PMID- 38382536
OWN - NLM
STAT- MEDLINE
DCOM- 20240223
LR  - 20240409
IS  - 1440-1681 (Electronic)
IS  - 0305-1870 (Linking)
VI  - 51
IP  - 4
DP  - 2024 Apr
TI  - Dapagliflozin alleviates high glucose-induced injury of endothelial cells via 
      inducing autophagy.
PG  - e13846
LID - 10.1111/1440-1681.13846 [doi]
AB  - Hyperglycaemia is a key factor in the progression of diabetes complications. 
      Dapagliflozin (DAPA), a new type of hypoglycaemic agent, has been shown to play 
      an important role in anti-apoptotic, anti-inflammatory and antioxidant 
      activities. Previous studies have demonstrated an endothelial protective effect 
      of DAPA, but the underlying mechanism was still unclear. Autophagy is a 
      homeostatic cellular mechanism that circulates unfolded proteins and damaged 
      organelles through lysosomal dependent degradation. In this study, we aimed to 
      investigate whether DAPA plays a protective role against high glucose 
      (HG)-induced endothelial injury through regulating autophagy. The results showed 
      that DAPA treatment resulted in increased cell viability. Additionally, DAPA 
      treatment decreased interleukin (IL)-1beta, IL-6, and tumour necrosis factor-alpha 
      levels in endothelial cells subjected to HG conditions. We observed that HG 
      inhibited autophagy, and DAPA increased the autophagy level by inhibiting the 
      protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway. 
      Chloroquine reversed all of these beneficial effects as an autophagy inhibitor. 
      In summary, the endothelial protective effect of DAPA in HG can be attributed in 
      part to its role in activating of autophagy via the AKT/mTOR signalling pathway. 
      Therefore, suggesting that the activation of autophagy by DAPA may be a novel 
      target for the treatment of HG-induced endothelial cell injury.
CI  - (c) 2024 John Wiley & Sons Australia, Ltd.
FAU - Li, Gen
AU  - Li G
AD  - Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 
      China.
FAU - Hou, Ningxin
AU  - Hou N
AD  - Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 
      China.
FAU - Liu, Huagang
AU  - Liu H
AD  - Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 
      Province, China.
FAU - Li, Jun
AU  - Li J
AD  - Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 
      China.
FAU - Deng, Hongping
AU  - Deng H
AD  - Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 
      Province, China.
FAU - Lan, Hongwen
AU  - Lan H
AD  - Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 
      China.
FAU - Xiong, Sizheng
AU  - Xiong S
AD  - Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 
      Province, China.
LA  - eng
GR  - WCYY2022Y03/Scientific Research Innovation Fund Project of Wuhan Wuchang 
      Hospital/
GR  - 2021KFY053/Hubei Province Key Laboratory Open Project/
GR  - 413000723/Fundamental Research Funds for the Central Universities/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Australia
TA  - Clin Exp Pharmacol Physiol
JT  - Clinical and experimental pharmacology & physiology
JID - 0425076
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 1ULL0QJ8UC (dapagliflozin)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Glucosides)
SB  - IM
MH  - Humans
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - Human Umbilical Vein Endothelial Cells
MH  - *Autophagy
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Glucose/metabolism
MH  - *Benzhydryl Compounds
MH  - *Glucosides
OTO - NOTNLM
OT  - AKT/mTOR signalling pathway
OT  - autophagy
OT  - dapagliflozin
OT  - human umbilical vein endothelial cells
EDAT- 2024/02/22 00:42
MHDA- 2024/02/23 06:43
CRDT- 2024/02/21 18:43
PHST- 2024/01/03 00:00 [revised]
PHST- 2023/10/30 00:00 [received]
PHST- 2024/01/29 00:00 [accepted]
PHST- 2024/02/23 06:43 [medline]
PHST- 2024/02/22 00:42 [pubmed]
PHST- 2024/02/21 18:43 [entrez]
AID - 10.1111/1440-1681.13846 [doi]
PST - ppublish
SO  - Clin Exp Pharmacol Physiol. 2024 Apr;51(4):e13846. doi: 10.1111/1440-1681.13846.