PMID- 31302140
OWN - NLM
STAT- MEDLINE
DCOM- 20200316
LR  - 20200316
IS  - 1096-0384 (Electronic)
IS  - 0003-9861 (Linking)
VI  - 671
DP  - 2019 Aug 15
TI  - Dulaglutide inhibits high glucose- induced endothelial dysfunction and NLRP3 
      inflammasome activation.
PG  - 203-209
LID - S0003-9861(19)30264-4 [pii]
LID - 10.1016/j.abb.2019.07.008 [doi]
AB  - 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-1beta 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-1beta 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.
CI  - Copyright (c) 2019. Published by Elsevier Inc.
FAU - Luo, Xiaojia
AU  - Luo X
AD  - Department of Cardiovascular Medicine, West China Hospital, Sichuan University, 
      Chengdu, Sichuan, 610000, China; Department of Cardiovascular Medicine, Chengdu 
      Second People's Hospital, Chengdu, Sichuan, 610000, China.
FAU - Hu, Yongmei
AU  - Hu Y
AD  - Department of Cardiovascular Medicine, West China Hospital, Sichuan University, 
      Chengdu, Sichuan, 610000, China.
FAU - He, Sen
AU  - He S
AD  - Department of Cardiovascular Medicine, Chengdu Second People's Hospital, Chengdu, 
      Sichuan, 610000, China.
FAU - Ye, Qiran
AU  - Ye Q
AD  - Department of Biotechnology, College of Life Science Sichuan University, Chengdu, 
      Sichuan, 610000, China.
FAU - Lv, Zhengbing
AU  - Lv Z
AD  - Department of Cardiovascular Medicine, West China Hospital, Sichuan University, 
      Chengdu, Sichuan, 610000, China.
FAU - Liu, Jianxiong
AU  - Liu J
AD  - Department of Cardiovascular Medicine, West China Hospital, Sichuan University, 
      Chengdu, Sichuan, 610000, China.
FAU - Chen, Xiaoping
AU  - Chen X
AD  - Department of Cardiovascular Medicine, Chengdu Second People's Hospital, Chengdu, 
      Sichuan, 610000, China. Electronic address: chenxp3105@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190711
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (CARD Signaling Adaptor Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
RN  - 0 (PYCARD protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TXNIP protein, human)
RN  - 62340-29-8 (Glucagon-Like Peptides)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (NOX4 protein, human)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - IY9XDZ35W2 (Glucose)
RN  - WTT295HSY5 (dulaglutide)
SB  - IM
MH  - CARD Signaling Adaptor Proteins/metabolism
MH  - Carrier Proteins/metabolism
MH  - Caspase 1/metabolism
MH  - Endothelial Cells/*drug effects
MH  - Glucagon-Like Peptides/*analogs & derivatives/pharmacology
MH  - Glucose/*pharmacology
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Immunoglobulin Fc Fragments/*pharmacology
MH  - Inflammasomes/*drug effects/metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - NADPH Oxidase 4/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Oxidative Stress/*drug effects
MH  - Protein Carbonylation/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Recombinant Fusion Proteins/*pharmacology
MH  - Sirtuin 1/metabolism
OTO - NOTNLM
OT  - Cardiovascular diseases
OT  - Dulaglutide
OT  - Endothelial dysfunction
OT  - IL-18
OT  - NLRP3 inflammasome
OT  - Type 2 diabetes mellitus
EDAT- 2019/07/16 06:00
MHDA- 2020/03/17 06:00
CRDT- 2019/07/15 06:00
PHST- 2019/04/11 00:00 [received]
PHST- 2019/07/08 00:00 [revised]
PHST- 2019/07/10 00:00 [accepted]
PHST- 2019/07/16 06:00 [pubmed]
PHST- 2020/03/17 06:00 [medline]
PHST- 2019/07/15 06:00 [entrez]
AID - S0003-9861(19)30264-4 [pii]
AID - 10.1016/j.abb.2019.07.008 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2019 Aug 15;671:203-209. doi: 10.1016/j.abb.2019.07.008. 
      Epub 2019 Jul 11.