The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Differential Sensitivity of Men and Women to Anorexigenic and Memory-Improving Effects of Intranasal Insulin
Abstract
CONTEXT: Brain insulin is critically involved in the regulation of body weight and memory processing. Long-term administration of intranasal insulin reduces body weight in men, but not in women, while improving hippocampus-dependent memory processing in both genders. OBJECTIVES: Our objectives were to assess the effects of a single dose of intranasal insulin on food intake and memory function in men and women, and to determine any gender differences. METHODS: A total of 32 healthy, normal-weight subjects (14 men, 18 women) were intranasally administered 160 IU regular human insulin or vehicle before performing a hippocampus-dependent two-dimensional-object location task, a working memory task (digit span), and a hippocampus-independent mirror tracing task. Subsequently, food intake from an ad libitum breakfast buffet was measured. RESULTS: Insulin treatment decreased food intake in men but not in women (difference to placebo condition, men: -192.57 +/- 78.48 kcal, P < 0.03; women: 18.54 +/- 42.89 kcal, P > 0.67). In contrast, hippocampus-dependent memory and working memory were improved in women (P < 0.03, P < 0.05, respectively), whereas men did not benefit from acute insulin treatment (P > 0.17, P > 0.20). Performance on the hippocampus-independent mirror tracing task was not affected by insulin in women or men. CONCLUSIONS: In accordance with animal data, results indicate that men are more sensitive than women to the acute anorexigenic effect of central nervous insulin signaling, whereas insulin's beneficial effect on hippocampus-dependent memory functions is more pronounced in women. Our findings provide support for the notion of a fundamental gender difference in central nervous insulin signaling that pertains to the regulation of energy homeostasis and memory functions.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In line with these findings, intranasal insulin delivery to the human brain reduced food intake in lean men but not in women24.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [24]
In the citing paper
“Of note, experimental studies suggest considerable sex differences in brain insulin sensitivity.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [24]
In the citing paper
“This procedure has been repeatedly shown to enable the precise assessment of primarily hunger-driven food intake in the fasted state (20–22).”
From Oxytocin Reduces Reward-Driven Food Intake in Humans (2013) · cites this paper as [20]
In the citing paper
“simple nasal atomisers, 37 which have been proven to reliably trigger functional effects in healthy humans”
From Intranasal insulin (2021) · cites this paper as [39]
In the citing paper
“fasted men ate less after IN insulin (160 IU) compared to placebo administration, whereas women consumed similar amounts of food from the breakfast buffet on offer in both conditions.”
From Intranasal insulin (2021) · cites this paper as [39]
In the citing paper
“suggesting that delivery schedules synced to food intake 39,42,44,47 might be necessary for the catabolic impact of IN insulin to emerge.”
From Intranasal insulin (2021) · cites this paper as [39]
In the citing paper
“The improving effect of IN insulin on memory function has been demonstrated in studies in healthy humans, [38][39][40]45,72 as well as individuals with memory impairments.[74][75][76][104][105][106][107]”
From Intranasal insulin (2021) · cites this paper as [39]
In the citing paper
“women, but not men, improved their performance on declarative and working memory tasks after receiving 160 IU of insulin vs. placebo.39”
From Intranasal insulin (2021) · cites this paper as [39]
Citations
Cites
Central nervous system control of food intake
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451
Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings.
