Increased fatty acid oxidation and decreased glucose utilization are the metabolic characteristics of diabetic hearts. However, whether this shift in substrate utilization is causally related to the development of diabetic cardiomyopathy is not fully understood. We investigated the functional impact of increased glucose transport/utilization on diabetic hearts. We hypothesized that increased glucose oxidation can prevent diabetic cardiomyopathy.Type I diabetes was induced by steptozotocin injection in mice with cardiac‐specific overexpression of GLUT1 (TG) and their wildtype littermates (WT). Saline injected mice were used as controls. Cardiac function, substrate utilization, pyruvate dehydrogenase (PDH) activity, and mortality rate were determined after four months.Mortality rate was 26% for WT and 16% for TG (P<0.05). In diabetic hearts, fatty acid oxidation increased significantly from 58±1% to 64±2% in WT, and from 39±2% to 48±4% in TG (P<0.05). Due to increased glucose uptake and PDH activity, diabetic TG hearts showed increased glucose oxidation than WT: 24±1% vs 7±1% (P<0.05). MRI study showed significant decrease in ventricular function in WT diabetic mice (P<0.05). However, ventricular function in diabetic TG mice was preserved.We concluded that enhanced glucose oxidation lead to improved survival rate and prevented the functional deterioration in diabetic hearts.
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