Obese men respond to cognitive but not to catabolic brain insulin signaling
Abstract
Context and objective Insulin acts in the brain to reduce food intake and body weight and is considered a major adiposity signal in energy homeostasis. In normal-weight men, intranasal insulin administration reduces body fat and improves declarative memory. The present experiments aimed to generalize these findings to obese patients, with a view to evaluate the therapeutic potential of the compound.Design, subjects and measurements Insulin and placebo, respectively, were intranasally administered four times a day (amounting to 160 IU day(-1)) over 8 weeks to two groups of 15 obese men each.Results Contrasting with the catabolic effects in normal-weight men, insulin treatment did not induce any significant reduction of body weight (P>0.50) and body fat (P>0.44) in the obese subjects. However, in accordance with the effects in normal-weight men, declarative memory and mood were improved (P<0.05) and hypothalamic-pituitary-adrenal axis activity as assessed by circulating ACTH (P<0.01) and cortisol levels (P<0.04) was reduced.Conclusions Our results indicate that in obese men, intranasal insulin is functionally active in the central nervous system but fails to affect the neuronal networks critically involved in body weight regulation. We conclude that obesity in men is associated with central nervous resistance to the adiposity signal insulin. This defect likely contributes to the persistence of obesity in spite of elevated levels of circulating insulin in obese patients.
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Eight-week administration of IN insulin failed to affect body weight and fat mass in obese individuals.
“8-week administration of IN insulin failed to affect body weight and fat mass in obese individuals.”
From Intranasal insulin (2021) · cites this paper as [87]
Signs of reduced hypothalamic-pituitary-adrenal axis activity as a result of IN insulin were observed in human participants under resting conditions after 8 weeks of daily administration.
“Signs of reduced hypothalamic-pituitary-adrenal (HPA) axis activity as a result of IN insulin were, however, also observed in human participants under resting conditions after 8 weeks of daily administration.”
From Intranasal insulin (2021) · cites this paper as [87]
The finding that IN insulin improves delayed declarative memory was replicated in obese men.
“This finding was later replicated in obese men.87”
From Intranasal insulin (2021) · cites this paper as [87]
The 8-week paradigm of IN insulin administration improved rated mood in normal-weight and obese participants.
“The 8-week paradigm of IN insulin administration described above improved rated mood in normal-weight,38 as well as obese participants.87”
From Intranasal insulin (2021) · cites this paper as [87]
Cites
Brain corticosteroid receptor balance in health and disease
de Kloet, E. R., Vreugdenhil, E., Oitzl, M. S., & Joëls, M. (1998) · Endocrine Reviews · doi:10.1210/edrv.19.3.0331 · Cited by 2,614 · see citing works
JACOBSON, L., & SAPOLSKY, R. (1991) · Endocrine Reviews · doi:10.1210/edrv-12-2-118 · Cited by 1,739 · see citing works
Sniffing neuropeptides: A transnasal approach to the human brain
Born, J., Lange, T., Kern, W., McGregor, G. P., Bickel, U., & Fehm, H. L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-849 · Cited by 1,356 · see citing works
Self-citationStructure and function of declarative and nondeclarative memory systems
Squire, L. R., & Zola, S. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13515 · Cited by 1,327 · see citing works
Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons
Woods, S. C., Lotter, E. C., McKay, L. D., & Porte, D. (1979) · Nature · doi:10.1038/282503a0 · Cited by 1,114 · see citing works
The stroop color-word test: A review
Jensen, A. R., & Rohwer, W. D. (1966) · Acta Psychologica · doi:10.1016/0001-6918(66)90004-7 · Cited by 958 · see citing works
Thorne, R. G., Pronk, G. J., Padmanabhan, V., & Frey, W. H. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.029 · Cited by 958 · see citing works
Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity
El-Haschimi, K., Pierroz, D. D., Hileman, S. M., Bjørbæk, C., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9842 · Cited by 887 · see citing works
Epidemiologic and economic consequences of the global epidemics of obesity and diabetes
Yach, D., Stückler, D., & Brownell, K. D. (2006) · Nature Medicine · doi:10.1038/nm0106-62 · Cited by 856 · see citing works
Diabetes, Obesity, and the Brain
