Glucagon-Like Peptide-1 Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells Under Basal and Hyperglycemia Conditions
Glucagon-Like Peptide-1 Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells Under Basal and Hyperglycemia Conditions
复制标题
DOI：
10.1007/s12031-015-0696-1
复制
发表时间：
2016-06-01
影响因子：
3.1
通讯作者：
Niwa, Masami
中科院分区：
文献类型：
--
作者：
Fukuda, Shuji;Nakagawa, Shinsuke;Niwa, Masami
本研究的目的是确定胰高血糖素样肽-1 (GLP-1) 对屏障功能的影响，并使用由大鼠脑毛细血管内皮细胞 (RBEC) 原代培养物组成的体外血脑屏障 (BBB) 模型评估其潜在机制。 GLP-1 以剂量和时间依赖性方式增加 RBEC 中的跨内皮电阻并降低荧光素钠的渗透性。 GLP-1 受体拮抗剂 exendin-3 (9-39) 和蛋白激酶 A (PKA) 抑制剂 H-89 的存在可显着降低对这些屏障功能的影响。 Western blot 分析显示，GLP-1 增加了 occludin 和 claudin-5 的量。 GLP-1 类似物被批准用于治疗 2 型糖尿病，因此，我们研究了 GLP-1 对高血糖引起的 BBB 损伤的影响。 GLP-1抑制高血糖条件下活性氧产生的增加，改善高血糖诱导的血脑屏障完整性。由于 GLP-1 可能通过 cAMP/PKA 信号传导稳定了 BBB 的完整性，因此应考虑 GLP-1 作为 BBB 保护药物的可能性。
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.