Research Paper|Volume 12, Issue 9|pp 8640—8651

Exenatide inhibits NF-κB and attenuates ER stress in diabetic cardiomyocyte models

Zhenhong Fu¹, David Mui², Hang Zhu¹, Ying Zhang¹

¹Department of Cardiology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
²Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

Received: October 15, 2019Accepted: April 17, 2020Published: May 11, 2020

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.