Researchers Identify Key Immune Target in Type 1 Diabetes
Miami, FL (May 11, 2005) -- Diabetes researchers announced today that they have clearly identified a portion of the insulin molecule as an immune target in the development of type 1 diabetes. This landmark finding is a result of collaborations between scientists at Harvard University, the Diabetes Research Institute (DRI) at the University of Miami Leonard M. Miller School of Medicine, and the University of Minnesota. Camillo Ricordi, M.D., scientific director and chief academic officer of the DRI and Norma Sue Kenyon, Ph.D., associate director of research and program development, were among the authors of the study, published in the May 12 issue of Nature.
For more than 15 years, diabetes researchers have debated which of two autoantigens were responsible for launching the immune system’s attack on the cells that produce insulin in the pancreas: glutamic acid decarboxylase (GAD) or insulin. Early animal studies suggested GAD played a major role in this disease process, but more recently the scale began to tip in favor of insulin.
Researchers conducting this study harvested cells from pancreatic lymph nodes obtained from six deceased organ donors -- three with type 1 diabetes and three without. “A very significant proportion of the T cells taken from the ‘diabetic’ pancreatic lymph nodes studied were reacting against a specific fragment of insulin; it was like identifying the killer a few blocks away from the crime scene,” said Ricordi. Researchers were able to demonstrate an insulin-specific response by T cells located in pancreatic lymph nodes, nodes which are in the physical vicinity and have a functional relationship with the pancreas.
“In my view, these findings put the nail in the coffin of GAD,” said Jay S. Skyler, M.D., professor of medicine at the UM Miller School of Medicine, and associate director of the DRI. “It says: here it is, the target is right there; it’s insulin. It’s a very important paper in our field of study.”
In patients with type 1 diabetes, T cells from the body’s immune system attack insulin-producing cells, which are dispersed throughout the pancreas in clusters of cells called islets. T cells are a vital component of the immune system, keeping a variety of bacteria and infection-causing agents in check, and helping our bodies stay healthy. In autoimmune diseases like type 1 diabetes, however, T cells mistakenly turn on the host and attack the body’s own cells, tissues and organs.
The study not only clearly identifies insulin as the target, but it also demonstrates which particular fragment of insulin (A1-15 residues in the insulin A chain) is specifically targeted by the T cells. This additional piece of the diabetes puzzle, the identification of the specific insulin fragment, opens another important door for researchers at the DRI where diabetes cure-focused research is the sole objective.
“Scientists can now try to use this fragment to treat or perhaps even prevent the disease, by targeting either the antigen itself or the T cells that target it,” adds Alberto Pugliese, M.D., head of the Immunogenetics Program at the DRI. The multi-center Diabetes Prevention Study Group, which includes the DRI among its collaborating centers, has already identified a subset of patients who responded well to oral insulin to prevent diabetes; this work could help guide that research as well.
Diabetes affects millions of individuals worldwide, and its incidence is on the rise. Of the estimated 18 million Americans diagnosed with the disease, approximately 5-10% have Type 1 diabetes, the form usually diagnosed during childhood or adolescence.
The Diabetes Research Institute, a recognized world leader in diabetes cure-focused research, is the most comprehensive diabetes research facility of its kind.
UM Leonard M. Miller School of Medicine
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