Toronto team-led research on Type 1 Diabetes 'groundbreaking'

December 16, 2006

A Toronto team of scientists have discovered a trigger for Type 1 diabetes, a breakthrough that could lead to the overall prevention of the common disease.

The team discovered that abnormal nerve endings in the pancreas' insulin-producing cells (Islets of Langerhan) initiated a chain reaction that caused Type 1 diabetes in lab mice. However, when they removed the nerve cells, the mice did not develop the disorder.

According to Dr. Hans Michael Dosch, a senior scientist at Toronto's Hospital for Sick Children and the study's lead investigator, this indicates the diabetes may be a disease of the nervous system, not just an autoimmune disease.

Traditionally, research has primarily been concentrated on the immune system and the reasons why it attacks and destroys the insulin-producing cells of the pancreas, which are grouped in islets.

But Dosch, working alongside colleagues at Sick Kids, the University of Calgary in Alberta and Maine's Jackson Laboratory, identified a control circuit between islet cells and their associated sensory nerves.

Disruption of this circuit led to inflammation around the islets and eventually to their destruction. Without these cells, the mice were unable to produce insulin.

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

Experts agree the findings, reported yesterday in the journal Cell, will dramatically change the foundations of diabetes research.

"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 plans to move quickly in transferring his tests on lab mice to human subjects. He plans to launch a clinical trial in January to figure out if human patients who have a high risk of Type 1 diabetes have the same sensory nerve abnormalities displayed by the mice.

"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 (University of Toronto).

Michelle Wing knows the toll diabetes takes on a family. Her 8-year-old daughter Marielle has the disorder, and her two young sons, ages 4 and 18 months, are considered high risk for developing it. Diabetes runs every aspect of their lives, she said, explaining how the family is bound by an extensive and relentless routine of blood tests, insulin injections and strict meal times. Dosch plans to invite the family to participate in the clinical trial.

Wing said she was moved to tears when she learned 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," she mused. "It's fantastic that there could be a prevention of this for other children."

More than 200,000 Canadians suffer from Type 1 diabetes, which mostly develops in childhood or in the teen years. It is not to be confused with the more common Type 2 diabetes, where the body doesn't make enough insulin or use the existing insulin efficiently.

Insulin is a hormone produced by the islet cells that stabilizes blood sugar levels in the body. Sufferers of Type 1 diabetes have to take regimented daily insulin injections and continuously monitor their blood sugars. The injections are not a cure, and many patients still develop side-effects of the disease like stroke, blindness, heart attack, and kidney failure.

More research will be put in motion quickly to see if the same treatment applied to the lab mice will be effective in humans for preventing Type 1 diabetes, or better still, if it will shed new light on treatment methods for Type 2 sufferers, according to Dosch.

Also, in a surprising twist, the researchers also found that injecting substance P, a chemical secreted by nerve cells, into the mice who had damaged or inflamed islet cells, not only eliminated the inflammation process, 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," he added. Dr. Ehud Ur, professor of medicine at Dalhousie University in Halifax, Nova Scotia and chair of the clinical and scientific division of the Canadian Diabetes Association cautioned that the research is still in its early days. Like some other experts, he is skeptical about whether diabetes can be cured, noting that these findings have no relevance to people who already have Type 1 diabetes.

"We have a whole new target for therapy," he said. "It's always been the pancreas or the immune system. Now we have a new player."

Still, he knows that the discovery of nerves controlling pancreatic functions is a major step towards developing more efficient treatment for the millions affected worldwide.