Intranasal insulin reduces olfactory sensitivity in normosmic humans.
BACKGROUND
High densities of insulin receptors are found throughout the human brain, including the olfactory bulb, an essential brain area for odor processing. This brain region is the phylogenetically oldest part of the olfactory central nervous system.


OBJECTIVE
We hypothesized that enhanced brain insulin signaling would modulate olfactory processing in humans.


METHODS
We applied a double-blind, placebo-controlled, balanced within-subject design.


METHODS
This study was conducted in the research unit of a university hospital. INTERVENTIONS/PARTICIPANTS/MAIN OUTCOME MEASURES: A single dose of either insulin (40 IU) or placebo was intranasally administered to 17 normal-weight normosmic participants (7 women). Subjects' olfactory abilities were examined by means of an olfactory threshold test (odorant n-butanol) and an olfactory discrimination test. In addition, circulating concentrations of glucose, insulin, and cortisol levels were measured.


RESULTS
After intranasal insulin administration, subjects' sensitivity for the odorant n-butanol was significantly decreased compared with that for the placebo condition (-13%; P = .025), whereas olfactory discrimination ability was not (P = .841). While serum insulin and serum cortisol were not altered after intranasal insulin administration, there was a small but significant drop in plasma glucose levels. Importantly, a correlational analysis demonstrated that this treatment-induced drop in plasma glucose was not related to the effects of intranasal insulin on olfactory sensitivity.


CONCLUSIONS
These findings suggest that intranasal insulin impairs olfactory sensitivity for a nonfood odorant, whereas no such effects were found for olfactory discrimination. Thus, variations in brain insulin signaling most likely have implications for the olfactory threshold of normosmic humans. Bearing in mind the fact that insulin acts as an anorexigenic signal in the human brain, further studies are needed to test whether intranasal insulin also impairs the ability of humans to perceive food-related odors.
Diagnostic and Interventional Neuroradiology, Uniklinik RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. ybruenner@ukaachen.de.
Yvonne F
YF
Brünner
Christian
C
Benedict
Jessica
J
Freiherr
D020001:1-Butanol; D000281:Administration, Intranasal; D000328:Adult; D001921:Brain / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D009830:Olfactory Bulb / Q000187:drug effects; D055696:Olfactory Perception / Q000187:drug effects*; D012903:Smell / Q000187:drug effects*
D007328:Insulin; D020001:1-Butanol