Tom Blackwell
Sun
TORONTO — 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 affecting 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.
The researchers caution they’ve yet to confirm their findings in humans, but say they expect results from those studies within a year or so.
Any treatment that may emerge from the work is likely still years away.
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 per cent of them with Type 1, contributing to 41,000 deaths a year. Insulin replacement therapy is the only treatment for Type 1, and can’t prevent many of the side effects, from heart attacks to kidney failure.
In Type 1 diabetes, the pancreas doesn’t produce enough insulin to shift glucose into the cells that need it. In Type 2 diabetes, the insulin produced isn’t 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. Hans Michael Dosch, an immunologist at the hospital and a leader of the studies, had concluded in a 1999 paper 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. Michael Salter, a pain expert at the Hospital for Sick Children, 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,” said Dr. Dosch. 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 the nerves in diabetic mice were releasing too little of the neuropeptides, resulting in a “vicious cycle” of stress on the islets.
The work is being published today in the journal Cell.
THE DISCOVERY
‘REALLY OUT OF LEFT FIELD’
Suspecting a link between the nerves and diabetes, researchers injected capsaicin, the active ingredient in hot chili peppers, to kill the pancreatic sensory nerves in mice that had an equivalent of Type 1 diabetes.
Almost immediately, the pancreatic cells began producing insulin normally. “It was a shock . . . really out of left field,” said immunologist Dr. Hans Michael Dosch, “because nothing in the literature was saying anything about this.”
© The Vancouver Sun 2006