Evidence for altered transport of insulin across the blood–brain barrier in insulin-resistant humans
Abstract
Eating behavior, body weight regulation, peripheral glucose metabolism, and cognitive function depend on adequate insulin action in the brain, and recent studies in humans suggested that impaired insulin action in the brain emerges upon fat intake, obesity, and genetic variants. As insulin enters into the brain in a receptor-mediated fashion, we hypothesized that whole-body insulin sensitivity might affect the transport of insulin into the brain and contribute to the aversive effect of insulin resistance in the central nervous system. In this study, we aimed to determine the ratio of insulin in the cerebrospinal fluid and serum to whole-body insulin sensitivity. Healthy human subjects participated in an oral glucose tolerance test to determine whole-body insulin sensitivity and underwent lumbar puncture. Blood and CSF concentrations of insulin were significantly correlated. The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity with reduced insulin transported into the CSF in insulin-resistant subjects. Together, our data suggest that transport of insulin into the CSF relates to peripheral insulin sensitivity and impairs insulin action in the brain. This underlines the need for sensitizing measures in insulin-resistant subjects.
Integrity signals
Registry
Cites
Statistics
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?
Other factors such as genetic background, elevated circulating free fatty acids and impaired insulin transport across the blood-brain barrier have also been implicated in brain insulin resistance.
“although other factors, such as genetic background19, elevated circulating free fatty acids20 and impaired insulin transport across the blood–brain barrier21,22, have also been implicated.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [22]
Cites
Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs.
Kaiyala, K. J., Prigeon, R. L., Kahn, S. E., Woods, S. C., & Schwartz, M. W. (2000) · Diabetes · doi:10.2337/diabetes.49.9.1525 · Cited by 324 · see citing works
Insulin and the Blood-Brain Barrier
Woods, S. C., Seeley, R. J., Baskin, D. G., & Schwartz, M. W. (2003) · Current Pharmaceutical Design · doi:10.2174/1381612033455323 · Cited by 321 · see citing works
Stümvoll, M., van Haeften, T. W., Fritsche, A., & Gerich, J. E. (2001) · Diabetes Care · doi:10.2337/diacare.24.4.796 · Cited by 305 · see citing works
Self-citationTschritter, O., Preissl, H., Hennige, A. M., Stumvoll, M., Porubska, K., Frost, R., Marx, H., Klösel, B., Lutzenberger, W., Birbaumer, N., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604404103 · Cited by 223 · see citing works
Self-citationInsulin sensitivity of the human brain
Ketterer, C., Tschritter, O., Preissl, H. T., Heni, M., Häring, H., & Fritsche, A. (2011) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(11)70013-4 · Cited by 52 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums
Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., Koenig, A. M., Wang, H.-Y., Ahima, R. S., Craft, S., Gandy, S., Buettner, C., Stoeckel, L. E., et al. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.185 · Cited by 1,597 · see citing works
Impaired 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 · see citing works
Self-citationBrain 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 · see citing works
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 · see citing works
Petrov, D., Pedrós, I., Artiach, G., Sureda, F. X., Barroso, E., Pallàs, M., Casadesús, G., Beas-Zarate, C., Carro, E., Ferrer, I., et al. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.05.004 · Cited by 163 · see citing works
Central insulin modulates food valuation via mesolimbic pathways
Tiedemann, L. J., Schmid, S. M., Hettel, J., Giesen, K., Francke, P., Büchel, C., & Brassen, S. (2017) · Nature Communications · doi:10.1038/ncomms16052 · Cited by 113 · see citing works
Insulin Action in the Human Brain: Evidence from Neuroimaging Studies
Kullmann, S., Heni, M., Fritsche, A., & Preissl, H. (2015) · Journal of Neuroendocrinology · doi:10.1111/jne.12254 · Cited by 83 · see citing works
Self-citationEffects 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 · see citing works
Self-citationWingrove, J., Swedrowska, M., Scherließ, R., Parry, M., Ramjeeawon, M., Taylor, D., Gauthier, G., Brown, L., Amiel, S., Zelaya, F., et al. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.03.032 · Cited by 67 · see citing works
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 · see citing works
Self-citationBrain 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 · see citing works
Self-citationPlomgaard, P., Hansen, J. S., Ingerslev, B., Clemmesen, J. O., Secher, N. H., van Hall, G., Fritsche, A., Weigert, C., Lehmann, R., Häring, H., et al. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13615 · Cited by 16 · see citing works
Self-citation
- Authors
- Heni, M., Schöpfer, P., Peter, A., Sartorius, T., Fritsche, A., Synofzik, M., Häring, H.-U., Maetzler, W., & Hennige, A. M.
- Affiliations
- University of Tübingen (DE)
- Helmholtz Munich (DE)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Fritsche, Andreas
- ORCID
- Venue
- Acta Diabetologica
- Published
- 2013-12-27
- Volume
- 51
- Issue
- 4
- Pages
- 679-681
- ISSN
- 0940-5429 (ISSN-L)
- 1432-5233
- OpenAlex
- W2077337447
- Cited by
- 158
- References
- 5
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 16 · 2023: 23 · 2022: 21 · 2021: 17 · 2020: 9 · 2019: 11 · 2018: 9 · 2017: 11 · 2016: 8 · 2015: 9 · 2014: 5
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Diabetologica (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- insulin resistance, blood-brain barrier, insulin transport, cerebrospinal fluid insulin, whole-body insulin sensitivity, obesity, dietary fat intake, genetic variants
- MeSH terms
- Adult, Aged, Biological Transport, Blood Glucose, Blood-Brain Barrier, Brain, Cerebrospinal Fluid, Female, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Male, Middle Aged
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