Tulving, E., Kapur, S., Craik, F. I. M., Moscovitch, M., & Houle, S. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.6.2016 · Cited by 1,621
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
Structure 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
Insulin receptors are widely distributed in the central nervous system of the rat
Havránková, J., Roth, J., & Brownstein, M. (1978) · Nature · doi:10.1038/272827a0 · Cited by 1,116
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
Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study
Whitmer, R. A., Gunderson, E. P., Barrett-Connor, E., Quesenberry, C. P., & Yaffe, K. (2005) · BMJ · doi:10.1136/bmj.38446.466238.e0 · Cited by 1,090
Thorne, R. G., Pronk, G. J., Padmanabhan, V., & Frey, W. H. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.029 · Cited by 958
Petrides, M., Alivisatos, B., Meyer, E., & Evans, A. C. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.3.878 · Cited by 897
Intranasal insulin improves cognition and modulates β-amyloid in early AD
Reger, M. A., Watson, G. S., Green, P. S., Wilkinson, C. W., Baker, L. D., Cholerton, B., Fishel, M. A., Plymate, S. R., Breitner, J. C. S., DeGroodt, W., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000265401.62434.36 · Cited by 830
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–200 of 296
Cedernaes, J., Lampola, L., Axelsson, E. K., Liethof, L., Hassanzadeh, S., Yeganeh, A., Broman, J., Schiöth, H. B., & Benedict, C. (2015) · Journal of Sleep Research · doi:10.1111/jsr.12340 · Cited by 69
“Given that insulin acts as an important satiety signal once it reaches the brain (Benedict et al., 2008), it could also be speculated that the rise in circulating insulin in response to food-related sensory stimulation may serve as an early peripheral satiety signal.”
BackgroundBroadening the definition of brain insulin resistance in aging and Alzheimer's disease
Frazier, H. N., Ghoweri, A. O., Anderson, K. L., Lin, R., Porter, N. M., & Thibault, O. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.12.007 · Cited by 69
“Nevertheless, as these trials continue, notable sex differences are beginning to emerge, further highlighting the complexity of this therapeutic approach (Benedict et al., 2008; Claxton et al., 2013; Hallschmid et al., 2004; Kullmann et al., 2013).”
Metabolic Syndrome, Cognitive Impairment and the Role of Diet: A Narrative Review
Kouvari, M., D'Cunha, N. M., Travica, N., Sergi, D., Zec, M. M., Marx, W., & Naumovski, N. (2022) · Nutrients · doi:10.3390/nu14020333 · Cited by 74
“Furthermore, in order to target the central nervous system, intranasal administration of insulin exerted beneficial effects on cognitive function in healthy adults, as well as individuals affected by mild cognitive impairment or AD [51].”
BackgroundObesity and episodic memory function
Loprinzi, P. D., & Frith, E. (2018) · The Journal of Physiological Sciences · doi:10.1007/s12576-018-0612-x · Cited by 63
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
“Experimental administration of insulin to the central nervous system (CNS) inhibits food intake and reduces body fat content in animals (3,4) and humans (5,6), suggesting that circulating insulin provides negative, anorexigenic feedback on the amount of body fat to the brain.”
BackgroundInfluentialSelf-citationChanges in Cells Associated with Insulin Resistance
Szablewski, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042397 · Cited by 78
“Results obtained in studies showed that intranasal administration of single-dose insulin decreases food intake in healthy males, although this effect was not observed in women [50].”
BackgroundBegg, D. P., & Woods, S. C. (2013) · AJP Advances in Physiology Education · doi:10.1152/advan.00167.2012 · Cited by 63
“Followup experiments found that men were more sensitive to the anorectic effects of insulin than women (20).”
BackgroundObesity-induced increases in sympathetic nerve activity: Sex matters
Brooks, V. L., Shi, Z., Holwerda, S. W., & Fadel, P. J. (2014) · Autonomic Neuroscience · doi:10.1016/j.autneu.2014.11.006 · Cited by 61
“, 2003) or intranasal administration in humans (Hallschmid et al., 2004; Benedict et al., 2008; Krug et al., 2010), decreases food intake in males, but notably not in females.”
Potential effects of current drug therapies on cognitive impairment in patients with type 2 diabetes
Palleria, C., Leporini, C., Maida, F., Succurro, E., Sarro, G. D., Arturi, F., & Russo, E. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.07.002 · Cited by 61
Ferreira, S. T. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12959 · Cited by 59
The regulation of food intake by insulin in the central nervous system
Mitchell, C. S., & Begg, D. P. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12952 · Cited by 62
Intranasal Insulin Reduces Olfactory Sensitivity in Normosmic Humans
Brünner, Y. F., Benedict, C., & Freiherr, J. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2061 · Cited by 58
Evidence for Central Regulation of Glucose Metabolism
Carey, M., Kehlenbrink, S., & Hawkins, M. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.506782 · Cited by 65
“(91) showed reduced postprandial serum insulin levels in healthy men following intranasal insulin administration, suggesting enhanced postprandial peripheral insulin sensitivity, and also reported decreased food intake in men after a single dose of intranasal insulin (92).”
