News from the Front

Urge Your Legislators to Co-Sponsor the Renewal of the Special Diabetes Program

From the JDRF: Earlier this year, Senators Dorgan (D-ND) and Domenici (R-NM) introduced S.1494, a bill to reauthorize the Special Diabetes Program. During the same time period, Representatives DeGette (D-CO) and Kildee (D-MI) introduced the House companion bill - H.R. 2762. These bills will extend the Special Diabetes Program for five years and increase funding from $150 million per year for type 1 diabetes research to $200 million per year. Please contact your Members of Congress and ask that they cosponsor these bills. 

Sensory nerves open door to new diabetes treatment

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, Dr. Hubert Tsui from SickKids, Sue Tsai from the University of Calgary and Dr.’s John Driver and David Serreze from The Jackson Laboratory, Bar Harbor, Maine.

Lettuce could be key to diabetes fight

Scientists in Florida say genetically modified lettuce could hold the key to restoring the body's ability to produce insulin.

Researchers at the University of Central Florida injected the plant early on with the human gene for insulin. Scientists say after eight weeks on the powdered lettuce mice were producing normal levels of insulin.

"When this is absorbed, we anticipate that this methodology would cure diabetes and not simply provide temporary relief," Henry Daniell, Ph.D., researcher at UCF.

Therapeutic insulin is usually injected because strong stomach acids basically break it down. But researchers say when insulin is surrounded in a plant cell it's protected.

Once it's put inside a plant cell and ingested in the stomach, that plant cell is surrounded by a cell wall. The cell wall protects it from amino acids in the stomach and enzymes for digesting. But, when the plant cell reaches the stomach, bacteria poke holes in the plant cell wall and release the insulin.

The hope is when it is delivered in capsule form to humans it could be used to prevent diabetes before there are any symptoms.

It may also treat the disease in later stages and even eliminate it for good.

If successful, the treatment would not only make life easier for millions of diabetic people worldwide, but it could also dramatically reduce the cost of fighting the disease.

Scientists say the capsules cost just pennies to produce.

The National Institutes of Health provided $2 million to help fund the UCF study.

Human trials are expected to begin in the next couple years.

The idea was originally tested in tobacco. Researchers say they switched over to lettuce because it can be produced cheaply and does not carry the stigma associated with tobacco.