Department of Endocrinology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.
Aging (Albany NY). 2020 Nov 26;13(1):525-536. doi: 10.18632/aging.202162.
Background and aims Advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE), are associated with cognition decline. We aim to investigate the effect of liraglutide on cognitive function in diabetic mice. Results Diabetic mice showed decreased cognitive function. Moreover, lower glucagon like peptide-1 (GLP-1) levels in plasma were detected in db/db mice. Additionally, up-regulated RAGE and down-regulated glucagon like peptide-1 (GLP-1R) levels were observed in db/db mice. However, decreased GLP-1R and increased RAGE were reversed by liraglutide. We also found decreased cellular activity in cells with AGEs. Moreover, AGEs up-regulated RAGE in PC12 and HT22 cells. However, liraglutide improved the cell activity damaged by AGEs. Although we did not discover the direct-interaction between RAGE and GLP-1R, elevated RAGE levels induced by AGEs were restored by liraglutide. Conclusion We demonstrated that the cognitive function of diabetic mice was improved by liraglutide via the down-regulation of RAGE. Methods db/db mice and db/m mice were used in this study. Liraglutide was used to remedy diabetic mice. Neurons and RAGE in hippocampus were shown by immunofluorescence. And then, PC12 cells or HT22 cells with AGEs were treated with liraglutide. GLP-1R and RAGE were measured by western blotting.
晚期糖基化终产物（AGEs）及其受体（RAGE）与认知功能下降有关。我们旨在研究利拉鲁肽对糖尿病小鼠认知功能的影响。
糖尿病小鼠表现出认知功能下降。此外，db/db 小鼠的血浆中胰高血糖素样肽-1（GLP-1）水平较低。此外，db/db 小鼠中观察到 RAGE 上调和 GLP-1R 下调。然而，利拉鲁肽逆转了 GLP-1R 的下调和 RAGE 的上调。我们还发现 AGEs 作用下细胞活性降低。此外，AGEs 可上调 PC12 和 HT22 细胞中的 RAGE。然而，利拉鲁肽改善了 AGEs 引起的细胞活性损伤。虽然我们没有发现 RAGE 和 GLP-1R 之间的直接相互作用，但 AGEs 升高的 RAGE 水平被利拉鲁肽所恢复。
我们通过下调 RAGE 证明了利拉鲁肽改善了糖尿病小鼠的认知功能。
本研究使用 db/db 小鼠和 db/m 小鼠。用利拉鲁肽治疗糖尿病小鼠。用免疫荧光法显示海马神经元和 RAGE。然后，用 AGEs 处理 PC12 细胞或 HT22 细胞，并通过 Western blot 检测 GLP-1R 和 RAGE。
