Insulin-sensitizing effects of a novel alpha-methyl- alpha -phenoxylpropionate derivative in vitro.
OBJECTIVE
To examine the insulin sensitizing effects of a novel alpha-methyl-alpha- phenoxylpropionate derivative YY20 in insulin-sensitive cell lines.


METHODS
The peroxisome proliferator-activated receptor gamma (PPAR gamma) 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 PPAR gamma 2, as well as the protein expression of insulin receptor substrate- 1 (IRS-1), glucose transporter-4 (GLUT4), and adiponectin (ACRP30). The effects on GLUT4 and ACRP30 could be reversed by the PPAR gamma 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.


CONCLUSIONS
YY20, a potential insulin-sensitizing agent like rosiglitazone, could enhance glucose consumption in HepG2 cells in a concentration- and insulindependent manner. It may improve the insulin resistance associated with type 2 diabetes.
Wu
Hao-Shu
HS
Department of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Yu
Juan-Hong
JH
Li
Ying-Yin
YY
Yang
Yu-She
YS
He
Qiao-Jun
QJ
Lou
Yi-Jia
YJ
Ji
Ru-Yun
RY
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects; D052242:Adiponectin / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins / Q000096:biosynthesis / Q000235:genetics; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000494:pharmacology*
D052242:Adiponectin; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047495:PPAR gamma; D010666:Phenylpropionates; D005947:Glucose