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.
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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]
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“Healthy young men were observed to consume fewer calories when they acutely received 160 U of regular human insulin via the intranasal pathway (25).”
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Role of Insulin in Health and Disease: An Update
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“In another study, it has been reported that intranasal administration of single-dose (160 IU) insulin declines food intake in healthy males but not in women [75].”
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Type 3 Diabetes and Its Role Implications in Alzheimer’s Disease
Nguyen, T. T., Ta, Q. T. H., Nguyen, T. K. O., Nguyen, T. T. D., & Giau, V. V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093165 · Cited by 424
“Insulin Only women presented improved working memory after treatment Healthy men and woman intranasally administrated [99]”
BackgroundAlzheimer’s disease and insulin resistance: translating basic science into clinical applications
Felice, F. G. D. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64595 · Cited by 336
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“Thus, insulin may relay both long-term and acute information and was shown to act in the brain to reduce food intake (Woods et al. 1979, Bruning et al. 2000, Benedict et al. 2008).”
Intranasal Treatment of Central Nervous System Dysfunction in Humans
Chapman, C. D., Frey, W. H., Craft, S., Danielyan, L., Hallschmid, M., Schiöth, H. B., & Benedict, C. (2013) · Pharmaceutical Research · doi:10.1007/s11095-012-0915-1 · Cited by 310
“This conclusion is reinforced by other studies demonstrating the same pattern of results in the acute setting, with men eating less following intranasal insulin administration, while women received a memory boost (39).”
BackgroundResultSelf-citationAberrant insulin signaling in Alzheimer's disease: current knowledge
Bedse, G., Domenico, F. D., Serviddio, G., & Cassano, T. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00204 · Cited by 313
“…insulin 160 IU Hippocampus-dependent memory and working memory were improved in women where as men did not benefit from acute insulin treatment Benedict et al., 2008; Krug et al., 2010 MCI and mild AD patients 20 or 40 IU of insulin acute treatment Acute intranasal insulin administration…”
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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 308
“However, men are more sensitive to the anorexigenic effects (feeding control) of insulin than women [152].”
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Neth, B. J., & Craft, S. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00345 · Cited by 284
“Similar memory improvement has been observed following administration of intranasal insulin (Benedict et al., 2004, 2008; Stockhorst et al., 2004; Reger et al., 2006, 2008; Craft et al., 2012; Schiöth et al., 2012; Claxton et al., 2013, 2015; Freiherr et al., 2013; Novak et al., 2014); these…”
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“Both animal and human studies have suggested that the response to intranasal insulin supplementation differs by sex, with insulin slowing cognitive decline in women but not men [96], especially in noncarriers of the APOE ε4 allele [97], whereas APOE ε4 carriers do not respond well to insulin [97].”
BackgroundDiabetes and Alzheimer’s disease crosstalk
Baglietto‐Vargas, D., Shi, J. J., Yaeger, D. M., Ager, R. R., & LaFerla, F. M. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.03.005 · Cited by 263
Impaired insulin action in the human brain: causes and metabolic consequences
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“…does not alter peripheral glucose homeostasis Central delivery of insulin is not reported to alter peripheral blood glucose (Reger and Craft, 2006; Benedict et al., 2008; Hallschmid et al., 2008); therefore, it was not anticipated that the IND-treated mice would undergo repetitive hypoglycemia…”
Central nervous pathways of insulin action in the control of metabolism and food intake
Kullmann, S., Kleinridders, A., Small, D. M., Fritsche, A., Häring, H.-U., Preissl, H., & Heni, M. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30113-3 · Cited by 233
Insulin Resistance in Alzheimer's Disease
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Insulin, cognition, and dementia
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“Several studies have reported that two months of daily insulin administration (4 40 international units/day) significantly improves verbal memory and enhanced mood in young healthy adults (Benedict et al., 2004, 2008; Hallschmid et al., 2008; Stockhorst et al., 2004).”
