Canadian Researchers Show a Lot of Nerve

The conventional wisdom that autoimmune dysfunction is solelyresponsible for type 1diabetes may go up in smoke after the discovery by Canadianresearchers that abnormal nerve endings are critical in the causeand cure of type 1diabetes in mice. In the December 15 issue of Cell,Dr. Michael Dosch and his team reported that eliminatingmalfunctioning sensory nerve cells in the pancreas of NOD mice(Non-Obese Diabetic mice, genetically predestined to developdiabetes) prevented the disease; equally surprising, inserting aprotein produced by healthy nerve cells into already diabetic micecured them of diabetes within a single day.

The discoveries were so unexpected that they stunned the researchersthemselves and sent a shock wave throughout the search-for-a-cureworld. "I couldn't believe it," said Dr. Michael Salter, Dr.Dosch’s colleague at the Canadian Hospital for Sick Children,describing what happened when the pancreas of a diabetic mouse wasinjected with protein produced by healthy sensory nerves. "Mice withdiabetes suddenly didn't have diabetes any more." Some mice, afterjust one injection, have remained diabetes free for as long as fourmonths.

The researchers have not yet confirmed their findings in humans, butexpect to do so within a year. They believe that nerveabnormalities will soon be implicated in many other diseases,including type 2 diabetes (they’ve already found this to bethe case) and inflammatory ailments such as Crohn’s andasthma.

Dr. Dosch was led to his discovery when he noted that around theinsulin-producing pancreatic islets were an "enormous" number ofpain-signaling nerves, the type that tell the brain when tissue hasbeen damaged. Suspecting a link between those nerves and diabetes,he and Dr. Salter killed the nerves in NOD mice that weregenetically programmed to develop type 1 diabetes. "Then we had the biggestshock of our lives," Dr. Dosch said. Almost immediately, the isletsbegan producing insulin normally.

The researchers, who included participants from the University ofCalgary and the Jackson Laboratory in Maine, learned that the nervecells secrete a protein (also called a neuropeptide) that isinstrumental in the proper functioning of the islets. The nervecells of NOD mice don’t secrete enough of the neuropeptide,called “substance P,” to sustain normal islet function.This causes inflammation around the islets and leads to theireventual destruction, resulting in type 1 diabetes in the mice. When theresearchers injected "substance P" into the pancreases of alreadydiabetic mice, the islet inflammation cleared up almost immediately,and the diabetes was gone.

The scientists believe that by secreting some, but not enough,“substance P,” the nerve cells initiate and sustain thecycle of inflammation and autoimmune responses culminating in type 1 diabetes.Consequently, either adding more “substance P” orremoving the neural circuit altogether essentially eliminates thedisease in mice. If this mechanism proves valid in humans, theimplications for new cure-related research are hopeful.

Sources: Juvenile Diabetes Research Foundation; University ofCalgary

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