Grant: Project Grant

Type 2 diabetes is a growing public health concern affecting over 3 million Canadians. The risk of cardiovascular disease is substantially higher in patients with type 2 diabetes (T2D), including increased risk of heart attack, stroke, and peripheral vascular disease. T2D causes the loss of the ability of pancreatic cells to produce sufficient insulin and the development of persistent high blood sugar. Excess glucose in the blood can damage blood vessels, further exacerbating factors that impair the body's ability to respond to insulin and clear glucose. These factors include vascular surface area, distance between capillaries and skeletal muscle, and the distribution of blood flow. We aim to examine how changes in capillary network structure, and defects in microvascular blood flow regulation contribute to impaired glucose uptake in T2D. Our approach uses an animal model that recreates the insulin resistance of T2D, combined with obesity, to replicate the conditions observed in human disease. Using microscopy we can then to look at capillaries, the smallest blood vessels in the body, and specialized software to measure blood flow in living muscle tissue. The predictable progression of T2D in our animal model makes it ideal to study microvascular changes similar to that which would be observed in humans. The data collected will also be integrated into a mathematical model of glucose and insulin transport to further our understanding of insulin resistance. Quantifying how T2D impacts microvascular function and structure in our animal model furthers our understanding of the progression of T2D in humans due to the similar physiology and physical properties of our vascular systems. This study will be the first to study oxygen mediated blood flow regulation and the impact of insulin on blood flow distribution in capillaries which informs our understanding of exercise intolerance in T2D as well as how insulin resistance is linked to microvascular factors.