PMID- 27544192
OWN - NLM
STAT- MEDLINE
DCOM- 20170127
LR  - 20240109
IS  - 1976-3786 (Electronic)
IS  - 0253-6269 (Linking)
VI  - 39
IP  - 10
DP  - 2016 Oct
TI  - Fucosterol activates the insulin signaling pathway in insulin resistant HepG2 
      cells via inhibiting PTP1B.
PG  - 1454-1464
AB  - Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) 
      and is characterized by defects in insulin signaling. This study investigated the 
      modulatory effects of fucosterol on the insulin signaling pathway in 
      insulin-resistant HepG2 cells by inhibiting protein tyrosine phosphatase 1B 
      (PTP1B). In addition, molecular docking simulation studies were performed to 
      predict binding energies, the specific binding site of fucosterol to PTP1B, and 
      to identify interacting residues using Autodock 4.2 software. Glucose uptake was 
      determined using a fluorescent D-glucose analogue and the glucose tracer 
      2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose, and the signaling 
      pathway was detected by Western blot analysis. We found that fucosterol enhanced 
      insulin-provoked glucose uptake and conjointly decreased PTP1B expression level 
      in insulin-resistant HepG2 cells. Moreover, fucosterol significantly reduced 
      insulin-stimulated serine (Ser307) phosphorylation of insulin receptor substrate 
      1 (IRS1) and increased phosphorylation of Akt, phosphatidylinositol-3-kinase, and 
      extracellular signal- regulated kinase 1 at concentrations of 12.5, 25, and 50 microM 
      in insulin-resistant HepG2 cells. Fucosterol inhibited caspase-3 activation and 
      nuclear factor kappa B in insulin-resistant hepatocytes. These results suggest 
      that fucosterol stimulates glucose uptake and improves insulin resistance by 
      downregulating expression of PTP1B and activating the insulin signaling pathway. 
      Thus, fucosterol has potential for development as an anti-diabetic agent.
FAU - Jung, Hyun Ah
AU  - Jung HA
AD  - Department of Food Science and Human Nutrition, Chonbuk National University, 
      Jeonju, 561-756, Republic of Korea.
FAU - Bhakta, Himanshu Kumar
AU  - Bhakta HK
AD  - Department of Food and Life Science, Pukyong National University, Busan, 608-737, 
      Republic of Korea.
FAU - Min, Byung-Sun
AU  - Min BS
AD  - College of Pharmacy, Catholic University of Daegu, Gyeongsan, 712-702, Republic 
      of Korea.
FAU - Choi, Jae Sue
AU  - Choi JS
AD  - Department of Food and Life Science, Pukyong National University, Busan, 608-737, 
      Republic of Korea. choijs@pknu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20160820
PL  - Korea (South)
TA  - Arch Pharm Res
JT  - Archives of pharmacal research
JID - 8000036
RN  - 0 (Insulin)
RN  - 504ZAM710C (fucosterol)
RN  - 99WUK5D0Y8 (Stigmasterol)
RN  - EC 3.1.3.48 (PTPN1 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
SB  - IM
MH  - Cell Survival/drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Hep G2 Cells
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin Resistance/*physiology
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1/*antagonists & 
      inhibitors/*metabolism
MH  - Signal Transduction/drug effects/*physiology
MH  - Stigmasterol/*analogs & derivatives/pharmacology
OTO - NOTNLM
OT  - Antdiabetic
OT  - Fucosterol
OT  - Glucose uptake
OT  - HepG2 cell
OT  - Molecular docking
OT  - Protein tyrosine phosphatase 1B
EDAT- 2016/08/22 06:00
MHDA- 2017/01/28 06:00
CRDT- 2016/08/22 06:00
PHST- 2016/05/17 00:00 [received]
PHST- 2016/08/12 00:00 [accepted]
PHST- 2016/08/22 06:00 [pubmed]
PHST- 2017/01/28 06:00 [medline]
PHST- 2016/08/22 06:00 [entrez]
AID - 10.1007/s12272-016-0819-4 [pii]
AID - 10.1007/s12272-016-0819-4 [doi]
PST - ppublish
SO  - Arch Pharm Res. 2016 Oct;39(10):1454-1464. doi: 10.1007/s12272-016-0819-4. Epub 
      2016 Aug 20.