Professor Anne Cooke,University of Cambridge
Professor Yuval Dor, The Hebrew University of Jerusalem
Professor Cooke and Professor Dor’s project focused on beta cells in the pancreas, which produces insulin that regulates sugar in the blood (in the form of glucose). The researchers combined their respective expertise in beta cell biology and autoimmune diabetes to investigate why beta cells die or become dysfunctional in diabetes, which could help identify ways of triggering their regeneration. They found that blood glucose could help to regenerate beta cells but that it was also potentially toxic to the cells, a phenomenon known as glucotoxicity. They then identified the pathways glucose triggered inside cells to bring about its opposing effects. When they studied glucotoxicity more closely - in beta cells from a mouse model of the disease and from diabetic patients - they found an unexpected feature: breaks within the DNA. In type I diabetes, the body destroys beta cells because of an autoimmune reaction in which the cells are mistakenly identified as 'foreign' by the immune system. DNA damage seen in beta cells could be part of the autoimmune response and could contribute to the development of diabetes. Future work will explore the role that it plays.
An outcome that unexpectedly emerged from the collaboration was the development of a method to detect beta cell death at very low levels. This simple method involves a blood test and measures fragments of DNA released from dying beta cells into the blood. The test opens up new opportunities for diagnosing type 1 diabetes early, before blood glucose levels rise abnormally, which is a hallmark of the disease.