Metabolic and hormonal regulation of pancreatic hormone secretion. (360G-Wellcome-095531_Z_11_Z)

In work to date, my laboratory has played a leading role in establishing the mechanisms linking changes in plasma glucose to stimulation or inhibition of the pancreatic islet hormones insulin, glucagon and somatostatin. This work sets a scientific and technical framework for the ultimate aim of the programme of research now proposed, which is to derive a complete mechanistic understanding of the pathways controlling pancreatic hormone secretion, including their integrated physiology, how they be come perturbed in diabetes, and responsiveness to novel pharmacological interventions. Specifically, this programme of research aims to: * unveil how pancreatic islet cells although being biochemically similar are able to respond to increased availability of nutrients with stimulation (beta- and delta-cells) or inhibition (alpha-cells) of electrical activity and secretion; * define how electrical activity culminates in fusion of the hormone-containing vesicles with the plasma membrane and identify defects in this process that increase diabetes risk; * examine the cross-talk between the pancreatic islets and the rest of the body (e.g. the gut); and * identify novel targets for (pharmacological) correction of human islet function in diabetes