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Research Paper|Volume 13, Issue 1|pp 525—536

Liraglutide improved the cognitive function of diabetic mice via the receptor of advanced glycation end products down-regulation

Haoqiang Zhang1,2, Yafen Chu3, Hongwei Zheng1, Jing Wang1, Bing Song1, Yao Sun4
  • 1Department of Endocrinology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
  • 2Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China
  • 3Department of Endocrinology, Ningbo Medical Center Lihuili Hospital, Ningbo, China
  • 4Department of Pharmacy, Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
Received: May 12, 2020Accepted: September 14, 2020Published: November 26, 2020
https://doi.org/10.18632/aging.202162

Copyright: © 2020 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.