A possible cure for diabetes
answer the elusive question of what causes the disease, enabling
them to develop to a new treatment that reverses its effects.
It has long been known that diabetes mellitus is characterised by a lack of insulin, the hormone secreted by the pancreas to break down carbohydrates to use as energy. However, it is only with this research that scientists at The Hospital for Sick Children (SickKids), allied with the University of Toronto, Canada, have discovered that it is damage to nociception (pain-related) nerve cells in the pancreas that prevents the body from producing insulin.
The work was in collaboration with the University of Calgary, Canada and the Jackson Laboratory, US.
The World Health Organization (WHO) estimates that the global number of diabetes sufferers will be 240m by the year 2010. Insulin deficiency is fatal so current treatments aim to replace the body's insulin directly or improve its ability to produce and use insulin. For example, inducing the pancreas to produce more of the hormone.
However, this does not prevent many side effects such as blindness, heart attacks, loss of limbs and kidney function.
In type I diabetics (T1D), the body's own immune system T-cells cause the pancreatic islet cells that are responsible for the production of insulin to become inflamed and eventually destroyed. This autoimmune reaction has traditionally been the focus of diabetes research. However, why the T-cells are not kept out of the pancreas specifically was not understood. It was this mechanism that researchers at SickKids aimed to explain.
They discovered that when someone is suffering from T1D, the nociception nerve cells (called TRPV1+) that surround the islet cells are damaged. This results in the nerves not being able to produce enough neuropeptides to keep the immune system cells out of the pancreas and therefore keep the islet cells producing insulin.
By injecting of neuropeptide substance P, the team discovered that they could reverse islet cell inflammation in mice within a day and normalise the associated insulin resistance. These two effects reversed the effects of the disease without causing toxic immunosuppression.
The studies were also successfully extended to type II diabetes, where insulin resistance is even more of a problem.
"Disease protection occurred despite the fact that autoimmunity continues," said Dr Michael Slater, a senior scientist at SickKids.
Prof Pete Santamaria, University of Calgary, co-collaborator on the study said: "This discovery opens up an entirely new field of investigations in Type I and possibly type II diabetes, as well as tissue selective autoimmunity in general.
"We have created a better understanding of both Type I and Type II diabetes, with new therapeutic targets and approaches derived for both diseases."
Dr Hans Dosch, another senior scientist at SickKids, said: "We are now working hard to extend our studies to patients, where many have sensory nerve abnormalities."
