(Press-News.org) A molecule that prevents Type 1 diabetes in mice has provoked an immune response in human cells, according to researchers at National Jewish Health and the University of Colorado. The findings, published online in the Proceedings of the National Academy of Sciences, suggest that a mutated insulin fragment could be used to prevent Type 1 diabetes in humans.
"The incidence of Type 1 diabetes is increasing dramatically," said John Kappler, PhD, professor of Biomedical Research at National Jewish Health. "Our findings provide an important proof of concept in humans for a promising vaccination strategy."
Type 1 diabetes is an autoimmune disease in which the immune system destroys the body's ability to produce insulin, a hormone essential for sugar metabolism. Researchers have tried administering insulin to people at risk for the disease as a form of immunotherapy similar to allergy shots. None of the trials has provoked an effective response.
The most recent findings suggest that an insulin fragment with a change to a single amino acid could provoke that elusive immune response. The idea for the substitution comes from more than a decade of work in Dr. Kappler's lab detailing the molecular minutiae of the immune system's response to insulin. This work suggests that insulin is presented to the immune system in an unconventional manner, and that mutating one amino acid in an insulin fragment might provoke better recognition by the immune system.
In 2011, a team from Harvard University and the Dana Farber Cancer Institute reported that the strategy suggested by Dr. Kappler and his colleagues did indeed prevent type 1 diabetes in mice. Mice and humans, however, differ in many ways, and strategies that work in mice often fail to produce any response in humans.
In their current paper, Dr. Kappler, Aaron Michels, MD, at the Barbara Davis Center for Childhood Diabetes, and their colleagues mixed the naturally occurring insulin fragment and the mutated insulin fragment with separate cultures of human cells. They found that human T cells responded minimally to the naturally occurring insulin fragment but quite strongly o the mutated one. The human T cells produced both pro-inflammatory and anti-inflammatory chemicals known as cytokines.
Researchers believe healthy immune responses balance pro- and anti-inflammatory factors. Autoimmune disease occurs when the pro-inflammatory response dominates.
While the current results do not prove that the mutated insulin fragment will work as a vaccine in humans, they do demonstrate a response in humans consistent with the vaccination response in mice. Some of the signals seen in human cells are associated T regulatory cells, which can dampen the immune response and hold it in check.
"The new findings confirm that the painstaking work we have done to understand the unconventional interaction of insulin and the immune system has relevance in humans and could lead to a vaccine and a treatment for diabetes," said Dr. Kappler. "We are eager to push this promising line of inquiry forward."
INFORMATION:
National Jewish Health is the leading respiratory hospital in the nation. Founded in 1899 as a nonprofit hospital, National Jewish Health today is the only facility in the world dedicated exclusively to groundbreaking medical research and treatment of patients with respiratory, cardiac, immune and related disorders. Patients and families come to National Jewish Health from around the world to receive cutting-edge, comprehensive, coordinated care. To learn more, visit http://www.njhealth.org.
Non-native plants are commonly listed as invasive species, presuming that they cause harm to the environment at both global and regional scales. New research by scientists at the University of York has shown that non-native plants - commonly described as having negative ecological or human impacts - are not a threat to floral diversity in Britain.
Using repeat census field survey data for British plants from 1990 and 2007, Professor Chris Thomas and Dr Georgina Palmer from the Department of Biology at York analysed changes in the cover and diversity of native and non-native ...
A 60-year-old maths problem first put forward by Nobel laureate Enrico Fermi has been solved by researchers at the University of East Anglia, the Università degli Studi di Torino (Italy) and the Rensselaer Polytechnic Institute (US).
In 1955, a team of physicists, computer scientists and mathematicians led by Fermi used a computer for the first time to try and solve a numerical experiment.
The outcome of the experiment wasn't what they were expecting, and the complexity of the problem underpinned the then new field of non-linear physics and paved the way for six ...
Researchers at Carnegie Mellon University who develop snake-like robots have picked up a few tricks from real sidewinder rattlesnakes on how to make rapid and even sharp turns with their undulating, modular device.
Working with colleagues at the Georgia Institute of Technology and Zoo Atlanta, they have analyzed the motions of sidewinders and tested their observations on CMU's snake robots. They showed how the complex motion of a sidewinder can be described in terms of two wave motions - vertical and horizontal body waves - and how changing the phase and amplitude of ...
Troy, N.Y. - A team of researchers, including Rensselaer professor Morgan Schaller, has used mathematical modeling to show that continental erosion over the last 40 million years has contributed to the success of diatoms, a group of tiny marine algae that plays a key role in the global carbon cycle. The research was published today in the Proceedings of the National Academy of Sciences.
Diatoms consume 70 million tons of carbon from the world's oceans daily, producing organic matter, a portion of which sinks and is buried in deep ocean sediments. Diatoms account for over ...
Archaeologists working in Guatemala have unearthed new information about the Maya civilization's transition from a mobile, hunter-gatherer lifestyle to a sedentary way of life.
Led by University of Arizona archaeologists Takeshi Inomata and Daniela Triadan, the team's excavations of the ancient Maya lowlands site of Ceibal suggest that as the society transitioned from a heavy reliance on foraging to farming, mobile communities and settled groups co-existed and may have come together to collaborate on construction projects and participate in public ceremonies.
The findings, ...
WINSTON-SALEM, N.C. - March 23, 2015 - The results of a blood test done immediately after heart surgery can be a meaningful indicator of postoperative stroke risk, a study by researchers at Wake Forest Baptist Medical Center has found.
An acutely elevated level of blood urea nitrogen (BUN) - a measure of kidney function detected through blood testing - was the most powerful predictor of postoperative stroke among the study's subjects.
Up to 9 percent of cardiac surgery patients suffer post-operative stroke, and these events are significantly more serious and more frequently ...
The concept was simple: If two compounds each individually show promise in preventing colon cancer, surely it's worth trying the two together to see if even greater impact is possible.
In this instance, Case Western Reserve cancer researcher Li Li, MD, PhD, could not have been more prescient.
Not only did the combination of the two improve outcomes in animal studies, but the dual-compound effect was dramatically better than either option alone. Even better, these impressive results required only modest amounts of metformin and Vitamin D3, making concerns about side ...
DURHAM, N.C. - Scientists have known for some time that people who carry a lot of weight around their bellies are more likely to develop diabetes and heart disease than those who have bigger hips and thighs. But what hasn't been clear is why fat accumulates in different places to produce these classic "apple" and "pear" shapes.
Now, researchers have discovered that a gene called Plexin D1 appears to control both where fat is stored and how fat cells are shaped, known factors in health and the risk of future disease.
Acting on a pattern that emerged in an earlier study ...
(MEMPHIS, Tenn. -- MARCH 23, 2015) Research led by scientists at St. Jude Children's Research Hospital has identified key molecules that trigger the immune system to launch an attack on the bacterium that causes tularemia. The research was published online March 16 in Nature Immunology.
The team, led by Thirumala-Devi Kanneganti, Ph.D., a member of the St. Jude Department of Immunology, found key receptors responsible for sensing DNA in cells infected by the tularemia-causing bacterium, Francisella. Tularemia is a highly infectious disease that kills more than 30 percent ...
MAYWOOD, Ill. - No cures are possible for most patients who suffer debilitating movement disorders called cerebellar ataxias.
But in a few of these disorders, patients can be effectively treated with regimens such as prescription drugs, high doses of vitamin E and gluten-free diets, according to a study in the journal Movement Disorders.
"Clinicians must become familiar with these disorders, because maximal therapeutic benefit is only possible when done early. These uncommon conditions represent a unique opportunity to treat incurable and progressive diseases," first ...
