Diabetes breakthrough: Toronto scientists cure disease in mice

[Guest guest]

Interesting: " While pain scientists have been receptive to the research,

immunologists have voiced skepticism at the idea of the nervous system playing

such a major role in the disease. " -D

 

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Diabetes breakthrough: Toronto scientists cure disease in mice; claim

malfunctioning nerve cells the cause…

http://www.canada.com/nationalpost/news/story.html?id=a042812e-492c-4f07-8245-8a\

598ab5d1bf & k=63970 & p=2

 

Published: Friday, December 15, 2006

 

In a discovery that has stunned even those behind it, scientists at a Toronto

hospital say they have proof the body's nervous system helps trigger diabetes,

opening the door to a potential near-cure of the disease that affects millions

of Canadians.

 

Diabetic mice became healthy virtually overnight after researchers injected a

substance to counteract the effect of malfunctioning pain neurons in the

pancreas.

 

" I couldn't believe it, " said Dr. Michael Salter, a pain expert at the

Hospital for Sick Children and one of the scientists. " Mice with diabetes

suddenly didn't have diabetes any more. "

 

The researchers caution they have yet to confirm their findings in people, but

say they expect results from human studies within a year or so. Any treatment

that may emerge to help at least some patients would likely be years away from

hitting the market.

 

But the excitement of the team from Sick Kids, whose work is being published

today in the journal Cell, is almost palpable.

 

" I've never seen anything like it, " said Dr. Hans Michael Dosch, an

immunologist at the hospital and a leader of the studies. " In my career, this is

unique. "

 

Their conclusions upset conventional wisdom that Type 1 diabetes, the most

serious form of the illness that typically first appears in childhood, was

solely caused by auto-immune responses -- the body's immune system turning on

itself.

 

They also conclude that there are far more similarities than previously

thought between Type 1 and Type 2 diabetes, and that nerves likely play a role

in other chronic inflammatory conditions, such as asthma and Crohn's disease.

 

The " paradigm-changing " study opens " a novel, exciting door to address one of

the diseases with large societal impact, " said Dr. Christian Stohler, a leading

U.S. pain specialist and dean of dentistry at the University of Maryland, who

has reviewed the work.

 

" The treatment and diagnosis of neuropathic diseases is poised to take a

dramatic leap forward because of the impressive research. "

 

About two million Canadians suffer from diabetes, 10% of them with Type 1,

contributing to 41,000 deaths a year.

 

Insulin replacement therapy is the only treatment of Type 1, and cannot

prevent many of the side effects, from heart attacks to kidney failure.

 

In Type 1 diabetes, the pancreas does not produce enough insulin to shift

glucose into the cells that need it. In Type 2 diabetes, the insulin that is

produced is not used effectively -- something called insulin resistance -- also

resulting in poor absorption of glucose.

 

The problems stem partly from inflammation -- and eventual death -- of

insulin-producing islet cells in the pancreas.

 

Dr. Dosch had concluded in a 1999 paper that there were surprising

similarities between diabetes and multiple sclerosis, a central nervous system

disease. His interest was also piqued by the presence around the

insulin-producing islets of an " enormous " number of nerves, pain neurons

primarily used to signal the brain that tissue has been damaged.

 

Suspecting a link between the nerves and diabetes, he and Dr. Salter used an

old experimental trick -- injecting capsaicin, the active ingredient in hot

chili peppers, to kill the pancreatic sensory nerves in mice that had an

equivalent of Type 1 diabetes.

 

" Then we had the biggest shock of our lives, " Dr. Dosch said. Almost

immediately, the islets began producing insulin normally " It was a shock ?

really out of left field, because nothing in the literature was saying anything

about this. "

 

It turns out the nerves secrete neuropeptides that are instrumental in the

proper functioning of the islets. Further study by the team, which also involved

the University of Calgary and the Jackson Laboratory in Maine, found that the

nerves in diabetic mice were releasing too little of the neuropeptides,

resulting in a " vicious cycle " of stress on the islets.

 

So next they injected the neuropeptide " substance P " in the pancreases of

diabetic mice, a demanding task given the tiny size of the rodent organs. The

results were dramatic.

 

The islet inflammation cleared up and the diabetes was gone. Some have

remained in that state for as long as four months, with just one injection.

 

They also discovered that their treatments curbed the insulin resistance that

is the hallmark of Type 2 diabetes, and that insulin resistance is a major

factor in Type 1 diabetes, suggesting the two illnesses are quite similar.

 

While pain scientists have been receptive to the research, immunologists have

voiced skepticism at the idea of the nervous system playing such a major role in

the disease. Editors of Cell put the Toronto researchers through vigorous review

to prove the validity of their conclusions, though an editorial in the

publication gives a positive review of the work.

 

" It will no doubt cause a great deal of consternation, " said Dr. Salter about

his paper.

 

The researchers are now setting out to confirm that the connection between

sensory nerves and diabetes holds true in humans. If it does, they will see if

their treatments have the same effects on people as they did on mice.

 

Nothing is for sure, but " there is a great deal of promise, " Dr. Salter said.

 

© National Post 2006