Interactions of glucagon-like peptide-1 (GLP-1) with the blood-brain barrier
- 1.1k Downloads
A rapid influx rate of 8.867±0.798 × 104 mL/g-min as measured by multiple-time regression analysis after iv injection in mice.
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.
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.
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.
Index EntriesFeeding blood-brain barrier GLP-1 peptide
Unable to display preview. Download preview PDF.
- Banks W. A., Fasold M. B., and Kastin A. J. (1997) Measurement of efflux rates from brain to blood, in Methods of Molecular Biology, Neuropeptide Protocols, Vol. 73 (Irvine G. B. and Williams C. H., eds.), Humana Press Inc., Totowa, NJ, pp. 353–360.Google Scholar
- Banks W. A. and Kastin A. J. (1989) Quantifying carrier-mediated transport of peptides from the brain to the blood, in Methods in Enzymology, Vol. 168, Conn, P. M. (ed.), Academic Press, San Diego, pp. 652–660.Google Scholar
- Hansen L., Deacon C. F., Orskov C., and Holst J. J. (1999) 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 intestine. Endocrinology 140, 5356–5363.PubMedCrossRefGoogle Scholar