Expression of Insulin System in the Olfactory Epithelium: First Approaches to its Role and Regulation

Abstract

Food odours are major determinants for food choice; their detection is influenced by nutritional status. Among different metabolic signals, insulin plays a major role in food intake regulation. The aim of the present study was to investigate a potential role of insulin in the olfactory mucosa (OM), using ex vivo tissues and in vitro primary cultures. We first established the expression of insulin receptor (IR) in rat olfactory mucosa. Transcripts of IR-A and IR-B isoforms, as well as IRS-1 and IRS-2, were detected in OM extracts. Using immunocytochemistry, IR protein was located in olfactory receptor neurones, sustentacular and basal cells and in endothelium of the lamina propria vessels. Moreover, the insulin binding capacity of OM was quite high compared to that of olfactory bulb or liver. Besides the main pancreatic insulin source, we demonstrated insulin synthesis at a low level in the OM. Interestingly 48 h of fasting, leading to a decreased plasmatic insulin, increased the number of IR in the OM. Local insulin concentration was also enhanced. These data suggest a control of OM insulin system by nutritional status. Finally, an application of insulin on OM, aiming to mimic postprandial insulin increase, reversibly decreased the amplitude of electro-olfactogramme responses to odorants by approximately 30%. These data provide the first evidence that insulin modulates the most peripheral step of odour detection at the olfactory mucosa level.

Association between diabetes mellitus and olfactory dysfunction: current perspectives and future directions

“…The olfactory bulb and olfactory mucosa are also targets for metabolic factors, suggesting the metabolic modulation may begin at the sensory level [52]. The actions of various molecules, such as ghrelin, orexins (hypocretins) [53,54], neuropeptide Y, insulin, leptin [55,56], and cholecystokinin, that are involved in the regulation of food intake and olfactory function [21], are altered in diabetes, obesity and other metabolic disorders.…”

Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease

“…212 Therefore, some have proposed that AD should be considered 'type 3 diabetes.' 213 Because of a lack of detectable insulin production in the CNS with the exception of a small group of cells in the olfactory mucosa, 214 CNS insulin is derived primarily from the circulation through BBB transport. 215 Pharmacokinetic studies of insulin uptake by the brain confirm that insulin crosses the BBB by a saturable transport system.…”

Leptin-sensitive OBP-expressing mucous cells in rat olfactory epithelium: a novel target for olfaction-nutrition crosstalk?

“…As early as 3 DIV, adherent and round cells were visible, in addition to a scaffold of several olfactory cells of various shapes and sizes; these probably reflected the heterogeneity of cell types previously described in other OM-derived cell culture systems (Lacroix et al 2008;Levasseur et al 2004). PAS staining of the 3-DIV culture confirmed that most of the round pink cells were oMC, exhibiting the same morphology on plating as that observed in vivo, except that they had a slightly larger diameter of about 30 μm (Fig.…”

“…Not only does this regulation enable accurate processing of the olfactory signal, but it can also modulate the composition of the overlying mucous layer, which probably affects the chemical interactions between odors and their olfactory receptor. In addition, the olfactory performance of an animal might be modulated according to its physiological state, such as nutritional status in the adult rat (Lacroix et al 2008) or ageing in the mouse OE (Poon et al 2005). Moreover, mutant mice defective in two subtypes of IP3 receptors predominantly expressed in the nasal glands display impaired nasal mucus secretion correlated to an elevation of the threshold for odorant sensitivity (Fukuda et al 2008).…”