The Juvenile Diabetes Research Foundation International (JDRFI) has announced the establishment of the $3million Center for the Study of Complications in Diabetes at Columbia University, designed to study how vascular, kidney and periodontal diseases develop and progress as complications of Type 1 (or juvenile) diabetes.

The grant is to be used over a three-year period and will strengthen the efforts of the Naomi Berrie Diabetes Center at Columbia-Presbyterian Medical Center (CPMC) to prevent the serious complications associated with diabetes. The grant addresses a central theme of the research effort in the division of surgical sciences and the Center for Vascular and Lung Pathobiology at the medical center.

More specifically, the center's researchers are studying key molecules located on the surface of cells, called Receptors for Advanced Glycation Endproducts (RAGE). To become activated, RAGE, like all cell receptors, must link up with other molecules in the body called ligands, using a kind of lock-and-key mechanism. RAGE can be conceived of as the lock and the ligand as the key. The ligand for RAGE is called Advanced Glycation Endproducts (AGE).

AGE levels increase in people with diabetes, due to hyperglycemic (or high blood sugar) episodes. AGE and RAGE interaction leads to cell damage that drives the disease process forward. RAGE plays a central role in the development of diabetes complications such as vascular, kidney and periodontal diseases. Researchers at the JDRFI Center for the Study of Complications in Diabetes at Columbia University are investigating whether it is possible to stop these lock and key interactions.

"This is a wonderful opportunity to be in the forefront of cutting-edge diabetes research," said David Hirsh, interim dean for research at Columbia University College of Physicians & Surgeons. "Diabetes is a devastating disease, and its complications extract an extremely high toll on individuals and families."

Eric A. Rose, Johnson & Johnson and Milstein Professor and chairman of the department of surgery, said: "The prevention and treatment of the complications of diabetes are major problems for our patients. We welcome this research effort as a novel approach for dealing with complications and hope it will lead to new and efficacious therapies for our patients."

Research conducted by David M. Stern, director of the new JDRFI Center and Gerald and Janet Carrus Professor of Surgical Science and Physiology and Cellular Biophysics at Columbia, will focus on RAGE and diabetic vascular disease. As these diseases of the veins and arteries include both stroke and heart attack, they are a major cause of death in people with both Type 1 and Type 2 diabetes. Stern is testing a new medicine, sRAGE, or soluble RAGE, that, when injected, absorbs the AGEs in the blood that cause blood vessel wall damage. This research is currently being conducted on rats.

"We have our most prestigious researchers collaborating on these investigations," said Stern, "The investigations into RAGE receptors could bring about groundbreaking discoveries applicable not only to diabetes but also to other diseases."

In diabetes, the kidneys can become clogged and eventually fail. Ann Marie Schmidt, associate professor of surgical sciences and medicine at Columbia and co-director of the center, is conducting research on RAGE and diabetic kidney disease. She is also working on testing sRAGE, this time on kidney tissue. Her lab also will work to develop and test other substances that might prove even more effective than sRAGE in diabetic nephropathy.

In the same way, Ira Lamster, vice dean and professor of dentistry at Columbia's School of Dental and Oral Surgery, is conducting research on RAGE and diabetic periodontal disease. Aggressive periodontal disease in diabetics damages gums, teeth and bones of the mouth. Center scientists will study whether sRAGE could "soak up" AGE and S100/calgranulin in the periodontal region. Preliminary studies show this technique to be an effective way to fight periodontal disease in patients with diabetes.

To dissect the RAGE molecule and gain insights into the design of low molecular weight inhibitors, it is essential to understand the structure of the receptor. For this reason, Joyce Lustbader, senior research scientist in the department of obstetrics and gynecology, is performing structural studies on soluble RAGE.

"The Center for the Study of Complications in Diabetes at Columbia University is an important addition to JDRFI's research into the causes, prevention and treatment of the dangerous complications of diabetes," said Robert Goldstein, chief scientific officer, JDRFI. "This exciting avenue of cellular research is extremely important in preventing and treating complications in people with diabetes."

The JDRFI's establishment of the Center for the Study of Complications in Diabetes at Columbia is of critical importance because of the long-term impact it will have on millions of lives, said Rudolph Leibel, professor of pediatrics and medicine, head of the division of molecular genetics at Columbia, and co-director of the Naomi Berrie Diabetes Center. "Through the combined efforts of JDRFI and the biomedical research community at Columbia, we have a real opportunity to attack the underlying mechanisms for the causes and complications of diabetes."

The Naomi Berrie Diabetes Center at CPMC combines unprecedented, family-oriented patient care and education with world-class diabetes research programs. The center, named after Russ Berrie's mother who, like her son, had diabetes, was established under the direction of Robin Goland, associate professor of medicine, and Leibel. It opened in its permanent space at the Russ Berrie Medical Science Pavilion at CPMC in November 1998.

JDRFI is the world's leading non-profit, non-governmental funder of diabetes research. It was founded in 1970 by parents of children with diabetes. JDRFI's mission is to find a cure for diabetes and related complications through the support of research, and since its inception JDRFI has provided more than $326 million to support diabetes research worldwide. For more information call 1-800-JDF-CURE.

--Office of External Relations, Columbia University Health Sciences Division, hsdnews@columbia.edu.