Schwartz, M. W., & Porte, D. (2005) · Science · doi:10.1126/science.1104344 · Cited by 841 · see citing works
Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats
Obici, S., Feng, Z., Karkanias, G., Baskin, D. G., & Rossetti, L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-861 · Cited by 719 · see citing works
Intranasal insulin improves memory in humans
Benedict, C., Hallschmid, M., Hatke, A., Schultes, B., Fehm, H. L., Born, J., & Kern, W. (2004) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2004.04.003 · Cited by 699 · see citing works
Self-citationReger, M. A., Watson, G. S., Frey, W. H., Baker, L. D., Cholerton, B., Keeling, M. L., Belongia, D., Fishel, M. A., Plymate, S. R., Schellenberg, G. D., et al. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.03.016 · Cited by 619 · see citing works
Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats
Obici, S., Feng, Z., Karkanias, G. B., et al. (2002) · Nature Neuroscience · doi:10.1038/nn861 · Cited by 572 · see citing works
Gonadal Hormones Determine Sensitivity to Central Leptin and Insulin
Clegg, D. J., Brown, L. M., Woods, S. C., & Benoit, S. C. (2006) · Diabetes · doi:10.2337/diabetes.55.04.06.db05-1339 · Cited by 552 · see citing works
Baura, G. D., Foster, D. M., Porte, D., Kahn, S. E., Bergman, R. N., Cobelli, C., & Schwartz, M. W. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116773 · Cited by 489 · see citing works
UNGER, J., Livingston, J. H., & Moss, A. (1991) · Progress in Neurobiology · doi:10.1016/0301-0082(91)90015-s · Cited by 403 · see citing works
Effects of early and late nocturnal sleep on priming and spatial memory
Plihal, W., & Born, J. (1999) · Psychophysiology · doi:10.1111/1469-8986.3650571 · Cited by 364 · see citing works
Intracerebroventricular insulin enhances memory in a passive-avoidance task
Park, C. R., Seeley, R. J., Craft, S., & WOODS, S. (2000) · Physiology & Behavior · doi:10.1016/s0031-9384(99)00220-6 · Cited by 343 · see citing works
Differential Sensitivity to Central Leptin and Insulin in Male and Female Rats
Clegg, D. J., Riedy, C. A., Smith, K. A. B., Benoit, S. C., & Woods, S. C. (2003) · Diabetes · doi:10.2337/diabetes.52.3.682 · Cited by 332 · see citing works
Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs.
Kaiyala, K. J., Prigeon, R. L., Kahn, S. E., Woods, S. C., & Schwartz, M. W. (2000) · Diabetes · doi:10.2337/diabetes.49.9.1525 · Cited by 324 · see citing works
Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes
Lin, X., Taguchi, A., Park, S., Kushner, J. A., Li, F., Li, Y., & White, M. F. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22217 · Cited by 313 · see citing works
Improving influence of insulin on cognitive functions in humans
Kern, W., Peters, A., Fruehwald-Schultes, B., Deininger, E., Born, J., & Fehm, H. L. (2001) · Neuroendocrinology · doi:10.1159/000054694 · Cited by 308 · see citing works
Self-citationIntranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart
Benedict, C., Hallschmid, M., Schmitz, K., Schultes, B., Ratter, F., Fehm, H. L., Born, J., & Kern, W. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301193 · Cited by 302 · see citing works
Self-citationThe Role of Insulin in Human Brain Glucose Metabolism
Bingham, E., Hopkins, D., Smith, D., Pernet, A., Hallett, W. A., Reed, L. J., Marsden, P. K., & Amiel, S. A. (2002) · Diabetes · doi:10.2337/diabetes.51.12.3384 · Cited by 293 · see citing works
Intranasal Insulin Reduces Body Fat in Men but not in Women
Hallschmid, M., Benedict, C., Schultes, B., Fehm, H.-L., Born, J., & Kern, W. (2004) · Diabetes · doi:10.2337/diabetes.53.11.3024 · Cited by 281 · see citing works
Self-citationCognitive effects of insulin in the central nervous system
Park, C. R. (2001) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(01)00016-1 · Cited by 270 · see citing works
Neuroendocrine abnormalities in visceral obesity
Björntorp, P. A., & Rosmond, R. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801285 · Cited by 262 · see citing works
Tschritter, O., Preissl, H., Hennige, A. M., Stumvoll, M., Porubska, K., Frost, R., Marx, H., Klösel, B., Lutzenberger, W., Birbaumer, N., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604404103 · Cited by 223 · see citing works
Glucocorticoids, chronic stress, and obesity
Dallman, M. F., Pecoraro, N. C., La Fleur, S. E., Warne, J. P., Ginsberg, A. B., Akana, S. F., Laugero, K. C., Houshyar, H., Strack, A. M., Bhatnagar, S., et al. (2006) · Progress in Brain Research · doi:10.1016/s0079-6123(06)53004-3 · Cited by 198 · see citing works
Central nervous system effects of intranasally administered insulin during euglycemia in men.
