Visualising replication and neogenesis of rodent and human pancreatic islets

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Diabetes mellitus is associated with severe complications and high mortality. This is the due to insufficient release of insulin in response to increased blood glucose concentrations after loss of functional pancreatic beta-cells, the sole source of insulin in the body. Despite the progress in medical research there is still no cure in sight and most currently available treatments do not enable patients to lead a normal life.Regeneration of insulin secreting beta-cells is a promising new approach towards the development of therapeutic targets. Hereby, the body’s ability to regenerate new functional cells from progenitor cells by neogenesis or from pre-existing beta-cells by replication is being used to replace the lost cells. The aim is to either increase the mass of functional beta-cells inside the patient’s body in vivo or before transplantation to a patient in the laboratory in vitro.So far knowledge of the signals and mechanisms leading to neogenesis or replication of beta-cells is quite limited. This is partially because studies on rodent but especially on human beta-cells in a natural environment, i.e. in vivo, are missing. The aim of this project is to evaluate the contribution of replication and neogenesis to beta-cell regeneration under diverse stimulatory conditions in vivo. Furthermore, we will investigate the role of specific regulatory molecules in the signaling pathways leading to replication. This we will be achieved using a novel in vivo imaging platform which enables longitudinal studies of beta-cell biology at cellular resolution.