UVa Researchers Find Treatment that Reverses Type 1 Diabetes

Charlottesville, Va., April 6, 2006 – Researchers at the University of Virginia Health System have made an exciting discovery: a combination of treatments reversed the course of Type 1diabetes in mice. Using this model, the researchers found that a combined therapy of lisofylline (LSF) and exendin-4 (Ex-4) effectively reversed newly acquired Type 1 diabetes, also called autoimmune diabetes.

Dr. Jerry Nadler, chief of the UVa Division of Endocrinology and Metabolism, Dr. Raghu Mirmira, GPP investigator and their colleagues theorized that simultaneously blocking a biological pathway that damages beta cells in the pancreas, while adding a growth-promoting stimulus for beta cells, might provide the critical ability to reverse Type 1 diabetes. "This finding is very exciting because it one day may provide an opportunity to restore insulin-producing cells in people with Type 1 diabetes without the need for toxic anti-rejection medications," Nadler said. Type 1 diabetes represents 5-10 percent of all diabetes cases diagnosed, and in the United States there may be 2 million people with Type 1 diabetes.

This treatment also helped the mice to return to and maintain normal, healthy levels of blood sugar. Even after treatment was stopped, blood sugar remained normal until the experiment was completed, as many as 145 days post-treatment. This is the first time that researchers have found a way to reverse diabetes by providing a combination treatment that also could help maintain normal levels of blood sugar in a mammalian model.

The research team used two treatments to reverse the course of diabetes in this model, according to their study, published online in Biochemical and Biophysical Research Communications. One treatment used in this study, lisofylline, suppresses certain immune cells that can destroy beta cells. Lisofylline also allows beta cells to keep producing insulin, as they normally would, even in the presence of destructive substances called cytokines that cause inflammation. In response to glucose stimulation, lisofylline helps the beta cells to enhance their insulin secretion. The second treatment was Exendin-4 (Ex-4), a potent substance that increases insulin secretion and helps the beta cells to grow.

The study looked at non-obese diabetic mice divided into four groups that received either LSF alone, Ex-4 alone, the combination of LSF and Ex-4 or normal saline solution (no treatment at all). Soon after being diagnosed with diabetes through blood testing, the mice received one of the study treatments. Only the group receiving both study treatments was able to keep blood sugar levels in a normal range as measured by glucose tolerance tests. Interestingly, the group of mice receiving only LSF was able to stabilize blood sugar levels, but did not reduce those levels to a healthy, normal range. Ex-4 alone did not lead to improvements in blood sugar in these already diabetic mice, and mice receiving saline solution steadily had higher blood sugar levels.

The researchers are excited about these promising findings that a blocker of immune cell damage used with a beta-cell growth factor can control autoimmunity and even help restore beta cell function. This treatment led to a long-lasting reduction of high blood sugar levels in mice with diabetes, even after treatment ended. “This treatment may someday benefit people with diabetes, because both LSF and Ex-4 have been tested in humans for other benefits and have been found to be safe,” Nadler said.