The secretion of insulin by the pancreatic beta-cell in response to glucose is critical for the maintenance of whole body glucose homeostasis. Dysregulation of this response can contribute to metabolic diseases such as diabetes. Although the basic control of glucose stimulated insulin release is well described, there are additional, less well understood, mechanisms which can further modulate hormone secretion. Understanding such interactions may allow the future development of novel therapeutic strategies to improve glycaemic control in patients with diabetes. We are investigating some of these processes to gain an improved understanding of the secretory process. Among the agents we study are cell surface receptor antagonists, potassium channel ligands, fatty acids and various neuroregulators. We have also examined the role of endogenous proteins such as FTO (an obesity and diabetes associated gene) in the modulation of insulin secretion.