Efeitos do treinamento físico combinado com insulinoterapia sobre o miocárdio de ratos com diabetes induzida

• Autor(a) principal: Silva, Márcia Ferreira da
• Data de Publicação: 2014
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: LOCUS Repositório Institucional da UFV
• Texto Completo: http://locus.ufv.br/handle/123456789/282
• topic: Diabetes; Insulina; Exercícios físicos; Miocárdio; Ratos como animal de laboratório; Diabetes; Insulin; Physical exercise; Infarction; Rats as laboratory animals; CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL

The Type 1 Diabetes Mellitus (T1DM) occurs due to decreased insulin secretion in the pancreas, which undertakes various organs. This disease is often associated with cardiac dysfunctions that characterize diabetic cardiomyopathy. The pharmacological treatment of T1DM is done by insulin and exercise has been used as a non-pharmacological strategy. The aim of this study was to investigate the effects of a swimming training program associated with insulin therapy on the myocardium of rats with experimental T1DM. Sixty male Wistar rats with 30 days of age at the onset of the experiment were divided into six experimental groups (n = 10), namely: sedentary control (CS); sedentary diabetic (DS); sedentary diabetic treated with insulin (DSI); exercised control (CE); exercised diabetic (DE); and insulin- treated diabetic exercised (DEI). Diabetes was induced by an injection of streptozotocin (i.p. 60 mg / kg body weight) diluted in sodium citrate buffer (0.1M, pH 4.5), whereas control animals receive the same dosage of the vehicle. The insulin therapy was initiated seven days after the induction of diabetes and consisted of a daily subcutaneous injection of 1-4 IU of insulin (i.p), for eight weeks. The exercise training was initiated seven days after the induction of diabetes or the use of placebo and consisted of swimming 90 minutes/day, five days/week, for eight weeks. The project was approved by the Ethics Committee on the use of animals of the Federal University of Viçosa (No. 51/2011). After treatments, the animals were evaluated by electrocardiography and echocardiography to analyze heart rate and left ventricular function, respectively. Then the animals were euthanized and the hearts were removed to analyze the intracellular global calcium transient ([Ca2+]i), oxidative stress, as well as mitochondrial ultrastructure and function. Diabetes reduced both fractional shortening and ejection fraction of the left ventricle, prolonged QT and QTc intervals and reduced resting heart rate. The exercise training program associated with insulin treatment increased the resting heart rate, fractional shortening and ejection fraction and reduced the QT and QTc intervals. Diabetes reduced the amplitude and prolonged the decay time of the [Ca2+]i, increased mitochondrial calcium uptake, the expression of NADPH oxidase 4 (Nox 4) and of uncoupling protein 2 (UCP 2), and decreased the expression of superoxide dismutase (SOD). Exercise training associated with insulin treatment increased the amplitude and decreased the decay time of the [Ca2+]i, the expression of UCP2 and of Nox4. Mitochondria isolated from diabetic rats produced smaller quantities of H2O2, as compared to controls. Neither exercise training nor insulin treatment alone affected mitochondrial H2O2 production. However, the combination of treatments normalized mitochondrial H2O2 release. It was observed an increased GSH / GSSG ratio in the hearts of diabetic animals. Such change was not affected by the treatments either isolated or in combination. There was higher protein oxidation in the hearts of diabetic rats; however, this effect was attenuated by either insulin treatment itself or in combination with exercise training. DMT1 disrupted mitochondrial cristae and augmented mitochondrial volume. Exercise training combined with insulin treatment attenuated such abnormalities. In conclusion, swimming training associated with insulin therapy during eight weeks attenuates the deleterious effects of DMT1 on the myocardium of rats.