Grant: Project Grant

Diabetes is a serious disease in which high levels of blood sugar (glucose) damage the body and markedly shortens life-span. Glucose is normally kept low by the hormone insulin, which is released from beta-cells in the pancreas. Diabetes develops, in large part, because the pancreatic beta-cells stop working or die and therefore do not produce the insulin we need. In Type 2 diabetes, the most common form of the disease, this is closely linked to obesity. Type 1 diabetes develops when beta-cells are attacked by the immune system. The overall goal of our research is to identify, and reverse, cellular events that contribute to the loss of normally functioning beta-cells. Recent research has discovered that cells under stress can change in ways that are similar to the changes that happen when we age. Importantly, this type of early aging may also happen to beta-cells and be a major reason why they begin failing and diabetes develops. Scientific evidence also suggests that specific proteins that regulate cell survival, called Bcl-2 family proteins, may have important roles in early cell aging. However, we still know very little about the functions of these Bcl proteins and how the early aging of pancreatic beta-cells is regulated. In this project, we will use gene manipulation, non-diabetic and diabetic beta-cells, drug treatments, and advanced cell microscopy to shed light on this. The outcomes of this research will help us understand why diabetes develops and how to best target the beta-cells for early treatments of this serious life-shortening disease.