GAINESVILLE, Fla. — As an autoimmune disease, Type 1 diabetes has long been thought to result from a complete immune system killing of the insulin-producing beta cells within the pancreas. Now, University of Florida Health researchers have made a striking discovery: some of the pancreas’ ability to produce insulin may remain for decades in people with Type 1 diabetes.
After studying the pancreata of those with Type 1 diabetes, researchers found insulin levels were low to undetectable among most — an expected finding given the absolute need for insulin therapy for all such patients. However, researchers found the amount of proinsulin, a protein precursor to insulin, were at near-normal levels and comparable to people without diabetes. The researchers also noted a small number of insulin-positive cells remain in pancreata of long-term Type 1 diabetes patients. That observation raised the question of how these cells avoided destruction by the immune system.
These findings, published today (Sept. 5) in the journal Cell Metabolism, have important implications for questions ranging from why Type 1 diabetes develops to how the disease might be reversed or cured, said Mark Atkinson, Ph.D., director of the UF Diabetes Institute and a professor in the UF College of Medicine’s departments of pathology and pediatrics.
In Type 1 diabetes, the body’s immune system attacks insulin-producing islet cells in the pancreas. The pancreas produces insulin to control the level of sugar in the blood. Elevated and uncontrolled blood sugar levels can lead to a variety of complications and, if left untreated, result in death.
Gaining a better understanding of the molecular machinery of the pancreas in Type 1 diabetes is an early but important step in fighting a lifelong disease that requires insulin replacement therapy and predominantly affects children and young adults, the researchers said.
“If we can identify what allows these insulin-positive cells to survive, it might uncover a new form of therapy to either prevent Type 1 diabetes or reverse the disease once it occurs,” Atkinson said.
The researchers studied pancreas tissue from deceased organ donors, including 40 patients who had Type 1 diabetes, with an average onset age of about 12 years. They compared the tissue with pancreas samples from 50 nondiabetic organ donors. They recovered proteins from the pancreatic samples and looked for insulin, which the body makes in a multistep process.
The pancreata of those with Type 1 diabetes patients had proinsulin protein as well as the genetic template to make insulin, but the proinsulin did not get converted into “mature” insulin, the researchers found. That’s partly because one of two crucial enzymes, called proconvertases, were diminished in the pancreas, said Harry S. Nick, Ph.D., a professor in the UF College of Medicine’s department of neuroscience and a co-author of the paper.
Although additional research remains to be done, knowing that single cells containing insulin and proinsulin can survive for years throughout the pancreata of those with Type 1 diabetes is a crucial discovery, Nick said.
“It gives us an opportunity to identify a mechanism within the cells to potentially coax them to make insulin at a level that might not be curative but would at least be more therapeutic,” he said.
Clive Wasserfall, a senior scientist in the department of pathology and the study’s lead author, said the next step is to better understand how single insulin-positive cells outside the islets survive in Type 1 diabetes patients and react to glucose.
Atkinson said the current findings are a direct result of the pancreatic biobank at UF. As the world’s largest pancreas research consortium, the Network for Pancreatic Organ donors with Diabetes (nPOD, https://www.jdrfnpod.org), has about 450 pancreata available to researchers around the world and has played a role in more than 160 scientific publications. The program has more than $4.5 million in annual funding and is supported by JDRF, the group formerly known as the Juvenile Diabetes Research Foundation. Additional funding for these efforts was provided by the National Institutes of Health and the Brehm Coalition for Diabetes Research.
Researchers at the University of Michigan, the University of Chicago and Dresden University of Technology in Dresden, Germany collaborated on the research.