The DOI matches its Crossref record; 22 of the 24 references it cites were found in a registry or an index.
Intranasal delivery of insulin via the olfactory nerve pathway
Abstract
Objectives: Intranasal delivery has been shown to target peptide therapeutics to the central nervous system (CNS) of animal models and induce specific neurological responses. In an investigation into the pathways by which intranasal administration delivers insulin to the CNS, this study has focused on the direct delivery of insulin from the olfactory mucosa to the olfactory bulbs via the olfactory nerve pathway. Methods: Nasal and olfactory tissues of mice were imaged with fluorescent and electron microscopy 30 min following intranasal administration. Key findings: Macroscopic analysis confirmed delivery to the anterior regions of the olfactory bulbs. Confocal microscopy captured delivery along the olfactory nerve bundles exiting the nasal mucosa, traversing the cribriform plate and entering the bulbs. With electron microscopy, insulin was found within cells of the olfactory nerve layer and glomerular layer of the olfactory bulbs. Conclusions: These results demonstrated that intranasal administration of labelled insulin targeted the CNS through the olfactory nerve pathway in mice.
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
“This is likely because of the limited number of routes to reach the brain, such as blood-brain barrier and extraneuronal/perineuronal routes along the trigeminal or olfactory nerves.10, 49, 50, 51, 52, 53”
From Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial (2016) · cites this paper as [53]
Citations
Cites
1 retracted
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
Self-citationRetractedCraft, S. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.233 · Cited by 1,253
Intranasal delivery to the central nervous system: Mechanisms and experimental considerations
Dhuria, S. V., Hanson, L. R., & Frey, W. H. (2010) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21924 · Cited by 1,239
Self-citationInsulin 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
Thorne, R. G., Pronk, G. J., Padmanabhan, V., & Frey, W. H. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.029 · Cited by 958
Self-citationThe source of cerebral insulin
Banks, W. A. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.02.040 · Cited by 489
UNGER, J., Livingston, J. H., & Moss, A. (1991) · Progress in Neurobiology · doi:10.1016/0301-0082(91)90015-s · Cited by 399
Quantitative analysis of the olfactory pathway for drug delivery to the brain
Thorne, R. G., Emory, C. R., Ala, T. A., & Frey, W. H. (1995) · Brain Research · doi:10.1016/0006-8993(95)00637-6 · Cited by 352
Self-citationBroadwell, R. D., & Balin, B. J. (1985) · The Journal of Comparative Neurology · doi:10.1002/cne.902420410 · Cited by 181
Li, Y., Field, P. M., & Raisman, G. (2005) · Glia · doi:10.1002/glia.20241 · Cited by 168
Effect 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
Baker, H. A., & Spencer, R. F. (1986) · Experimental Brain Research · doi:10.1007/bf00237470 · Cited by 147
Uptake of exogenous proteins in mouse olfactory cells
Kristensson, K., & Olsson, Y. (1971) · Acta Neuropathologica · doi:10.1007/bf00688493 · Cited by 117
Ensheathment of the olfactory nerves in the adult rat
Field, P., Li, Y., & Raisman, G. (2003) · Journal of Neurocytology · doi:10.1023/b:neur.0000010089.37032.48 · Cited by 98
Westin, U., Piras, E., Jansson, B., Bergström, U., Dahlin, M., Brittebo, E. B., & Björk, E. (2005) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2005.01.009 · Cited by 96
Visualization of In Vivo Olfactory Uptake and Transfer Using Fluorescein Dextran
Jansson, B., & Björk, E. (2002) · Journal of drug targeting · doi:10.1080/1061186021000001823 · Cited by 82
Smith, R. M., & Jarett, L. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.2.459 · Cited by 82
Pan, W., Hsuchou, H., Xu, C., Wu, X., Bouret, S. G., & Kastin, A. J. (2010) · Journal of Molecular Neuroscience · doi:10.1007/s12031-010-9470-6 · Cited by 50
Larsson, P. (2000) · Toxicological Sciences · doi:10.1093/toxsci/55.2.383 · Cited by 43
Shah, N., Zhang, S., Harada, S., Smith, R. M., & Jarett, L. (1995) · Endocrinology · doi:10.1210/endo.136.7.7789307 · Cited by 35
Mechanisms of nuclear translocation of insulin
Harada, S., Smith, R. M., & Jarett, L. (1999) · Cell Biochemistry and Biophysics · doi:10.1007/bf02738245 · Cited by 33
[Olfactory disorders in Alzheimer's disease and in Parkinson's disease. Review of the literature].
Norès, J. M., Biacabe, B., & Bonfils, P. (2000) · PubMed · Cited by 13
Research works printed but not linked: 3
- Frey, 1997, Method of Administering Neurologic Agents to the Brain
- Frey, 2001, Method for Administering Insulin to the Brain
- Frey, 1991, Neurologic Agents for Nasal Administration to the Brain
Cited by
Sorted by citations
Kellar, D., & Craft, S. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30231-3 · Cited by 832
Intranasal drug delivery: opportunities and toxicologic challenges during drug development
Keller, L.-A., Merkel, O. M., & Popp, A. (2021) · Drug Delivery and Translational Research · doi:10.1007/s13346-020-00891-5 · Cited by 636
“8 kDa) [48], also gold particle (50 nm) [49, 50] and aluminium salts [51] are known to endocytose.”
BackgroundFreiherr, J., Hallschmid, M., Frey, W. H., Brünner, Y. F., Chapman, C. D., Hölscher, C., Craft, S., Felice, F. G. D., & Benedict, C. (2013) · CNS Drugs · doi:10.1007/s40263-013-0076-8 · Cited by 477
“Thus, this method selectively increases CNS insulin levels and is therefore suitable for the investigation of both the shortand long-term effects of insulin on the human brain without the potential confound of peripheral side effects [92].”
BackgroundSelf-citationIntranasal 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
“pons and the cribriform plate, which allows for drug delivery to both the anterior and posterior regions of the brain (9,12).”
BackgroundSelf-citationImpaired insulin action in the human brain: causes and metabolic consequences
Heni, M., Kullmann, S., Preissl, H., Fritsche, A., & Häring, H.-U. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.173 · Cited by 245
Metadata
- Authors
- Renner, D. B., Svitak, A. L., Gallus, N. J., Ericson, M. E., Frey, W. H., & Hanson, L. R.
- Affiliations
- Regions Hospital (US)
- Corresponding author
- Renner, Dan B
- Venue
- Journal of Pharmacy and Pharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-12-01
- Volume
- 64
- Issue
- 12
- Pages
- 1709-1714
- ISSN
- 0022-3573 (ISSN-L)
- 2042-7158
- OpenAlex
- W1612293997
- Cited by
- 116
- References
- 24
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 11 · 2023: 14 · 2022: 7 · 2021: 13 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 10 · 2016: 4 · 2015: 7 · 2014: 9 · 2013: 6 · 2012: 1
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Pharmacy and Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- olfactory bulb, olfactory epithelium, central nervous system targeting, peptide therapeutics, cribriform plate, glomerular layer, intranasal drug delivery
- MeSH terms
- Administration, Intranasal, Animals, Central Nervous System, Ethmoid Bone, Insulin, Male, Mice, Inbred C57BL, Microscopy, Nasal Mucosa, Olfactory Bulb, Olfactory Nerve, Olfactory Pathways, Mice
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