Diabetes impairs heart mitochondrial function without changes in resting cardiac performance

BOMBICINO SS; D' ANNUNZIO V; VALDEZ LB; RUKAVINA MIKUSIC IA; BOVERIS A; IGLESIAS DE; GELPI RJ; BOMBICINO SS; D' ANNUNZIO V; VALDEZ LB; RUKAVINA MIKUSIC IA; BOVERIS A; IGLESIAS DE; GELPI RJ

INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND CELLULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2016 vol. 81 p. 335 - 345

1357-2725

Diabetes is a chronic disease associated to a cardiac contractile dysfunction that is not attributable to underlying coronaryartery disease or hypertension, and could be consequence of a progressive deterioration of mitochondrial function. Wehypothesized that impaired mitochondrial function precedes Diabetic Cardiomyopathy. Thus, the aim of this work was tostudy the cardiac performance and heart mitochondrial function of diabetic rats, using an experimental model of type I Diabetes.Rats were sacrificed after 28 days of Streptozotocin injection (STZ, 60 mg kg−1, ip.). Heart O2 consumption wasdeclined, mainly due to the impairment of mitochondrial O2 uptake. The mitochondrial dysfunction observed in diabeticanimals included the reduction of state 3 respiration (22%), the decline of ADP/O ratio (∼15%) and the decrease of therespiratory complexes activities (22?26%). An enhancement in mitochondrial H2O2 (127%) and NO (23%) productionrates and in tyrosine nitration (58%) were observed in heart of diabetic rats, with a decrease in Mn-SOD activity (∼50%).Moreover, a decrease in contractile response (38%), inotropic (37%) and lusitropic (58%) reserves were observed in diabeticrats only after a β‐adrenergic stimulus. Therefore, in conditions of sustained hyperglycemia, heart mitochondrialO2 consumption and oxidative phosphorylation efficiency are decreased, and H2O2 and NO productions are increased,leading to a cardiac compromise against a work overload. This mitochondrial impairment was detected in the absence ofheart hypertrophy and of resting cardiac performance changes, suggesting that mitochondrial dysfunction could precedethe onset of diabetic cardiac failure, being H2O2, NO and ATP the molecules probably involved in mitochondrion-cytosolsignalling.