Research Paper Volume 12, Issue 9 pp 8640—8651
Exenatide inhibits NF-κB and attenuates ER stress in diabetic cardiomyocyte models
- 1 Department of Cardiology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- 2 Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Received: October 15, 2019 Accepted: April 17, 2020 Published: May 11, 2020
https://doi.org/10.18632/aging.103181How to Cite
Copyright © 2020 Fu 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
Exenatide is used to treat patients with type-2 diabetes and it also exerts cardioprotective effects. Here, we tested whether Exenatide attenuates hyperglycemia-related cardiomyocyte damage by inhibiting endoplasmic reticulum (ER) stress and the NF-κB signaling pathway. Our results demonstrated that hyperglycemia activates the NF-κB signaling pathway, eliciting ER stress. We also observed cardiomyocyte contractile dysfunction, inflammation, and cell apoptosis induced by hyperglycemia. Exenatide treatment inhibited inflammation, improved cardiomyocyte contractile function, and rescued cardiomyocyte viability. Notably, re-activation of the NF-κB signaling pathway abolished Exenatide’s protective effects on hyperglycemic cardiomyocytes. Taken together, our results demonstrate that Exenatide directly reduces hyperglycemia-induced cardiomyocyte damage by inhibiting ER stress and inactivating the NF-κB signaling pathway.