PMID- 29311680
OWN - NLM
STAT- MEDLINE
DCOM- 20181121
LR  - 20181121
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Jan 8
TI  - Inhibition of insulin resistance by PGE1 via autophagy-dependent FGF21 pathway in 
      diabetic nephropathy.
PG  - 9
LID - 10.1038/s41598-017-18427-2 [doi]
LID - 9
AB  - Insulin resistance is a critical process in the initiation and progression of 
      diabetic nephropathy (DN). Alprostadil (Prostaglandin E1, PGE1) had protective 
      effects on renal function. However, it is unknown whether PGE1 inhibited insulin 
      resistance in renal tubule epithelial cells via autophagy, which plays a 
      protective role in DN against insulin resistance. Insulin resistance was induced 
      by palmitic acid (PA) in human HK-2 cells, shown as the decrease of 
      insulin-stimulated AKT phosphorylation, glucose transporter-4 (GLUT4), glucose 
      uptake and enhanced phosphorylation of insulin receptor substrate 1(IRS-1) at 
      site serine 307 (pIRS-1ser307) and downregulated expression of IRS-1. Along with 
      less abundance of p62, autophagy markers LC3B and Beclin-1 significantly 
      increased in HK-2 cells exposed to PA. Such abnormal changes were significantly 
      reversed by PGE1, which mimicked the role of autophagy gene 7 small interfering 
      RNA (ATG7 siRNA). Furthermore, PGE1 promoted the protein expression of 
      autophagy-related fibroblast growth factor-21 (FGF21), which alleviated insulin 
      resistance. Results from western blotting and immunohistochemistry indicated that 
      PGE1 remarkably restored autophagy, insulin resistance and the FGF21 expression 
      in rat kidney of type 2 diabetes mellitus (T2DM). Collectively, we demonstrated 
      the potential protection of PGE1 on insulin resistance in renal tubules via 
      autophagy-dependent FGF21 pathway in preventing the progression of DN.
FAU - Wei, Wei
AU  - Wei W
AD  - Department of Clinical Pharmacy, School of Basic Medical Sciences and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
FAU - An, Xing-Rong
AU  - An XR
AD  - Department of Clinical Pharmacy, School of Basic Medical Sciences and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
FAU - Jin, Shi-Jie
AU  - Jin SJ
AD  - School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, 311400, China.
FAU - Li, Xiao-Xue
AU  - Li XX
AD  - Department of Pathology, Medical School of Southeast University, Nanjing, 210009, 
      China.
FAU - Xu, Ming
AU  - Xu M
AD  - Department of Clinical Pharmacy, School of Basic Medical Sciences and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. 
      mingxu@cpu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180108
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (fibroblast growth factor 21)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - F5TD010360 (Alprostadil)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Alprostadil/*pharmacology
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Cell Survival/drug effects
MH  - Diabetes Mellitus, Type 2/metabolism/pathology
MH  - Diabetic Nephropathies/*etiology/*metabolism
MH  - Disease Models, Animal
MH  - Fibroblast Growth Factors/*metabolism
MH  - Glucose/metabolism
MH  - Humans
MH  - *Insulin Resistance
MH  - Kidney Function Tests
MH  - Palmitic Acid/metabolism
MH  - Rats
MH  - Signal Transduction/*drug effects
PMC - PMC5758726
COIS- The authors declare that they have no competing interests.
EDAT- 2018/01/10 06:00
MHDA- 2018/11/22 06:00
PMCR- 2018/01/08
CRDT- 2018/01/10 06:00
PHST- 2017/07/07 00:00 [received]
PHST- 2017/12/11 00:00 [accepted]
PHST- 2018/01/10 06:00 [entrez]
PHST- 2018/01/10 06:00 [pubmed]
PHST- 2018/11/22 06:00 [medline]
PHST- 2018/01/08 00:00 [pmc-release]
AID - 10.1038/s41598-017-18427-2 [pii]
AID - 18427 [pii]
AID - 10.1038/s41598-017-18427-2 [doi]
PST - epublish
SO  - Sci Rep. 2018 Jan 8;8(1):9. doi: 10.1038/s41598-017-18427-2.