Visualisation of insulin granule pools in β-Cells: The loss of Phase 1 insulin secretion in diabetic islets

Diabetes is a world-wide problem caused by either altered insulin secretion and/or response to insulin in the organism. A relatively new treatment for Type-1 Diabetes is pancreatic islet transplantation. Pancreatic islet transplantation stabilises glycemic control in Type-1 diabetes; notably, Scotland has world leading expertise in this therapy and a highly successful transplantation programme. Insulin secretion from pancreatic islets is known to occur in ‘phases’ after a meal (ie after elevated blood glucose levels); a first, or immediate burst of secretion, followed by a second, sustained phase of insulin release. Curiously, however, after islet transplantation, implanted islets do not recover the first phase of insulin release in recipient patients, but the second phase is restored. Therefore, much fundamental and translational biology remains to be determined. My PhD aims to study the release of insulin at the level of intracellular granule pools in so-called β-Cells in situ within pancreatic islets, before and after transplant, using mouse models and human donor islets, combined with high-resolution 4-D microscopy and molecular biology. In my talk, I will discuss the background to the project, along with some early data I have acquired.