Kern, W., Jan Born, A., Schreiber, H., & Fehm, H. (1999) · Diabetes · doi:10.2337/diabetes.48.3.557 · Cited by 192 · see citing works
Self-citationStockhorst, U., de Fries, D., Steingrüber, H.-J., & Scherbaum, W. A. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.07.022 · Cited by 191 · see citing works
Memory consolidation in human sleep depends on inhibition of glucocorticoid release
Plihal, W., & Born, J. (1999) · NeuroReport · doi:10.1097/00001756-199909090-00009 · Cited by 171 · see citing works
Acute third ventricular administration of insulin decreases food intake in two paradigms
Air, E. L., Benoit, S. C., Smith, K. A. B., Clegg, D. J., & Woods, S. C. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00780-8 · Cited by 153 · see citing works
Low cerebrospinal fluid insulin levels in obese humans
Kern, W., Benedict, C., Schultes, B., Plohr, F., Moser, A., Jan Born, A., Fehm, H. L., & Hallschmid, M. (2006) · Diabetologia · doi:10.1007/s00125-006-0409-y · Cited by 143 · see citing works
Self-citationIntracerebroventricular infusions of 3-OHB and insulin in a rat model of dietary obesity
Arase, K., Fisler, J. S., Shargill, N. S., York, D. A., & Bray, G. A. (1988) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1988.255.6.r974 · Cited by 132 · see citing works
Stockhorst, U., DEFRIES, D., Steingrueber, H.-J., et al. (2004) · Physiology & Behavior · doi:10.1016/s0031-9384(04)00348-8 · Cited by 127 · see citing works
Effects of Cortisol Suppression on Sleep-Associated Consolidation of Neutral and Emotional Memory
Wagner, U., Degirmenci, M., Drosopoulos, S., Perras, B., & Born, J. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.05.008 · Cited by 119 · see citing works
Potential behavioral modification of glucocorticoid damage to the hippocampus
Sapolsky, R. M. (1993) · Behavioural Brain Research · doi:10.1016/0166-4328(93)90133-b · Cited by 103 · see citing works
Carbohydrate-Induced Memory Impairment in Adults With Type 2 Diabetes
Greenwood, C. E., Kaplan, R. J., Hebblethwaite, S., & Jenkins, D. J. A. (2003) · Diabetes Care · doi:10.2337/diacare.26.7.1961 · Cited by 94 · see citing works
Stein, L. J., Dorsa, D. M., Baskin, D. G., Figlewicz, D. P., Porte, D., & Woods, S. C. (1987) · Endocrinology · doi:10.1210/endo-121-5-1611 · Cited by 84 · see citing works
Engler, D., Redei, E., & Kola, I. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.4.0376 · Cited by 79 · see citing works
Fruehwald-Schultes, B., Kern, W., Bong, W., Wellhoener, P., Kerner, W., Born, J., Fehm, H. L., & Peters, A. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.9.5953 · Cited by 75 · see citing works
Self-citationManipulating neuropeptidergic pathways in humans: a novel approach to neuropharmacology?
