> Tom Blackwell, National Post
> 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 e{*filter*}ment 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.
>  Tools
> Page 2
>  Tom Blackwell, National Post
> Published: Friday, December 15, 2006
> "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.
> C National Post 2006