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Intranasal Insulin Targeting to Brain and Cerebrospinal Fluid (CSF): A Review of its Clinical Effects and Mechanisms

Cedernaes J, Chapman CD, Brünner Y, Schiöth HB, Freiherr J, Benedict C.

RDD Europe 2013. Volume 1, 2013: 59-68.

Abstract:

Under physiological conditions, the central nervous system (CNS) utilizes glucose energy independent of insulin. This has led many researchers to believe that CNS functions are not sensitive to insulin. However, this prevailing concept was challenged in the late seventies when insulin receptors were found localized, in high density, in many CNS regions, particularly in regions involved in memory processing (e.g., the hippocampus) and energy metabolism (e.g., the hypothalamus). Further studies showed that infusions of insulin in proximity to these CNS regions reduced food intake in baboons, and improved the formation of hippocampus-dependent memory in rats. While these seminal results suggested a prominent role of insulin in memory processing and body weight control, their relevance to human cognition remained unclear. Using the intranasal administration route – a method that has been alleged to deliver certain substances (including insulin) directly to the brain with minimal systemic exposure – it has since been demonstrated that acutely enhancing brain insulin signaling leads to improved memory functioning, enhanced mood, reduced food intake, and improved postprandial glucose tolerance in healthy young adults. These findings provide further evidence that CNS functions are sensitive to insulin. In addition, they suggest that intranasal insulin could be a promising method for the treatment of disorders with an etiology that is proposed to involve disturbances in brain insulin signaling, such as Alzheimer’s disease (AD), obesity, and type 2 diabetes.