@phdthesis{oai:nagasaki-u.repo.nii.ac.jp:00003856, author = {福田, 修志}, month = {Feb}, note = {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., 長崎大学学位論文 学位記番号:博(医歯薬)甲第908号 学位授与年月日:平成29年2月1日, Author: Shuji Fukuda, Shinsuke Nakagawa, Rie Tatsumi, Yoichi Morofuji, Tomonori Takeshita, Kentaro Hayashi, Kunihiko Tanaka, Takayuki Matsuo, Masami Niwa, Citation: Journal of Molecular Neuroscience, 59(2), pp.211-219; 2016, Nagasaki University (長崎大学), 博士(医学) (2017-02-01)}, school = {Nagasaki University (長崎大学)}, title = {Glucagon-Like Peptide-1 Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells Under Basal and Hyperglycemia Conditions}, year = {2017} }