Olfactory Dysfunction in Obesity and Type 2 Diabetes

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Abstract

The article analyzes literature data on the close relationship between energy balance and sense of smell. Olfaction is one of the main modalities of hedonic evaluation of food. Odor is one of the most important sensory signals predicting food quality and plays a key role in food selection and consumption. Appetite can be stimulated by various stimuli, but the leading role belongs to olfactory signals (tasty smells) and levels of hormones that signal hunger and satiety. Olfactory perception is subject to hormonal modulation. In this regard, special attention in the article is paid to the modulating function of insulin. Insulin, one of the main metabolic hormones that controls food intake, has an anorexigenic effect not only at the level of the hypothalamus, but also at the level of the olfactory pathway, especially strong in the olfactory bulb. It has a rate of insulin transport two to eight times higher than in other parts of the brain, and it contains the highest concentration of insulin and the highest density of insulin receptor kinase. Thus, insulin is not only able to penetrate to the site of olfactory information processing, but do so quickly. At the same time, insulin and its receptors are localized in the olfactory epithelium, namely in mature olfactory sensory neurons. Therefore, insulin affects the primary stage of perception of an odorous molecule – odor detection, which occurs at the level of the olfactory epithelium. The sense of smell is impaired up to its complete loss in obesity and type 2 diabetes, worsening the quality of life of such patients. The paper examines the effectiveness of intranasal insulin administration to restore olfactory function in metabolic disorders and other diseases.

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About the authors

E. V. Bigday

St. Petersburg State Pediatric Medical University of the Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: bigday50@mail.ru
Russian Federation, St. Petersburg

A. A. Zuykova

St. Petersburg State Pediatric Medical University of the Ministry of Healthcare of the Russian Federation

Email: bigday50@mail.ru
Russian Federation, St. Petersburg

A. V. Pozdnyakov

St. Petersburg State Pediatric Medical University of the Ministry of Healthcare of the Russian Federation

Email: bigday50@mail.ru
Russian Federation, St. Petersburg

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2. Fig. 1. Central pathways of the olfactory sensory system. Olfactory epithelium – olfactory epithelium; olfactory nerves – olfactory nerves; olfactory bulb – olfactory bulb; direct projections from the olfactory bulb: olfactory tract – olfactory tract; anterior olfactory nucleus – anterior olfactory nucleus; piriform lobe – pear–shaped lobe; primary olfactory cortex – primary olfactory cortex ( prepiriform cortex - pregrushoid cortex; periamygdaloid cortex – periamygdalar cortex) and secondary olfactory cortex – secondary olfactory cortex (entorhinal cortex – entorhinal cortex); amygdala – amygdala; orbitofrontal and dorsolateral cortices – orbitofrontal and dorsolateral cortex; insular cortex – insular cortex; thalamus – thalamus; hippocampus – hippocampus; hypothalamus is the hypothalamus.

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3. Fig. 2. Schematic representation of the distribution of receptors for the main metabolic factors in the olfactory mucosa. OSN is an olfactory sensory neuron, IR is an insulin receptor kinase, Ob-R is a leptin receptor, OXR is an orexin receptor, GLUT is a glucose transporter, CB1 is a type 1 cannabinoid receptor, SUS are support cells, NPY Y1 is a Y1 receptor for neuropeptide Y, AdipoR 1 is an adiponectin receptor of the 1st type kind of.

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4. Fig. 3. The proposed mechanism of olfactory sensitivity attenuation under the influence of insulin. The action of insulin on the insulin receptor activates phospholipase C to form diacylglycerol (DAG) and inositol-(1,4,5)-triphosphate (IP3) from PIP2. IP3 opens an IP3-dependent channel in the OSN plasmolemma for the entry of calcium ions, increasing its concentration in the cytosol. An increase in the concentration of Ca2+ under the action of insulin leads to the activation of calmodulin, which stimulates CaMKII, which inhibits ACIII. A decrease in cAMP reduces the activity of CNG channels, leading to olfactory dysfunction. IR – insulin receptor; PIP2 – phosphatidylinositol -(4,5)-diphosphate; IP3 – inositol- (1,4,5)-triphosphate; IP3 channel – IP3-dependent channel; CNG channel – ion channel dependent on cyclic nucleotides; CaM – calmodulin; CaMKII – Ca2+/calmodulin-dependent protein kinase II; ACIII – adenylate cyclase type III; cAMP – cyclic 3`,5`-adenosine monophosphate. Solid arrows indicate activation processes. Dotted lines

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5. Fig. 4. Scheme of the mechanism of excitotoxicity of NMDAR in the main. The increased level of glutamate, which occurs in pathology, causes excessive activation of ionotropic NMDAR, manifested in the launch of a significant influx of extracellular Ca2+ into the OSN. As a result, calcium overload occurs in the cytosol and mitochondria. Excessive Ca2+ content leads to mitochondrial dysfunction, accompanied by depolarization of the mitochondrial membrane potential (ΔΨM), decreased ATP production, accumulation of reactive oxygen species (ROS) and release of the cytochrome C apoptosis inducer. NMDAR is an ionotropic glutamate receptor binding N-methyl-D-aspartate; mPTP is a pore that changes the permeability of the mitochondrial membrane, ΔΨM is the mitochondrial membrane potential; ROS are reactive oxygen species.

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