Odor Sensitivity After Intranasal Insulin Application Is Modulated by Gender

Abstract

Obesity constitutes a global health care problem, and often eating habits are to blame. For intervention, a thorough understanding of energy intake and expenditure is needed. In recent years, the pivotal role of insulin in connection to energy intake was established. Olfactory sensitivity may be a target of cerebral insulin action to maintain body weight. With this experiment, we aimed to explore the influence of intranasal insulin on olfactory sensitivity for the odors n-butanol and peanut in a placebo-controlled, double-blind setting in a within-subject design. All subjects participated in two experimental sessions on separate days and received either intranasal insulin or placebo in a pseudorandomized order. Application was followed by two olfactory threshold tests for n-butanol and peanut in a pseudorandomized order. After a single dose of intranasal insulin (40 IU) or placebo (0.4 ml), olfactory sensitivity for the odorants n-butanol and peanut were examined in 30 healthy normosmic participants (14 females). Measured blood parameters revealed no decrease in plasma glucose, however, insulin, leptin and cortisol levels were affected following intranasal application. Females' but not males' olfactory sensitivity for n-butanol was lower after intranasal insulin administration vs. placebo. In contrast, olfactory sensitivity for peanut was not influenced by intranasal insulin application. Our results indicate that the effects of cortical insulin levels on processing of specific odors is likely modulated by gender, as central increase of insulin concentration led to a reduced olfactory sensitivity for n-butanol in women only, which might be due to differentially regulated insulin and leptin signaling in men and women.

Intranasal insulin

“…47 (A comprehensive account of sex differences in the neuroendocrine control of food intake is provided elsewhere. 69 ) IN insulintriggered decreases in olfactory sensitivity were restricted to women in some, 70 but not all, 71 experiments that were performed in participants of both sexes. Declarative memory benefitted from 8-week IN insulin delivery in both men and women, 38 whereas acute insulin-induced improvements in declarative and working memory were restricted to women.…”

“…146 In line with findings of decreased olfactory sensitivity during hyperinsulinaemia, 148 an individual IN dose of 40 IU of insulin vs. placebo (diluent) decreased olfactory sensitivity as assessed by an olfactory threshold test using n-butanol in normosmic men and women but did not affect discrimination ability 71 ; in follow-up experiments in a larger sample of normosmic participants, this effect was restricted to women. 70 which, notably, have a higher prevalence in women. 155 Considering that impaired glucose tolerance as a result of diet-induced obesity abrogates the memory-improving and anxiolytic impact of insulin in mice, 152 impaired CNS insulin signalling might contribute to the association between metabolic disorders such as obesity and diabetes and cognitive impairments, as well dysthymia.…”

Virtual grocery shopping and cookie consumption following intranasal insulin or placebo application.

“…A former study reporting an effect size or η p 2 (Lenhard, 2016; Richardson, 2011) for intranasal insulin using 160 IU is Ketterer et al (2014). Those that reported an unadjusted effect size ∼0.35% (large) and using 40 IU insulin include Rodriguez-Raecke et al (2017), who reported η p 2 = 0.16 (large, f = 0.4364); Schilling et al (2014), who reported η p 2 = 0.063 (medium, f = 0.2593); and Rodriguez-Raecke et al (2018), who reported η p 2 = 0.136 (large, f = 0.396). These previously reported effect sizes are larger than our required effect size, indicating that our paradigm would have likely detected such an effect.…”

Intranasal Insulin for Alzheimer’s Disease

“…In subsequent experiments, IN insulin in comparison to placebo (diluent) administration before nocturnal sleep tended to improve the acquisition of word-pairs on the subsequent evening in women, with opposite effects in men [ 65 ]. In an acute experiment that only included healthy male participants [ 66 ], IN insulin compared with placebo (diluent) enhanced the odor-cued recall of spatial memory, while an impairing effect of IN insulin (vs diluent) on olfactory sensitivity was observed in young healthy women but not men [ 68 ]. Although experimental indicators of a preponderance of metabolic effects of IN insulin in men rather than women [ 62 , 69 ] buttress the assumption of a sex difference in the functional response to IN insulin, studies in larger samples of male and female participants with cognitive impairments have only yielded sporadic evidence [ 70 ].…”