BackgroundOxytocin Reduces Reward-Driven Food Intake in Humans
Ott, V., Finlayson, G., Lehnert, H., Heitmann, B., Heinrichs, M., Born, J., & Hallschmid, M. (2013) · Diabetes · doi:10.2337/db13-0663 · Cited by 226
“Therefore, we applied a twofold assessment of food intake that relied on the one hand on a large breakfast buffet following an overnight fast to investigate homeostatic, primarily hunger-driven energy intake (20-22), and on the other hand on a collection of snacks of varying palatability offered after breakfast intake…”
BackgroundMethodSelf-citationInsulin regulates astrocyte gliotransmission and modulates behavior
Cai, W., Xue, C., Sakaguchi, M., Konishi, M., Shirazian, A., Ferris, H. A., Li, M. E., Yu, R., Kleinridders, A., Pothos, E. N., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99366 · Cited by 229
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“Benedict et al. [21] reported that women, but not men, noted significant improvement on memory and working memory tasks after acute dosing with intranasal insulin.”
InfluentialАнатольевич, П. И., Costa-Nunes, J. P., Kasatkin, V. N., Veniaminova, E. A., Demchenko, A. G., Lyundup, A. V., Lesch, K., Ponomarev, E. D., & Strekalova, T. V. (2018) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12866 · Cited by 215
Enhancement of Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes
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“Testing on insulin versus placebo (day 2 and day 3) had to be completed within a short time-frame of 2 h after insulin administration because of insulin pharmacokinetics (10,11,22).”
BackgroundBrain insulin signalling in metabolic homeostasis and disease
Scherer, T., Sakamoto, K., & Buettner, C. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00498-x · Cited by 205
Insulin Regulates Brain Function, but How Does It Get There?
Gray, S. M., Meijer, R. I., & Barrett, E. J. (2014) · Diabetes · doi:10.2337/db14-0340 · Cited by 206
“However, chronic intranasal insulin administration, which allows more direct access to the cerebrospinal fluid (CSF) than systemic insulin administration, decreased food intake in fasting men and acutely affected postprandial selection of palatable food by women without causing hypoglycemia (8,9).”
BackgroundJohnson, N. J., Hanson, L. R., & Frey, W. H. (2010) · Molecular Pharmaceutics · doi:10.1021/mp100029t · Cited by 194
Driver, J. A. (2014) · Biogerontology · doi:10.1007/s10522-014-9523-2 · Cited by 184
“Intranasal insulin improves memory and attention in patients with mild cognitive impairment (Benedict et al. 2008; Craft et al. 2012; Shemesh et al. 2012) and is currently being evaluated as treatment for early PD.”
Francis, G. J., Martinez, J. A., Liu, W. Q., Xu, K., Ayer, A. B., Fine, J. M., Tuor, U. I., Glazner, G. W., Hanson, L. R., Frey, W. H., et al. (2008) · Brain · doi:10.1093/brain/awn288 · Cited by 175
RetractedHallschmid, M., Higgs, S., Thienel, M., Ott, V., & Lehnert, H. (2012) · Diabetes · doi:10.2337/db11-1390 · Cited by 181
“Considering that remembering a preceding meal has been previously shown to decrease snack consumption (15,16) and that intranasal insulin improves declarative, hippocampus-dependent memory functions (6,17), experiment I included a free recall of lunch memory which, however, did not yield any signs of insulinimproved m…”
BackgroundResultInfluentialNose-to-brain peptide delivery – The potential of nanotechnology
Samaridou, E., & Alonso, M. J. (2017) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.11.001 · Cited by 183
Intranasal Insulin for Alzheimer’s Disease
Hallschmid, M. (2021) · CNS Drugs · doi:10.1007/s40263-020-00781-x · Cited by 188
Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood
Lee, S.-H., Zabolotny, J. M., Huang, H., Lee, H., & Kim, Y.-B. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.06.011 · Cited by 176
“In normal weight adults, intranasal insulin (160 IU) acutely decreased food intake in men, however body weight was not altered under these conditions in pre or post menopausal women [72,73].”
BackgroundZhang, H., Hao, Y., Manor, B., Novak, P., Milberg, W., Zhang, J., Fang, J., & Novak, V. (2015) · Diabetes · doi:10.2337/db14-1000 · Cited by 176
“Cognitive assessment on insulin versus placebo (days 2 and 3) was performed after MRI scan and had to be completed within 2 h after drug administration because of insulin pharmacokinetics (8,21,22).”
