Glucagon-Like Peptide-1 Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells Under Basal and Hyperglycemia Conditions : -1
Institution: | Nagasaki University / |
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Department: | |
Year: | 2016 |
Keywords: | Blood-brain barrier; Glucagon-like peptide 1; cAMP/PKA signaling; Tight junctions; Hyperglycemia |
Posted: | 02/01/2018 |
Record ID: | 2162410 |
Full text PDF: | http://hdl.handle.net/10069/37602 |
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 (939) 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.