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

Type-2 diabetes results from insufficient release of insulin relative the functional requirements to maintain plasma glucose within the normal range. Insulin is produced by the pancreatic beta-cells. This project will establish how insulin secretion is regulated under physiological conditions and why it becomes impaired in diabetes. An additional aim is to understand how the insulin-producing cells interact with the neighbouring glucagon- and somatostatin-releasing cells within the pancre atic islets and how the release of these hormones cross-talks with the rest of the body (including the fat cells, the gut and the brain). Recent advances in genetics have led to the identification of ~50 genes increasing the risk of diabetes but in most cases the mechanisms involved remain unestablished. We will address this by application of a battery of advanced high-resolution techniques. In this context it is highly relevant that we have regular access to human islets (from healthy an d diabetic organ donors). The ultimate goal of this research is to understand and correct the defects that cause human type-2 diabetes.