Heart mitochondrial dysfunction in diabetic rats

BOMBICINO SS; IGLESIAS DE; D´ANNUNZIO V; GELPI RJ; BOVERIS A; VALDEZ LB

Buenos Aires

Congreso; VIII Meeting of the Society for Free Radical Biology and Medicine, South American Group; 2013

Society for Free Radical Biology and Medicine, South American Group

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, 60 mg/kg, ip)-induced diabetic rats. Experiments were performed 4 weeks after injection. After a β-adrenergic stimulus, left-ventricle diastolic pressure was 47% lower in diabetic hearts than in control hearts, showing a cardiac dysfunction in diabetic animals. State 3 mitochondrial respiration supported by malate-glutamate and succinate were significantly reduced by 36% and 33%, respectively. Furthermore, mitochondrial respiratory complexes activities were decreased in DM animals (Complexes: I-III, 25%; II-III, 32% and IV, 22%). Cytochrome oxidase activity performed in total homogenate showed that the proportion of mitochondrial mass per tissue mass was 25% higher in diabetic than in control hearts, suggesting that DM leads to mitochondrial biogenesis. In addition, mtNOS activity (20%) and expression (90%) were higher in diabetic rats, suggesting the involvement of mitochondrial NO in the biogenesis process. These results provide evidence that a state of mitochondrial dysfunction is produced in hearts of diabetic rats leading to a cardiac dysfunction. The mitochondrial biogenesis could be part of the response to the hyperglycemia and the mitochondrial NO increased may be a signal involved in this mechanism.