Interactions of Glucagon-Like Peptide-1 (GLP-1) with the Blood-Brain Barrier

Kastin, Abba J.; Akerstrom, Victoria; Pan, Weihong

doi:10.1385/jmn:18:1-2:07

Cited by 484Barrier Structure and Function StudiesDiabetes Treatment and ManagementRegulation of Appetite and Obesity

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Interactions of Glucagon-Like Peptide-1 (GLP-1) with the Blood-Brain Barrier

Kastin, Abba J., Akerstrom, Victoria, Pan, Weihong·2002·Journal of Molecular Neuroscience

DOI 10.1385/jmn:18:1-2:07

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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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GLP-1 is produced in the brain and passively diffuses across the blood-brain barrier.
“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]

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.
Flint, A., Raben, A., Astrup, A., & Holst, J. J. (1998) · Journal of Clinical Investigation · doi:10.1172/jci990 · Cited by 1,402
Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV.
Kieffer, T. J., McIntosh, C. H., & Pederson, R. A. (1995) · Endocrinology · doi:10.1210/endo.136.8.7628397 · Cited by 1,124
Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem
Larsen, P. J., Tang-Christensen, M., Holst, J. J., & Ørskov, C. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00434-4 · Cited by 663
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
Glucagon-Like Peptide-1-(7–36)Amide Is Transformed to Glucagon-Like Peptide-1-(9–36)Amide by Dipeptidyl Peptidase IV in the Capillaries Supplying the L Cells of the Porcine Intestine1
Hansen, L., Deacon, C. F., Ørskov, C., & Holst, J. J. (1999) · Endocrinology · doi:10.1210/endo.140.11.7143 · Cited by 595
Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2
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
Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients.
Toft-Nielsen, M.-B., Madsbad, S., & Holst, J. J. (1999) · Diabetes Care · doi:10.2337/diacare.22.7.1137 · Cited by 339
Distribution of glucagonlike peptide I (GLP‐I), glucagon, and glicentin in the rat brain: An immunocytochemical study
Jin, S.-L. C., Han, V. K. M., Simmons, J. G., Towle, A. C., Lauder, J. M., & Lund, P. K. (1988) · The Journal of Comparative Neurology · doi:10.1002/cne.902710405 · Cited by 332
Glucagonostatic Actions and Reduction of Fasting Hyperglycemia by Exogenous Glucagon-Like Peptide I(7–36) amide in type I diabetic patients
Creutzfeldt, W., Kleine, N., Willms, B., Ørskov, C., Holst, J. J., & Nauck, M. A. (1996) · Diabetes Care · doi:10.2337/diacare.19.6.580 · Cited by 328
Orexin A but Not Orexin B Rapidly Enters Brain from Blood by Simple Diffusion
Kastin, A. J., & Akerstrom, V. L. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38126-1 · Cited by 325
Self-citation
Identification and Localization of Glucagon-Like Peptide-1 and Its Receptor in Rat Brain*
Shimizu, I., Hirota, M., Ohboshi, C., & Shima, K. (1987) · Endocrinology · doi:10.1210/endo-121-3-1076 · Cited by 173
Functional interactions between melanin-concentrating hormone, neuropeptide Y, and anorectic neuropeptides in the rat hypothalamus.
Tritos, N. A., Vicent, D., Gillette, J. A., Ludwig, D. S., Flier, E. S., & Maratos–Flier, E. (1998) · Diabetes · doi:10.2337/diabetes.47.11.1687 · Cited by 138
Leptin interacts with glucagon‐like peptide‐1 neurons to reduce food intake and body weight in rodents
Goldstone, A. P., Mercer, J. G., Gunn, I., Moar, K. M., Edwards, C. M. B., Rossi, M., Howard, J. K., Rasheed, S., Turton, M. D., Small, C. J., et al. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01103-4 · Cited by 131
Nonsaturable entry of neuropeptide Y into brain
Kastin, A. J., & Akerstrom, V. L. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.3.e479 · Cited by 119
Self-citation
Identification and characterization of glucagon‐like peptide‐1 7–36 amide‐binding sites in the rat brain and lung
Kanse, S. M., Kreymann, B., Ghatei, M. A., & Bloom, S. R. (1988) · FEBS Letters · doi:10.1016/0014-5793(88)81063-9 · Cited by 104
