PMID- 31383790
OWN - NLM
STAT- MEDLINE
DCOM- 20200909
LR  - 20200909
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 39
IP  - 8
DP  - 2019 Aug 30
TI  - Liraglutide inhibits the apoptosis of human nucleus pulposus cells induced by 
      high glucose through PI3K/Akt/caspase-3 signaling pathway.
LID - BSR20190109 [pii]
LID - 10.1042/BSR20190109 [doi]
AB  - Diabetes mellitus (DM) is a potential etiology of disc degeneration. 
      Glucagon-like peptide-1 (GLP-1) is currently regarded as a powerful treatment 
      option for type 2 diabetes. Apart from the beneficial effects on glycaemic 
      control, GLP-1 has been reported to exert functions in a variety of tissues on 
      modulation of cell proliferation, differentiation, and apoptosis. However, little 
      is known regarding the effects of GLP-1 on nucleus pulposus cells (NPCs). In the 
      present study, we investigated the effects of liraglutide (LIR), a long-lasting 
      GLP-1 analogue, on apoptosis of human NPCs and the underlying mechanisms 
      involved. We confirmed the presence of GLP-1 receptor (GLP-1R) in NPCs. Our data 
      demonstrated that liraglutide inhibited the apoptosis of NPCs induced by high 
      glucose (HG), as detected by Annexin V/Propidium Iodide (PI) and ELISA assays. 
      Moreover, liraglutide down-regulated caspase-3 activity at intermediate 
      concentration (100 nM) for maximum effect. Further analysis suggested that 
      liraglutide suppressed reactive oxygen species (ROS) generation and stimulated 
      the phosphorylation of Akt under HG condition. Pretreatment of cells with the 
      Phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (LY) and small interfering 
      RNAs (siRNAs) GLP-1R abrogated the liraglutide-induced activation of Akt and the 
      protective effects on NPCs' apoptosis. In conclusion, liraglutide could directly 
      protect NPCs against HG-induced apoptosis by inhibiting oxidative stress and 
      activate the PI3K/Akt/caspase-3 signaling pathway via GLP-1R.
CI  - (c) 2019 The Author(s).
FAU - Ming-Yan, Yao
AU  - Ming-Yan Y
AD  - Department of Endocrinology, Baoding NO.1 Central Hospital, 320 Changcheng North 
      Street, Lianchi District, Baoding City, Hebei Province, China.
FAU - Jing, Zhang
AU  - Jing Z
AD  - Department of Cardiology, Affiliated Hospital of Hebei University, Baoding City, 
      Hebei Province, China.
FAU - Shu-Qin, Guo
AU  - Shu-Qin G
AD  - Department of Endocrinology, Baoding NO.1 Central Hospital, 320 Changcheng North 
      Street, Lianchi District, Baoding City, Hebei Province, China.
FAU - Xiao-Liang, Bai
AU  - Xiao-Liang B
AD  - Department of Endocrinology, Baoding NO.1 Central Hospital, 320 Changcheng North 
      Street, Lianchi District, Baoding City, Hebei Province, China.
FAU - Zhi-Hong, Li
AU  - Zhi-Hong L
AUID- ORCID: 0000-0003-1010-2628
AD  - Department of Endocrinology, Baoding NO.1 Central Hospital, 320 Changcheng North 
      Street, Lianchi District, Baoding City, Hebei Province, China 
      lizhihongmd@163.com.
FAU - Xue, Zhou
AU  - Xue Z
AD  - Department of Endocrinology, Baoding NO.1 Central Hospital, 320 Changcheng North 
      Street, Lianchi District, Baoding City, Hebei Province, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190819
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 839I73S42A (Liraglutide)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Caspase 3/*metabolism
MH  - Cells, Cultured
MH  - Diabetes Complications/metabolism/pathology
MH  - Glucose/*pharmacology
MH  - Humans
MH  - Intervertebral Disc Degeneration/metabolism/pathology
MH  - Liraglutide/*pharmacology
MH  - Nucleus Pulposus/*metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/*drug effects
PMC - PMC6702359
OTO - NOTNLM
OT  - apoptosis
OT  - liraglutide
OT  - nucleus pulposus cells
OT  - oxidative stress
OT  - signaling pathway
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2019/08/07 06:00
MHDA- 2020/09/10 06:00
PMCR- 2019/08/19
CRDT- 2019/08/07 06:00
PHST- 2019/01/12 00:00 [received]
PHST- 2019/07/04 00:00 [revised]
PHST- 2019/08/01 00:00 [accepted]
PHST- 2019/08/07 06:00 [pubmed]
PHST- 2020/09/10 06:00 [medline]
PHST- 2019/08/07 06:00 [entrez]
PHST- 2019/08/19 00:00 [pmc-release]
AID - BSR20190109 [pii]
AID - 10.1042/BSR20190109 [doi]
PST - epublish
SO  - Biosci Rep. 2019 Aug 19;39(8):BSR20190109. doi: 10.1042/BSR20190109. Print 2019 
      Aug 30.