In a discovery reported to have stunned even those behind it, scientists at the Hospital for Sick Children in Toronto, Canada, 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.

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 have yet to confirm their findings in people, but say they expect results from human studies within a year or so.

The researchers’ work was published on December 15 in the journal Cell.

The researchers’ findings have overturned 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 concluded 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.

Insulin replacement therapy is currently the primay treatment of Type 1 diabetes. It is associated with many side effects, from heart attacks to kidney failure. The problems in diabetes stem partly from inflammation — and eventual death — of insulin-producing islet cells in the pancreas.

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 utilization of glucose.

Dr. Hans Michael Dosch, an immunologist at the hospital and a leader of the studies, 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.

The paradigm-shifting discovery is a fascinating story. Suspecting a link between the nerves and diabetes, he and Dr. Michael Salter, a pain expert at the Hospital for Sick Children and one of the 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. The researchers were shocked to discover that almost immediately the islets began producing insulin normally.

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 and 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.

Now we wait. Hopefully Salter and Dosch will succeed in heralding in a new era in the understanding and treatment of many pathologies, including diabetes. It will not be easy because paradigm shifts by definition unsettle the status quo and those with vested interests as diverse as academic prestige to financial gain from treatment systems will all be out to see it fail. We wish the researchers the very best success and reception of their future work.

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