Heart mitochondrial dysfunction in diabetic rats

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

Kyoto

Congreso; 17th Biennial Meeting of Society for Free Radical Research International - SFRRI 2014; 2014

Society for Free Radical Research International

Diabetic cardiomyopathy is a common complication of Diabetes Mellitus (DM). The aim of this work was to study heart mitochondrial function of streptozotocin (60 mg/kg, ip)-induced diabetic rats, 4 weeks after injection. After a β-adrenergic stimulus, left-ventricle diastolic pressure was 39% lower in diabetic than in control hearts. Heart O2 consumption was lower in DM than in control rats, due to a decline in mitochondrial O2 uptake. State 3 respiration supported by malate-glutamate (26%) and succinate (32%) were significantly reduced. ATP production sustained by malate-glutamate was 50% lower in DM rats. Mitochondrial respiratory complexes activities were decreased in DM animals (Complexes: I-III, 26%; II-III, 32% and IV, 22%). Cytochrome oxidase activity performed in total homogenate showed that the amount of mitochondrial mass per tissue mass was 32% higher in diabetic animals, suggesting that DM leads to mitochondrial biogenesis. 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 mitochondrial NO may be a signaling molecule involved in this mechanism.