Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 671, Issue -, Pages 203-209Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2019.07.008
Keywords
Cardiovascular diseases; NLRP3 inflammasome; Dulaglutide; Endothelial dysfunction; Type 2 diabetes mellitus; IL-18
Categories
Funding
- National Natural Science Foundation of China [81600299]
- Sichuan Science and Technology Support Plan Project [2014SZ0240]
- Chengdu Science and Technology Benefit People Project [2014-HM01-00349-SF]
Ask authors/readers for more resources
Activation of the NLRP3 inflammasome plays an important role in high glucose-induced endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM). Dulaglutide, a newly developed glucagon-like peptide-1 receptor (GLP-1R) agonist, has been approved for the management of T2DM. In the current study, we aimed to investigate whether dulaglutide possesses a protective effect against high glucose-induced activation of the NLRP3 inflammasome. Our results indicate that dulaglutide treatment prevented high glucose-induced generation of reactive oxygen species (ROS) and protein carbonyl, as well as the expression of NADPH oxidase 4 (NOX-4) in human umbilical vein endothelial cells (HUVECs). Dulaglutide treatment could inhibit high glucose-induced release of lactate dehydrogenase (LDH) and the expression of TXNIP. Dulaglutide suppressed high glucose-induced activation of NLRP3 inflammasome by reducing the expression of NLRP3, ASC, and cleaved caspase 1 (P10). Notably, dulaglutide treatment suppressed high glucose-induced maturation of IL-1 beta and IL-18. Mechanistically, our findings indicate that SIRT1 was involved in this process by showing that knockdown of SIRT1 by transfection with SIRT1 siRNA abolished the inhibitory effects of dulaglutide on IL-1 beta and IL-18 secretion via suppression of NLRP3, ASC, and p10. These data suggest that dulaglutide might serve as a potential drug for the treatment of cardiovascular complications in T2DM patients.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available