Fehm, H. L., Perras, B., Smolnik, R., Kern, W., & Jan Born, A. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00540-9 · Cited by 69 · see citing works
Self-citationCentral insulin and macronutrient intake in the rat
Chavez, M., Riedy, C. A., van Dijk, G., & Woods, S. C. (1996) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1996.271.3.r727 · Cited by 68 · see citing works
Chronic Corticosterone Impairs Inhibitory Avoidance in Rats
Bisagno, V., Ferrini, M. G., Rı́os, H., Zieher, L. M., & Wikinski, S. (2000) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(00)00265-3 · Cited by 47 · see citing works
Benedict, C., Dodt, C., Hallschmid, M., Lepiorz, M., Fehm, H. L., Jan Born, A., & Kern, W. (2005) · Metabolism · doi:10.1016/j.metabol.2005.04.026 · Cited by 38 · see citing works
Self-citationInsulin stimulates inositol incorporation in hippocampus of lean but not obese Zucker rats
Figlewicz, D. P., Szot, P., & Greenwood, M. R. C. (1990) · Physiology & Behavior · doi:10.1016/0031-9384(90)90150-3 · Cited by 18 · see citing works
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Self-citationSex differences in the physiology of eating
Asarian, L., & Geary, N. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00446.2012 · Cited by 513 · see citing works
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Ghasemi, R., Haeri, A., Dargahi, L., Mohamed, Z., & Ahmadiani, A. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8339-9 · Cited by 291 · see citing works
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Belgardt, B., Okamura, T., & Brüning, J. C. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.179192 · Cited by 245 · see citing works
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RetractedHallschmid, M., Higgs, S., Thienel, M., Ott, V., & Lehnert, H. (2012) · Diabetes · doi:10.2337/db11-1390 · Cited by 181 · see citing works
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Brain Insulin Signaling and Alzheimer's Disease: Current Evidence and Future Directions
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Benedict, C., Brede, S., Schiöth, H. B., Lehnert, H., Schultes, B., Born, J., & Hallschmid, M. (2011) · Diabetes · doi:10.2337/db10-0329 · Cited by 129 · see citing works
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Benedict, C., Brooks, S. J., Kullberg, J., Burgos, J., Kempton, M. J., Nordenskjöld, R., Nylander, R., Kilander, L., Craft, S., Larsson, E., et al. (2012) · Diabetes Care · doi:10.2337/dc11-2075 · Cited by 128 · see citing works
Self-citationShefer, G., Marcus, Y., & Stern, N. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.07.015 · Cited by 124 · see citing works
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Migliore, M. M., Vyas, T. K., Campbell, R. B., Amiji, M. M., & Waszczak, B. L. (2009) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21939 · Cited by 117 · see citing works
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Self-citationHallschmid, M. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12934 · Cited by 113 · see citing works
Self-citationTsaousidou, E., Paeger, L., Belgardt, B., Pál, M., Wunderlich, C. M., Brönneke, H. S., Collienne, U., Hampel, B., Wunderlich, F. T., Schmidt‐Supprian, M., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.045 · Cited by 108 · see citing works
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Diabetes as a chronic metabolic stressor: Causes, consequences and clinical complications
Reagan, L. P. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.02.004 · Cited by 101 · see citing works
Dhuria, S. V., Hanson, L. R., & Frey, W. H. (2008) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.145565 · Cited by 102 · see citing works
Higgs, S., Spetter, M. S., Thomas, J. M., Rotshtein, P., Lee, M. D., Hallschmid, M., & Dourish, C. T. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117736917 · Cited by 103 · see citing works
Self-citationIntranasal insulin in Alzheimer's disease: Food for thought
Chapman, C. D., Schiöth, H. B., Grillo, C. A., & Benedict, C. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.037 · Cited by 101 · see citing works
