The normal regulation of glucose homeostasis requires the co-ordinated regulation of hormones released mainly from the gut, pancreas and adipose tissues. These have direct actions on muscle, liver and fat tissues that have long been known. More recently it has been found many of these hormones act in the brain (mainly in the hypothalamus) and this triggers a range of neuronal responses that regulate appetite, energy expenditure and liver function. The interactions between the body's nutrient levels, these hormonal systems and the target tissues is complex and only partially understood. It is vital to understand these, as dysregulation of these mechanisms plays an important role in the development of obesity, of insulin resistance and of Type-2 diabetes. The skills required to study the role of the brain in regulating metabolism are quite distinct from those required to study glucose metabolism in the peripheral tissues and a feature of this programme is that it has brought together groups with expertise in these two areas; the neuroendocrinology experience of the Grattan lab and the peripheral glucose metabolism and signal transduction experience of the Shepherd lab. As a result of the greater collaborative links the programme has begun to integrate the complementary skills into the different projects, in particular in studies investigating the roles of PI 3-kinase and Wnt/-catenin pathways in the brain.