�Scientists at the Stanford University School of Medicine are sloughing light on how type-1 diabetes begins.
Doctors have known the disease is caused by an autoimmune flack on the pancreas, merely the exact trigger of the attack has been unclear. Now, a new study in mice implicates the immune signal interferon-alpha as an early culprit in a chain of events that upend lucre metabolism and make patients dependent on lifelong insulin injections.
"We never considered that interferon-alpha could be a major actor in early type-1 diabetes," said Qing Li, MD, PhD, a postdoctoral scholar in microbiology and immunology who was the master author of a newspaper describing the new result. The study is published in today's issue of Proceedings of the National Academy of Sciences. "This was a pretty surprising finding."
Interferon-alpha usually helps the body battle viruses. Synthetic interferon-alpha is injected as a drug for treating hepatitis C and some forms of cancer, Li noted.
"Everybody's been wondering what process initiates type-1 diabetes," said Hugh McDevitt, MD, professor of microbiology and immunology and the study's senior author.
Type-1 diabetes is caused by complete deficiency of insulin, a endocrine that helps the body store and burn sugar. About 1 million Americans have the disease, too known as juvenile diabetes because it tends to be diagnosed in children and youth adults, for which at that place is no effective bar or cure. Diabetes is a leading cause of heart disease, blindness, limb amputations and kidney failure.
The early pathology of type-1 diabetes is hard to study in humans, McDevitt said, because it's well-nigh impossible to predict world Health Organization will get the disease and when it will develop. Scientists have relied on animate being models, such as diabetic mice, because they predictably develop high gear blood sugar and other features of the human disease.
To pinpoint interferon-alpha, Li and McDevitt worked backwards from what they knew about how type-1 diabetes starts. Prior studies in diabetic mice showed a pathogenic role for immune cells called CD4+ T cells. These cells ar an early player in the immune attack on the body's insulin factories, pancreatic genus Beta cells. The scientists used silicon gene chip technology to measure which genes ar revved up in the CD4+ T cells just before they assault the pancreas. The measurements hide into a pattern: many of the upregulated genes were known to be controlled by interferon-alpha.
To confirm the signal's nefarious role, the researchers gave mice an antibody that blocks interferon-alpha natural process several weeks before the animals were expected to develop diabetes. Thwarting interferon-alpha delayed the start of the disease by an average of four weeks, and, in 60 pct of toughened mice, it prevented diabetes entirely.
The finding confirmed the importance of interferon-alpha and helped the scientists connect the dots between normal mouse physiology and early diabetes. Mice are born with more pancreatic beta cells than they want, Li noted. The extras soon undergo programmed cell death, going away plenty of working beta cells to pump out insulin. However, in mice that develop diabetes, debris left behind by the dying cells triggers an inappropriate immune response, with lots of interferon-alpha. The interferon-alpha cues immune end of more than and more than beta cells, causing insulin deficiency and diabetes.
The mechanics may be more composite in mankind, the scientists cautioned, explaining that patch their new finding goes a long way toward explaining the beginnings of diabetes in the mice, additional genetic and environmental factors influence the human disease. But the basic principle of disease is likely the same in diabetic mice and humankind, they said.
"A normal process - programmed cell death - causes a normal response," McDevitt said. "But it does this in such a way that, in a small subset of the population, it starts them on the road to type-1 diabetes."
Li and McDevitt collaborated with Stanford colleagues Baohui Xu, PhD, fourth-year research scientist in pathology; Sara Michie, MD, professor of pathology; and Kathleen Rubins, PhD, a quondam postdoctoral assimilator at Stanford who is now a research cuss at the Massachusetts Institute of Technology; and with Robert Schreiber, a professor at the Washington University School of Medicine in St. Louis.
The research was funded by grants from the Juvenile Diabetes Research Foundation, the American Diabetes Association Mentor-Based Postdoctoral Fellowship and the National Institutes of Health.
Stanford University Medical Center integrates research, medical education and patient upkeep at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please bring down the Web site of the aesculapian center's Office of Communication & Public Affairs at http://mednews.stanford.edu/.
Source: Erin Digitale
Stanford University Medical Center
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