Islet Transplant Program Offers Hope to Diabetes Patients

Center Update, Issue 2, Spring 2001 Washington Regional Primate Research Center

Among the Washington RPRC's many programs that bear directly on human health is Dr. Lakshmi Gaur's study of diabetes mellitus in macaques and her related Islet Transplant Program. Diabetes mellitus is a common disorder characterized by a lack of insulin, which the body needs in order to control glucose in the blood. Patients without glucose control are at risk for diseases of the retina and peripheral nerves, chronic kidney failure, and atherosclerosis. There are two types of diabetes: one that is insulin-dependent (type I) and one that is not (type II). Dr. Gaur's work is focused primarily on type I, called insulin-dependent diabetes mellitus (IDDM). This autoimmune disease causes progressive destruction of insulin-producing cells in the pancreas. IDDM can be treated with insulin injections, but to date there is no permanent cure. Recent developments in diabetes research suggest that this situation could change dramatically.

Pancreatic transplantation has been established as a treatment option for both type I and type II diabetes mellitus. This technology could offer a permanent cure, but numerous factors, most especially graft rejection, have impeded the success of such transplantation. Transplantation of pancreatic islets, rather than the whole pancreas, is perhaps the best long-term solution for IDDM. However, this technique also conventionally involves the use of an immuno- suppressive regimen with toxic side effects.

To find a solution to this problem, Dr. Gaur has developed a diabetic model in pigtailed macaques to explore the effectiveness of transplanting pancreatic islets without immunosuppressive agents. In the Islet Transplant Program, jointly funded by the Juvenile Diabetes Foundation and NIH, Dr. Gaur is testing two approaches. In one set of experiments she uses nonsteroidal immunosuppressive agents that are less toxic than have been used in human studies. In other experiments she uses no immunosuppressive agents and tries, instead, to induce donor-specific tolerance by infusing stem cells or stem-cell fractions along with the islet allograft.

Within the last two years, numerous islet transplants have yielded exciting results. Allografts in five of seven macaques that received stem cell infusions along with the islets survived longer than allografts in macaques that received islets without stem cells. One of these macaques has maintained normal glucose levels, without the use of insulin injections, for more than a year after the islet transplant. In a baboon that also became normoglycemic and insulin free following islet transplantation, insulin-secreting donor islets were identified at the transplant site.

These results in nonhuman primates offer genuine hope of a permanent cure for thousands of patients with IDDM. As type I diabetes usually occurs in children and adolescents, who are not naturally inclined to watch their diets and monitor their blood glucose levels as regularly as they should, it will be "a consummation devoutly to be wished" if these nonhuman primate studies lead to a permanent cure of this insidious disease.