BackgroundErichsen, J. M., Fadel, J. R., & Reagan, L. P. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108877 · Cited by 58
Shpakov, A. O., Zorina, I. I., & Derkach, K. V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043278 · Cited by 59
Insulin receptor substrate 2 is a negative regulator of memory formationPreprint
Irvine, E. E., Drinkwater, L., Radwańska, K., Al‐Qassab, H., Smith, M. A., O’Brien, M. S., Kielar, C., Choudhury, A. I., Krauss, S. J. K., Cooper, J. D., et al. (2011) · Learning & Memory · doi:10.1101/lm.2111311 · Cited by 57
“There is an increasing body of evidence suggesting that insulin and insulin/ Igf-1 signaling contribute to cognitive function in humans and animals (Park et al. 2000; Park 2001; Zhao and Alkon 2001; Benedict et al. 2004, 2008; Zhao et al. 2004).”
Altered gene expression profiles in the hippocampus and prefrontal cortex of type 2 diabetic rats
Abdul-Rahman, O., Sasvári‐Székely, M., Vér, Á., Rosta, K., Szász, B. K., Kereszturi, É., & Keszler, G. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-81 · Cited by 58
“On the other hand, intranasal and intravenous insulin administration has reportedly improved the cognitive functions of patients suffering from memory disorders, while intracerebroventricular insulin enhanced memory formation in rodents [15,16].”
BackgroundInsulin action on astrocytes: From energy homeostasis to behaviour
González‐García, I., Gruber, T., & García‐Cáceres, C. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12953 · Cited by 52
Derkach, K. V., Bogush, I. V., Berstein, L. M., & Shpakov, A. O. (2015) · Hormone and Metabolic Research · doi:10.1055/s-0035-1547236 · Cited by 54
Kanazawa, T. (2015) · Medical Devices Evidence and Research · doi:10.2147/mder.s70856 · Cited by 54
Brain insulin resistance and cognitive function: influence of exercise
Malin, S. K., Stewart, N. R., Ude, A. A., & Alderman, B. L. (2022) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00375.2022 · Cited by 53
Begg, D. P., Mul, J. D., Liu, M., Reedy, B. M., D’Alessio, D. A., Seeley, R. J., & Woods, S. C. (2013) · Endocrinology · doi:10.1210/en.2012-1929 · Cited by 51
Hogenkamp, P. S., Zhou, W., Dahlberg, L. S., Stark, J., Larsen, A. L., Olivo, G., Wiemerslage, L., Larsson, E.-M., Sundbom, M., Benedict, C., et al. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.105 · Cited by 50
Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase
Hummel, J., Benkendorff, C., Fritsche, L., Prystupa, K., Vosseler, A., Gancheva, S., Trenkamp, S., Birkenfeld, A. L., Preissl, H., Roden, M., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00869-w · Cited by 48
Insulin resistance is associated with poorer verbal fluency performance in women
Ekblad, L. L., Rinne, J. O., Puukka, P. J., Laine, H. K., Ahtiluoto, S., Sulkava, R. O., Viitanen, M. H., & Jula, A. (2015) · Diabetologia · doi:10.1007/s00125-015-3715-4 · Cited by 49
“Previous studies indicate a sex difference in the response to intranasal insulin treatment [14, 15].”
BackgroundInfluentialGeijselaers, S. L. C., Aalten, P., Ramakers, I. H. G. B., Deyn, P. P. D., Heijboer, A. C., Koek, H. L., Olde-Rikkert, M. G. M., Papma, J. M., Reesink, F. E., Smits, L. L., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170522 · Cited by 46
“It has been suggested [24] that these sex differences can be explained by the cognitive effects of estrogen [50].”
