Canadian scientists reverse Type 1 diabetes in mice

[kd]

Researchers working on a "breakthrough" discovery that identifies the
role of pain nerves in the cells that produce insulin have prevented
and reversed diabetes in mice.

The work "led us to fundamentally new insights into the mechanisms of
this disease," Dr. Michael Salter, co-principal investigator, said in
a release Thursday that characterized the findings as a breakthrough.

Researchers concluded that the pain receptors don't secrete enough
neuropeptides -- chemical elements found in the brain -- to keep the
pancreatic islets, which produce insulin, working normally. Without
insulin, humans die, and even the current replacement therapies cannot
prevent side effects, such as heart attack, blindness, stroke, loss of
limbs and kidney failure.

But by supplying neuropeptides to diabetes-prone mice, "the research
group learned how to treat the abnormality ... and even reversed
established diabetes," without bad side effects, the release said.

"The major discovery was that removal of sensory neurons expressing
the receptor TRPV1 neurons in NOD (non-obese diabetic) mice prevented
islet cell inflammation and diabetes in most animals," Salter said.

Reduced insulin resistance
The islet inflammation cleared up in a day in NOD mice injected with
neuropeptide substance P, and reduced the elevated insulin resistance
normally associated with diabetes. "The two effects synergized to
reverse diabetes without severely toxic immunosuppression," the
release said.


Researchers at Toronto's Hospital for Sick Children had been tracking
the links between diabetes and the nervous system, when they found an
unsuspected control circuit between the islets that produce insulin
and the associated pain nerves. The circuit keeps the islets operating
normally.

"We started to look at nervous system elements that seemed to play a
role in Type 1 diabetes and found that specific sensory neurons are
critical for islet immune attack in the pancreas," said Dr. Hans
Michael Dosch, the principal investigator. "These nerves secrete
insufficient neuropeptides which sustain normal islet function,
creating a vicious circle of progressive islet stress."


Both Salter and Dosch are senior scientists at the Hospital for Sick
Children and professors at the University of Toronto. Other
researchers on the project came from the University of Calgary and the
Jackson Laboratory in Bar Harbor, Maine.