MethodBrain Insulin Signaling and Alzheimer's Disease: Current Evidence and Future Directions
Schiöth, H. B., Craft, S., Brooks, S. J., Frey, W. H., & Benedict, C. (2011) · Molecular Neurobiology · doi:10.1007/s12035-011-8229-6 · Cited by 168
“While the delayed onset of insulin's action on memory points to the involvement of more gradual plastic processes determining neuronal function, recent data also indicate that a single dose of intranasal insulin acutely improves hippocampus-dependent memory in both young [9] and middle-aged [35] women.”
ResultIntranasal delivery of neurotrophic factors BDNF, CNTF, EPO, and NT-4 to the CNS
Alcala, S. R., Lee, M. S., Hanson, L. R., McDonald, A. A., Frey, W. H., & McLoon, L. K. (2009) · Journal of drug targeting · doi:10.3109/10611860903318134 · Cited by 165
“However, recent studies demonstrate intranasal delivery to the CNS occurs in nonhuman primates (Thorne et al, 2008; Yamada et al., 2008) and humans (Hallschmid et al., 2004; Benedict et al., 2008), supporting the potential clinical relevance of this approach.”
BackgroundIntranasal Insulin Suppresses Food Intake via Enhancement of Brain Energy Levels in Humans
Jauch‐Chara, K., Friedrich, A., Rezmer, M., Melchert, U. H., Scholand-Engler, H. G., Hallschmid, M., & Oltmanns, K. M. (2012) · Diabetes · doi:10.2337/db12-0025 · Cited by 163
“serum insulin levels accompanied by a slight drop in plasma glucose (7,21).”
BackgroundMethodInfluentialEffect of Intranasal Insulin on Cognitive Function: A Systematic Review
Shemesh, E., Rudich, A., Harman-Boehm, I., & Cukierman-Yaffe, T. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1802 · Cited by 162
Strategies To Deliver Peptide Drugs to the Brain
Lalatsa, A., Schätzlein, A. G., & Uchegbu, I. F. (2014) · Molecular Pharmaceutics · doi:10.1021/mp400680d · Cited by 167
Insulin resistance and pathological brain ageing
Cholerton, B., Baker, L. D., & Craft, S. (2011) · Diabetic Medicine · doi:10.1111/j.1464-5491.2011.03464.x · Cited by 164
Intranasal insulin as a therapeutic option in the treatment of cognitive impairments
Benedict, C., Frey, W. H., Schiöth, H. B., Schultes, B., Jan Born, A., & Hallschmid, M. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.08.026 · Cited by 165
“Recent data indicate that the memoryimproving effects of acutely administered insulin are more pronounced in women than in men, pointing to the potential relevance of gender differences in the emergence of central nervous insulin effects (Benedict et al., 2008).”
Insulin Modulates Food-Related Activity in the Central Nervous System
Guthoff, M., Grichisch, Y., Canova, C., Tschritter, O., Veit, R., Hallschmid, M., Häring, H., Preissl, H. T., Hennige, A. M., & Fritsche, A. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1677 · Cited by 157
Insulin and Alzheimer's Disease: Untangling the Web
Craft, S., Cholerton, B., & Baker, L. D. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129042 · Cited by 161
“Several studies have reported that two months of daily insulin administration (4×40 IU/day) significantly improves verbal memory and enhanced mood in young healthy adults [Stockhorst et al, unpublished results, [79–82]].”
Stein, M. S., Scherer, S. C., Ladd, K. S., & Harrison, L. C. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110149 · Cited by 153
“On the other hand, nasal insulin, which enters the CSF [9] but not the systemic circulation without absorption promoting agents [10], improves word recall and mood in healthy volunteers [11–13] and declarative memory in AD [14, 15], but the studies of nasal insulin in AD have”
BackgroundInsulin action in the brain regulates both central and peripheral functions
Agrawal, R., Reno, C. M., Sharma, S., CHRISTENSEN, C. G., Huang, Y., & Fisher, S. J. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00642.2020 · Cited by 153
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“by promoting weight gain in the form of muscle and fat mass [73,74], IN and ICV insulin administration in humans and animals, respectively, induces catabolic effects by reducing food intake [19,23] and as a consequence body fat content [20,21] particularly in the male organism [21–23].”
