UF to house pancreas research repository for the study of diabetes

August 30, 2007

GAINESVILLE, Fla. — The University of Florida will house a newly organized international research center for the study of the human pancreas that will bank organs from thousands of patients with or at risk for type 1 diabetes in an effort to learn more about the disease.

Known as nPOD, the Network for Pancreatic Organ Donors with Diabetes is supported by nearly $3 million per year in grant funding from the Juvenile Diabetes Research Foundation, monies that also fuel research efforts at major medical centers worldwide.

Type 1 or “insulin-dependent” diabetes occurs when white blood cells vital to the body’s defenses against infectious diseases launch a self-directed or “autoimmune” attack on cells in the pancreas that produce insulin, which helps regulate how the body uses and stores sugar and other nutrients for energy.

But much remains to be learned about how type 1 diabetes develops, and the organ repository will help support a massive research effort to answer key questions, said Mark Atkinson, the American Diabetes Association Eminent Scholar for diabetes research at UF’s College of Medicine and nPOD’s director.

“Essentially, we need to learn a lot more about the human pancreas,” said Atkinson, a pathologist. “Eight thousand organ donors a year donate their pancreas. A large number go to pancreatic or islet cell transplantation. Some go to research. But sad to say, many go unutilized. With nPOD, we hope to change that.

“Some of our theories on how diabetes develops date back to autopsy-based research studies that occurred during the 1960s. It is time to address old concepts with more modern tools,” he added.

The effort is partly in response to new federal funding mandates that organ procurement organizations no longer focus solely on organ transplantation – they also must dedicate time and resources to support research.

The bank will receive donated organs in three ways. First, researchers will aim to screen at least 2,000 pancreas donors per year after their death with the assistance of national organ procurement agencies that will – in cooperation with local academic institutions – look for risk factors associated with disease development, including the presence of autoantibodies that signal the immune system is on the attack, Atkinson said.

“If we find organ donors who have autoantibodies, it tells us those individuals, if they had lived, were going to be at high risk for developing type 1 diabetes,” he said.

The organs will arrive at UF within eight to 12 hours of removal from the donors. Researchers also will study spleen, lymph nodes and blood, which play a role in supporting the immune system’s destruction of insulin-producing cells. After processing, organs and tissue samples also will be shipped to various labs around the world, from Harvard to King’s College London and beyond.

The second way nPOD will receive pancreases will be through a collaborative agreement with the National Disease Research Interchange, the nation’s largest placement unit for donated organs slated for research. For that effort, organs will be obtained from any donor with type 1 diabetes — regardless of autoantibody status — to confirm whether individuals with longstanding diabetes truly harbor large numbers of insulin-producing cells.

Since the 1970s UF researchers have been striving to identify at-risk individuals via markers present in the blood. The autoimmune attack, thought to occur in individuals who are genetically predisposed to the disease, can continue for months to years before enough cells are destroyed to cause diabetes.

“The dogma of type 1 diabetes has always been that you develop the symptoms of diabetes only after a long process of months to years to decades of that autoimmune process,” Atkinson said. “Once you hit a certain point … all those insulin-producing cells are gone.”

But within the past couple years, new study findings emerged, after scientists elsewhere evaluated the pancreases of nearly 50 patients with type 1 diabetes, up to 60 years after onset.

“When they looked at the pancreases, they found to their surprise that people who had type 1 diabetes even for decades still had insulin-positive cells in their pancreas,” Atkinson said. “That went totally against everything we were taught. If that’s true, that some insulin-positive cells remain, it opens up a whole new avenue of trying to cure this disease and brings new hope to 1 million people in the U.S. who have type 1 diabetes. The idea would then be to develop new treatments to boost these cells, helping to control or even reverse the disease.”

The third way nPOD will eventually obtain organs will be in cooperation with Dr. George King, from Harvard’s Joslin Diabetes Center. Under a proposal not yet finalized, pancreases obtained from deceased patients who have had type 1 diabetes for more than 50 years will be sent to UF.

Collaborators within nPOD include scientists at medical schools at Harvard University, the University of California-San Diego, the University of California-San Francisco, the University of Pennsylvania, the University of Pittsburgh and the University of Michigan, and sites in England, Finland, Canada and Australia. UF is coordinating organ recovery efforts through facilities in six U.S. cities and, locally, through LifeQuest Organ Recovery Services and Shands HealthCare.

“Basically, we have almost no information on what’s happening in the pancreas while children and adults are developing type 1 diabetes,” said Dr. George Eisenbarth, executive director of the Barbara Davis Center for Childhood Diabetes and a professor of pediatrics and cellular and structural biology at the University of Colorado who has been running a small pilot program similar to nPOD. “(Yet) about 1 in 300 individuals in the U.S. population at the time of untimely death have the hallmarks that they are developing type 1 diabetes. So now the program will be expanded and there will be close to 10 times as many individuals screened as was possible for one center to do. It’s a very rare pancreas that we think will hold the key to what causes diabetes. It’s unexplored, unknown territory. Without this large cooperative effort there’s no way we can find this out.”