interesting article on type 1

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Researchers Provide World's First View of Type 1 Diabetes as it Develops

7-Dec-2011

A war is being waged in the pancreases of millions of people throughout the

world. The siege leads to the development of type 1 diabetes and has been a

battlefield largely hidden from view -- until now. Researchers at the La

Jolla Institute for Allergy & Immunology have created the first cellular

movies showing the destruction underlying type 1 diabetes in real-time in

mouse models. This detailed, dynamic view will provide the worldwide

scientific community insights into this disease process as never before

possible and may profoundly affect future directions in type 1 diabetes

research.

" We are presenting the first images at cellular resolution of type 1

diabetes as-it-unfolds, " said Matthias von Herrath, M.D. one of the world's

top type 1 diabetes researchers and director of the Diabetes Research Center

at the La Jolla Institute for Allergy & Immunology. " Being able to view

these insulin-producing cells while they interact in the pancreas, rather

than in a static state under the microscope, will greatly enhance our

ability - and that of the broader scientific community -- to find

interventions for type 1 diabetes. "

A paper on the team's scientific findings, along with the cellular movies

taken by the researchers, were published online today in the Journal of

Clinical Investigation. The movies are freely available and can be seen at

http://www.jci.org/articles/view/59285 (movie links at end of paper). Ken

Coppieters, Ph.D., formerly of the La Jolla Institute and now at Ghent

University, Belgium, is first author on the study. Dr. von Herrath is senior

author.

" This live imaging of the white blood cells that cause diabetes is quite

remarkable, " said Eisenbarth, M.D., Ph.D., a prominent type 1

diabetes researcher and executive director of the Barbara Center for

Childhood Diabetes in Colorado. " These images provide critical information

about the disease process, in particular showing us the reasons why the beta

cell destruction (underlying type 1 diabetes) occurs very slowly over time.

Such information may enable new approaches to stop the destruction process,

with the ultimate goal being prevention. "

The studies are illuminating cell processes that previously had to be

extrapolated from photos, computer modeling or lab experiments. Bart Roep,

M.D., Ph.D., a diabetes expert and professor at Leiden University Medical

Center in the Netherlands, called the work a technological breakthrough. " I

thought this was unfeasible (in vivo imaging of type 1 diabetes). But

thankfully, they proved me wrong, " he said. " These videos show the cellular

interactions in incredible detail, things are moving. The information they

have found thus far is amazing and this is just the beginning of the

knowledge that can be gained through this technology. "

Dr. Coppieters said the movies have provided a number of surprising

insights. " We have drawn several scientific conclusions from these studies

in mice that we believe will influence future therapeutic directions, " he

said. " We are continuing our studies and hope that other researchers will

also find these movies valuable in enhancing their research efforts. "

In the movies, objects resembling ants can be seen furiously scampering

about looking for their prey. The " ants " are actually immune system T cells,

the body's cellular soldiers. The " prey " is insulin-producing beta cells,

which the T cells mistakenly attack and destroy, eventually leading to type

1 diabetes.

The groundbreaking studies were enabled through the use of a two-photon

microscope and a new procedure developed by Dr. von Herrath that allowed the

microscope's use in the pancreas. The pancreas is a small, soft and

difficult to access organ that has long presented special challenges for

researchers. Up to this point, the scientific community has used the

two-photon to study lymph nodes, the liver and other organs in vivo, but

never the pancreas.

" The two-photon microscope enables researchers to " see " into living tissues

at a much greater depth than conventional imaging methods, " said Dr. von

Herrath. " It uses intense pulses of light that enable us to monitor

interactions of cells without destroying them. "

The Brehm Coalition, a unique type 1 diabetes research collaboration,

provided major funding for the two-photon microscope. The Juvenile Diabetes

Research Foundation (JDRF) was a significant contributor to the research

studies. " Dr. von Herrath was one of a very limited, select group of

scientists chosen to receive funding through the JDRF Scholar Award

program, " said Insel, M.D., the JDRF's chief scientific officer,

noting the award targets high-risk, high-reward endeavors. " We are thrilled

that Dr. von Herrath's research has provided new insights into the

pathogenesis of type 1 diabetes that could lead to novel therapeutic

approaches. This is just the kind of pioneering research that the Scholar

Award was designed to encourage. "

Dr. Coppieters said the as-it-happens movies reveal the specific behaviors

of various cells. " We're able to see how the beta cells eventually die and

how the immune T cells access the pancreas from the blood stream, " he said.

Among the many insights gained, the researchers were able to identify the

specific blood vessels where the T cells (normally none of these reside in

the pancreas) enter the pancreas, how the T cells launch an attack and the

time sequence of events.

The movies also illuminated particularly interesting information regarding

the beta cell destruction process. " The T cells move randomly throughout the

pancreas until they encounter the beta cells, where they slow down and

release toxic substances that eventually kill the beta cells. What was most

surprising is that this 'kiss of death' takes quite a while, elaborate

calculations indicated a timeline in the order of hours (to kill a few beta

cells), " said Dr. Coppieters.

The scientists also found remarkable the large numbers of T cells needed in

the mice - tens of millions -- to produce massive beta cell destruction.

" These factors may help to explain the long pre-clinical stage in type 1

diabetes, " said Dr. von Herrath, since T cell numbers in the human pancreas

are thought to be significantly lower than in mice.

" This means that the autoimmune attack is already ongoing for years before

the number of beta cells drops below a critical threshold, resulting in

clinical diagnosis, " he said, noting that 90 percent of beta cells are

destroyed in humans before the disease is usually recognized. " From a

therapeutic perspective, these studies suggest that we may need to find a

way to prevent the T cells from accessing the pancreas in the first place,

since once they do, they have the ability to destroy several beta cells at a

time. "

Source: La Jolla Institute for Allergy and Immunology

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