Insulin-sensitizing effects of a novel a-methyl-a-phenoxylpropionate derivative in vitro

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 ）, （PPART） 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 PPART2, 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 PPARγinhibitor 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 insulindependent manner. It may improve the insulin resistance associated with type 2 diabetes.