The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Intranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart
Abstract
There is compelling evidence that intranasal administration of regular human insulin (RH-I) improves memory in humans. Owing to the reduced tendency of its molecules to form hexamers, the rapid-acting insulin analog insulin aspart (ASP-I) is more rapidly absorbed than RH-I after subcutaneous administration. Since after intranasal insulin administration, ASP-I may also be expected to access the brain, we examined whether intranasal ASP-I has stronger beneficial effects on declarative memory than RH-I in humans. Acute (40 IU) and long-term (4 x 40 IU/day over 8 weeks) effects of intranasally administered ASP-I, RH-I, and placebo on declarative memory (word lists) were assessed in 36 healthy men in a between-subject design. Plasma insulin and glucose levels were not affected. After 8 weeks of treatment, however, word list recall was improved compared to placebo in both the ASP-I (p<0.01) and the RH-I groups (p<0.05). ASP-I-treated subjects performed even better than those of the RH-I-treated group (p<0.05). Our results indicate that insulin-induced memory improvement can be enhanced by using ASP-I. This finding may be especially relevant for a potential clinical administration of intranasal insulin in the treatment of memory disorders like Alzheimer's disease.
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“Administering the rapid-acting insulin analogue insulin aspart intensifies the improvement in declarative memory.40”
From Intranasal insulin (2021) · cites this paper as [40]
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Cites
Steen, E., Terry, B. M., J. Rivera, E., Cannon, J. L., Neely, T. R., Tavares, R., Xu, X. J., Wands, J. R., & de la Monte, S. M. (2005) · Journal of Alzheimer's Disease · doi:10.3233/jad-2005-7107 · Cited by 1,703
The Neurobiology of Consolidations, Or, How Stable is the Engram?
Dudai, Y. (2004) · Annual Review of Psychology · doi:10.1146/annurev.psych.55.090902.142050 · Cited by 1,671
Eichenbaum (2004) · doi:10.1016/j.neuron.2004.08.028 · Cited by 1,464
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
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
Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity
Liu, L., Wong, T. P., Pozza, M. F., Lingenhoehl, K., Wang, Y., Sheng, M., Auberson, Y. P., & Wang, Y. T. (2004) · Science · doi:10.1126/science.1096615 · Cited by 1,131
Thorne, R. G., Pronk, G. J., Padmanabhan, V., & Frey, W. H. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.029 · Cited by 958
Transport of drugs from the nasal cavity to the central nervous system
Illum, L. (2000) · European Journal of Pharmaceutical Sciences · doi:10.1016/s0928-0987(00)00087-7 · Cited by 907
Underwood, B. J. (1957) · Psychological Review · doi:10.1037/h0044616 · Cited by 853
Insulin and neurodegenerative disease: shared and specific mechanisms
Craft, S., & Stennis Watson, G. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00681-7 · Cited by 830
Kurtzhals, P., Schäffer, L., Sørensen, A., Kristensen, C., Jonassen, I., Schmid, C., & Trüb, T. (2000) · Diabetes · doi:10.2337/diabetes.49.6.999 · Cited by 739
Rivera, E. J., Goldin, A., Fulmer, N., Tavares, R., Wands, J. R., & de la Monte, S. M. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-8304 · Cited by 723 · cited 1×
“…disorder with strikingly reduced CNS expression of genes encoding insulin, IGF-I and IGF-II, as well as the insulin and IGF-I receptors (Rivera et al, 2005), our finding of improved memory performance after intranasal intake of insulin and its analogs may be of significance for the…”
BackgroundIntranasal 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
Self-citationThe assessment of insulin resistance in man
Wallace, T. M., & Matthews, D. R. (2002) · Diabetic Medicine · doi:10.1046/j.1464-5491.2002.00745.x · Cited by 685
Reger, 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
Memory improvement following induced hyperinsulinemia in Alzheimer’s disease
Craft, S., Newcomer, J., Kanne, S., Dagogo-Jack, S., Cryer, P., Sheline, Y., Luby, J., Dagogo-Jack, A., & Alderson, A. (1996) · Neurobiology of Aging · doi:10.1016/0197-4580(95)02002-0 · Cited by 538
Brain Insulin Receptors and Spatial Memory
Zhao, W., Chen, H., Xu, H., Moore, E., Meiri, N., Quon, M. J., & Alkon, D. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.49.34893 · Cited by 532
Insulin and the insulin receptor in experimental models of learning and memory
Zhao, W., Chen, H., Quon, M. J., & Alkon, D. L. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.02.045 · Cited by 508
Monomeric Insulins and Their Experimental and Clinical Implications
Brange, J., Owens, D. R., Kang, S., & Vølund, A. (1990) · Diabetes Care · doi:10.2337/diacare.13.9.923 · Cited by 369
Hermansen, K., Fontaine, P., Kukolja, K. K., Peterkova, V., Leth, G., & Gall, M.-A. (2004) · Diabetologia · doi:10.1007/s00125-004-1365-z · Cited by 365
O'Kusky, J. R., Ye, P., & D'Ercole, A. J. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-22-08435.2000 · Cited by 358
The hippocampus and mechanisms of declarative memory
Eichenbaum, H. (1999) · Behavioural Brain Research · doi:10.1016/s0166-4328(99)00044-3 · Cited by 353
Enhancement of Memory in Alzheimer Disease With Insulin and Somatostatin, but Not Glucose
