Doctor of Philosophy
Dr. C. W. James Melling
Insulin resistance is a characteristic of Type 2 Diabetes (T2D) and metabolic syndrome, and until recently has not been considered in the context of Type 1 Diabetes (T1D). A new classification, Double Diabetes, encompasses the presence of insulin resistance in T1D. Unfortunately, these individuals are at significantly higher risk of cardiovascular complications than those with T1D alone. In T2D, abnormal skeletal muscle lipid metabolism and the accumulation of insulin desensitizing lipid metabolites contribute the development of insulin resistance. There is some evidence to suggest this occurs in the context of T1D as well. Exercise training is an effective means to enhance insulin sensitivity, however, the fear of hypoglycemia remains a significant barrier in T1D. Using our rodent model of T1D, the objectives of this dissertation were as follows: 1) To determine whether insulin resistance is associated with increased skeletal muscle lipid content, and whether this is ameliorated with aerobic exercise 2) to compare the efficacy of combined aerobic and resistance exercise compared to aerobic exercise itself on skeletal muscle oxidative capacity and lipid metabolism, and 3) to compare the effects of the optimal exercise modality (combined exercise training) and the current recommendation of intensive insulin therapy on insulin resistance and the composition of skeletal muscle lipid. The findings of this dissertation were as follows: 1) There is an association between insulin resistance and the accumulation of intramyocellular lipid metabolites, which is ameliorated with aerobic exercise training. 2) Muscle lipid accumulation in sedentary T1D animals may result from a reduced oxidative capacity, coupled to greater lipid uptake. Aerobic exercise is sufficient to restore oxidative capacity, however combined exercise induces more robust improvements to oxidative capacity. 3) Combined exercise significantly enhances insulin sensitivity, while intensive insulin therapy is sufficient to prevent the drastic decline in insulin sensitivity observed with conventional insulin treatment. Further, muscle lipid composition differs between sedentary and exercised diabetic animals. These findings indicate a reduction in oxidative capacity, coupled to increased lipid accumulation and insulin resistance in sedentary T1D animals. Combined exercise is an effective modality to enhance insulin sensitivity and modify muscle lipid metabolism.
Dotzert, Michelle, "Insulin Resistance and T1D: The Effect of Exercise on Skeletal Muscle Lipid Metabolism" (2017). Electronic Thesis and Dissertation Repository. 4800.
Available for download on Saturday, September 01, 2018