Grant: Project Grant

Our bodies rely on 3 major fuel sources we obtain from the food we eat; fats, sugars, and protein. However, during starvation our livers make a 4th fuel source that our organs (brain, heart, and muscle are the main users) can use to make energy, the ketone body. Past research has heavily focused on understanding the regulation of fat, sugar, and protein metabolism in health, and how they malfunction in various diseases such as obesity and diabetes. The regulation of ketone body metabolism in health and disease has received much less attention. However, exciting data in our lab has shown that decreasing the muscle's ability to burn ketone bodies for energy improves blood sugar control in obesity/diabetes. In addition, we have identified an old-group of drugs previously used to treat psychoses, which are able to decrease the ability of the muscle to burn ketone bodies for energy. Unfortunately, this old group of drugs is used less frequently for treating psychoses, due to the development of next generation anti-psychotic drugs, despite this old group of drugs being significantly cheaper. Importantly, this old group of drugs also appears to improve blood sugar control in obesity, but does have some brain-related side effects (e.g. drowsiness, dizziness, etc.) that may hinder its use as a therapy for diabetes. Thus, the goal of our research is to use both pharmaceutical science and chemistry methods to develop new drugs that are similar to these old group of drugs for psychoses, but are modified in a manner where they cannot reach the brain. We believe these new drugs may represent an exciting new treatment option to lower blood sugar levels in people with diabetes.