Studies of mice performed by a Canadian-led research team have shown that the body’s nervous system appears to play an important, but previously unrecognized, role in triggering diabetes. This discovery led the researchers to develop a treatment protocol that reversed diabetes in mice and may have potential for treating humans.
The studies were conducted by researchers affiliated with the Hospital for Sick Children in Toronto, Ontario, the University of Calgary in Calgary, Alberta, and The Jackson Laboratory in Bar Harbor, Maine, and results were published in the December 15 issue of the scientific journal Cell.
Because a large number of sensory (or pain-related) nerves exist in close proximity to the pancreas’s insulin-producing beta cells, the researchers decided to see if there was a link between the nerves’ action and the development of diabetes. In one experiment, they injected a substance called capsaicin (the active ingredient in hot peppers) into newborn mice that had been bred to have a high risk of developing the equivalent of Type 1 diabetes. The substance killed specific sensory nerves in the pancreases of the mice. Knocking out these nerves apparently prevented the mice from developing diabetes; they didn’t even experience inflammation of the beta cells (one of the early signs of Type 1 diabetes).
What’s the connection between these pancreatic nerves and the organ’s ability to produce insulin? The researchers discovered that the nerves in the pancreas normally secrete substances called neuropeptides that are necessary for the proper functioning of the beta cells. However, in mice that are already in the process of developing diabetes, these nerves release too little of the neuropeptides, resulting in stress on the beta cells.
In a second experiment, the researchers injected one specific neuropeptide known as “substance P” into the pancreases of mice with inflamed beta cells, insulin resistance, and diabetes. By the following day, the inflammation had been reversed and blood glucose levels returned to normal. After the single injection, some of the mice stayed free of diabetes for as long as four months, which is the equivalent of six to eight years in humans.
These studies have been called “paradigm-changing” because they open the door for a new model of Type 1 diabetes as not simply an autoimmune disease, but a disease of the nervous system as well. And because treatment of nervous system abnormalities in the mice helped clear up diabetes in part by reducing insulin resistance—usually a sign of Type 2
diabetes—the researchers also concluded that Type 1 and Type 2 diabetes may be much more similar than was previously thought, with insulin resistance playing an important role in both.
The apparent nervous system component of diabetes may indicate similarities to certain other medical conditions. A previous paper published by the leader of these mouse studies showed similarities between diabetes and multiple sclerosis, a disease of the nervous system. And the researchers now believe that there may be a nervous system component to other “chronic inflammatory conditions” such as asthma and Crohn disease. The researchers also hypothesize that diabetic neuropathy (nerve disease) could possibly have something to do with the nervous system’s overall role in diabetes development, rather than exist simply a result of having diabetes.
The researchers are moving on to test the connection between sensory nerve function and diabetes development in humans and expect to have results within the next year or so. However, even if the results of a human study are positive, treatments based on this research would still be years away from widespread availability.