INTERNACIONAL (DGECI) CICLO ESCOLAR 2019
II. APARTADO DE CONSIDERACIONES DE CARÁCTER GENERAL PARA LA PRESENTACIÓN DE PROPUESTAS
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Conclusion
The objective of this thesis was to examine the effects of aerobic training on vascular mitochondrial respiration, with a follow-up investigation focusing on T1DM. Our research provides novel insight on how vascular mitochondrial respiratory capacity is affected by aerobic exercise and whether mitochondria-specific therapy could be used in the future to help reduce the risk of cardiovascular disease in T1DM patients.
Mitochondria are dynamic organelles and highly adaptable to various physiological stimuli, including physical activity. Our results derived from healthy aortic vessels support this notion, with significant increases in complex I-linked, glucose-based substrate respiration and capacity as major findings. However, in the context of diabetes, the opposite was observed in which aerobic exercise appeared to induce a decrease in vascular mitochondrial complex I respiration, indicating that training has the potential to exacerbate mitochondria-mediated diabetic complications in the vasculature.
Given the significant implications of mitochondrial dysfunction in the pathophysiology of diabetes, mitochondria-specific therapy may provide novel ways to treat the disease, or at least reduce the severity of complications associated with it. This project demonstrated that aerobic training led to a decrease in vascular mitochondrial content and function in poorly regulated T1DM models, and thus negated all previously demonstrated benefits of exercise. However, it is important to note that exercise is still important in maintaining a healthy lifestyle, and so more work needs to be done to investigate the exact dosage of aerobic training required to induce benefits in the vasculature of T1DM patients as a way to help reduce the risk of cardiovascular disease. Furthermore, it is important to determine the overall effects of the drug streptozotocin and its’ potential involvement in multi-system organ damage which could also explain the high mortality rate in the T1DM subjects of our study. In order to refine our understanding of the role of aerobic exercise and untreated T1DM on mitochondrial function, future long-term adjuvant studies should focus on investigating insulin therapy as well as different exercise parameters that best elicit positive mitochondrial adaptations. Consequently, new treatment strategies for diabetes are required to address both mitochondrial function and oxidative stress. Pharmacological interventions that target mitochondrial biogenesis and respiration have potential therapeutic importance, with antioxidant
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molecules already garnering much research attention to effectively control ROS production and protect against oxidative damage in diabetes.
Overall, this thesis contributes to potentially identifying novel methods to treat the metabolic and vascular complications of diabetes: from the specific modification of branched-chain amino acid intake in reducing the severity of T2DM to investigating the roles of aerobic exercise on mitochondrial respiration of vascular smooth muscle cells in T1DM patients.
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