Self-citationLaron, Z. (2009) · Archives of Physiology and Biochemistry · doi:10.1080/13813450902949012 · Cited by 97 · see citing works
Hypothalamic Insulin Resistance in Obesity: Effects on Glucose Homeostasis
Chen, W., Balland, É., & Cowley, M. A. (2017) · Neuroendocrinology · doi:10.1159/000455865 · Cited by 99 · see citing works
The diabetic brain and cognition
Riederer, P., Korczyn, A. D., Ali, S. S., Bajenaru, O. A., Choi, M. S., Chopp, M., Dobrota, V. Đ., Grünblatt, E., Jellinger, K. A., Kamal, M. A., et al. (2017) · Journal of Neural Transmission · doi:10.1007/s00702-017-1763-2 · Cited by 96 · see citing works
Benedict, C., & Grillo, C. A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00215 · Cited by 96 · see citing works
Self-citationSchmidt, H., Kern, W., Giese, R. M., Hallschmid, M., & Enders, A. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2008.062141 · Cited by 94 · see citing works
Self-citationDevelopmental programming of hypothalamic neuronal circuits: impact on energy balance control
Ramamoorthy, T. G., Begum, G., Harno, E., & White, A. E. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00126 · Cited by 96 · see citing works
Hallschmid, M., & Schultes, B. (2009) · Diabetologia · doi:10.1007/s00125-009-1501-x · Cited by 90 · see citing works
Self-citationGruber, J., Hanßen, R., Qubad, M., Bouzouina, A., Schack, V., Sochor, H., Schiweck, C., Aichholzer, M., Matura, S., Slattery, D. A., et al. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105179 · Cited by 91 · see citing works
Bohringer, A., Schwabe, L., Richter, S., & Schachinger, H. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.08.002 · Cited by 89 · see citing works
Repetitive electric brain stimulation reduces food intake in humans
Jauch‐Chara, K., Kistenmacher, A., Herzog, N., Schwarz, M., Schweiger, U., & Oltmanns, K. M. (2014) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.075481 · Cited by 88 · see citing works
Intranasal insulin therapy for cognitive impairment and neurodegeneration: current state of the art
de la Monte, S. M. (2013) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2013.856877 · Cited by 87 · see citing works
Diabetes, a Contemporary Risk for Parkinson’s Disease: Epidemiological and Cellular Evidences
Sergi, D., Renaud, J., Simola, N., & Martinoli, M. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00302 · Cited by 85 · see citing works
Steculorum, S. M., Solas, M., & Brüning, J. C. (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.12.008 · Cited by 80 · see citing works
Impaired peripheral glucose homeostasis and Alzheimer's disease
Wijesekara, N., Gonçalves, R. A., Felice, F. G. D., & Fraser, P. E. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.027 · Cited by 80 · see citing works
Calvo‐Ochoa, E., & Arias, C. (2014) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2531 · Cited by 80 · see citing works
A histological and functional study on hippocampal formation of normal and diabetic rats
Amin, S. N., Younan, S. M., Youssef, M. F., Rashed, L. A., & Mohamady, I. (2013) · F1000Research · doi:10.12688/f1000research.2-151.v1 · Cited by 79 · see citing works
Grillo, C. A., Woodruff, J. L., Macht, V. A., & Reagan, L. P. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.04.012 · Cited by 74 · see citing works
Schöpf, V., Kollndorfer, K., Pollak, M., Mueller, C. A., & Freiherr, J. (2015) · Rhinology Journal · doi:10.4193/rhino15.065 · Cited by 74 · see citing works
Potential role of insulin on the pathogenesis of depression
Zou, X.-H., Sun, L.-H., Yang, W., Li, B.-J., & Cui, R.-J. (2020) · Cell Proliferation · doi:10.1111/cpr.12806 · Cited by 66 · see citing works
State of the science on brain insulin resistance and cognitive decline due to Alzheimer's disease
Rhea, E. M., Leclerc, M., Yassine, H. N., Capuano, A. W., Tong, H., Petyuk, V. A., Macauley, S. L., Fioramonti, X., Carmichael, O., Calon, F., et al. (2023) · Aging and disease · doi:10.14336/ad.2023.0814 · Cited by 70 · see citing works
Short Term Voluntary Overfeeding Disrupts Brain Insulin Control of Adipose Tissue Lipolysis
