Type 1 Diabetes

Pancreatic beta-cells

Pancreatic beta-cells

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 binds to insulin receptors present on every cell in the body. When insulin binds these receptors, it allows this sugar (glucose) to enter the cell and be used for energy.

Since type 1 diabetics lack insulin-producing beta-cells, glucose remains in the blood and cells starve. Glucose is a highly reactive molecule that damages the cells and tissues it contacts, particularly 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.

SBP research on type 1 diabetes

SBP scientists are unraveling the molecular causes of type 1 (juvenile) diabetes and using that information to develop alternative methods of treating and preventing the disease. In 2004, SBP researchers discovered PTPN22, a gene that predisposes people to type 1 diabetes. Now they want to cure the disease by generating new beta-cells and keeping the immune system at bay.

Boosting beta-cells

One approach to treating type 1 diabetes is to kick-start a person’s own dwindling beta-cell population. Several of our research groups are tweaking beta-cell genes in a way that tricks these cells into a constant state of proliferation, producing more insulin. SBP scientists are also coaxing other cell types in the pancreas—including adult stem cells and alpha-cells—to generate more beta-cells. Another method for restoring insulin production in type 1 diabetics is to transplant new beta-cells from an external source to the patient. To do this, our scientists are manipulating stem cells in the laboratory to produce large quantities of beta-cells for transplantation.

Dampening autoimmunity

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, our scientists are looking for ways to selectively suppress the immune system so that autoimmune immune cells are silenced but patients can still fight infection. They have developed cell-based therapies where some of a patient's immune cells are removed from the blood, re-educated in the laboratory to become immune suppressors, and returned to the body to selectively suppress the autoimmune cells that attack beta-cells.

Our researchers have also 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. In pre-clinical trials using animal models, this encapsulation device prevents immune rejection of transplanted beta-cells and cures diabetes.

Searching for new medicines

SBP Conrad Prebys Center for Chemical Genomics allows diabetes researchers to search for new therapeutics using robotic technologies that screen hundreds of thousands of chemical compounds. Using these sophisticated tools, our scientists have discovered chemicals that stimulate adult stem cells to become beta-cells. They have also found chemicals that suppress the immune system in a more targeted way than current medications. Our researchers are now fine-tuning these chemicals into new medicines for type 1 diabetes.

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

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