Our lab is developing methods for pancreatic beta-cell regeneration as an approach to treat diabetes.
Pancreatic beta-cells are the insulin secreting cells in our body. Insulin is the survival hormone for tissues and cells in our body. Insulin is responsible for granting glucose (sugar) entry into cells. Glucose is the fuel that keeps cells alive. If the body doesn’t produce enough insulin, or if the tissue cannot sense it, glucose is barred entry and cells starve to death. Blood-sugar levels also build up, because the cells aren’t able to consume the glucose.
This describes the imbalance found in diabetic patients. On the one hand body tissues are starving, which in acute cases develops into gangrene and necrosis. On the other hand, blood-sugar levels rise, creating osmotic pressure that causes problems such as atherosclerosis (disease of the arteries), kidney failure, strokes, and heart attacks, to name a few.
Both type I (juvenile) and type II (adult onset) diabetes are characterized by a deficiency of insulin-producing beta-cells. Type I diabetes is an autoimmune disease. The body attacks and kills beta-cells, which results in less insulin. Type II diabetes is brought on by a collection of different metabolic illnesses. Generally speaking, the body is suffering from one of two problems. If the patient has poor eating habits and consumes too many carbohydrates, this leads to glucose overload, which overworks and eventually kills beta-cells. Alternatively, other patients demonstrate resistance or insensitivity to insulin causing the beta-cells to secrete more insulin, also resulting in beta-cell exhaustion and death.
Current Research Objectives
Our goal is to replenish the beta-cell population in diabetic patients. Our strategy is to use drugs to convert neighboring alpha-cells into beta-cells in order to step up insulin production. We were successful using this approach in mice. Our efforts are directed towards increasing the conversion rate from alpha- to beta-cells in different diabetic models, with our growing knowledge of how the PAR2 receptor mediates this process. We are also attempting to stabilize the newly formed beta-cells by preventing their continued transdifferentiation into delta-cells.
Regenerative medicine is not limited to beta-cells, and our findings are therefore relevant to other fields where regeneration therapy is needed. So far, our discoveries have been shown to have implications for the treatment of hepatitis and limb amputations.