Journal
JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 59, Issue 2, Pages 211-219Publisher
HUMANA PRESS INC
DOI: 10.1007/s12031-015-0696-1
Keywords
Blood-brain barrier; Glucagon-like peptide 1; cAMP/PKA signaling; Tight junctions; Hyperglycemia
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Funding
- Japan Society for the Promotion of Science (JSPS) [24790258]
- Grants-in-Aid for Scientific Research [15K08321, 26462167, 24790258] Funding Source: KAKEN
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The objective of the present study was to determine the effects of glucagon-like peptide-1 (GLP-1) on barrier functions and to assess the underlying mechanism using an in vitro blood-brain barrier (BBB) model comprised of a primary culture of rat brain capillary endothelial cells (RBECs). GLP-1 increased transendothelial electrical resistance and decreased the permeability of sodium fluorescein in RBECs in a dose- and time-dependent manner. The effects on these barrier functions were significantly reduced in the presence of the GLP-1 receptor antagonist exendin-3 (9-39) and the protein kinase A (PKA) inhibitor H-89. Western blot analysis showed that GLP-1 increased the amount of occludin and claudin-5. GLP-1 analogs are approved for treatment of type 2 diabetes mellitus, and thus, we examined the effects of GLP-1 on hyperglycemia-induced BBB damage. GLP-1 inhibited the increase in production of reactive oxygen species under hyperglycemia conditions and improved the BBB integrity induced by hyperglycemia. As GLP-1 stabilized the integrity of the BBB, probably via cAMP/PKA signaling, the possibility that GLP-1 acts as a BBB-protective drug should be considered.
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