Type 1 diabetes is an autoimmune disorder – a person’s own immune system attacks beta cells found in the pancreas. Beta cells normally respond to high levels of sugar in the blood by releasing insulin, a protein hormone that acts like a key binding to a lock (or receptor) that is present on every cell in the body. When insulin binds to its receptor, it unlocks a door in cells that allows this sugar—known as glucose– to enter and be used for energy.Since type 1 diabetics lack insulin-producing beta cells, glucose remains in the blood and cells starve. Even with insulin therapy, the level of blood glucose in type 1 diabetics is not normal. Glucose is a highly reactive molecule that damages the cells and tissues that it contacts, particularly the cells that line blood vessels. As a result, diabetes is a leading cause of blindness, kidney disease, limb amputation and heart disease. Because type 1 diabetes commonly manifests in childhood, it has traditionally been called “juvenile” diabetes. Type 1 diabetes treatment is life-long; diabetics must carefully monitor their blood sugar and receive daily insulin injections or wear an insulin-delivering pump.
At Sanford-Burnham, scientists are studying the molecular causes of type 1 diabetes in order to develop alternative methods of treating and preventing the disease. In particular, they are interested in how to generate new beta cells and how immune cells attack the pancreas. In 2004, Sanford-Burnham scientists discovered that PTPN22, an immune system gene, is also one of the most important genes that predisposes individuals to developing type 1 diabetes.
Pumping up the body’s own beta cells
One approach to treating type 1 diabetes is to kick-start a person’s own dwindling beta cell population to replicate and produce more insulin. To do this, several Sanford-Burnham research groups are trying to understand the complex network of proteins that control beta cell growth and function. Investigators are using this information to tweak genes in a way that tricks remaining beta cells into a constant state of proliferation before they are completely destroyed by the immune system.
Re-supplying with new beta cells
Another method for restoring insulin production in type 1 diabetics is to transplant beta cells from an external source to the patient. To do this, researchers must generate a supply of beta cells and then develop ways to protect them from the autoimmune response that destroyed the original cells. At Sanford-Burnham, scientists are investigating ways to use stem cells to produce new beta cells for transplantation. Stem cells are undifferentiated cells, meaning that they have not yet settled on a specific function. These researchers have identified a population of stem cells in the human adult pancreas that can form new beta cells. They are now conducting studies to better understand how these stem cells develop so that the process can be manipulated to create large quantities of beta cells.
Beta-cell transplantation in type 1 diabetics often requires constant treatment with immunosuppressive drugs that keep the immune system from eradicating the new cells. Since long-term use of these drugs can have serious side effects, Sanford-Burnham scientists are developing an alternative approach to hide transplanted beta cells from the immune system. They have created an encapsulation device that protects transplanted beta-cells from destruction. The device allows insulin to exit and nutrients and glucose to enter, but keeps immune cells out.
Screening for new drugs
Sanford-Burnham’s Conrad Prebys Center for Chemical Genomics allows diabetes researchers to search for potential new therapeutics using robotic technologies that screen hundreds of thousands of chemical compounds. Scientists are now looking for compounds that stimulate stem cells to become beta-cells or turn on insulin-producing genes. They hope these findings will lead to the design of novel drugs that enhance insulin secretion in diabetics.
For more information
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the NIH
Juvenile Diabetes Research Foundation (JDRF)
American Diabetes Association (ADA)
The Sanford Project