BackgroundInfluentialSelf-citationIntranasal drug targeting of hypocretin-1 (orexin-A) to the central nervous system
Dhuria, S. V., Hanson, L. R., & Frey, W. H. (2008) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21604 · Cited by 135
Cheke, L. G., Bonnici, H. M., Clayton, N. S., & Simons, J. S. (2017) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2017.01.013 · Cited by 133
“…(while keeping glucose levels stable) has been found to improve hippocampal-dependant (word-list) memory (Kern et al., 1999), and such findings have been reflected in trials using intranasal infusions of insulin (Benedict et al., 2004, 2008; Hallschmid et al., 2008; Stockhorst et al., 2004).”
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
“Notably, intranasal insulin reduces food intake (9) and body fat content (10) in healthy men, indicating that following intranasal administration, the hormone accesses neuronal networks relevant for energy homeostasis.”
BackgroundResultInfluentialSelf-citationObesity – A neuropsychological disease? Systematic review and neuropsychological model
Jauch‐Chara, K., & Oltmanns, K. M. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.12.001 · Cited by 136
Intranasal Insulin Ameliorates Tau Hyperphosphorylation in a Rat Model of Type 2 Diabetes
Yang, Y., Ma, D., Wang, Y., Jiang, T., Hu, S., Zhang, M., Yu, X., & Gong, C. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-121294 · Cited by 119
“Because insulin enhances hippocampusdependent learning and memory, intranasal insulin has been used in several small clinical trials that have yielded beneficial outcomes [30, 31].”
BackgroundSex and race differences in caloric intake during sleep restriction in healthy adults
Spaeth, A. M., Dinges, D. F., & Goel, N. (2014) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.114.086579 · Cited by 118
Insulin Resistance Exacerbates Alzheimer Disease via Multiple Mechanisms
Wei, Z.-H., Koya, J., & Reznik, S. E. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.687157 · Cited by 133
Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke
Lioutas, V., Alfaro-Martinez, F., Bedoya, F. J., Chung, C., Maldonado, D. P., & Novak, V. (2015) · Translational Stroke Research · doi:10.1007/s12975-015-0409-7 · Cited by 115
Binge Drinking Induces Whole-Body Insulin Resistance by Impairing Hypothalamic Insulin Action
Lindtner, C., Scherer, T., Zieliński, E., Filatova, N., Faßhauer, M., Tonks, N. K., Puchowicz, M., & Buettner, C. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005123 · Cited by 114
“Because there are gender differences in brain insulin action in mice and humans (22, 37), we first tested whether insulin delivered directly to the MBH suppressed hGP and lipolysis in female SD rats as we and others have reported for male SD rats (10, 11).”
Hallschmid, M. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12934 · Cited by 113
Kullmann, S., Frank, S., Heni, M., Ketterer, C., Veit, R., Häring, H.-U., Fritsche, A., & Preissl, H. (2013) · Neuroendocrinology · doi:10.1159/000341406 · Cited by 110
Safety of intranasal human insulin: A review
Schmid, V., Kullmann, S., Gfrörer, W., Hund, V., Hallschmid, M., Lipp, H., Häring, H., Preissl, H., Fritsche, A., & Heni, M. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13279 · Cited by 110
Dash, S., Xiao, C., Morgantini, C., Koulajian, K., & Lewis, G. F. (2015) · Diabetes · doi:10.2337/db14-0685 · Cited by 108
“In human studies of INI, an acute reduction in appetite was reported after a single dose in men (10), with a reduction in postprandial satiety and intake of palatable food in women (11).”
BackgroundRodriguez, M., Lapierre, J., Ojha, C. R., Kaushik, A. K., Batrakova, E. V., Kashanchi, F., Dever, S. M., Nair, M., & El‐Hage, N. (2017) · Scientific Reports · doi:10.1038/s41598-017-01819-9 · Cited by 106
Molecular Mechanisms of Hypothalamic Insulin Resistance
Ono, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061317 · Cited by 112
“When insulin is sprayed into the nostrils of humans, food intake [5] and endogenous glucose production [6] are both suppressed.”
BackgroundHiggs, 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 108
“For example, intranasal insulin improves declarative memory and working memory in humans (Benedict et al., 2004, 2008; Hallschmid et al., 2008, 2012; Stockhorst et al., 2004).”
