Nervous system appears
key role in developing
Type 1 diabetes: study
December 15, 2006: Toronto (Canadian Press) Sheryl Ubelacker
It's long been accepted wisdom that Type 1 diabetes occurs
after a severe miscue by the immune system causes insulin-producing cells in
the pancreas to be destroyed. Now Canadian-led research suggests immune
cells aren't the only culprits in developing the disease - the nervous
system also plays a pivotal role.
With Type 1 diabetes, the destruction of the islet cells in the pancreas
leaves the body without insulin to regulate the metabolism of blood glucose,
or sugar. The disease, which affects about 200,000 Canadians, can lead to
severe complications even with daily insulin injections, including
blindness, limb amputation and kidney failure.
In studies of laboratory mice specially bred to make them susceptible to
Type 1 diabetes, researchers at the Hospital for Sick Children and the
University of Calgary discovered that a control circuit exists between
insulin-producing cells and their associated sensory, or pain-related,
It turns out that this control circuit is necessary to retain the health and
normal function of islet cells, said principal investigator Dr. Michael
Dosch, an immunologist at Sick Kids Hospital.
"What we really have discovered is that the immune system is under much
closer control by the nervous system than we thought, that this control to a
large extent involves sensory nerves," said Dosch, explaining that such
nerves are the same kind that signal the brain to send out pain messages
when an ankle is broken or a finger is burned on a hot stove.
As part of their studies, the scientists knocked out specific pain-related
nerve cells in newborn lab mice. These nerve cells secrete a chemical called
"substance P," which is known to amplify pain signals as well as boosting
The mice were "perfectly fine . . . except that instead of getting diabetes
90 per cent (of the time), they got none or very little," said Dosch. "Not
only did they not get diabetes, but their pancreas was clean - there was no
inflammation, no nasties that make the disease in the pancreas."
"That was the real wow."
In other words, a dysfunctional immune response is not the only thing needed
to get diabetes - the nerve cells are also critical, he said.
In another experiment, the researchers injected substance P into mice whose
islet cells were already inflamed and on the way to being destroyed. By the
next day, the inflammation in the animals' pancreatic islets had
"That was our first shock. To make an islet clean that's fully inflamed,
that's hard," said Dosch.
"The blood glucose normalizes overnight and it stays low for weeks to months
- this is with a single shot," he enthused. "We now have four-month-old mice
that are non-diabetic that used to be diabetic" - a period equivalent to six
to eight years in humans.
While the team isn't about to start injecting humans with substance P, they
are planning a study of people with a family history of type 1 diabetes to
test for abnormalities in pain sensitivity, which could point to a higher
risk for developing the disease.
Diabetics often suffer from peripheral neuropathy, a condition in the
extremities experienced as numbness or as pain described as burning or "pins
and needles." The research suggests that neuropathy is not merely a result
of diabetes but could be related to the nervous system's role in the whole
disease process, Dosch hypothesized.
DIABETES CAUSED HUMAN DISEASES
The sensitivity study is just the first step, he said. "The ultimate goal is
to see if substance P would work. If we find that indeed humans and
(diabetes-prone) mice are comparable in this respect, then we will be very
quick into clinical trials because it's not a toxic trial, it's easy to do."
"In families with the disease where we have good tools, we can identify kids
that are at risk and are in progression to disease development. We could
step in early and prevent the whole thing from going to completion into
overt diabetes. And that would be a great thing."
Commenting on the paper, which appears in Friday's edition of the scientific
journal Cell, immunologist Terry Delovitch said the work illustrates the
importance of not viewing one system of the body in isolation.
"It's an excellent example of system biology, where different systems
interact and cross-regulate each other's activity," said Delovitch, a
specialist in the immune system and diabetes at the Robarts Research
"If you're a patient with diabetes, one of the last places to think of a
possible cure to come from would be the nervous system," he said Thursday
from London, Ont. "It provides now the hope to the population that a
component of one system can bring a very positive, potentially preventive
effect to a disease in the other system."
"And so new approaches for therapy are going to be even more abundant and
provide more hope for treatment of these diseases."
In a commentary accompanying the study, Helene Bour-Jordan and Jeffrey
Bluestone of the University of California, San Francisco, Diabetes Center,
questioned the researchers' conclusion that the nervous system can alter
inflammation and "indirectly affect" the development of autoimmunity.
"An equally plausible possibility is that an autoimmune component targeting
the nervous system directly influences the development of autoreactive
responses against pancreatic islets," they write, noting that additional
studies are needed to confirm which system is the primary catalyst.
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© The Canadian Press 2006