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Development of a systems biomedicine approach for risk identification, prevention and treatment of type 2 diabetes

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Beta cell database brings fresh hope for diabetes patients

An open access resource containing Big Data on pancreatic beta cell preparations could be key to helping researchers better understand how diabetes develops, and lead to more effective therapies in the future.

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A key challenge facing diabetes researchers is the fact that beta cells – the only insulin-producing cells in the body – are extremely difficult to access. “These cells are found in groups of pancreatic cells called islets, which are scattered across the pancreas, a gland that lies deep in the abdomen,” explains project coordinator Miriam Cnop, professor of medicine at the Free University of Brussels (ULB) in Belgium. “This means we cannot just go and take a sample.” As a result, diabetes remains a significant global health challenge. Some 463 million people in the world are affected by diabetes, according to the latest figures from the International Diabetes Federation. This number is set to increase by 50 % over the next 25 years. In Europe alone, some 59 million people live with diabetes. “This is not a trivial condition,” adds Cnop. “It is associated with significant morbidity and mortality. Diabetes is the most common cause of blindness in Europe, and is the leading cause of kidney failure. It increases several-fold the risk of cardiovascular disease and can lead to nerve damage.” Treating diabetes also places great pressure on healthcare services and resources, especially when patients develop chronic conditions.

Pooling data and expertise

Cnop and her colleagues believed that by pooling together available resources, they could develop a database of islets with sufficient scope to make major breakthroughs. This was the inspiration behind the T2DSystems project. The initiative brought together European laboratories and islet isolation centres to collate and review data, and to build up an open access resource to help researchers better understand the causal factors behind diabetes. The end result of this collective endeavour is the Translational human pancreatic Islet Genotype tissue Expression Resource (TIGER), a platform that currently contains 500 human islet datasets. More are continually being added. The human islet preparations come from pancreatic human islet donors across a broad spectrum of age, sex and genetic characteristics.

Valuable research resource

The scope and depth of the TIGER database will help researchers to better understand how genetic variants actually work, and to identify biological pathways that underlie beta cell failure. “Pancreatic beta cells are at the very heart of the development of diabetes and its progression,” says Cnop. “If a person does not have a pancreatic beta cell problem, then they will not develop diabetes.” The resource, ultimately, could lead to new treatments and therapies. TIGER is openly available to the research community, and will continue to be maintained and expanded. “This has never been achieved before to this extent anywhere in the world,” says Cnop. “We can now use islets in TIGER to look at gene expression, or to look at changes in gene expression after treatments of, say, high glucose.” Another application could be to identify biomarkers for beta cell imaging. “This was actually achieved during the project,” says Cnop. “We identified proteins specific to beta cells that are expressed on the cell surface, and developed tools to image and quantify beta cell mass.” Some T2DSystems partners are currently involved in the EU Innovative Medicine Initiative (IMI)-funded RHAPSODY project, which aims to improve diabetes prevention and treatment. There is an agreement between the two consortia to share data – another example of the benefits of cooperation.

Keywords

T2DSystems, TIGER, diabetes, pancreatic, beta cells, islets, Rhapsody, Cnop, cardiovascular, blindness

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