Craft, S., Asthana, S., Newcomer, J. W., Wilkinson, C. W., Matos, I. T., Baker, L. D., Cherrier, M., Lofgreen, C., Latendresse, S., Petrova, A., et al. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.12.1135 · Cited by 312
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
Self-citationSkeberdis, V. A., Lan, J.-Y., Zheng, X., Zukin, R. S., & Bennett, M. V. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051634698 · Cited by 303
Van Der Heide, L. P., Kamal, A., Artola, A., Gispen, W. H., & Ramakers, G. M. J. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03269.x · Cited by 278
Potential roles of insulin and IGF-1 in Alzheimer's disease
Gasparini, L., & Xu, H. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00163-2 · Cited by 275
Craft, S., Asthana, S., Cook, D. G., Baker, L. D., Cherrier, M. M., Purganan, K., Wait, C., Petrova, A., Latendresse, S. J., Watson, G. S., et al. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00087-2 · Cited by 254
Ross, T. M., Martinez, P. M., Renner, J. C., Thorne, R. G., Hanson, L. R., & Frey, W. H. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.02.011 · Cited by 242
Varieties of human spatial memory: a meta-analysis on the effects of hippocampal lesions
Kessels, R. P. C., de Haan, E. H. F., Kappelle, L. J., & Postma, A. (2001) · Brain Research Reviews · doi:10.1016/s0165-0173(01)00058-3 · Cited by 236
NMDA Receptors and Learning and Memory Processes
Castellano, C., Cestari, V., & Ciamei, A. (2001) · Current Drug Targets · doi:10.2174/1389450013348515 · Cited by 197
Insulin analogs with improved pharmacokinetic profiles
Brange, J., & Vølund, A. (1999) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(98)00079-9 · Cited by 194
Insulin detemir and insulin aspart: a promising basal-bolus regimen for type 2 diabetes
Rašlová, K., Bogoev, M. K., Raz, I., Leth, G., Gall, M. ‐., & Hâncu, N. (2004) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2004.03.003 · Cited by 193
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
Self-citationThe Neuroanatomy of Remote Memory
Bayley, P. J., Gold, J. J., Hopkins, R. O., & Squire, L. R. (2005) · Neuron · doi:10.1016/j.neuron.2005.04.034 · Cited by 178
Wickelgren, I. (1998) · Science · doi:10.1126/science.280.5363.517 · Cited by 169
New Twist on Neuronal Insulin Receptor Signaling in Health, Disease, and Therapeutics
Wada, A., Yokoo, H., Yanagita, T., & Kobayashi, H. (2005) · Journal of Pharmacological Sciences · doi:10.1254/jphs.crj05006x · Cited by 95
Kang, S., CREAGH, F. M., Peters, J. R., Brange, J., Vølund, A., & Owens, D. R. (1991) · Diabetes Care · doi:10.2337/diacare.14.7.571 · Cited by 88
Insulin receptor substrate-1 (IRS-1) expression in rat brain
Baskin, D. G., Schwartz, M. W., Sipols, A. J., D’Alessio, D. A., Goldstein, B. J., & White, M. F. (1994) · Endocrinology · doi:10.1210/endo.134.4.7511094 · Cited by 86
Adaptation of cognitive function to hypoglycemia in healthy men.
Fruehwald‐Schultes, B., Jan Born, A., Kern, W., Peters, A., & Fehm, H. L. (2000) · Diabetes Care · doi:10.2337/diacare.23.8.1059 · Cited by 68
Self-citationInsulin Affects the Neuronal Response in the Medial Temporal Lobe in Humans
Rotte, M., Baerecke, C., Pottag, G., Klose, S., Kanneberg, E., Heinze, H., & Lehnert, H. (2005) · Neuroendocrinology · doi:10.1159/000084874 · Cited by 48
Insulin aspart: a novel rapid-acting human insulin analogue
Gammeltoft, S., Hansen, B. F., Dideriksen, L., Lindholm, A., Schäffer, L., Trüb, T., Dayan, A. D., & Kurtzhals, P. (1999) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.8.9.1431 · Cited by 43
The temporal course of proactive inhibition for serial lists.
Postman, L. J. (1962) · Journal of Experimental Psychology · doi:10.1037/h0048063 · Cited by 39
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Alzheimer’s disease is type 3 diabetes—Evidence reviewed
de la Monte, S. M., & Wands, J. R. (2008) · Journal of Diabetes Science and Technology · doi:10.1177/193229680800200619 · Cited by 1,158
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Metadata
- Authors
- Benedict, C., Hallschmid, M., Schmitz, K., Schultes, B., Ratter, F., Fehm, H. L., Born, J., & Kern, W.
- Affiliations
- University of Lübeck (DE)
- Kantonsspital St. Gallen (CH)
- Novo Nordisk (Germany) (DE)
- Corresponding author
- Benedict, Christian
- Venue
- Neuropsychopharmacology
- Published
- 2006-08-16
- Volume
- 32
- Issue
- 1
- Pages
- 239-243
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2156600347
- Cited by
- 302
- References
- 43
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 8 · 2023: 16 · 2022: 18 · 2021: 15 · 2020: 17 · 2019: 16 · 2018: 28 · 2017: 16 · 2016: 13 · 2015: 16 · 2014: 17 · 2013: 19 · 2012: 14
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB654)
- Novo Nordisk
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Keywords
- intranasal insulin, insulin aspart, regular insulin, declarative memory, memory enhancement, insulin analogues, word list recall, Alzheimer's disease, cognitive impairment treatment
- MeSH terms
- Administration, Intranasal, Adolescent, Adult, Analysis of Variance, Blood Glucose, Double-Blind Method, Drug Administration Schedule, Humans, Hypoglycemic Agents, Insulin, Male, Memory, Neuropsychological Tests, Insulin Aspart
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