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      Odor Sensitivity After Intranasal Insulin Application Is Modulated by Gender

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          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.

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          Most cited references37

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          Hypothalamic K(ATP) channels control hepatic glucose production.

          Obesity is the driving force behind the worldwide increase in the prevalence of type 2 diabetes mellitus. Hyperglycaemia is a hallmark of diabetes and is largely due to increased hepatic gluconeogenesis. The medial hypothalamus is a major integrator of nutritional and hormonal signals, which play pivotal roles not only in the regulation of energy balance but also in the modulation of liver glucose output. Bidirectional changes in hypothalamic insulin signalling therefore result in parallel changes in both energy balance and glucose metabolism. Here we show that activation of ATP-sensitive potassium (K(ATP)) channels in the mediobasal hypothalamus is sufficient to lower blood glucose levels through inhibition of hepatic gluconeogenesis. Finally, the infusion of a K(ATP) blocker within the mediobasal hypothalamus, or the surgical resection of the hepatic branch of the vagus nerve, negates the effects of central insulin and halves the effects of systemic insulin on hepatic glucose production. Consistent with these results, mice lacking the SUR1 subunit of the K(ATP) channel are resistant to the inhibitory action of insulin on gluconeogenesis. These findings suggest that activation of hypothalamic K(ATP) channels normally restrains hepatic gluconeogenesis, and that any alteration within this central nervous system/liver circuit can contribute to diabetic hyperglycaemia.
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            Transport of drugs from the nasal cavity to the central nervous system.

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              Olfaction under metabolic influences.

              Recently published work and emerging research efforts have suggested that the olfactory system is intimately linked with the endocrine systems that regulate or modify energy balance. Although much attention has been focused on the parallels between taste transduction and neuroendocrine controls of digestion due to the novel discovery of taste receptors and molecular components shared by the tongue and gut, the equivalent body of knowledge that has accumulated for the olfactory system, has largely been overlooked. During regular cycles of food intake or disorders of endocrine function, olfaction is modulated in response to changing levels of various molecules, such as ghrelin, orexins, neuropeptide Y, insulin, leptin, and cholecystokinin. In view of the worldwide health concern regarding the rising incidence of diabetes, obesity, and related metabolic disorders, we present a comprehensive review that addresses the current knowledge of hormonal modulation of olfactory perception and how disruption of hormonal signaling in the olfactory system can affect energy homeostasis.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                02 October 2018
                2018
                : 9
                : 580
                Affiliations
                [1] 1Diagnostic and Interventional Neuroradiology, University Hospital, RWTH Aachen University , Aachen, Germany
                [2] 2Sensory Analytics, Fraunhofer Institute for Process Engineering and Packaging IVV , Freising, Germany
                [3] 3Department of Neuroscience, Uppsala University , Uppsala, Sweden
                Author notes

                Edited by: Ignacio Torres-Aleman, Consejo Superior de Investigaciones Científicas (CSIC), Spain

                Reviewed by: Nils Lambrecht, University of California, Irvine, United States; Yu Chen, National Institutes of Health (NIH), United States

                *Correspondence: Rea Rodriguez-Raecke rrodriguez@ 123456ukaachen.de

                This article was submitted to Neuroendocrine Science, a section of the journal Frontiers in Endocrinology

                †These authors have contributed equally to this work

                Article
                10.3389/fendo.2018.00580
                6190874
                68fb237e-ee8f-4f21-b18b-39918c7bdb9e
                Copyright © 2018 Rodriguez-Raecke, Brünner, Kofoet, Mutic, Benedict and Freiherr.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 May 2018
                : 12 September 2018
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 43, Pages: 8, Words: 6278
                Funding
                Funded by: Deutsche Forschungsgemeinschaft 10.13039/501100001659
                Award ID: FR 3114/6-1
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                intranasal insulin,odor sensitivity,olfaction,olfactory threshold,n-butanol,peanut

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