PMID- 30684546
OWN - NLM
STAT- MEDLINE
DCOM- 20190520
LR  - 20191210
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 224
DP  - 2019 May 1
TI  - MicroRNA-125b-5p improves pancreatic beta-cell function through inhibiting JNK 
      signaling pathway by targeting DACT1 in mice with type 2 diabetes mellitus.
PG  - 67-75
LID - S0024-3205(19)30042-6 [pii]
LID - 10.1016/j.lfs.2019.01.031 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is a progressive disease, accompanied by 
      increased insulin resistance and deteriorating beta-cell function. Previous studies 
      have revealed that microRNA (miRNA) plays a crucial role in the treatment of 
      T2DM. Hence, we aim to investigate the role of microRNA-125b-5p (miR-125b-5p) in 
      pancreatic beta-cell function and insulin sensitivity of mice with T2DM with the 
      involvement of Dishevelled antagonist Dapper1 (DACT1) and the c-Jun NH2-terminal 
      kinases (JNK) signaling pathway. Firstly, a mouse model of T2DM was established 
      by administering a high-fat diet plus low dosage of streptozotocin, and function 
      of pancreatic beta-cell and insulin sensitivity in the normal and T2DM mice were 
      detected. Then, the pancreatic beta-cells were collected from pancreatic islet 
      tissues and treated with different mimics, inhibitors and siRNAs. After that, the 
      relationship among miR-125b-5p, DACT1, and the JNK signaling-related factors in 
      T2DM mice was determined. Finally, cell proliferation and apoptosis were 
      determined. Mice with T2DM had lower pancreatic beta-cell function and insulin 
      sensitivity, as well as diminished expression of miR-125b-5p but enhanced 
      expressions of DACT1, JNK and c-Jun. miR-125b-5p inhibited DACT1 expression and 
      the activation of the JNK signaling pathway, as well as restrained cell 
      proliferation and promoted cell apoptosis. The current results suggest that 
      up-regulated miR-125b-5p promotes insulin sensitivity and enhances pancreatic 
      beta-cell function through inhibiting the JNK signaling pathway by negatively 
      mediating DACT1.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Yu, Cheng-Yong
AU  - Yu CY
AD  - Clinical Laboratory, Weihai Central Hospital, Weihai 264400, PR China.
FAU - Yang, Chun-Yun
AU  - Yang CY
AD  - Clinical Laboratory, Laizhou City People's Hospital, Laizhou 261400, PR China. 
      Electronic address: Laizhou001@126.com.
FAU - Rui, Zhi-Lian
AU  - Rui ZL
AD  - Clinical Laboratory, Liyang People's Hospital, Affiliated Liyang Hospital of 
      Jiangsu Province People's Hospital, Liyang 213300, PR China. Electronic address: 
      zlianrui@126.com.
LA  - eng
PT  - Journal Article
DEP - 20190123
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn125 microRNA, mouse)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (frodo protein, mouse)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cell Differentiation
MH  - *Cell Proliferation
MH  - Diabetes Mellitus, Experimental/genetics/pathology/*prevention & control
MH  - Diabetes Mellitus, Type 2/genetics/pathology/*prevention & control
MH  - Insulin Resistance
MH  - Insulin-Secreting Cells/cytology/*physiology
MH  - Intracellular Signaling Peptides and Proteins/*antagonists & 
      inhibitors/genetics/metabolism
MH  - *MAP Kinase Signaling System
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - MicroRNAs/*genetics
MH  - RNA-Binding Proteins
MH  - Signal Transduction
OTO - NOTNLM
OT  - DACT1
OT  - Insulin
OT  - JNK signaling pathway
OT  - MicroRNA-125b-5p
OT  - Pancreatic beta cell
OT  - Type 2 diabetes mellitus
EDAT- 2019/01/27 06:00
MHDA- 2019/05/21 06:00
CRDT- 2019/01/27 06:00
PHST- 2018/09/15 00:00 [received]
PHST- 2019/01/08 00:00 [revised]
PHST- 2019/01/18 00:00 [accepted]
PHST- 2019/01/27 06:00 [pubmed]
PHST- 2019/05/21 06:00 [medline]
PHST- 2019/01/27 06:00 [entrez]
AID - S0024-3205(19)30042-6 [pii]
AID - 10.1016/j.lfs.2019.01.031 [doi]
PST - ppublish
SO  - Life Sci. 2019 May 1;224:67-75. doi: 10.1016/j.lfs.2019.01.031. Epub 2019 Jan 23.