Team finds hope for diabetes cure
Dec. 15, 2006. 07:02 AM
MEGAN OGILVIE
HEALTH REPORTER


A Toronto-led team of researchers has discovered a trigger for Type 1 diabetes, a breakthrough that has long evaded scientists and could lead the way to preventing the disease.

The team found that abnormal nerve endings in the insulin-producing cells of the pancreas initiated a chain of events that caused Type 1 diabetes in mice. When they removed the nerve cells, the mice did not develop the disorder.

That means diabetes may be a disease of the nervous system, not just an autoimmune disease, said Dr. Hans Michael Dosch, a senior scientist at the Hospital for Sick Children and the study's main investigator.

Until now, research has primarily focused on the immune system and why it attacks and destroys the insulin-producing cells, called islets.

But Dosch, working with colleagues at Sick Kids, the University of Calgary and Maine's Jackson Laboratory, identified a control circuit between islet cells and their related sensory nerves. Disrupting this circuit led to inflammation around the islets and eventually to their destruction. Without these cells, the mice could not make insulin.

"This control circuit is the real cause of diabetes," Dosch said.

Experts say the findings, reported yesterday in the journal Cell, will change the way scientists think about diabetes.

"It really is a breakthrough for the diabetes community," said Pam Ohashi, a professor of immunology at the University of Toronto and a senior scientist at the Campbell Family Institute for Breast Cancer Research.

Dosch has immediate plans to move his research from mice to humans. He is launching a clinical trial in January to figure out if patients who have a high risk of Type 1 diabetes have the same sensory nerve abnormalities.

"If they do, then we have fantastic new therapeutic strategies," said Dosch, who is also a professor of pediatrics and immunology at U of T.

Michelle Wing knows the toll diabetes brings to a family. Her 8-year-old daughter Marielle has the disease, and her two young sons, ages 4 and 18 months, are at high risk of getting it.

Diabetes affects every aspect of their lives, she said, describing how the Oakville family is bound by an extensive routine of blood tests, insulin injections and strict meal times. Dosch plans to invite the family to join the clinical trial.

Wing said she came close to tears after hearing that researchers may have found a way to one day prevent Type 1 diabetes.

"Seeing what Marielle goes through every day of her life, to prevent other children from going through that," Wing said. "To prevent other parents in the middle of the night worrying their child will go into a diabetic coma...


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`It's fantastic that there could be a prevention of this for other children'

Michelle Wing, whose daughter has diabetes and two sons are at risk of getting it

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``It's fantastic that there could be a prevention of this for other children."

Toronto has a long history of diabetes research, including the discovery of insulin by Dr. Frederick Banting and Charles Best in 1921-22.

More than 200,000 Canadians have Type 1 diabetes, which most people get as children or teenagers. It should not be confused with the more common Type 2 diabetes, where the body doesn't make enough insulin or doesn't use the insulin it makes.

Insulin is a hormone produced by the islet cells that helps regulate blood sugar levels in the body.

People with Type 1 diabetes have to take daily insulin injections and regularly monitor their blood sugars. But the injections aren't a cure and they can't prevent side effects such as stroke, blindness, heart attack and kidney failure.

In the lab mice, so-called TRPV1 sensory neurons produced a specific kind of neuropeptide responsible for maintaining a healthy environment for the insulin-producing islet cells. If the balance was disrupted in any way, the immune system launched an attack on the islets, triggering Type 1 diabetes.

Eliminating these neurons or stopping their signals to the immune system prevented the chain of events that initiate Type 1 diabetes.

More research is needed to find out if this theory will work in humans, not to mention if it will shed light on new therapies for Type 2 diabetes, Dosch said.

In a reversal of what they expected, the researchers also found injecting substance P a chemical secreted by nerve cells into mice whose islet cells were inflamed and on the way to being destroyed not only eliminated the inflammation but reversed it.

"The blood glucose normalizes overnight and it stays low for weeks to months this is with a single shot," Dosch said.

"We now have 4-month-old mice that are non-diabetic that used to be diabetic" a period equivalent to six to eight years in humans.

The research is still in its early days, cautioned Dr. Ehud Ur, professor of medicine at Dalhousie University and chair of the clinical and scientific section of the Canadian Diabetes Association. Like other experts, he is less convinced about whether diabetes can be cured, noting the team's findings have no relevance to people who already have Type 1 diabetes.

Still, he added, the discovery that nerves are involved in regulating the pancreas opens up new avenues of research.

"We have a whole new target for therapy.

``It's always been the pancreas or the immune system. Now we have a new player."

With files from Canadian Press