Master of Science
Melling, C.W. J.
The etiology of insulin resistance (IR) development in type 1 diabetes mellitus (T1DM) remains unclear; however, impaired skeletal muscle metabolism may play a role. While IR development has been established in male T1DM rodents, female rodents have yet to be examined in this context. Resistance exercise training (RT) has been shown to improve IR and is associated with a lower risk of hypoglycemia onset in T1DM compared to aerobic exercise. Additionally, the molecular mechanisms mediating RT-induced improvements in insulin sensitivity remain unclear. Therefore, the purpose of this study was to investigate the effects of RT on IR development in female T1DM rodents. Forty Sprague-Dawley eight-week-old female rats were divided into four groups: control sedentary (CS; n=10), control trained (CT; n=10), T1DM sedentary (DS; n=10), T1DM trained (DT; n=10). Multiple low-dose Streptozotocin injections (20 mg/kg each day for seven consecutive days) were used to induce T1DM. Blood glucose levels were maintained in normal range (4-9mmol/L) with intensive insulin therapy (one implanted insulin pellet; 2IU/day). CT and DT underwent weighted ladder climbing 5 days/week for six weeks. Intravenous glucose tolerance tests (IVGTT) were conducted on all animals following the six-week period. Results demonstrate that DS animals exhibited significantly increased weekly blood glucose measures compared to all groups including DT (p
Summary for Lay Audience
Type 1 diabetes mellitus (T1DM) is a disease which develops when the body’s immune system attacks the pancreas resulting in the loss of insulin production in the body. Insulin is an important hormone produced by the pancreas which allows sugar (glucose) to be used as energy by different tissues in the body. As a result, people with T1DM have unregulated blood glucose levels which can cause a variety of negative health effects such as heart disease. The current treatment for T1DM involves the use of injected insulin which works to replace the lost hormone in the body. Unfortunately, some patients with T1DM develop a resistance to insulin whereby the blood glucose-utilizing effects of injected insulin does not work as efficiently anymore in important tissues such as skeletal muscle, known as insulin resistance (IR). Our understanding of why and how IR develops in people with T1DM is relatively unclear because limited research has focused on this issue, especially in females. Exercise has been shown to improve IR in different diseases, however certain forms of exercise such as aerobic exercise can cause a large and potentially dangerous decrease in blood glucose levels in people with T1DM. Resistance exercise on the other hand has been shown to result in more stable blood glucose levels during exercise in people with T1DM. However, it is not known if resistance exercise training is able to improve IR in females with T1DM. This study aimed to determine if resistance exercise training is effective in improving IR in female rodents with T1DM and how IR may develop in muscle tissue. We found that six weeks of resistance exercise training prevents IR from developing in female rodents with T1DM. We also found that IR in female rodents with T1DM was associated with alterations in the storage form of glucose (glycogen) in muscle tissue which is also prevented with resistance exercise training. This suggests that improper storage of glucose in muscle may contribute to the development of IR and that resistance exercise training is an effective exercise intervention to improve IR and muscle glycogen storage in female rodents with T1DM.
Sammut, Mitchell James, "The Effects of Resistance Exercise Training on Insulin Resistance Development in Female Rodents with Type 1 Diabetes" (2023). Electronic Thesis and Dissertation Repository. 9454.