The brain as an insulin-sensitive metabolic organ

BACKGROUND: The brain was once thought of as an insulin-insensitive organ. We now know that the insulin receptor is present throughout the brain and serves important functions in whole-body metabolism and brain function. Brain insulin signaling is involved not only in brain homeostatic processes but also neuropathological processes such as cognitive decline and Alzheimer's disease. SCOPE OF REVIEW: In this review, we provide an overview of insulin signaling within the brain and the metabolic impact of brain insulin resistance and discuss Alzheimer's disease, one of the neurologic diseases most closely associated with brain insulin resistance. MAJOR CONCLUSIONS: While brain insulin signaling plays only a small role in central nervous system glucose regulation, it has a significant impact on the brain's metabolic health. Normal insulin signaling is important for mitochondrial functioning and normal food intake. Brain insulin resistance contributes to obesity and may also play an important role in neurodegeneration.