Pharmacokinetics of Intranasal versus Subcutaneous Insulin in the Mouse
Nedelcovych, M. T., Gadiano, A. J., Wu, Y., Manning, A. A., Thomas, A. G., Khuder, S. S., Yoo, S., Xu, J., McArthur, J. C., Haughey, N. J., et al. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00434 · Cited by 46
Insulin Signals Through the Dorsal Vagal Complex to Regulate Energy Balance
Filippi, B., Bassiri, A., Abraham, M. A., Duca, F. A., Yue, J. T. Y., & Lam, T. K. T. (2013) · Diabetes · doi:10.2337/db13-1044 · Cited by 45
Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?
Gratuze, M., Joly‐Amado, A., Vieau, D., Buée, L., & Blum, D. L. (2018) · Neuroendocrinology · doi:10.1159/000487641 · Cited by 51
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 44
“Spatial and working memory tasks that reflect hippocampus-dependent memory processes [49] and verbal working memory, which is an indicator of frontal cortex activation, could improve after only a single dose of intranasal insulin delivery [50].”
BackgroundMorgen, K., & Frölich, L. (2015) · Journal of Neural Transmission · doi:10.1007/s00702-015-1377-5 · Cited by 43
Insulin and glucagon signaling in the central nervous system
Filippi, B., Abraham, M. A., Yue, J. T. Y., & Lam, T. K. T. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9258-4 · Cited by 43
LUPIEN, S. J., Lord, C., Sindi, S., Wilkinson, C. W., & Fiocco, A. J. (2009) · Elsevier eBooks · doi:10.1016/b978-008088783-8.00097-8 · Cited by 42
Underwood, E. L., & Thompson, L. T. (2016) · Biology of Sex Differences · doi:10.1186/s13293-016-0060-3 · Cited by 42
“In humans, acute intranasal insulin administration has been shown to reduce food intake in men, but not in women, whereas it improves spatial memory function in women, but not men [62].”
BackgroundXu, J., Ni, B., Ma, C., Rong, S., Gao, H. Y., Zhang, L., Xia, X., Huang, Q., Deng, Q., & Huang, F. (2022) · Journal of Advanced Research · doi:10.1016/j.jare.2022.04.015 · Cited by 39
“Numerous studies have indicated memory-improving effects of insulin [36,37], and insulin”
BackgroundInconsistencies in the assessment of food intake
Woods, S. C., & Langhans, W. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00415.2012 · Cited by 39
Keel, P. K., Bodell, L. P., Forney, K. J., Appelbaum, J., & Williams, D. L. (2019) · Physiology & Behavior · doi:10.1016/j.physbeh.2019.112565 · Cited by 38
Benedict, C., Kern, W., Schmid, S. M., Schultes, B., Born, J., & Hallschmid, M. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.10.010 · Cited by 37
“In particular, upregulation of insulin and leptin in conjunction with reduced HPA axis secretion can add to this effect (Schwartz et al., 2000; Dallman et al., 2004; Benedict et al., 2008).”
BackgroundSelf-citationNijssen, K. M. R., Mensink, R. P., & Joris, P. J. (2022) · Neuroendocrinology · doi:10.1159/000526717 · Cited by 43
Intranasal insulin and orexins to treat age-related cognitive decline
Erichsen, J. M., Calva, C. B., Reagan, L. P., & Fadel, J. R. (2021) · Physiology & Behavior · doi:10.1016/j.physbeh.2021.113370 · Cited by 38
Dodd, G. T., Kim, S. J., Méquinion, M., Xirouchaki, C. E., Brüning, J. C., Andrews, Z. B., & Tiganis, T. (2021) · Science Advances · doi:10.1126/sciadv.abf4100 · Cited by 39
“Early studies established that the intracerebroventricular administration of insulin could repress food intake in rats (17) and baboons (18), whereas more recent studies have shown that intranasal-administered insulin represses food intake in humans (19, 20).”
