Type 1 diabetes

July 30, 2002, Acurian
Source: National Jewish Medical and Research Center
A synthetic antioxidant developed by researchers at National Jewish
Medical and Research Center improves the survival of islet cells used
in transplants for diabetes. The findings, reported in the August
2002 issue of the journal Diabetes by researchers at the University
of Pittsburgh, could help overcome a significant drawback of
the “Edmonton Protocol,” a promising treatment for diabetes.
“The antioxidant neutralizes the harmful free radicals generated when
islet cells are isolated from the pancreas,” said senior author Jon
Piganelli, Ph.D., assistant professor of Pediatrics at the Diabetes
Institute, Children’s Hospital of Pittsburgh, and the University of
Pittsburgh School of Medicine. “More of the islet cells survived in
culture. And when we transplanted islet cells into diabetic,
immunodeficient mice, it took fewer of the antioxidant-treated islet

cells to normalize their blood sugar.”
In type 1 diabetes, a person’s immune system mistakenly attacks and
destroys islet cells that secrete insulin necessary for the
metabolism of sugar. Many diabetes patients take insulin shots to
make up for the lost islet cells. In 2000, researchers from Edmonton,
Alberta, reported new techniques that have made islet-cell
transplantation a promising option for patients with type 1 diabetes.
It allows patients to produce their own insulin. Patients have to
take immunosuppressive drugs to prevent rejection of the transplants,
but they maintain better control of their insulin levels, thus
reducing the chances of future complications. They also avoid the
daily insulin injections. Clinical trials of the “Edmonton protocol”
are being conducted at several medical centers around the nation.
One drawback to the Edmonton protocol is that pancreata from at least
two donors are needed to supply enough islet cells for one successful
transplant. Many cells die during isolation and shortly after
transplantation. Since islet cells also rapidly die in culture,
surgeons are forced to transplant the cells immediately after they
have been isolated. This prevents physicians from taking several
steps that could improve the likelihood of a successful transplant.
Isolation of the islet cells from the pancreas stresses them, leading
to inflammation and islet-cell death. Highly reactive free-radical
molecules contribute to this stress. Dr. Piganelli and his colleagues
reasoned that an antioxidant compound might help islet cells survive
and improve transplant success by neutralizing the free radicals.
The researchers used two synthetic antioxidants developed several
years earlier by Dr. James Crapo, M.D., Chairman of the Department of
Medicine at National Jewish, and his colleagues. The antioxidants,
dubbed AEOL10113 and AEOL10150, mimic the naturally occurring
antioxidant superoxide dismutase, but are effective against a wider
range of oxygen radicals and last longer in the body. Now licensed by
Incara Pharmaceuticals Corporation, they have shown promise in
preventing damage to cells caused by stroke and radiation therapy for
cancer. Earlier this year, Dr. Piganelli and his colleagues showed
that the antioxidants could prevent the development of type 1
diabetes in mice when given T cells that normally causes the disease.
“We are excited that these synthetic antioxidants are protecting
cells in such a wide range of hazardous conditions,” said Dr. Crapo.
Islet-cell loss was cut in half over a six-day period, from 60% to
30%, when the antioxidants were applied during isolation of the islet
cells. The antioxidants also improved the effectiveness of the islet-
cell transplants. When large amounts of islet cells (700-1,000 islet
equivalents) were transplanted into six diabetic mice, all the
animals became healthy. But when smaller amounts of islet cells (200-
220 islet equivalents) were transplanted into nine diabetic mice,
half the mice who got untreated islet cells remained diabetic while
all the animals with antioxidant-treated islet cells returned to full
health.
“The antioxidant-treated cells are healthier when they are
transplanted into the mice and survive better after the transplant,”
said Dr. Piganelli. “We think it may be worthwhile to use the
antioxidant during preservation of the pancreas, before the isolation
begins, and after transplantation.”
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