O6 Cardiac mitochondrial dysfunction time course in Type 1 Diabetes

Introduction: Results from our laboratory (Bombicino et al., 2016, 2017) have shown that sustained hyperglycemia for 25 days leads to generalized cardiac mitochondrial dysfunction that includes reduction of tissue and mitochondrial O2 consumption, complexes I-III, II-III and IV activities, ATP production, ADP/O, and Mn-SOD activity; accompanied by enhancement of H2O2, NO and ONOO- generation rates, in addition to the triggering of mitochondrial biogenesis, although the "new" cardiac mitochondria of diabetic animals show structural alterations. This mitochondrial dysfunction occurs in the absence of hypertrophy and of changes in resting cardiac performance, but with cardiac compromise after a work overload, suggesting that mitochondrial dysfunction precedes myocardial failure in diabetic patients. Aim: To study the early events and to analyze the cardiac mitochondrial dysfunction time course in a type 1 Diabetes Mellitus model. Materials and methods: Diabetes was induced by Streptozotocin (STZ, single ip dose, 60 mg/kg) in male Wistar rats. Glycemia was measured at 72 h (C: 127 ± 5, DM: 415 ± 23 mg/dl). Animals were sacrificed 7, 10 or 14 days after STZ-injection (4, 7 or 11 days of hyperglycemia) and hearts were removed. Mitochondrial function and biogenesis, reactive oxygen and nitrogen species generation and redox state were determined