Grant: Doctoral Research Award: Canada Graduate Scholarships

It is estimated that over 450 million people suffer from diabetes, a disease defined by high blood sugar. The 1st-line medication for people with diabetes is metformin, which has also been shown to cause weight loss by increasing the production of a protein called growth differentiation factor 15 (GDF15). Therefore, GDF15 is being investigated as a potential drug for obesity and diabetes, as it can also lower blood sugar. However, all drugs being developed for the treatment of diabetes must also undergo studies on how they affect the heart, since heart disease represents the number 1 cause of death for these individuals. In particular, people with diabetes often have a heart disease where their heart cannot relax as well between the pumping of blood, which is known as diabetic heart disease. Unfortunately, there are no specific treatments available for diabetic heart disease. To my excitement, my research has shown that GDF15 treatment improves diabetic heart disease, and this improvement is independent of its weight loss effects. While these results are promising, we have limited information on how GDF15 is able to improve heart function. As such, we will investigate how GDF15 is beneficial in the context of diabetic heart disease. Although the exact cause of diabetic heart disease is unknown, elevated inflammation (a stress response) in the heart of diabetic individuals play a key role. Drugs that lower inflammation have been shown to improve heart function in animal models of diabetes. Using computer modelling, we discovered that GDF15 interacts with a protein known as toll-like receptor 2 (TLR2), which normally produces a strong inflammatory response when activated. Therefore, we hypothesize that GDF15 could decrease inflammation in the heart by blocking TLR2. If we are correct, our research will not only progress GDF15 as a potential medication for obesity and diabetic heart disease but may also open the door for its use in other inflammation-related diseases.