Open AccessInsulin‐sensitizing effects of a novel α‐methyl‐α‐phenoxylpropionate derivative in vitro 4
Author(s) -
WU Haoshu,
YU Juanhong,
LI Yingyin,
YANG Yushe,
HE Qiaojun,
LOU Yijia,
JI Ruyun
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00506.x
Subject(s) - glut4 , rosiglitazone , insulin , endocrinology , adiponectin , medicine , insulin resistance , insulin receptor substrate , glucose transporter , downregulation and upregulation , insulin receptor , peroxisome proliferator activated receptor , adipogenesis , chemistry , cell culture , irs2 , receptor , biology , biochemistry , adipose tissue , gene , genetics
Aim: To examine the insulin sensitizing effects of a novel α‐methyl‐α‐phenoxylpropionate derivative YY20 in insulin‐sensitive cell lines. Methods: The peroxisome proliferator‐activated receptor γ (PPARγ) agonist bioactivities of YY20 were detected by a preadipocyte differentiation assay. RT‐PCR and Western blotting analysis were used to detect the expression of the target gene or protein. The effects of YY20 on insulin‐mediated glucose consumption were determined in the HepG2 human hepatocellular carcinoma line. Results: YY20 could enhance the differentiation of preadipocytes to adipocytes and upregulate the gene expression of PPARγ 2 , as well as the protein expression of insulin receptor sub‐strate‐1 (IRS‐1), glucose transporter‐4 (GLUT4), and adiponectin (ACRP30). The effects on GLUT4 and ACRP30 could be reversed by the PPARγ inhibitor SR‐202. Furthermore, YY20 efficiently reduced glucose consumptions in HepG2 cells after 24 h culture, and the effects were related to insulin and YY20 concentrations. Conclusion: YY20, a potential insulin‐sensitizing agent like rosiglitazone, could enhance glucose consumption in HepG2 cells in a concentration‐ and insulin‐dependent manner. It may improve the insulin resistance associated with type 2 diabetes.