Antioxidant Enhances Islet Cells' Ability to Produce Insulin In Experimental Models

April 09, 1997

NEW ORLEANS -- Pre-treating insulin-producing pancreatic islet cells with the antioxidant glutathione preserves their ability to regulate sugar levels in an experimental model, according to Duke University Medical Center researchers. This advance appears to solve one hurdle hindering the eventual transplantation of pancreatic islet cells into humans as a treatment for diabetes, the researchers said.

"While not the only hurdle to making islet cell transplants a reality, the harvesting of islets that will function properly is an important one that must be overcome," said Duke surgical research fellow Dr. Marc Garfinkel. He prepared the results of his research for presentation Tuesday (April 8) at the annual meeting of the Federation of American Societies for Experimental Biology.

Insulin, a hormone produced and secreted by specialized cells in the pancreas called islets of Langerhans, converts sugars, starches and other foods into the energy needed for everyday life. Insulin-dependent diabetics must inject insulin to stave off the long-term effects of the disease, which include blindness, kidney disease, nerve damage, limb loss and potentially death.

Islet cells are isolated by treating the pancreas with different chemical agents that dissolve everything but the islet cells. In response to being removed from the nourishing environment of the pancreas, the isolated islet cells produce as a byproduct chemicals known as oxygen-free radicals. These unstable radicals are damaging to surrounding cells.

"Glutathione is a potent chemical scavenger that appears to neutralize the destructive properties of these oxygen free-radicals and prevents cellular injuries," Garfinkel said in an interview. "In our experimental model, the untreated islets secreted insulin, but did not respond at all when glucose was added. The pre-treated islets didn't secrete as much as the untreated islets initially, but when challenged with glucose, they produced more insulin and responded as islets should."

While the exact causes of diabetes are unknown, it is thought that the body's own immune system mistakingly attacks and destroys the islet cells. Surgeons have performed more than 7,000 human pancreas transplants since 1966. Pancreas transplants have permitted many diabetics to stop injecting insulin, but there are not enough organs to go around. It is estimated that more than 1 million Americans could benefit immediately from such a transplant; however, only about 1,000 of the glands become available each year for transplantation.

"Transplantation of a whole pancreas from human to human has a one-year survival rate of about 70 percent, but like all transplants, it is fraught with complications," Garfinkel said. "It is a major operation and recipients must take immunosuppressive agents for life. By contrast, islet cells can be placed with minimally invasive techniques."

In the late 1960s, scientists developed the method for isolating islet cells. Since then, about 200 procedures have been performed; however, in many of the patients, the islets have stopped working and the patients must return to injectable insulin.

Because of the process employed to isolate the islets, it can take as many as three to four human glands to provide the approximately 1 million islet cells needed to survive transplant. Researchers have looked to other sources for islet cells.

"Pigs would be an excellent source of islets," Garfinkel said. "More than 90 million are killed each year for food. Before insulin was synthesized in the laboratory, diabetics used pig insulin to control their disease."

Garfinkel said the major obstacles to pig islet cell transplantation include inadequate yields of functional islets, rejection of the islets by the recipient's immune system, and the potential for the same autoimmune process that destroyed the original islets to destroy the new cells.

"We have been focusing on increasing the yield of the harvest," Garfinkel said. "If we can reduce the damage caused to the islets in the beginning of the process, we should be able to reduce the number of cells that need to be implanted into diabetics."

Now that it appears that glutathione has been found to protect pig islet cells, the Duke researchers are currently working on encapsulation strategies, whereby pre-treated islet cells are encased by a material that selectively allows insulin to be released from the capsule, but bars the entry of immune cells that could injure the islets.

Joining Garfinkel in the research from Duke were Emmanuel Opara, Ph.D., Dr. Surinder Yadav, Dr. Robert Harland, and Diane Hatchell, Ph.D. Garfinkel's research was supported by Duke's department of surgery.

Duke University

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