Our Research

Immune Regulation

One of the research efforts supported by the Diabetes National Research Group is to identify antigens. Antigens are substances capable of inducing an immune response that might be involved in the onset of diabetes. T cells, immune cells that destroy invading organisms and help other cells make antibodies that cause diabetes, are transferred into recipient experimental models.

"Libraries", composed of millions of compounds are then used to find and further test those compounds which are active in fighting the T cell clones. Current research shows that some compounds transferred into recipient experimental models in an attempt to cause diabetes, have actually prevented the disease.

Two possible explanations can be considered:

* These highly active compounds actually "exhaust" or destroy the T cells, or

* These compounds actually activate "regulatory" T cells in the recipient mice and inhibit the maturation of disease-causing T cells. These research efforts over the next year will be directed at better understanding this phenomenon.



Fatty Acid Transport

One of the common symptoms in diabetes is the increased blood sugar levels in the human body due to the body's inability to produce insulin. The disease also results in increased free fatty acids in the blood.

Increasing evidence indicates that consequences of diabetes are due in part to these free fatty acids. A study currently funded by us focuses on the mechanism of fatty acid (FA) transport across membranes, and how it relates to diabetes. In order for FA to be utilized, they must be transported out across the plasma membrane and into cells, such as muscle, where they are metabolized.

Scientists realize that understanding FA transport and how it works is critical for understanding normal physiology. Because of the high FA levels in diabetes, it is possible that defects in the transport system, or its regulation, may contribute to the cause of the disease.

The group is trying to find new strategies for treating diabetes if specific transport mechanisms can be discovered. To study the transport of free fatty acids (FFA), scientists supported by us have developed ADIFAB, a fluorescent probe that can study specific proteins that can regulate FFA transport and regulation.



Antigen Processing and Presentation

One characteristic of Type 1 diabetes is the attack of insulin producing cells in the pancreas by the body's own T cells (immune cells that destroy invading organisms). By understanding how the pancreatic self-antigens (substances capable of inducing an immune response) are processed and presented, a cure for Type 1 diabetes would be one step closer.

Scientists are now examining a prominent member of antigen-presenting cells, glutamic acid decarboxylase, GAD. A large majority of individuals who will develop diabetes have antibodies to GAD in their serum long before the symptoms are visible. Scientists are interested in the unique characteristics of GAD and its processing and presentation. A variety of approaches are being taken by scientists trying to figure out under which conditions certain members of the T cell family will be activated, with the purpose of the eventual control of this responsiveness.



Other Studies

Scientific collaborators from Spain have provided T cell clones from patients with diabetes, which are then tested against the "libraries" of compounds, the data is then analyzed to select and identify individual peptides that could be further tested as potential candidates for treatment.

In another current study, glucagon, the hormone that raises blood sugar, is being tested against "libraries" to find a possible inhibitors. Future research of glucagon will focus on the use of an inhibitor in additional experimental models for diabetes.