Scherer, T., Lindtner, C., Zieliński, E., O’Hare, J., Filatova, N., & Buettner, C. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.307348 · Cited by 70 · see citing works
Central Insulin Administration Improves Odor-Cued Reactivation of Spatial Memory in Young Men
Brünner, Y. F., Kofoet, A., Benedict, C., & Freiherr, J. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-3018 · Cited by 68 · see citing works
Self-citationSasaki, T. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00109 · Cited by 66 · see citing works
Insulin Regulates Hepatic Triglyceride Secretion and Lipid Content via Signaling in the Brain
Scherer, T., Lindtner, C., O’Hare, J., Hackl, M. T., Zieliński, E., Freudenthaler, A., Baumgartner-Parzer, S. M., Tödter, K., Heeren, J., Krššák, M., et al. (2016) · Diabetes · doi:10.2337/db15-1552 · Cited by 66 · see citing works
Deciphering Brain Insulin Receptor and Insulin‐Like Growth Factor 1 Receptor Signalling
Kleinridders, A. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12433 · Cited by 65 · see citing works
Berends, L. M., Dearden, L., Tung, Y. L., Voshol, P. J., Fernandez‐Twinn, D. S., & Ozanne, S. E. (2018) · Diabetologia · doi:10.1007/s00125-018-4694-z · Cited by 65 · see citing works
Hallschmid, M., Jauch-Chara, K., Korn, O., Mölle, M., Rasch, B., Born, J., Schultes, B., & Kern, W. (2010) · Diabetes · doi:10.2337/db09-1493 · Cited by 61 · see citing works
Self-citationBegg, D. P., & Woods, S. C. (2013) · AJP Advances in Physiology Education · doi:10.1152/advan.00167.2012 · Cited by 61 · see citing works
Antidiabetic Drugs in Alzheimer’s Disease: Mechanisms of Action and Future Perspectives
Femminella, G. D., Bencivenga, L., Petraglia, L., Visaggi, L., Gioia, L., Grieco, F. V., de Lucia, C., Komici, K., Corbi, G., Edison, P., et al. (2017) · Journal of Diabetes Research · doi:10.1155/2017/7420796 · Cited by 56 · see citing works
Modulation of midbrain neurocircuitry by intranasal insulin
Edwin Thanarajah, S., Iglesias, S., Kuzmanovic, B., Rigoux, L., Stephan, K. E., Brüning, J. C., & Tittgemeyer, M. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.03.050 · Cited by 55 · see citing works
Investigating the molecular mechanisms of learning and memory using Caenorhabditis elegans
Rahmani, A., & Chew, Y. L. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15510 · Cited by 52 · see citing works
Is the Brain a Key Player in Glucose Regulation and Development of Type 2 Diabetes?
Lundqvist, M., Almby, K. E., Abrahamsson, N., & Eriksson, J. W. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00457 · Cited by 49 · see citing works
Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer’s Disease Prevention
Schelke, M. W., Attia, P., Palenchar, D. J., Kaplan, B., Mureb, M., Ganzer, C. A., Scheyer, O., Rahman, A., Kachko, R., Krikorian, R., et al. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00096 · Cited by 49 · see citing works
Type 2 Diabetes and Alzheimer’s Disease: The Emerging Role of Cellular Lipotoxicity
Marrano, N., Biondi, G., Borrelli, A., Rella, M., Zambetta, T., Gioia, L. D., Caporusso, M., Logroscino, G., Perrini, S., Giorgino, F., et al. (2023) · Biomolecules · doi:10.3390/biom13010183 · Cited by 44 · see citing works
Intranasal delivery: circumventing the iron curtain to treat neurological disorders
Jiang, Y., Li, Y., & Liu, X. (2015) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2015.1065812 · Cited by 43 · see citing works
McCoy, C. R., Rana, S., Stringfellow, S. A., Day, J. J., Wyss, J. M., Clinton, S. M., & Kerman, I. A. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13404 · Cited by 42 · see citing works
Central nervous system regulation of hepatic lipid and lipoprotein metabolism
Taher, J., Farr, S., & Adeli, K. (2016) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000373 · Cited by 42 · see citing works
Nijssen, K. M. R., Mensink, R. P., & Joris, P. J. (2022) · Neuroendocrinology · doi:10.1159/000526717 · Cited by 37 · see citing works
Santiago, J. C. P., & Hallschmid, M. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.03.007 · Cited by 36 · see citing works
Self-citationIntranasal Neuropeptide Administration To Target the Human Brain in Health and Disease
