Odor Sensitivity After Intranasal Insulin Application Is Modulated by Gender

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.

[1]  Marco Piñón I Overview , 2020, The Diaries and Letters of Lord Woolton 1940-1945.

[2]  I. Croy,et al.  The impact of severity, course and duration of depression on olfactory function. , 2018, Journal of affective disorders.

[3]  J. Freiherr,et al.  Olfactory functioning in adults with Tourette syndrome , 2018, PloS one.

[4]  A. Rezaeian Effect of Intranasal Insulin on Olfactory Recovery in Patients with Hyposmia: A Randomized Clinical Trial , 2018, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[5]  J. Freiherr,et al.  Intranasal insulin influences the olfactory performance of patients with smell loss, dependent on the body mass index: A pilot study. , 2015, Rhinology.

[6]  A. Amali,et al.  Evaluation of the olfactory bulb volume and olfactory threshold in patients with nasal polyps and impact of functional endoscopic sinus surgery: a longitudinal study , 2015, International forum of allergy & rhinology.

[7]  W. Banks,et al.  Intranasal Administration as a Route for Drug Delivery to the Brain: Evidence for a Unique Pathway for Albumin , 2014, The Journal of Pharmacology and Experimental Therapeutics.

[8]  Nicolas Fourcaud-Trocmé,et al.  Insulin modulates network activity in olfactory bulb slices: impact on odour processing , 2014, The Journal of physiology.

[9]  René Westerhausen,et al.  Intranasal insulin increases regional cerebral blood flow in the insular cortex in men independently of cortisol manipulation , 2014, Human brain mapping.

[10]  P. Novak,et al.  Enhancement of Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes , 2014, Diabetes Care.

[11]  J. Freiherr,et al.  Intranasal insulin reduces olfactory sensitivity in normosmic humans. , 2013, The Journal of clinical endocrinology and metabolism.

[12]  M. Wong,et al.  Leptin therapy, insulin sensitivity, and glucose homeostasis , 2012, Indian journal of endocrinology and metabolism.

[13]  M. Lacroix,et al.  Olfaction under metabolic influences. , 2012, Chemical senses.

[14]  S. Baron-Cohen,et al.  Olfactory Detection Thresholds and Adaptation in Adults with Autism Spectrum Condition , 2012, Journal of autism and developmental disorders.

[15]  Manfred Hallschmid,et al.  Intranasal Insulin Suppresses Food Intake via Enhancement of Brain Energy Levels in Humans , 2012, Diabetes.

[16]  Jessica Freiherr,et al.  The 40-item Monell Extended Sniffin’ Sticks Identification Test (MONEX-40) , 2012, Journal of Neuroscience Methods.

[17]  R. Veit,et al.  Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions , 2012, Diabetologia.

[18]  Manfred Hallschmid,et al.  Postprandial Administration of Intranasal Insulin Intensifies Satiety and Reduces Intake of Palatable Snacks in Women , 2012, Diabetes.

[19]  M. Heni,et al.  Acute, short-term hyperinsulinemia increases olfactory threshold in healthy subjects , 2011, International Journal of Obesity.

[20]  A. Astrup,et al.  Video game playing increases food intake in adolescents: a randomized crossover study. , 2011, The American journal of clinical nutrition.

[21]  Johan N Lundström,et al.  Central Processing of the Chemical Senses: an Overview. , 2011, ACS chemical neuroscience.

[22]  J. Brüning,et al.  CNS leptin and insulin action in the control of energy homeostasis , 2010, Annals of the New York Academy of Sciences.

[23]  J. Born,et al.  Intranasal Insulin Enhances Postprandial Thermogenesis and Lowers Postprandial Serum Insulin Levels in Healthy Men , 2010, Diabetes.

[24]  Hubert Preissl,et al.  Insulin modulates food-related activity in the central nervous system. , 2010, The Journal of clinical endocrinology and metabolism.

[25]  M. Wong,et al.  Changes in insulin sensitivity during leptin replacement therapy in leptin-deficient patients. , 2008, American journal of physiology. Endocrinology and metabolism.

[26]  J. Born,et al.  Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin. , 2008, The Journal of clinical endocrinology and metabolism.

[27]  J. Born,et al.  Targeting metabolic and cognitive pathways of the CNS by intranasal insulin administration , 2007, Expert opinion on drug delivery.

[28]  N. Birbaumer,et al.  The cerebrocortical response to hyperinsulinemia is reduced in overweight humans: A magnetoencephalographic study , 2006, Proceedings of the National Academy of Sciences.

[29]  Gary J. Schwartz,et al.  Hypothalamic KATP channels control hepatic glucose production , 2005, Nature.

[30]  J. Cummings,et al.  The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment , 2005, Journal of the American Geriatrics Society.

[31]  Jan Born,et al.  Intranasal insulin reduces body fat in men but not in women. , 2004, Diabetes.

[32]  S. Woods,et al.  Differential sensitivity to central leptin and insulin in male and female rats. , 2003, Diabetes.

[33]  Jan Born,et al.  Sniffing neuropeptides: a transnasal approach to the human brain , 2002, Nature Neuroscience.

[34]  L. Illum Transport of drugs from the nasal cavity to the central nervous system. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[35]  C. Baird The pilot study. , 2000, Orthopedic nursing.

[36]  A. Beck,et al.  Screening for major depression disorders in adolescent medical outpatients with the Beck Depression Inventory for Primary Care. , 1999, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[37]  D. Yousem,et al.  Gender effects on odor-stimulated functional magnetic resonance imaging , 1999, Brain Research.

[38]  T. Hummel,et al.  'Sniffin' sticks': olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. , 1997, Chemical senses.

[39]  K. Krauel,et al.  Olfactory information processing during the course of the menstrual cycle , 1996, Biological Psychology.

[40]  M. First,et al.  The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. , 1992, Archives of general psychiatry.

[41]  M. Hashida,et al.  The transport of a drug to the cerebrospinal fluid directly from the nasal cavity: the relation to the lipophilicity of the drug. , 1991, Chemical & pharmaceutical bulletin.

[42]  L. Wetterberg,et al.  Evidence for the presence of specific receptors for insulin-like growth factors 1 (IGF-1) and 2 (IGF-2) and insulin throughout the adult human brain , 1982, Neuroscience Letters.

[43]  M. Brownstein,et al.  Identification of insulin in rat brain. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[44]  M. Brownstein,et al.  Insulin receptors are widely distributed in the central nervous system of the rat , 1978, Nature.

[45]  Maja O’Connor,et al.  A Longitudinal Study , 2013 .

[46]  M. Jones-Gotman,et al.  The human brain distinguishes between single odorants and binary mixtures. , 2009, Cerebral cortex.

[47]  E. Glaser The randomized clinical trial. , 1972, The New England journal of medicine.