Insulin and the CNS: effects on food intake, memory, and endocrine parameters and the role of intranasal insulin administration in humans

Insulin is mainly known for its peripheral effects on the metabolism of glucose, fats, and proteins. However, insulin also exerts important actions within the brain, and functions as a neuropeptide. The brain can thus be regarded as both an insulin-sensitive and a glucose-sensitive organ. Its neuroanatomical basis is the localization of insulin receptors, predominantly in the olfactory bulbs, hypothalamus, and hippocampus. Data obtained in animal experiments reveal an interesting insulin profile in the brain. Central insulin affects glucoregulation. As long as peripheral euglycemia is maintained, it was shown to reduce food intake and body weight and to improve learning and memory. Cognitive dysfunctions in dementia of the Alzheimer type (DAT) are associated with insulin deficiency within the brain, and memory improves in DAT patients when insulin levels increase. After describing these actions of insulin in the brain, we address here the transport of insulin into the brain. Insulin can either be transported from the periphery to the brain, or be administered directly into the brain. To reach insulin receptors directly, animals are typically administered insulin via the cerebral ventricles. For humans, the intranasal route is a practicable way to reach the brain while maintaining euglycemia. Additionally, the localization of insulin receptors in the olfactory bulb makes insulin interesting for the nose-to-brain pathway. Promising initial results have been reported with intranasally administered insulin corresponding to the diverse actions of insulin in the brain. Interestingly, initial data indicate that states of central insulin deficiencies (DAT and obesity) are accompanied by olfactory deviations. Thus, the nose-to-brain pathway deserves further attention. (C) 2004 Elsevier Inc. All rights reserved.