Intranasal insulin's effects on the sense of smell

Intranasal insulin (IN) administration is a promising way to deliver the peptide to the central nervous system (CNS), bypassing the blood-brain-barrier and gastrointestinal absorption inhibition. IN receptors are localized in the olfactory mucosa and the brain, mainly in the olfactory bulb, hypothalamus, hippocampus, amygdala, cerebral cortex, and cerebellum. The pleiotropic mechanism of insulin action is characterized by its anti-inflammatory properties, antithrombotic, vasodilatory, and antiapoptotic effects. It prevents energy failure and has regenerative properties, affects neuro-regeneration and counteracts insulin resistance. Hence, insulin has been suggested for various pathological states including neurocognitive disorders, obesity, and as a therapeutic option for smell loss. A sharply increased prevalence of olfactory dysfunction was observed due to the COVID-19 pandemic. The pandemic also emphasized the lack of therapeutic options for smell loss. Intranasal insulin administration has therefore been suggested to serve as potential treatment, influencing the regenerative capacities of the olfactory mucosa. This narrative review summarizes current knowledge on possible effects of intranasal insulin on the sense of smell.