CNS control of glucose metabolism: response to environmental challenges

Over the last 15 years, considerable work has accumulated to support the role of the CNS in regulating postprandial glucose levels. As discussed in the first section of this review, the CNS receives and integrates information from afferent neurons, circulating hormones, and postprandially generated nutrients to subsequently direct changes in glucose output by the liver and glucose uptake by peripheral tissues. The second major component of this review focuses on the effects of external pressures, including high fat diet and changes to the light:dark cycle on CNS-regulating glucose homeostasis. We also discuss the interaction between these different pressures and how they contribute to the multifaceted mechanisms that we hypothesize contribute to the dysregulation of glucose in type 2 diabetes mellitus (T2DM). We argue that while current peripheral therapies serve to delay the progression of T2DM, generating combined obesity and T2DM therapies targeted at the CNS, the primary site of dysfunction for both diseases, would lead to a more profound impact on the progression of both diseases.