PMID- 22384078
OWN - NLM
STAT- MEDLINE
DCOM- 20120827
LR  - 20230106
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 2
DP  - 2012
TI  - (+)-Rutamarin as a dual inducer of both GLUT4 translocation and expression 
      efficiently ameliorates glucose homeostasis in insulin-resistant mice.
PG  - e31811
LID - 10.1371/journal.pone.0031811 [doi]
LID - e31811
AB  - Glucose transporter 4 (GLUT4) is a principal glucose transporter in response to 
      insulin, and impaired translocation or decreased expression of GLUT4 is believed 
      to be one of the major pathological features of type 2 diabetes mellitus (T2DM). 
      Therefore, induction of GLUT4 translocation or/and expression is a promising 
      strategy for anti-T2DM drug discovery. Here we report that the natural product 
      (+)-Rutamarin (Rut) functions as an efficient dual inducer on both 
      insulin-induced GLUT4 translocation and expression. Rut-treated 3T3-L1 adipocytes 
      exhibit efficiently enhanced insulin-induced glucose uptake, while diet-induced 
      obese (DIO) mice based assays further confirm the Rut-induced improvement of 
      glucose homeostasis and insulin sensitivity in vivo. Subsequent investigation of 
      Rut acting targets indicates that as a specific protein tyrosine phosphatase 1B 
      (PTP1B) inhibitor Rut induces basal GLUT4 translocation to some extent and 
      largely enhances insulin-induced GLUT4 translocation through PI3 kinase-AKT/PKB 
      pathway, while as an agonist of retinoid X receptor alpha (RXRalpha), Rut potently 
      increases GLUT4 expression. Furthermore, by using molecular modeling and 
      crystallographic approaches, the possible binding modes of Rut to these two 
      targets have been also determined at atomic levels. All our results have thus 
      highlighted the potential of Rut as both a valuable lead compound for anti-T2DM 
      drug discovery and a promising chemical probe for GLUT4 associated pathways 
      exploration.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, 
      Chinese Academy of Sciences, Shanghai, China.
FAU - Zhang, Haitao
AU  - Zhang H
FAU - Yao, Xin-Gang
AU  - Yao XG
FAU - Shen, Hong
AU  - Shen H
FAU - Chen, Jing
AU  - Chen J
FAU - Li, Chenjing
AU  - Li C
FAU - Chen, Lili
AU  - Chen L
FAU - Zheng, Mingyue
AU  - Zheng M
FAU - Ye, Jiming
AU  - Ye J
FAU - Hu, Lihong
AU  - Hu L
FAU - Shen, Xu
AU  - Shen X
FAU - Jiang, Hualiang
AU  - Jiang H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120227
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Benzopyrans)
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Insulin)
RN  - 0 (Slc2a4 protein, mouse)
RN  - 14882-94-1 (rutamarin)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
RN  - EC 3.1.3.48 (Ptpn1 protein, mouse)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Benzopyrans/metabolism
MH  - CHO Cells
MH  - Cricetinae
MH  - Cricetulus
MH  - Diabetes Mellitus, Type 2/therapy
MH  - Gene Expression Regulation
MH  - Glucose/*metabolism
MH  - Glucose Transporter Type 4/genetics/*physiology
MH  - HEK293 Cells
MH  - Homeostasis
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin Resistance
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - NIH 3T3 Cells
MH  - Protein Transport
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism
PMC - PMC3288053
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/03/03 06:00
MHDA- 2012/08/28 06:00
PMCR- 2012/02/27
CRDT- 2012/03/03 06:00
PHST- 2011/07/04 00:00 [received]
PHST- 2012/01/16 00:00 [accepted]
PHST- 2012/03/03 06:00 [entrez]
PHST- 2012/03/03 06:00 [pubmed]
PHST- 2012/08/28 06:00 [medline]
PHST- 2012/02/27 00:00 [pmc-release]
AID - PONE-D-11-12524 [pii]
AID - 10.1371/journal.pone.0031811 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(2):e31811. doi: 10.1371/journal.pone.0031811. Epub 2012 Feb 27.