Coordinated regulation of energy and glucose homeostasis by insulin and the NPY system

Insulin is a major contributor to many important physiological processes. Although its function in the periphery has been studied in detail, the contributions that it makes to functions in the brain are far less understood. The neuropeptide Y (NPY) neurones comprise a major target of insulin in the brain and are inhibited by its action. In particular, NPY neurones in the arcuate nucleus of the hypothalamus are critical control centres for insulin's central action on control energy homeostasis, as well as glucose homeostasis regulation. However, the colocalisation of insulin receptors with NPY neurones is also found in many other brain areas, although very little is known about their interactions and control functions. In this review, we explore the recent advances that have been made to further the understanding of the hypothalamic insulin receptor-NPY network, as well as provide insights from other lesser explored areas, such as the amygdala and hippocampus. We will also look at the peripheral interaction of the NPY system with insulin release, thereby closing the loop between these two energy and glucose homeostasis controlling systems and highlighting the critical interaction points that may be dysregulated in conditions of obesity and diabetes.