Acta Pharmacologica Sinica 2007 March; 28 (3): 417-422; doi: 10.1111/j.1745-7254.2007.00506.x

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 g (PPARg) 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 PPARg₂, 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 PPARg 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.

Keywords: YY20; peroxisome proliferator-activated receptor γ; insulin sensitivity; glucose consumption