CONICET | Buscador de Institutos y Recursos Humanos

Diabetic cardiomyopathy is a common complication of Diabetes Mellitus (DM) which leads to heightened risk of heart failure and death. The aim of this work was to study heart mitochondrial function and biogenesis of streptozotocin (STZ, 65 mg/kg, ip)-induced diabetic rats. Rats were considered diabetic if their fasting blood glucose were higher than 200 mg/dl, 72 hours after STZ administration. All the experiments were performed 4 weeks after injection. Typical diabetic symptoms were observed: polyuria, polyphagia, polydipsia and weight loss. Whereas the weight of control animals augmented by 70% after 4 weeks, the weight of diabetic rats was not modified. Malate-glutamate and succinate supported mitochondrial state 3 respiration were significantly reduced by 36% and 33%, respectively. Moreover, complexes I-III (478 ± 22 nmol/min.mg protein), II-III (289 ± 8 nmol/min.mg protein) and IV (55 ± 2 min-1/mg protein) activities were decreased in DM animals by 22%, 32% and 13%, respectively. When cytochrome oxidase activity was performed in total homogenates, this activity was 80% higher in diabetic than in control hearts, suggesting that DM leads to mitochondrial biogenesis. In addition, heart mtNOS activity (0.74 nmol/min. mg protein) was 54% higher in diabetic rats in comparison with control rats, suggesting the involvement of mitochondrial NO in the biogenesis process. These results show a mitochondrial dysfunction in diabetic heart, with a decline in mitochondrial electron transport and in O2 consumption and an increase in mitochondrial NO production and biogenesis, the latter as part of the response to injury.