OCDEM, Churchill Hospital, University of Oxford, Oxford OX3 7LJ

The pancreatic islets play a central role in plasma glucose regulation. The aim of our research is to explain how changes in blood glucose levels regulate the release of the islet hormones insulin, glucagon and somatostatin. This is essential for understanding the molecular mechanisms underlying type 2 diabetes, in which both the initial and sustained phases of insulin secretion are markedly impaired. Loss of insulin secretion in type 2 diabetes is also accompanied by defects in the release of the other islet hormones, in particular, glucagon. Thus it is also important to elucidate mechanisms underlying stimulus-secretion coupling in these cells.

Our work involves a combination of techniques to study secretion at the molecular, cellular and systemic levels. This requires sophisticated methodology both to record the minute electrical currents (10^-12 A) flowing across biological membranes and to measure secretion from individual cells at millisecond (0.001 s) resolution. We also use optical techniques that allow us to monitor the movements of single secretory granules within the cell prior to and during secretion.

These studies will promote our understanding of the fundamental processes that control insulin secretion under physiological conditions and help determine the defects associated with clinical diabetes. Ultimately, our studies will provide the knowledge base needed for the development of new diabetes therapies by identifying novel drug targets.

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