BackgroundIntranasal 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 111
“…the vast majority of studies dealing with effects of intranasal insulin on memory in cognitively healthy humans did not report adverse effects, except for some reporting transient drops in plasma glucose (Benedict et al., 2008) and an acute elevation of blood pressure (Benedict et al., 2005).”
Sex differences in Alzheimer’s disease: Understanding the molecular impact
Toro, C. A., Zhang, L., Cao, J., & Cai, D. (2019) · Brain Research · doi:10.1016/j.brainres.2019.05.031 · Cited by 105
Laron, Z. (2009) · Archives of Physiology and Biochemistry · doi:10.1080/13813450902949012 · Cited by 97
“As the intranasal administration of insulin also produced metabolic changes, dropping plasma glucose levels (Benedict et al., 2008), it is uncertain to what extent the cognitive effect is due to a direct insulin action.”
BackgroundBenedict, C., & Grillo, C. A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00215 · Cited by 101
“Interestingly, single dose intranasal insulin reduces food intake in healthy normal-weight males but not in females; conversely, hippocampus-dependent memory and working memory were improved in females, but not in males (Benedict et al., 2008).”
BackgroundNon-Invasive Strategies for Nose-to-Brain Drug Delivery.
Ja, T., Quispe, R. C., Khan, F. A., & Новак (2020) · PubMed · Cited by 114
Role of Insulin Resistance in the Alzheimer's Disease Progression
Nguyen, T. T., Ta, Q. T. H., Nguyen, T. T. D., Le, T. T. H., & Giau, V. V. (2020) · Neurochemical Research · doi:10.1007/s11064-020-03031-0 · Cited by 103
Stress disrupts context-dependent memoryPreprint
Schwabe, L., Böhringer, A., & Wolf, O. T. (2009) · Learning & Memory · doi:10.1101/lm.1257509 · Cited by 95
“Similar to other authors who used the same object-location task (Rasch et al. 2007; Benedict et al. 2008), we suggest that accuracy parameters are more sensitive to the influence of memory modulators, such as stress, than speed parameters.”
ResultSchmidt, H., Kern, W., Giese, R. M., Hallschmid, M., & Enders, A. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2008.062141 · Cited by 94
“Intranasal insulin administration improves declarative memory in healthy subjects and patients with Alzheimer’s disease [7-12].”
BackgroundKullmann, S., Heni, M., Veit, R., Scheffler, K., Machann, J., Häring, H., Fritsche, A., & Preissl, H. T. (2017) · Scientific Reports · doi:10.1038/s41598-017-01907-w · Cited by 93
Stern, S. A., Chen, D. Y., & Alberini, C. M. (2014) · Learning & Memory · doi:10.1101/lm.029348.112 · Cited by 89
“In line with this hypothesis, more persistent memory-enhancing effects of insulin, and specifically on memories relying on hippocampal functions such as declarative memories, have been reported in human with prolonged intranasal administrations, whereas nondeclarative memories, such as wordstem priming, were found to…”
BackgroundWu, H., Zhou, Y., Wang, Y., Tong, L., Wang, F., Song, S., Xu, L., Liu, B., Yan, H., & Sun, Z. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.717192 · Cited by 90
“…the greatest TLS were as follows: Illum L (Illum, 2000; Illum, 2003), Thorne RG (Thorne and Frey, 2001; Thorne et al., 2004), Dhuria SV (Dhuria et al., 2009; Dhuria et al., 2010), Benedict C (Benedict et al., 2004; Benedict et al., 2008), and Born J (Benedict et al., 2004; Hallschmid et al., 2004).”
BackgroundHallschmid, M., & Schultes, B. (2009) · Diabetologia · doi:10.1007/s00125-009-1501-x · Cited by 90
“These controversial findings do not permit solid conclusions regarding a sex-related difference in central nervous processing of adiposity signals, although, in accordance with this assumption, intranasal insulin acutely reduces test buffet consumption in men but not in women [19].”
BackgroundResultGruber, 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 96
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
Maimaiti, S., Anderson, K. L., DeMoll, C., Brewer, L. D., Rauh, B. A., Gant, J. C., Blalock, E. M., Porter, N. M., & Thibault, O. (2015) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu314 · Cited by 86
“Clearly, the memory enhancing effects of insulin are depend on treatment regimen (acute vs subchronic), but also on the age and gender of the subject (73), as well as on the insulin formulation used (52,74).”
