Grant: Operating Grant

Diabetes is a serious metabolic disease that affects over 360 million people worldwide. Obesity and diets high in sugar and fat contribute to type 2 diabetes by putting extra demand on the pancreatic beta-cells to secrete insulin, a hormone that normally maintains normal blood sugar (glucose) levels. Often the body can initially adjust to the increased demand for insulin, and keep glucose levels in control, by increasing in the function and number of beta-cells. However, under continued stress these important pancreatic cells eventually fail and die. As a result, too little insulin is released, glucose levels stay too high, and diabetes develops. It remains a critical unanswered question how the switch from beta-cell adaptation to beta-cell dysfunction happens, and how failure and death of the cells can be prevented. Our research group recently found that two related proteins, called Bcl-2 and Bcl-xL, not only promote beta-cell survival but also regulates normal insulin secretion. They do so, in part, by affecting the beta-cell's mitochondria; the 'powerhouses' that produce important energy signals needed for insulin to be released into the bloodstream. In this project we will clarify if and how the Bcl proteins control beta-cell stress levels under conditions of high glucose and fat, and we aim to determine if the Bcl proteins influence the loss of glucose control that precedes diabetes in obese mice. Answering these research questions will provide important new information of how beta-cells function, and what causes the loss of insulin secretion that ultimately leads to diabetes. This knowledge will help identify new ways to protect the pancreatic beta-cells and treating this serious disease.