New insight into how type-1 diabetes begins
Washington, Aug 27 : Researchers at the Stanford University School of Medicine have
offered new insight into how type-1 diabetes begins.
An autoimmune attack on the pancreas causes type-1 diabetes, but the exact trigger of
the attack has not been unclear.
Now, a new study in mice implicates that the immune signal interferon-alpha as an early
culprit in a chain of events that upend sugar metabolism and make patients dependent on
lifelong insulin jabs.
"We never considered that interferon-alpha could be a major player in early type-1
diabetes. This was a pretty surprising finding," said Qing Li, MD, PhD, a postdoctoral
scholar in microbiology and immunology who was the primary author of the new study.
Li noted that interferon-alpha normally helps the body fight viruses. Synthetic
interferon-alpha is injected as a drug for treating hepatitis C and some forms of
cancer.
Hugh McDevitt, MD, professor of microbiology and immunology and the study's senior
author, said that the early pathology of type-1 diabetes is hard to study in humans
because it's almost impossible to predict who will get the disease and when it will
develop.
Therefore, the researchers relied on animal models, such as diabetic mice, because they
predictably develop high blood sugar and other features of the human disease.
In order to pinpoint interferon-alpha, researchers worked backwards from what they knew
about how type-1 diabetes starts.
Previous studies in diabetic mice showed a pathogenic role for immune cells called CD4+
T cells. These cells are an early player in the immune attack on the body's insulin
factories, pancreatic beta cells.
The researchers used silicon gene-chip technology to measure which genes are revved up
in the CD4+ T cells just before they assault the pancreas. The measurements fell into a
pattern: many of the upregulated genes were known to be controlled by
interferon-alpha.
In order to confirm the signal's nefarious role, the researchers gave mice an antibody
that blocks interferon-alpha activity 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 percent of treated mice, it prevented diabetes entirely.
The finding confirmed the importance of interferon-alpha and helped the researchers
connect the dots between normal mouse physiology and early diabetes. Li noted that the
mice are born with more pancreatic beta cells than they need.
The extras soon undergo programmed cell death, leaving 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 destruction of more and more beta cells, causing insulin
deficiency and diabetes.
"A normal process - programmed cell death - causes a normal response. 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," McDevitt said.
The study is published in today's issue of Proceedings of the National Academy of
Sciences.
--ANI
