Islet biology

They are interested in how beta, alpha and delta cells sense changes in metabolic status and release hormones appropriately, and why this fails in diabetes and associated conditions. The research uses mouse models, and rodent and donor human islets, and is taking advantage of authentic models from human induced pluripotent stem cell-derived beta cells to study disease mechanisms and, in the longer-term, to evaluate new therapies. Areas studied within the field include the pathways involved in glucose metabolism and lipid signalling, the structure-function relationship of ATP-sensitive potassium channels needed for insulin secretion, and the effects that drugs and gut hormones have on secretion. There are also groups studying the secretory granules that contain insulin and how these are stored and released in beta cells.

Some of the type 2 diabetes-associated genetic variants identified via genome-wide association studies appear to act via the pancreatic islet. Researchers are using rodent islets, primary human islets and authentic beta-cell models together with state-of-the-art genome engineering techniques and generation of complex datasets to probe the functional consequence of variants. With advances in iPS cell differentiation, they are now able to investigate how variants impact on the development of islets as well as on the function of mature islets. 

An important resource at Oxford is OXCIT, the Oxford Consortium for Islet Transplantation, which combines a world-class human islet isolation facility and clinical transplant programme with an innovative research programme. The islet isolation facility, based at OCDEM, provides islets for both clinical transplantation and a broad range of research projects. 

The Diabetes and Metabolism theme within the Oxford NIHR Biomedical Research Centre supports clinical research in many of these areas.