Grant: Doctoral Research Award: Canada Graduate Scholarships

Blood sugar levels can rise after a meal. To control blood sugar levels, the pancreas releases the hormone insulin. Insulin converts sugar from food into energy for our cells. In people with type 2 diabetes, certain tissues become unresponsive to insulin, causing high blood sugar levels. Over time, this leads to serious health issues such as blindness and kidney failure. In Canada, over three million people are diagnosed with diabetes. Of these, 90% have type 2 diabetes, which has no cure. It is alarming that diabetes prevalence is increasing even among overweight children around the world. An annual economic burden of 15 billion dollars is imposed on Canada by costs associated with diagnosis and patient care. A lack of physical activity, poor eating habits, and obesity can lead to type 2 diabetes, but we are particularly interested in the genetic mutations that cause it. To discover novel diabetes treatments and preventative measures, we study the protein called PGC. PGC regulates several key genes in order to supply energy to cells. PGC is abundant in tissues with high energy requirements, such as the brain, liver, muscle and pancreas. A mutation in the gene from which PGC is produced has been shown to be associated with type 2 diabetes and obesity. We think this mutation might affect the stability of PGC, its function, its 3D structure, and its interaction with other proteins. We observed that the mutant version of PGC becomes unstable in pancreatic and liver cells. We also found that the mutation affects the way overweight people use fat versus carbs. Indicating people with the mutation may have a higher fat storage capacity. Further testing will be done using human cells and mice that carry the mutation. Our unique cells can be transformed into whatever type of cells we wish to study. With this research project, we hope to identify drugs that could stabilize PGC, as well as therapies that target dysfunctional pathways in people who carry the mutation.