Outcomes and clinical implications of intranasal insulin administration to the central nervous system

Abstract

Insulin signaling in the brain plays a critical role in metabolic control and cognitive function. Targeting insulinergic pathways in the central nervous system via peripheral insulin administration is feasible, but associated with systemic effects that necessitate tight supervision or countermeasures. The intranasal route of insulin administration, which largely bypasses the circulation and thereby greatly reduces these obstacles, has now been repeatedly tested in proof-of-concept studies in humans as well as animals. It is routinely used in experimental settings to investigate the impact on eating behavior, peripheral metabolism, memory function and brain activation of acute or long-term enhancements in central nervous system insulin signaling. Epidemiological and experimental evidence linking deteriorations in metabolic control such as diabetes with neurodegenerative diseases imply pathophysiological relevance of dysfunctional brain insulin signaling or brain insulin resistance, and suggest that targeting insulin in the brain holds some promise as a therapy or adjunct therapy. This short narrative review gives an overview over recent findings on brain insulin signaling as derived from human studies deploying intranasal insulin, and evaluates the potential of therapeutic interventions that target brain insulin resistance.