BackgroundIntranasal 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 89
“Men were found to be more sensitive than women to appetite/anorexogenic and metabolic effects of intranasal insulin [69,74], while both premenopausal and postmenopausal women were found to be more sensitive to insulin stimulation of hippocampus-dependent memory functions [74,75].”
Schilling, T. M., de Sá, D. S. F., Westerhausen, R., Strelzyk, F., Larra, M. F., Hallschmid, M., Savaskan, E., Oitzl, M. S., Busch, H., Naumann, E., et al. (2013) · Human Brain Mapping · doi:10.1002/hbm.22304 · Cited by 84
“Although intranasal insulin provokes a decrease in food intake in men, hunger ratings do not seem to reflect this tendency, suggesting that the acute anorexigenic effects of central insulin are mediated by satiation signals but not by motivation to eat or a conscious behavioral process [Benedict et al., 2008].”
BackgroundResultHölscher, C. (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.12.006 · Cited by 86
Deregulation of brain insulin signaling in Alzheimer’s disease
Chen, Y., Deng, Y., Zhang, B., & Gong, C. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1408-x · Cited by 82
“Besides, insulin signaling is associated with the regulation of memory and cognition, modulation of tau phosphorylation, APP expression and Aβ clearance, and cerebral glucose metabolism([58-67]).”
BackgroundGlucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity
Anandhakrishnan, A., & Korbonits, M. (2016) · World Journal of Diabetes · doi:10.4239/wjd.v7.i20.572 · Cited by 83
Effects of Intranasal Insulin on Hepatic Fat Accumulation and Energy Metabolism in Humans
Gancheva, S., Koliaki, C., Bierwagen, A., Nowotny, P., Heni, M., Fritsche, A., Häring, H.-U., Szendroedi, J., & Roden, M. (2015) · Diabetes · doi:10.2337/db14-0892 · Cited by 81
“All participants were studied using identical protocols on 2 study days spaced by at least 7 days, except for the intranasal administration of insulin or placebo at time 0 (18).”
MethodResultGLP-1 receptor agonists show neuroprotective effects in animal models of diabetes
Gault, V. A., & Hölscher, C. (2018) · Peptides · doi:10.1016/j.peptides.2017.11.017 · Cited by 83
“In clinical trials, verbal and spatial memory was improved after administration of a single dose of insulin (Benedict et al., 2008; Krug et al., 2010).”
Hypothalamic inflammation in metabolic disorders and aging
Bhusal, A., Rahman, M. H., & Suk, K. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04019-x · Cited by 87
“The exogenous administration of insulin in the brain might act on these receptors and reduce food intake, body weight [156], and endogenous glucose production [157].”
BackgroundYu, I.-C. I., Lin, H., Liu, N.-C., Sparks, J. D., Yeh, S., Fang, L., Chen, L., & Chang, C. (2012) · Diabetes · doi:10.2337/db12-0135 · Cited by 79
“Moreover, a single dose of insulin reduces food intake in men, but not in women (15).”
BackgroundDose-Dependent Effects of Intranasal Insulin on Resting-State Brain Activity
Kullmann, S., Veit, R., Peter, A., Pohmann, R., Scheffler, K., Häring, H.-U., Fritsche, A., Preissl, H., & Heni, M. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01976 · Cited by 78
Krug, R., Benedict, C., Jan Born, A., & Hallschmid, M. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0744 · Cited by 74
Role of Insulin in Neurotrauma and Neurodegeneration: A Review
Shaughness, M., Acs, D., Brabazon, F., Hockenbury, N., & Byrnes, K. R. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.547175 · Cited by 78
“Women demonstrated improved hippocampus-dependent memory and working memory with intranasal insulin, while men did not (Benedict et al., 2008).”
BackgroundState 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
“Furthermore, there is a differential sensitivity to INL insulin between men and women [210, 238] and sex differences in brain insulin signaling have been noted [224].”
BackgroundCentral 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
“Since insulin possesses anorexigenic properties in humans (6), both food, as well as nonfood odors, were utilized as memory cues.”
MethodPeptides as Potential Therapeutics for Alzheimer’s Disease
Ribarič, S. (2018) · Molecules · doi:10.3390/molecules23020283 · Cited by 69
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
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