Central Nervous Insulin Signaling in Sleep-Associated Memory Formation and Neuroendocrine Regulation
Feld, G. B., Wilhem, I., Benedict, C., Rüdel, B., Klameth, C., Born, J., & Hallschmid, M. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.312 · Cited by 36
“Notably, immediate improving effects of intranasal insulin on declarative memory were found in healthy women (on estrogendominant oral contraceptives), whereas men did not benefit (Benedict et al, 2008).”
BackgroundResultInfluentialSantiago, J. C. P., & Hallschmid, M. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.03.007 · Cited by 37
Formulation strategies for nose-to-brain delivery of therapeutic molecules
Pandey, V., Gadeval, A., Asati, S., Jain, P., Jain, N., Roy, R. K., Tekade, M., Soni, V., & Tekade, R. K. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814487-9.00007-7 · Cited by 36
The Role of Insulin Signaling in Hippocampal-Related Diseases: A Focus on Alzheimer’s Disease
Liu, Q., Wang, Z., Cao, J., Dong, Y., & Chen, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214417 · Cited by 42
Intranasal 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
Schneider, 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 38
“The dose was based on previous studies that reported significant effects of insulin on food intake [4, 6, 16, 23].”
The Central Insulin System and Energy Balance
Begg, D. P., & Woods, S. C. (2011) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-24716-3_5 · Cited by 36
“…to increase central insulin levels, it was found that there is a dose-dependent reduction of food intake during an ad libitum breakfast buffet (Hallschmid et al. 2004), and follow-up experiments found that men were more sensitive to insulin’s anorexigenic action than women (Benedict et al. 2008).”
Ott, V., Lehnert, H., Staub, J., Wönne, K., Jan Born, A., & Hallschmid, M. (2014) · Diabetes · doi:10.2337/db14-0931 · Cited by 36
“insulin administration that directly targets the brain (6,7) and effectively modulates central nervous system (CNS) functions, including the regulation of energy balance (8,9), electroencephalographic brain activity (10), and cognition (8,11,12).”
BackgroundBell, G. A., & Fadool, D. A. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.02.044 · Cited by 34
Gabbouj, S., Natunen, T., Koivisto, H., Jokivarsi, K. T., Takalo, M., Marttinen, M., Wittrahm, R., Kemppainen, S., Naderi, R., Posado-Fernández, A., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.11.008 · Cited by 37
Gladding, 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 33
“In addition to the beneficial effects of insulin administration seen in obese humans (58), numerous studies in rodents (25, 27–29) and healthy, non-obese humans (27, 59, 60) have demonstrated a potential for CNS insulin administration as a cognitive enhancer.”
BackgroundStockhorst, U., de Fries, D., Steingrüber, H.-J., & Scherbaum, W. A. (2011) · Diabetologia · doi:10.1007/s00125-011-2111-y · Cited by 33
“Of eight published studies in humans where acute intranasal insulin was administered, only one found an increase in peripheral insulin [9], one a decrease of blood glucose [10], and one both changes [11].”
BackgroundWagner, L., Veit, R., Fritsche, L., Häring, H., Fritsche, A., Birkenfeld, A. L., Heni, M., Preissl, H. T., & Kullmann, S. (2022) · International Journal of Obesity · doi:10.1038/s41366-022-01167-3 · Cited by 33
“The sex differences of central insulin action in the DLPFC further support the notion that women and men differ in central insulin signaling when eating behavior-related cognitive processes are involved [6, 20].”
BackgroundInfluentialBegg, 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
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
Hammoud, H., Netsyk, O., Tafreshiha, A. S., Korol, S. V., Jin, Z., Li, J.-P., & Birnir, B. (2021) · Acta Physiologica · doi:10.1111/apha.13623 · Cited by 29
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
Adams, D. M., Reay, W. R., Geaghan, M. P., & Cairns, M. J. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-00847-w · Cited by 30
“An example of this has been demonstrated using intranasal insulin administration, in which hunger was decreased only in male participants, conversely, there were positive cognitive enhancing effects seen only in women [87], although this was a small study (N= 32) that warrants replication in a larger cohort.”
