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Gene That May Cause Diabetes Found By Paul Recer WASHINGTON –– A gene that causes the body to kill insulin-producing cells has been identified by researchers who say the finding is a key step toward a vaccine to prevent childhood diabetes. Using a strain of rodent that always gets diabetes, called the nonobese diabetic mouse, a team led by Dr. Ji-Won Yoon showed that the presence of the gene GAD is what causes the body's immune system to kill the insulin-producing cells. Yoon, of the University of Calgary in Alberta, Canada, is lead author of a study appearing today in the journal Science. "We found that if we suppress GAD expression in the pancreatic cells, then we can prevent diabetes," said Yoon. "It is that simple." In the mouse, when the GAD gene is active, it expresses, or causes the cell to make, a protein called glutamic acid decarboxylase. When this GAD protein is circulating in the body, the immune system detects it and attacks as if it were a foreign substance. Killer T-cells from the immune system also attack the beta cells that have the GAD gene. This attack kills the beta cells, which means the body no longer has the insulin needed to process glucose, or sugar, in the blood. The result is Type I diabetes. Dr. Robert Goldstein, medical director of the Juvenile Diabetes Foundation, said Yoon's discovery is a "very important step" toward, perhaps, some day developing a diabetes vaccine. "This approach has the promise of modulating the autoimmune response and going toward prevention," said Goldstein. He cautioned, however, that the finding is "only one brick in the house" and that scientists will need to answer many basic questions before a vaccine can be developed. Type I diabetes frequently is diagnosed in childhood, forcing patients to spend their lives taking up to four insulin shots a day and to carefully monitor their blood sugar levels. About 29,000 new cases of Type I diabetes are diagnosed annually in the United States, mostly among children and young adults. The Juvenile Diabetes Foundation estimates that about 1 million Americans are being treated for Type I diabetes. Another form of the disease, called Type II diabetes, most commonly occurs in people over 40. In this disease, the body may still make insulin, but cells have lost their sensitivity to the hormone. Type II diabetes commonly is treated successfully with pills, diet and lifestyle changes. When not controlled, either type of diabetes can cause kidney failure, blindness, limb amputation, heart disease and death. It is estimated that diabetes claims the lives of about 190,000 Americans annually. Yoon said his study suggests it may be possible to prevent Type I diabetes with a vaccine that would desensitize the immune system to the presence of the GAD gene. He said such a vaccine would, in effect, educate the immune system not to attack pancreatic cells that have the GAD gene. "If you inject GAD then the T-cell will learn to tolerate GAD and will not attack the beta cells (which make insulin)," said Yoon. "The concept is that you inject GAD into young children; then they would not get diabetes. That is prevention." Yoon said it will take 10 to 15 years to develop such a vaccine because researchers would have to prove that manipulating the GAD gene would not cause dangerous side effects. He said the gene has no known function in the pancreas, but it is present in the brain. © Copyright 1999 The Associated Press |