> So they found an antidote to whatever was poisoning the livers of these
> mice.
Hi William;
It addresses changes (inflammation) right at the islets in the pancreas. I
have copied the text from the site here. Inflammation seems to be rearing
its ugly head all over - both in coronary disease and now diabetes.
Marilyn
http://www.sickkids.ca/mediaroom/custom/diabetesopen06.asp
Discovery of a critical role for sensory nerves in diabetes opens door to
new treatment strategies
TORONTO - Researchers at The Hospital for Sick Children (SickKids), the
University of Calgary and The Jackson Laboratory, Bar Harbor, Maine have
found that diabetes is controlled by abnormalities in the sensory nociceptor
(pain-related) nerve endings in the pancreatic islet cells that produce
insulin. This discovery, a breakthrough that has long been the elusive goal
of diabetes research, has led to new treatment strategies for diabetes,
achieving reversal of the disease without severe, toxic immunosuppression.
This research is reported in the December 15 issue of the journal Cell.
Type 1 diabetes is an autoimmune disorder that affects more than ten per
cent of the two million Canadians diagnosed with diabetes. Studies have
focused on the immune system as the sole offender and research into the
fundamental mechanisms of the disease have been overdue. Pancreatic islet
cells, the cells responsible for the production of pancreatic hormones such
as insulin, play a key role in the disease. In diabetes, islets become
inflamed and are ultimately destroyed, making insulin production impossible.
Insulin deficiency is fatal and current insulin replacement therapies cannot
prevent many side effects such as heart attacks, blindness, strokes, loss of
limbs and kidney function.
The SickKids research group has long been pursuing links between diabetes
and the nervous system, studying both humans and animal models of the
disease. Recently, the group found an unsuspected control circuit between
insulin-producing islets and their associated sensory or pain nerves. This
circuit sustains normal islet function.
"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.
Other members of the research team included Rozita Razavi (lead author), Yin
Chan, Dr. F. Nikoo Afifiyan, Dr. Xue Jun Liu, Dr. Xiang Wan, Jason Yantha,
Dr. Lan Tang from SickKids, Sue Tsai from the University of Calgary and Dr.'s
John Driver and David Serreze from The Jackson Laboratory, Bar Harbor,
Maine.
This research was supported by the Canadian Institutes of Health Research,
the Alberta Heritage Foundation, Banting & Best Diabetes Centre, the Heart &
Stroke Foundation of Ontario, the Canadian Arthritis Network, the Canadian
MS Society and SickKids Foundation.
The Hospital for Sick Children (SickKids), affiliated with the University of
Toronto, is Canada's most research-intensive hospital and the largest centre
dedicated to improving children's health in the country. As innovators in
child health, SickKids improves the health of children by integrating care,
research and teaching. Our mission is to provide the best in complex and
specialized care by creating scientific and clinical advancements, sharing
our knowledge and expertise and championing the development of an
accessible, comprehensive and sustainable child health system. For more
information, please visit www.sickkids.ca. SickKids is committed to
healthier children for a better world.
For more information, please contact:
Chelsea Novak, Public Affairs
The Hospital for Sick Children
(416) 813-5045
[log in to unmask]
> William
>
|
