mitochondrial uncoupling may also contribute to reduced cardiac efficiency and contractile dysfunction in the type 1 diabetic Akita mouse model (Akita). Research Design and Methods: Cardiac function and substrate utilization was determined in isolated working hearts, and in vivo function by echocardiography. Mitochondrial function and coupling were determined in saponin-permeabilized fibers and proton leak kinetics in isolated mitochondria. H(2)O(2)...
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