Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Kinesiology

Supervisor

Melling, Jamie

Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting in the destruction of pancreatic beta cells leading to deficient insulin production. Insulin plays a crucial role in regulating glucose metabolism, facilitating the utilization of dietary energy. Individuals with T1DM exhibit dysregulated blood glucose concentration and necessitate exogenous insulin administration. Intensive insulin therapy (IIT) is employed commonly, typically via subcutaneous (SQ) injections to treat individuals with T1DM. However, SQ insulin delivery fails to mimic endogenous insulin secretion, particularly its physiological distribution directly to the liver via the hepatic portal vein. Insulin concentration in the liver contributes significantly to glucose homeostasis, notably during aerobic bouts of exercise. Individuals with T1DM lack direct hepatic insulin exposure and exhibit depleted liver glycogen reserves. Lower liver glycogen results in a diminished ability to release glucose into the bloodstream, leading to greater susceptibility of exercise-induced hypoglycemia. This study examined an alternative route of insulin administration directly into the Omentum pouch (OP.). The OP is an anatomical structure located within the abdominal cavity, vascularly akin to the pancreas. This study aimed to evaluate the efficacy of OP insulin delivery in enhancing liver glycogen storage and mitigating post-aerobic exercise (AE) hypoglycemia. Contrary to expectations, OP insulin administration exhibited inferior glycemic control and impaired glycogen utilization compared to traditional SQ administration. This finding was attributed to abnormally increased insulin concentration in the hepatic portal vein.

Summary for Lay Audience

Type 1 diabetes mellitus (T1DM) arises when an individual's immune cells attack the pancreas resulting in the loss of insulin production in the body. This is a prominent issue as insulin is a hormone that is responsible for the utilization of energy stored in food. Consequently, people with T1DM tend to have increased, unregulated blood sugar (BG)concentration which requires external sources of insulin. To treat patients with T1DM, intensive insulin therapy (IIT) is used. IIT involves multiple SQ injections which keep BG within the normal physiological range. However, SQ insulin injections do not replicate how the body would physiologically produce insulin in individuals without diabetes. The body produces a specific quantity of insulin in the pancreas to match intestinal blood glucose, which in turn travels directly to the liver, via the hepatic portal vein. Among many other roles, the insulin in the liver is important for storage of glycogen (molecules of glucose). Liver glycogen is important for many physiological processes including regulating decreasing blood glucose during exercise via a process called hepatic glycogenolysis, where hepatic glycogen is converted to glucose, a usable energy source of the body. During exercise, in individuals with T1DM, the SQ insulin only reaches the liver after muscle, fat and other insulin sensitive tissues utilize it first, thus rendering hepatic glycogen stores low. This contributes to individuals with T1DM being more susceptible to entering a hypoglycemic (low blood sugar) state while exercising. An alternative method for administering insulin via the Omentum pouch (OP) has been theorized to combat the indirect supply of insulin to the liver. The OP is a large two-fold organ located adjacent to the pancreas, with very similar vasculature to the pancreas. This study sought to determine whether insulin administration to the OP would result in better liver glycogen storage andas a result mitigate the drop in blood glucose post-aerobic exercise (AE). The current study found that OP insulin administration results in poorer blood insulin regulation and a decreased ability to utilize stored glycogen, suggesting too much insulin was being administered to the hepatic portal vein causing negative outcomes.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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