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Genetic resistance to chemically-induced diabetes in mice linked to elevated antioxidant levels

Research at The Jackson Laboratory comparing mice bred for resistance or susceptibility to chemically-induced insulin-dependent (Type 1) diabetes suggests that the major difference is in the genetic control of antioxidant enzymes. These enzymes help protect against pancreatic beta-cell destruction caused by free radical-mediated stress in both mice and humans.

The results add a new dimension in understanding why some humans with "high-risk" genes for developing Type 1 diabetes remain free of this disease. Identification of the gene or genes conferring such remarkable resistance could lead to therapies to boost natural defenses against diabetes and improve survival of pancreatic islet transplants.

"These studies in model systems suggest that the extent to which an individual can detoxify free radicals as they form in pancreatic beta cells may be an important component of genetically inherited susceptibility or resistance to diabetes," said Clayton E. Mathews, a Postdoctoral Associate at The Jackson Laboratory.

The research is published in the August 1999 issue of Free Radical Biology & Medicine by Dr. Mathews and Senior Staff Scientist Dr. Edward H. Leiter. Their paper is entitled, "Constitutive Differences in Antioxidant Defense Status Distinguish Alloxan-Resistant and Alloxan-Susceptible Mice."

The scientists focused on ALR (alloxan-resistant) and ALS (alloxan-susceptible) inbred mice, developed by F. Sekiguchi and colleagues in Japan as a model animal system for diabetes induced by an environmental toxin known as alloxan. This potent chemical generates free radicals, or reactive oxygen species, which contribute to beta cell destruction in Type 1 diabetes and damage to eyes, kidney, heart, and nerves associated with both Type 1 and Type 2 (non-insulin dependent) diabetes.

Past research has shown that the beta-cell death induced by alloxan can be inhibited by the use of antioxidants. Dietar
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Contact: Luther Young
loy@jax.org
207-288-6052
Jackson Laboratory
10-Aug-1999


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