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A Systems Biology Approach to Model Skeletal Muscle Response to Aerobic Exercise Training Open Access

Type 2 diabetes is a condition with poorly regulated glucose metabolism. The incidence of Type 2 diabetes has increased tremendously in the past few decades in most countries and is highly prevalent in certain ethnic group particularly. The rise in incidence of Type 2 diabetes is connected to the `Western life style', with calorie rich food, lack of exercise, and obesity. Type 2 diabetics show poor quality of life with higher risk of all the obesity-associated complications such as Stroke, Diabetes, Hypertension, Cardiovascular Disorders and even Cancer.Efforts to reduce Type 2 diabetes, or prevent the onset of the disease, typically focus on diet, activity, and pharmacological interventions. Physical activity has been an effective approach in controlling and preventing or even reversing Type 2 diabetes. Physical activity leads to several beneficial structural and functional adaptations which are mediated through different processes and pathways in the skeletal muscle. In order to understand the association of physical inactivity with these complications, it is important to know the genes that are regulated by exercise which lead to improvements in these conditions. Moreover, these changes might be epigenetically regulated, which makes it crucial for therapeutic applications. Thus, it is important to integrate different levels of data, including both mRNA and DNA level regulation, to better understand these adaptive changes. In this study, our goal was to define the adaptive changes in the skeletal muscle of patients with Type 2 diabetes after 16 weeks of aerobic exercise training. The patient group studied was Polynesian; indigenous [Maori] and more recent residents of Pacific Island migrants to New Zealand that showed grade III obesity and Type 2 Diabetes Mellitus. We describe bioinformatics and data analysis by integrating mRNA, microRNA and epigenetic data from these subjects in muscle biopsies taken before and after the intervention.The research was a pilot study to model the skeletal muscle response in T2DM subjects due to 16 weeks of aerobic exercise training. The approach used an integrated data to represent the molecular mechanism underlying this intervention and study the DNA (due to methylation) and RNA (due to miRNA) level of regulation. The networks generated showed an improvement in muscular development, endurance and carbohydrate metabolism following the intervention. We would further integrate the proteomics data into these networks using Bayesian approaches for a more probabilistic model of these adaptations followed by validation using methods like RT-PCR and/or functional assays. This would give an insight into the beneficial adaptive changes due to aerobic exercise training in the diabetic skeletal muscle.

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