Spetter, M. S., & Hallschmid, M. (2015) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00047 · Cited by 35 · see citing works
Self-citationSchneider, E. M., Spetter, M. S., Martin, E., Sapey, E., Yip, K. P., Manolopoulos, K. N., Tahrani, A. A., Thomas, J. M., Lee, M. D., Hallschmid, M., et al. (2022) · International Journal of Obesity · doi:10.1038/s41366-022-01115-1 · Cited by 35 · see citing works
Self-citationGladding, J. M., Abbott, K. N., Antoniadis, C. P., Stuart, A., & Begg, D. P. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00752 · Cited by 34 · see citing works
Insulin deficiency: A possible link between obesity and cognitive function
Nameni, G., Farhangi, M. A., Hajiluian, G., Shahabi, P., & Abbasi, M. M. (2017) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2017.02.008 · Cited by 32 · see citing works
Begg, D. P., May-Zhang, A. A., Mul, J. D., Liu, M., D’Alessio, D. A., Seeley, R. J., & Woods, S. C. (2015) · Diabetes · doi:10.2337/db14-1364 · Cited by 31 · see citing works
Insulin Transport into the Brain and Cerebrospinal Fluid
Begg, D. P. (2015) · Vitamins and hormones · doi:10.1016/bs.vh.2014.12.007 · Cited by 31 · see citing works
Central nervous system insulin signaling can influence the rate of insulin influx into brain
Nguyễn, V. H., Thomas, P., Pemberton, S., Babin, A., Noonan, C., Weaver, R. R., Banks, W. A., & Rhea, E. M. (2023) · Fluids and Barriers of the CNS · doi:10.1186/s12987-023-00431-6 · Cited by 30 · see citing works
Ritze, Y., Kern, W., Ebner, E.-M., Jahn, S., Benedict, C., & Hallschmid, M. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00663 · Cited by 28 · see citing works
Self-citationWingrove, J. O., O’Daly, O., Forbes, B., Swedrowska, M., Amiel, S. A., & Zelaya, F. O. (2020) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14213 · Cited by 28 · see citing works
Intranasal Insulin: a Treatment Strategy for Addiction
Kashyap, B., Hanson, L. R., & Frey, W. H. (2020) · Neurotherapeutics · doi:10.1007/s13311-019-00822-4 · Cited by 27 · see citing works
Small, D. M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00134 · Cited by 27 · see citing works
Insulin effects on beta and theta activity in the human brain are differentially affected by ageing
Tschritter, O., Hennige, A. M., Preissl, H. T., Grichisch, Y., Kirchhoff, K., Kantartzis, K., Machicao, F. E., Fritsche, A., & Häring, H. (2008) · Diabetologia · doi:10.1007/s00125-008-1187-5 · Cited by 27 · see citing works
Alberry, B., & Silveira, P. P. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105350 · Cited by 27 · see citing works
Dai, C., Li, H., Hu, X. Y., Zhang, J., Liu, F., Iqbal, K., & Gong, C. (2020) · Neurotoxicity Research · doi:10.1007/s12640-020-00223-y · Cited by 24 · see citing works
Diabetes, Insulin and Alzheimer's Disease
Craft, S., & Christen, Y. (2010) · Research and perspectives in Alzheimer's disease · doi:10.1007/978-3-642-04300-0 · Cited by 24 · see citing works
de Sá, D. S. F., Römer, S., Brueckner, A. H., Issler, T. C., Hauck, A., & Michael, T. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-019-0593-3 · Cited by 23 · see citing works
- Authors
- Hallschmid, M., Benedict, C., Schultes, B., Born, J., & Kern, W.
- Affiliations
- University of Lübeck (DE)
- Kantonsspital St. Gallen (CH)
- Corresponding author
- Hallschmid, M
- Venue
- International Journal of Obesity
- Published
- 2007-09-11
- Volume
- 32
- Issue
- 2
- Pages
- 275-282
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W2015016479
- Cited by
- 165
- References
- 46
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 14 · 2022: 6 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 11 · 2017: 14 · 2016: 9 · 2015: 9 · 2014: 10 · 2013: 13 · 2012: 8
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- intranasal insulin, obesity, brain insulin signaling, declarative memory, hypothalamic-pituitary-adrenal axis, ACTH, cortisol, body weight regulation, energy homeostasis, sex differences
- MeSH terms
- Adipose Tissue, Administration, Intranasal, Adult, Affect, Body Weight, Brain, Cognition, Humans, Hypoglycemic Agents, Insulin, Male, Memory, Obesity, Treatment Outcome, Body Size
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