Characterization of glucagon-like peptide-1-(7–36)amide in the hypothalamus
Kreymann, B., Ghatei, M. A., Burnet, P. W. J., Williams, G., Kanse, S. M., Diani, A. R., & Bloom, S. R. (1989) · Brain Research · doi:10.1016/0006-8993(89)90628-8 · Cited by 99
Presynaptic NMDA receptor subunit immunoreactivity in GABAergic terminals in rat brain
Paquet, M., & Smith, Y. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20000724)423:2 · Cited by 95
Quantifying carrier-mediated transport of peptides from the brain to the blood
Banks, W. A., & Kastin, A. J. (1989) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(89)68047-0 · Cited by 81
Self-citation
Association of leptin receptor (OB-Rb), NPY and GLP-1 gene expression in the ovine and murine brainstem
Mercer, J. G., Moar, K. M., Findlay, P. A., Hoggard, N., & Adam, C. L. (1998) · Regulatory Peptides · doi:10.1016/s0167-0115(98)00078-0 · Cited by 74
A synthetic glucagon-like peptide-1 analog with improved plasma stability
Ritzel, U., Leonhardt, U., Ottleben, M., Rühmann, A., Eckart, K., Spiess, J., & Ramadori, G. P. (1998) · Journal of Endocrinology · doi:10.1677/joe.0.1590093 · Cited by 61
Entry of CART into brain is rapid but not inhibited by excess CART or leptin
Kastin, A. J., & Akerstrom, V. L. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.5.e901 · Cited by 52
Self-citation
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Kastin, A. J., Akerstrom, V. L., & Hackler, L. (2000) · Metabolism · doi:10.1053/meta.2000.16556 · Cited by 50
Self-citation
Measurement of Efflux Rates from Brain to Blood
Banks, W. A., Fasold, M. B., & Kastin, A. J. (2003) · Humana Press eBooks · doi:10.1385/0-89603-399-6:353 · Cited by 40
Self-citation
Phe13, Tyr19‐Melanin‐Concentrating Hormone and the Blood—Brain Barrier
Kastin, A. J., Akerstrom, V. L., Hackler, L., & Zadina, J. E. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0740385.x · Cited by 37
Self-citation
A survey of the cerebral regionalization and ontogeny of eight exo- and endopeptidases in murines
Dauch, P., Masuo, Y., Vincent, J., & Checler, F. (1993) · Peptides · doi:10.1016/0196-9781(93)90150-f · Cited by 32
Regional differences in peptide degradation by rat cerebral microvessels
Kastin, A. J., Hahn, K., & Zadina, J. E. (2001) · Life Sciences · doi:10.1016/s0024-3205(01)01211-5 · Cited by 18
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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
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Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trials studying glucagon‐like peptide‐1 receptor agonists: A systematic analysis of published clinical trials
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Lejeune, M. P., Westerterp, K. R., Adam, T. C., Luscombe-Marsh, N. D., & Westerterp-Plantenga, M. S. (2006) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.1.89 · Cited by 363
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Self-citation
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Pipatpiboon, N., Pintana, H., Pratchayasakul, W., Chattipakorn, N., & Chattipakorn, S. C. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12088 · Cited by 183
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Nogueiras, R., Pérez-Tilve, D., Veyrat-Durebex, C., Morgan, D. A., Varela, L., Haynes, W. G., Patterson, J. T., Disse, E., Pfluger, P. T., López, M., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5977-08.2009 · Cited by 182
Brain insulin resistance: role in neurodegenerative disease and potential for targeting
Hölscher, C. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1738383 · Cited by 180
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Hsu, T. M., Hahn, J. D., Konanur, V. R., Lam, A., & Kanoski, S. E. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.175 · Cited by 176
GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents
Ye, J., Hao, Z., Mumphrey, M. B., Townsend, R. L., Patterson, L. M., Stylopoulos, N., Münzberg, H., Morrison, C. D., Drucker, D. J., & Berthoud, H. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00491.2013 · Cited by 174
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Schirra, J. R. J., & Göke, B. (2004) · Regulatory Peptides · doi:10.1016/j.regpep.2004.06.018 · Cited by 151
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Chelikani, P. K., Haver, A. C., & Reidelberger, R. D. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00870.2004 · Cited by 131
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Fortin, S. M., Lipsky, R. K., Lhamo, R., Chen, J., Kim, E., Borner, T., Schmidt, H. D., & Hayes, M. R. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay8071 · Cited by 127
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Kimura, R., Okouchi, M., Fujioka, H., Ichiyanagi, A., Ryuge, F., Mizuno, T., Imaeda, K., Okayama, N., Kamiya, Y., Asai, K., et al. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.05.025 · Cited by 127
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Neural effects of gut‐ and brain‐derived glucagon‐like peptide‐1 and its receptor agonist
Katsurada, K., & Yada, T. (2016) · Journal of Diabetes Investigation · doi:10.1111/jdi.12464 · Cited by 126
Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity
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Roles of bile acids signaling in neuromodulation under physiological and pathological conditions
Chen, X., Huang, X., Wang, D., Yu, D., Hou, S., Cui, H., & Song, L. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01053-z · Cited by 123
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Update on incretin hormones
Phillips, L. K., & Prins, J. B. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06491.x · Cited by 122
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Hsu, T. M., Noble, E. E., Liu, C. M., Cortella, A. M., Konanur, V., Suarez, A. N., Reiner, D. J., Hahn, J. D., Hayes, M. R., & Kanoski, S. E. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.91 · Cited by 121
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Parthsarathy, V., & Hölscher, C. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.12.012 · Cited by 119
Glucagon‐like peptide‐1 in the rat brain: Distribution of expression and functional implication
Gu, G., Roland, B. L., Tomaselli, K. J., Dolman, C. S., Lowe, C., & Heilig, J. S. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23282 · Cited by 119
The Glucagon‐Like Peptides
Brubaker, P. L. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1317.006 · Cited by 118
Two novel dual GLP-1/GIP receptor agonists are neuroprotective in the MPTP mouse model of Parkinson's disease
Feng, P., Zhang, X., Li, D., Ji, C., Yuan, Z., Wang, R., Xue, G., Li, G., & Hölscher, C. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.02.012 · Cited by 117
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Yuan, Z., Li, D., Feng, P., Xue, G., Ji, C., Li, G., & Hölscher, C. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.06.029 · Cited by 112

Transport of Insulin Across the Blood-Brain Barrier: Saturability at Euglycemic Doses of Insulin
Banks, W. A., Jaspan, J. B., Huang, W., & Kastin, A. J. (1997) · Peptides · doi:10.1016/s0196-9781(97)00231-3 · Cited by 318
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Fu, Z., Gong, L., Liu, J., Wu, J., Barrett, E. J., Aylor, K. W., & Liu, Z. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00555 · Cited by 52
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Authors: Kastin, A. J., Akerstrom, V., & Pan, W.
Affiliations: Tulane University (US)
ORCID: Pan, Weihong
Venue: Journal of Molecular Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2002
Volume: 18
Issue: 1-2
Pages: 07-13
ISSN: 0895-8696 (ISSN-L)
DOI: 10.1385/jmn:18:1-2:07
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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Interactions of Glucagon-Like Peptide-1 (GLP-1) with the Blood-Brain Barrier

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