ResultRitze, 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
“Experiments in animals (7–9) and humans (10, 11) indicate that insulin administered directly to the brain reduces food intake.”
BackgroundResultInfluentialSelf-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
“Hunger is often prompted by foodrelated cues, and even in studies where food intake has been reduced by acute IN-INS (160 IU), hunger scores were not affected.(38) Thus, here hunger ratings were, and perhaps are, of little value for understanding the actual effects on predicted food intake.”
BackgroundCognitive control of meal onset and meal size: Role of dorsal hippocampal-dependent episodic memory
Parent, M. B. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.03.036 · Cited by 29
Insulin to treat Alzheimer’s disease: just follow your nose?
Schiöth, H. B., Frey, W. H., Brooks, S. J., & Benedict, C. (2011) · Expert Review of Clinical Pharmacology · doi:10.1586/ecp.11.70 · Cited by 26
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
“Intranasal insulin has been shown to reduce food intake in adult men [111] and snacks in women if given in a”
BackgroundStockhorst, U., Huenig, A., Ziegler, D., & Scherbaum, W. A. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.01.014 · Cited by 27
Alberry, B., & Silveira, P. P. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105350 · Cited by 28
Preventing Alzheimer's disease by means of natural selection
Demetrius, L., & Driver, J. A. (2014) · Journal of The Royal Society Interface · doi:10.1098/rsif.2014.0919 · Cited by 24
Dai, Y., Zhao, Y., Tomi, M., Shin, B., Thamotharan, S., Mazarati, A. M., Sankar, R., Wang, E. A., Cepeda, C., Levine, M. S., et al. (2017) · Endocrinology · doi:10.1210/en.2016-1816 · Cited by 25
Al-Zubaidi, A., Heldmann, M., Mertins, A., Brabant, G. E., Nolde, J. M., Jauch‐Chara, K., & Münte, T. F. (2019) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2019.00162 · Cited by 25
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
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
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 24
Schultes, B., Panknin, A.-K., Hallschmid, M., Jauch‐Chara, K., Wilms, B., de Courbière, F., Lehnert, H., & Schmid, S. M. (2016) · Appetite · doi:10.1016/j.appet.2016.06.032 · Cited by 24
“Previous studies (Beglinger, & Degen, 2006; Benedict et al., 2008; Chapman et 223 al., 1998) have shown that changes in voluntary food intake upon experimental manipulation 224 can occur even without subjective changes in hunger, appetite, satiety, and fullness.”
BackgroundBrain insulin responsiveness is linked to age and peripheral insulin sensitivity
Wagner, L., Veit, R., Kübler, C., Fritsche, A., Häring, H., Birkenfeld, A. L., Heni, M., Preissl, H., & Kullmann, S. (2023) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.15094 · Cited by 22
Li, H., Dai, C., Gu, J., Peng, S., Li, J., Yu, Q., Iqbal, K., Liu, F., & Gong, C. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00706 · Cited by 22
Hunt, K. F., Dunn, J., le Roux, C. W., Reed, L. J., Marsden, P. K., Patel, A. G., & Amiel, S. A. (2016) · Diabetes Care · doi:10.2337/dc15-2721 · Cited by 21
Therapies for Alzheimer’s disease: a metabolic perspective
Domingues, R., Pereira, C., Cruz, M. T., & Silva, A. (2021) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2021.01.011 · Cited by 21
Insulin resistance in Alzheimer's disease: signalling mechanisms and therapeutics strategies
Dahiya, M., Yadav, M., Goyal, C., & Kumar, A. (2025) · Inflammopharmacology · doi:10.1007/s10787-025-01704-2 · Cited by 22
“…the intranasal route bypassed the blood–brain barrier, resulting in increased insulin concentrations in brain regions, which proved to be neuroprotective by enhancing brain insulin signalling and attenuating cognitive dysfunctions in AD patients (Benedict et al. 2007, 2008; Ferreira et al. 2014).”
