Interactions of glucagon-like peptide-1 (GLP-1) with the blood-brain barrier
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- Kastin, A.J., Akerstrom, V. & Pan, W. J Mol Neurosci (2002) 18: 7. doi:10.1385/JMN:18:1-2:07
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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.