Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. Feb-Apr 2002;18(1-2):7-14.
doi: 10.1385/JMN:18:1-2:07.

Interactions of Glucagon-Like peptide-1 (GLP-1) With the Blood-Brain Barrier

Affiliations

Interactions of Glucagon-Like peptide-1 (GLP-1) With the Blood-Brain Barrier

Abba J Kastin et al. J Mol Neurosci. .

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.

Similar articles

See all similar articles

Cited by 121 articles

See all "Cited by" articles

References

    1. Am J Physiol. 1996 Oct;271(4 Pt 2):R848-56 - PubMed
    1. Endocrinology. 1995 Aug;136(8):3585-96 - PubMed
    1. J Endocrinol. 1998 Oct;159(1):93-102 - PubMed
    1. Diabetes. 1998 Nov;47(11):1687-92 - PubMed
    1. Methods Mol Biol. 1997;73:353-60 - PubMed

Publication types

MeSH terms

LinkOut - more resources

Feedback