Basal Insulin: Beyond Glycemia
Niswender, K. D. (2011) · Postgraduate Medicine · doi:10.3810/pgm.2011.07.2301 · Cited by 20
“Indeed, administration of intranasal insulin in healthy subjects decreased appetite in men (as it did in male rats) and improved cognitive function (memory) in women.(26) These fi ndings suggest that insulin action in the CNS is involved in regulating appetite and memory in humans.”
BackgroundEvolution of Human Sex-Specific Cognitive Vulnerabilities
Geary, D. C. (2017) · The Quarterly Review of Biology · doi:10.1086/694934 · Cited by 19
Cortisol, but not intranasal insulin, affects the central processing of visual food cues
de Sá, D. S. F., Schulz, A., Streit, F., Turner, J. D., Oitzl, M. S., Blumenthal, T. D., & Schächinger, H. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.09.006 · Cited by 19
The Rationale for Insulin Therapy in Alzheimer’s Disease
Ribarič, S. (2016) · Molecules · doi:10.3390/molecules21060689 · Cited by 20
“Intranasal insulin treatment, for early AD or mild cognitive impairment (MCI), improved memory and attention abilities in four phase 2 clinical trials without significant adverse effects or changes in blood levels of insulin or glucose [117,122,260,263,321–325].”
BackgroundSantiago, J. C. P., & Hallschmid, M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00054 · Cited by 18
“…insulin on food intake has been mainly investigated by means of the intranasal route of peptide administration (Hallschmid et al., 2004a, 2012; Benedict et al., 2008), a non-invasive method of substance delivery to the brain that largely bypasses the blood-brain barrier (Born et al., 2002;…”
BackgroundResultInfluentialSelf-citationBhattamisra, S. K., Shin, L. Y., Saad, H. I. B. M., Rao, V., Candasamy, M., Pandey, M., & Choudhury, H. (2020) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527319666200518102130 · Cited by 18
Stahel, P., Lee, S. J., Sud, S. K., Floh, A. A., & Dash, S. (2019) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13661 · Cited by 18
“Intranasal insulin decreased food intake and body mass in men but not women, and improved cognitive function in women but not men.(29,30) The mechanisms underlying these potential gender differences remain to be established.”
BackgroundIs Insulin Action in the Brain Clinically Relevant?
Filippi, B., Mighiu, P. I., & Lam, T. K. T. (2012) · Diabetes · doi:10.2337/db12-0048 · Cited by 18
“Unfortunately, the current study did not offer mechanistic insights responsible for the differential anorectic responses induced by CNS insulin in women and men (11), as well as in fasting and postprandial conditions.”
BackgroundMethodFood image-induced brain activation is not diminished by insulin infusion
Belfort‐DeAguiar, R., Seo, D., Naik, S., Hwang, J. J., Lacadie, C., Schmidt, C., Constable, R. T., Sinha, R., & Sherwin, R. S. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.152 · Cited by 19
“In human studies, intranasal insulin has been reported to increase satiety and decrease food intake(16, 17).”
Early adversity and insulin: neuroendocrine programming beyond glucocorticoids
Batra, A., Latsko, M. S., Portella, A. K., & Silveira, P. P. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.09.003 · Cited by 17
Vugt, D. A. V., Krzemien, A. A., Alsaadi, H., Frank, T. C., & Reid, R. L. (2014) · Brain Research · doi:10.1016/j.brainres.2014.02.037 · Cited by 17
Insulin and Estrogen Independently and Differentially Reduce Macronutrient Intake in Healthy Men
Krug, R., Mohwinkel, L., Drotleff, B., Born, J., & Hallschmid, M. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01835 · Cited by 16
Position on zinc delivery to olfactory nerves in intranasal insulin phase I–III clinical trials
Hamidovic, A. (2015) · Contemporary Clinical Trials · doi:10.1016/j.cct.2015.08.011 · Cited by 16
“Intranasal insulin doses administered thus far range from 20 IU [39] to 160 IU [40].”
