PMID- 30461198
OWN - NLM
STAT- MEDLINE
DCOM- 20200617
LR  - 20210109
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 23
IP  - 2
DP  - 2019 Feb
TI  - Pancreatic fibroblast growth factor 21 protects against type 2 diabetes in mice 
      by promoting insulin expression and secretion in a PI3K/Akt signaling-dependent 
      manner.
PG  - 1059-1071
LID - 10.1111/jcmm.14007 [doi]
AB  - Fibroblast growth factor 21 (FGF21) is important in glucose, lipid homeostasis 
      and insulin sensitivity. However, it remains unknown whether FGF21 is involved in 
      insulin expression and secretion that are dysregulated in type 2 diabetes 
      mellitus (T2DM). In this study, we found that FGF21 was down-regulated in 
      pancreatic islets of db/db mice, a mouse model of T2DM, along with decreased 
      insulin expression, suggesting the possible involvement of FGF21 in maintaining 
      insulin homeostasis and islet beta-cell function. Importantly, FGF21 knockout 
      exacerbated palmitate-induced islet beta-cell failure and suppression of 
      glucose-stimulated insulin secretion (GSIS). Pancreatic FGF21 overexpression 
      significantly increased insulin expression, enhanced GSIS, improved islet 
      morphology and reduced beta-cell apoptosis in db/db mice. Mechanistically, FGF21 
      promoted expression of insulin gene transcription factors and soluble 
      N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, 
      the major regulators of insulin secretion, as well as activating 
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling in islets of db/db mice. In 
      addition, pharmaceutical inhibition of PI3K/Akt signaling effectively suppressed 
      FGF21-induced expression of insulin gene transcription factors and SNARE 
      proteins, suggesting an essential role of PI3K/Akt signaling in FGF21-induced 
      insulin expression and secretion. Taken together, our results demonstrate a 
      protective role of pancreatic FGF21 in T2DM mice through inducing PI3K/Akt 
      signaling-dependent insulin expression and secretion.
CI  - (c) 2018 The Authors. Journal of Cellular and Molecular Medicine published by John 
      Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
FAU - Pan, Yingying
AU  - Pan Y
AD  - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
FAU - Wang, Baile
AU  - Wang B
AD  - State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine, The 
      University of Hong Kong, Hong Kong.
FAU - Zheng, Jujia
AU  - Zheng J
AD  - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
FAU - Xiong, Rongrong
AU  - Xiong R
AD  - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
FAU - Fan, Zhichao
AU  - Fan Z
AD  - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
FAU - Ye, Yanna
AU  - Ye Y
AD  - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
FAU - Zhang, Saisai
AU  - Zhang S
AD  - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
FAU - Li, Qinyao
AU  - Li Q
AD  - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
FAU - Gong, Fanghua
AU  - Gong F
AD  - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
FAU - Wu, Chaoming
AU  - Wu C
AD  - The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
FAU - Lin, Zhuofeng
AU  - Lin Z
AD  - The First Affiliated Hospital of Jinan University, Guangzhou, China.
FAU - Li, Xiaokun
AU  - Li X
AD  - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
FAU - Pan, Xuebo
AU  - Pan X
AUID- ORCID: 0000-0002-8014-5538
AD  - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181120
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Insulin)
RN  - 0 (fibroblast growth factor 21)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Fibroblast Growth Factors/*metabolism
MH  - Glucose/metabolism
MH  - Insulin/*metabolism
MH  - Insulin Resistance/physiology
MH  - Insulin-Secreting Cells/metabolism
MH  - Islets of Langerhans/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Pancreas/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/*physiology
PMC - PMC6349243
OTO - NOTNLM
OT  - FGF21
OT  - diabetes
OT  - insulin
OT  - pancreatic beta-cell
EDAT- 2018/11/22 06:00
MHDA- 2020/06/18 06:00
PMCR- 2019/02/01
CRDT- 2018/11/22 06:00
PHST- 2018/05/30 00:00 [received]
PHST- 2018/10/11 00:00 [accepted]
PHST- 2018/11/22 06:00 [pubmed]
PHST- 2020/06/18 06:00 [medline]
PHST- 2018/11/22 06:00 [entrez]
PHST- 2019/02/01 00:00 [pmc-release]
AID - JCMM14007 [pii]
AID - 10.1111/jcmm.14007 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2019 Feb;23(2):1059-1071. doi: 10.1111/jcmm.14007. Epub 2018 Nov 
      20.