PMID- 30459620
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220410
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 9
DP  - 2018
TI  - Metformin Modulates High Glucose-Incubated Human Umbilical Vein Endothelial Cells 
      Proliferation and Apoptosis Through AMPK/CREB/BDNF Pathway.
PG  - 1266
LID - 10.3389/fphar.2018.01266 [doi]
LID - 1266
AB  - Cardiovascular disease (CVD) is a leading cause of mortality and morbidity among 
      patients with diabetes. Endothelial dysfunction is an early physiological event 
      in CVD. Metformin, a common oral antihyperglycemic agent, has been demonstrated 
      to directly affect endothelial cell function. Brain-derived neurotrophic factor 
      (BDNF), originally discovered in the brain as a neurotrophin, has also been 
      reported to play a protective role in the cardiovascular system. In our study, we 
      demonstrated that high glucose (HG) reduced cell proliferation and induced cell 
      apoptosis via changes in BDNF expression and that metformin reversed the effects 
      of HG injury by upregulating BDNF expression. Furthermore, we found that cyclic 
      AMP response element binding (CREB) phosphorylation was reduced in HG-treated 
      human umbilical vein endothelial cells (HUVECs), and this effect was reversed by 
      the metformin treatment. However, the metformin effect on BDNF levels in 
      HG-incubated HUVECs was blocked by a CREB inhibitor, which indicated that BDNF 
      expression is regulated by metformin through CREB activation. In addition, we 
      found that adenosine monophosphate-activated protein kinase (AMPK) activation is 
      involved in CREB/BDNF regulation in HG-incubated HUVECs treated with metformin 
      and that an AMPK inhibitor impaired the protective effects of metformin on 
      HG-treated HUVECs. In conclusion, this study demonstrated that metformin affects 
      cell proliferation and apoptosis via the AMPK/CREB/BDNF pathway in HG-incubated 
      HUVECs.
FAU - Han, Xiqiong
AU  - Han X
AD  - Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, 
      Nanjing, China.
FAU - Wang, Bilei
AU  - Wang B
AD  - Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, 
      Nanjing, China.
FAU - Sun, Yuning
AU  - Sun Y
AD  - Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, 
      Nanjing, China.
FAU - Huang, Jia
AU  - Huang J
AD  - Department of Cardiology, Shanghai First People's Hospital Affiliated to Shanghai 
      Jiao Tong University, Shanghai, China.
FAU - Wang, Xin
AU  - Wang X
AD  - Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, 
      Nanjing, China.
FAU - Ma, Wenqi
AU  - Ma W
AD  - Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, 
      Nanjing, China.
FAU - Zhu, Yi
AU  - Zhu Y
AD  - Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, 
      Nanjing, China.
FAU - Xu, Rongfeng
AU  - Xu R
AD  - Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, 
      Nanjing, China.
FAU - Jin, Hong
AU  - Jin H
AD  - Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, 
      Nanjing, China.
FAU - Liu, Naifeng
AU  - Liu N
AD  - Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, 
      Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20181106
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6232387
OTO - NOTNLM
OT  - AMPK
OT  - BDNF
OT  - CREB
OT  - HUVECs
OT  - diabetes mellitus
OT  - metformin
EDAT- 2018/11/22 06:00
MHDA- 2018/11/22 06:01
PMCR- 2018/11/06
CRDT- 2018/11/22 06:00
PHST- 2018/08/07 00:00 [received]
PHST- 2018/10/17 00:00 [accepted]
PHST- 2018/11/22 06:00 [entrez]
PHST- 2018/11/22 06:00 [pubmed]
PHST- 2018/11/22 06:01 [medline]
PHST- 2018/11/06 00:00 [pmc-release]
AID - 10.3389/fphar.2018.01266 [doi]
PST - epublish
SO  - Front Pharmacol. 2018 Nov 6;9:1266. doi: 10.3389/fphar.2018.01266. eCollection 
      2018.