BackgroundEffects of Intranasal Insulin on Triglyceride-Rich Lipoprotein Particle Production in Healthy Men
Xiao, C., Dash, S., Stahel, P., & Lewis, G. F. (2017) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.309705 · Cited by 16
Odor Sensitivity After Intranasal Insulin Application Is Modulated by Gender
Rodriguez‐Raecke, R., Brünner, Y. F., Kofoet, A., Mutic, S., Benedict, C., & Freiherr, J. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00580 · Cited by 17
“Since the effects of intranasal insulin on energy homeostasis are sex-specific (20, 21), sex effects related to odor detection are probably relevant as well.”
BackgroundResultvan Golen, L. W., IJzerman, R. G., Huisman, M. C., Hensbergen, J. F., Hoogma, R. P. L. M., Drent, M. L., Lammertsma, A. A., & Diamant, M. (2013) · Diabetes Care · doi:10.2337/dc13-0093 · Cited by 16
“decreased food intake inmen (6), whereas”
Editorial: Insulin and The Brain
Taouis, M., & Torres‐Alemán, I. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00299 · Cited by 16
“Indeed, an acute intranasal insulin administration reduces food intake in healthy males (2).”
BackgroundDevelopments in the discovery and design of intranasal antidepressants
Panek, M., Kawalec, P., Pilc, A., & Lasoń, W. (2020) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2020.1776697 · Cited by 17
Li, J., Li, X., Liu, E., Copeland, P. M., Freudenreich, O., GOFF, D. C., Henderson, D. C., Song, X., & Fan, X. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2013.01.034 · Cited by 15
“Insulin treatment decreased food intake in men but not in women (Benedict et al. 2008).”
BackgroundProtective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury
Kikuta, S., Kuboki, A., & Yamasoba, T. (2021) · Frontiers in Neural Circuits · doi:10.3389/fncir.2021.803769 · Cited by 14
“Beneficial effects of intranasal insulin administration have been shown in clinical trials of its use to improve memory and cognition, and to reduce the memory loss caused by Alzheimer’s disease and diabetes (Kern et al., 1999; Benedict et al., 2008; Reger et al., 2008).”
BackgroundKlement, J., Kubera, B., Eggeling, J., Rädel, C., Wagner, C., Park, S. Q., & Peters, A. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.01.014 · Cited by 14
Bruce, K., Garrido, A. N., Zhang, S., & Lam, T. K. T. (2024) · Endocrinology and Metabolism · doi:10.3803/enm.2024.2025 · Cited by 13
“For example, intranasal administration of leptin into rodents reaches the DVC and hypothalamus [30], while in humans, intranasal leptin or insulin administration reduces body weight [31,32] and glucose production ARTICLE IN PRESS [33,34].”
Background
Metadata
- Authors
- Benedict, C., Kern, W., Schultes, B., Born, J., & Hallschmid, M.
- Affiliations
- University of Lübeck (DE)
- Kantonsspital St. Gallen (CH)
- Corresponding author
- Benedict, Christian
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2008-04
- Volume
- 93
- Issue
- 4
- Pages
- 1339-1344
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2046140771
- Cited by
- 296
- References
- 33
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 11 · 2023: 11 · 2022: 11 · 2021: 23 · 2020: 22 · 2019: 14 · 2018: 27 · 2017: 20 · 2016: 17 · 2015: 17 · 2014: 20 · 2013: 26 · 2012: 14
- FWCI
- 5.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- 10th European Congress of Endocrinology
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- intranasal insulin, sex differences, dietary intake, anorectic effect, hippocampal-dependent memory, working memory, mirror tracing, energy homeostasis, memory enhancement
- MeSH terms
- Administration, Intranasal, Adult, Blood Glucose, Eating, Female, Hippocampus, Humans, Insulin, Male, Memory, Sex Characteristics, Signal Transduction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
