st1\:*{behavior:url(#default#ieooui) } 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
========================================
st1\:*{behavior:url(#default#ieooui) } 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-4f07-8245-8a598ab5d1bf&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
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