PMID- 31411368
OWN - NLM
STAT- MEDLINE
DCOM- 20201201
LR  - 20201201
IS  - 1520-7560 (Electronic)
IS  - 1520-7552 (Linking)
VI  - 36
IP  - 2
DP  - 2020 Feb
TI  - Liraglutide combined with human umbilical cord mesenchymal stem cell 
      transplantation inhibits beta-cell apoptosis via mediating the ASK1/JNK/BAX 
      pathway in rats with type 2 diabetes.
PG  - e3212
LID - 10.1002/dmrr.3212 [doi]
AB  - OBJECTIVE: Accumulating evidence suggests an association between beta-cell 
      apoptosis and the ASK1/JNK/BAX pathway. The aim of this study was to investigate 
      the effects of a combined therapy of liraglutide and human umbilical cord 
      mesenchymal stem cells (hUC-MSCs) on the glucose metabolism and islet beta-cell 
      apoptosis, and further explore its relationship to the ASK1/JNK/BAX pathway. 
      METHOD: Type 2 diabetes mellitus (T2DM) rat model was induced by a high-sugar and 
      high-fat diet and intraperitoneal injection of low-dose streptozotocin (STZ) (30 
      mg/kg). Three days after STZ injection, diabetic rats were randomly treated with 
      subcutaneous injection of liraglutide (200 mug/kg/12 h) for 8 weeks and or 
      hUC-MSCs (1 x 10(6) /rat) at the first and fifth weeks. Diabetes-related physical 
      and biochemical parameters, pancreatic histopathological changes, 
      immunohistochemical staining, quantitative real-time polymerase chain reaction, 
      and western blot were used to measure the expression of apoptosis 
      signal-regulating kinase 1 (ASK1), Jun N-terminal kinase (JNK), Bcl-2 associated 
      X protein (BAX), and B-cell lymphoma-2 (Bcl-2). RESULTS: Eight weeks after 
      liraglutide or human umbilical cord mesenchymal stem cell administration, FPG, 
      HbA(1c) , glucagon, body weight, and pancreatic ASK1, JNK, and BAX mRNA and 
      proteins were significantly decreased, and the levels of serum C-p, INS and 
      GLP-1, ratio of insulin positive area, and Bcl-2 expression were significantly 
      increased in three treatment groups compared with T2DM group (P<.05). CONCLUSION: 
      Liraglutide combined with hUC-MSCs improve glucose metabolism and inhibit islet 
      beta-cell apoptosis in a ASK1/JNK/BAX pathway-dependent manner.
CI  - (c) 2019 John Wiley & Sons, Ltd.
FAU - Wang, Wei
AU  - Wang W
AD  - Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China.
AD  - Department of Endocrinology, Fuzhou General Hospital, Fuzhou, China.
FAU - Wu, Rong Dan
AU  - Wu RD
AD  - Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China.
AD  - Department of Endocrinology, Fuzhou General Hospital, Fuzhou, China.
FAU - Chen, Pin
AU  - Chen P
AUID- ORCID: 0000-0002-7546-0082
AD  - Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China.
AD  - Department of Endocrinology, Fuzhou General Hospital, Fuzhou, China.
FAU - Xu, Xiang Jin
AU  - Xu XJ
AD  - Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China.
AD  - Department of Endocrinology, Fuzhou General Hospital, Fuzhou, China.
FAU - Shi, Xiao Zhi
AU  - Shi XZ
AD  - Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China.
AD  - Department of Endocrinology, Fuzhou General Hospital, Fuzhou, China.
FAU - Huang, Li Hong
AU  - Huang LH
AD  - Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China.
AD  - Department of Endocrinology, Fuzhou General Hospital, Fuzhou, China.
FAU - Shao, Zhu Lin
AU  - Shao ZL
AD  - Department of Endocrinology, Fuzhou General Hospital, Fuzhou, China.
FAU - Guo, Wen
AU  - Guo W
AD  - Department of Endocrinology, Fuzhou General Hospital, Fuzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190902
PL  - England
TA  - Diabetes Metab Res Rev
JT  - Diabetes/metabolism research and reviews
JID - 100883450
RN  - 0 (Bax protein, rat)
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 839I73S42A (Liraglutide)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 5)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Biomarkers/*analysis
MH  - Blood Glucose/analysis
MH  - Combined Modality Therapy
MH  - Diabetes Mellitus, Experimental/metabolism/pathology/*therapy
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Hypoglycemic Agents/pharmacology
MH  - Insulin-Secreting Cells/metabolism/*pathology
MH  - Liraglutide/*pharmacology
MH  - MAP Kinase Kinase Kinase 5/genetics/metabolism
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mitogen-Activated Protein Kinase 8/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Umbilical Cord
MH  - bcl-2-Associated X Protein/genetics/metabolism
OTO - NOTNLM
OT  - JNK pathway
OT  - human umbilical cord mesenchymal stem cell
OT  - islet beta-cell apoptosis
OT  - liraglutide
OT  - type 2 diabetes mellitus
EDAT- 2019/08/15 06:00
MHDA- 2020/12/02 06:00
CRDT- 2019/08/15 06:00
PHST- 2018/11/11 00:00 [received]
PHST- 2019/06/15 00:00 [revised]
PHST- 2019/08/09 00:00 [accepted]
PHST- 2019/08/15 06:00 [pubmed]
PHST- 2020/12/02 06:00 [medline]
PHST- 2019/08/15 06:00 [entrez]
AID - 10.1002/dmrr.3212 [doi]
PST - ppublish
SO  - Diabetes Metab Res Rev. 2020 Feb;36(2):e3212. doi: 10.1002/dmrr.3212. Epub 2019 
      Sep 2.