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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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]
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- 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
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 ›
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