Pancreatic islet cell transplantation has become a promising treatment for type 1 diabetes in humans in recent years. But without several powerful immunosuppressive drugs, the body's immune system would destroy the engrafted islet cells in transplant patients leading to insulin deficiency, an excess of glucose in the blood and the return of diabetes.
Lisofylline, or LSF, has the potential to help prevent this cellular destruction by preserving insulin secretion by pancreatic beta cells in the presence of autoimmune attackers called inflammatory cytokines, according to U.Va. researchers.
"Our findings are very encouraging and we are excited that Lisofylline worked so well in this animal model," said Dr. Jerry Nadler, chief of the division of endocrinology and metabolism at U.Va. and director of the Diabetes and Hormone Center of Excellence. "We have discovered a potentially new way to protect islet cells in a clinical transplant setting. It's possible this research could form a basis for additional studies to use LSF or related anti-inflammatory compounds in humans to limit the need for more toxic immunosuppressant drugs in islet cell transplant patients."
In the study, diabetic mice that can only mount an autoimmune attack were given islet transplants in the kidney and then daily injections of LSF for 3 weeks. A control group was treated with only saline. Results of blood glucose tests showed that the LSF-treated mice maintained healthy glucose levels, without immunosuppressants and insulin, for more than 65 days. Mice treated with saline maintained healthy glucose levels for just six days. After researchers removed the kidneys, tests showed that insulin-positive beta cells had been retained in the islet cell grafts of the LSF-treated mice.
"We have found that Lisofylline has a unique function in protecting insulin-producing beta cells," said Dr. Zandong Yang, study co-author and assistant professor of research in the division of endocrinology and metabolism at U.Va. "At the cellular level, LSF inhibits a pathway that delivers cytokine damage to beta cells. At the molecular level, we believe LSF enhances the life-span and energy production of beta cells by increasing metabolism in the cellular mitochondria, the engine of a cell."
Yang says U.Va. researchers are hoping to test LSF in human islet cell transplant patients as part of the solution that surrounds the isolated islets. "This would be a great help and protect these cells from dying," he said.
The study was funded in part by grants from the Juvenile Diabetes Research Foundation and the Islet Replacement Research Foundation in Gordonsville, Va.