Canadian scientists reverse diabetes in mice

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.

Researchers working on a "breakthrough" discovery thatidentifies the role ofpain 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 keepthe 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 todiabetes-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 twoeffects synergized to reverse diabetes without severely toxic immunosuppression," the release said.

Researchers atToronto's Hospital for Sick Childrenhad been tracking thelinks between diabetes and the nervous system, when theyfound 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 aresenior scientists at the Hospital for Sick Children andprofessors at the University of Toronto. Otherresearchers on the project came from the University of Calgary and the Jackson Laboratory in Bar Harbor, Maine.

Study extended to Type 2 diabetes

The researchers had been studying Type 1 diabetes, where the islets stop producing insulin. But they have extended their studies to the much more commonType 2 (obesity-associated) diabetes, where they believe there is strong evidence that treating the islet-sensory nerve circuits can normalize insulin resistance.

"This discovery opens up an entirely new field of investigations in Type 1 and possibly Type 2 diabetes, as well as tissue selective autoimmunity in general," said Dr. Pere Santamaria, study collaborator and a professor at the University of Calgary.

"We have created a better understanding of both Type 1 and Type 2 diabetes, with new therapeutic targets and approaches derived for both diseases."

The researchers are now working to extend the studies to humans.

Type 1 diabetes is an autoimmune disorder that affects more than 200,000 Canadians. Type 1 usually means the body produces no insulin, a hormone necessary to use sugars in thebody.It is treated with insulin injections.

Type2, affecting more than 1.8 million Canadians, occurs when thebody either does not make enough insulin or makes it but cannot use it properly. It can often be controlled through diet. About 60,000 new cases are diagnosed each year.