Following work on the role of insulin in the brain, evidence has been obtained that impaired insulin signaling in neurons and glial cells, both due to central insulin resistance (IR) and brain insulin deficiency, may be one of the main causes of neurodegenerative diseases and is closely associated with many metabolic and endocrine disorders, including type 2 diabetes mellitus (T2DM), metabolic syndrome (MS), and obesity. This evidence concerns the gene INS and neurodegenerative disease.