The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Interactions of Glucagon-Like Peptide-1 (GLP-1) with the Blood-Brain Barrier
Abstract
Glucagon-like peptide-1 (GLP-1) reduces insulin requirement in diabetes mellitus and promotes satiety. GLP-1 in the periphery (outside the CNS) has been shown to act on the brain to reduce food ingestion. As GLP-1 is readily degraded in blood, we focused on the interactions of [Ser8]GLP-1, an analog with similar biological effects and greater stability, with the blood-brain barrier (BBB). The influx of radiolabeled [Ser8]GLP-1 into brain has several distinctive characteristics: 1. A rapid influx rate of 8.867 +/- 0.798 x 10(4) mL/g-min as measured by multiple-time regression analysis after iv injection in mice. 2. Lack of self-inhibition by excess doses of the unlabeled [Ser8]GLP-1 either iv or by in situ brain perfusion, indicating the absence of a saturable transport system at the BBB. 3. Lack of modulation by short-term fasting and some other ingestive peptides that may interact with GLP-1, including leptin, glucagon, insulin, neuropeptide Y, and melanin-concentrating hormone. 4. No inhibition of influx by the selective GLP-1 receptor antagonist exendin(9-39), suggesting that the GLP-1 receptor is not involved in the rapid entry into brain. Similarly, there was no efflux system for [Ser8]GLP-1 to exit the brain other than following the reabsorption of cerebrospinal fluid (CSF). The fast influx was not associated with high lipid solubility. Upon reaching the brain compartment, substantial amounts of [Ser8]GLP-1 entered the brain parenchyma, but a large proportion was loosely associated with the vasculature at the BBB. Finally, the influx rate of [Ser8]GLP-1 was compared with that of GLP-1 in a blood-free brain perfusion system; radiolabeled GLP-1 had a more rapid influx than its analog and neither peptide showed the self-inhibition indicative of a saturable transport system. Therefore, we conclude that [Ser8]GLP-1 and the endogenous peptide GLP-1 can gain access to the brain from the periphery by simple diffusion and thus contribute to the regulation of feeding.
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“From a biological perspective, these observations are plausible since GLP-1 is produced in the brain and passively diffuses across the blood-brain barrier (21).”
From Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans (2008) · cites this paper as [21]
Citations
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A role for glucagon-like peptide-1 in the central regulation of feeding
Turton, M. D., O'Shea, D., Gunn, I., Beak, S. A., Edwards, C. M. B., Meeran, K., Choi, S. J., Taylor, G. M., Heath, M. M., Lambert, P. D., et al. (1996) · Nature · doi:10.1038/379069a0 · Cited by 1,950
Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans.
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Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats
Tang-Christensen, M., Larsen, P. J., Goke, R., Fink-Jensen, A., Jessop, D. S., Moller, M., & Sheikh, S. P. (1996) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1996.271.4.r848 · Cited by 597
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Gutzwiller, J., Drewe, J., Göke, B., Schmidt, H., Rohrer, B., Lareida, J., & Beglinger, C. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.5.r1541 · Cited by 518
Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men.
Näslund, E., Barkeling, B., King, N., Gutniak, M., Blundell, J., Holst, J., Rössner, S., & Hellström, P. (1999) · International Journal of Obesity · doi:10.1038/sj.ijo.0800818 · Cited by 468
Toft-Nielsen, M.-B., Madsbad, S., & Holst, J. J. (1999) · Diabetes Care · doi:10.2337/diacare.22.7.1137 · Cited by 339
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Glucagon-like peptide 1 (GLP-1)
Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868
The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss
Secher, A., Jelsing, J., Baquero, A. F., Hecksher-Sørensen, J., Cowley, M. A., Dalbøge, L. S., Hansen, G., Grove, K. L., Pyke, C., Raun, K., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci75276 · Cited by 961
Glucagon-like peptide-1 receptor is involved in learning and neuroprotection
During, M. J., Cao, L., Zuzga, D. S., Francis, J. S., Fitzsimons, H. L., Jiao, X., Bland, R. J., Klugmann, M., Banks, W. A., Drucker, D. J., et al. (2003) · Nature Medicine · doi:10.1038/nm919 · Cited by 851
Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health
Parker, A., Fonseca, S., & Carding, S. R. (2019) · Gut Microbes · doi:10.1080/19490976.2019.1638722 · Cited by 745
Semaglutide lowers body weight in rodents via distributed neural pathways.
Gabery, S., Salinas, C. G., Paulsen, S. J., Ahnfelt-Rønne, J., Alanentalo, T., Baquero, A. F., Buckley, S. T., Farkas, E., Fekete, C., Frederiksen, K. S., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.133429 · Cited by 717
Metadata
- Authors
- Kastin, A. J., Akerstrom, V., & Pan, W.
- Affiliations
- Tulane University (US)
- ORCID
- Pan, Weihong
- Venue
- Journal of Molecular Neuroscience
- Published
- 2002
- Volume
- 18
- Issue
- 1-2
- Pages
- 07-13
- ISSN
- 0895-8696 (ISSN-L)
- OpenAlex
- W2076140273
- Cited by
- 480
- References
- 28
- Citations by year
- 2026: 8 · 2025: 22 · 2024: 21 · 2023: 18 · 2022: 24 · 2021: 28 · 2020: 24 · 2019: 29 · 2018: 24 · 2017: 23 · 2016: 25 · 2015: 27 · 2014: 31 · 2013: 27 · 2012: 23
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-54880)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- glucagon-like peptide-1, blood-brain barrier, brain uptake, passive diffusion, GLP-1 receptor, exendin-9-39, satiety, food intake regulation, cerebrospinal fluid reabsorption
- MeSH terms
- Animals, Appetite Regulation, Blood-Brain Barrier, Brain, Cerebrovascular Circulation, Dose-Response Relationship, Drug, Food Deprivation, Glucagon, Hypothalamic Hormones, Insulin, Male, Melanins, Mice, Inbred ICR, Neuropeptide Y, Peptide Fragments, Pituitary Hormones, Protein Precursors, Leptin, Mice, Glucagon-Like Peptide 1
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