Remember how peptic ulcer disease was put on its head, when it was shown to have an infectious etiology, with the discovery of H. pylori? Today we are dealing with diabetes research that is opening completely new frontiers. In a finding that may revolutionize diabetes treatment, scientists from The Hospital for Sick Children, the University of Calgary, and The Jackson Laboratory (Bar Harbor, Maine), showed that injecting a piece of protein, or peptide, cured diabetic mice overnight. How? Read on:
“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, study principal investigator, senior scientist at SickKids and professor of Paediatrics and Immunology at the University of Toronto. “These nerves secrete insufficient neuropeptides which sustain normal islet function, creating a vicious circle of progressive islet stress.”
Using diabetes-prone NOD mice, the gold-standard diabetes model, the research group learned how to treat the abnormality by supplying neuropeptides and even reversed established diabetes.
“The major discovery was that removal of sensory neurons expressing the receptor TRPV1 neurons in NOD mice prevented islet cell inflammation and diabetes in most animals, which led us to fundamentally new insights into the mechanisms of this disease,” said Dr. Michael Salter, co-principal investigator, senior scientist at SickKids, professor of Physiology and director of the Centre for the Study of Pain at the University of Toronto. “Disease protection occurred despite the fact that autoimmunity continues in the animals. This helped us to focus our studies on finding the new control circuit in the islets.”
Strikingly, injection of the neuropeptide substance P cleared islet inflammation in NOD mice within a day and independently normalized the elevated insulin resistance normally associated with the disease. The two effects synergized to reverse diabetes without severely toxic immunosuppression.
The studies were extended to Type 2 (obesity-associated) diabetes, in which insulin resistance is even more severe, using a number of additional model systems, thus generating strong evidence that treating the islet-sensory nerve circuit can work to dramatically normalize insulin resistance in models of Type 2 diabetes.
“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 professor of Microbiology and Infectious Diseases 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.”
“We are now working hard to extend our studies to patients, where many have sensory nerve abnormalities, but we don’t yet know if these abnormalities start early in life and if they contribute to disease development,” added Dosch.
The announcement at The Hospital for Sick Children…