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

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:xushieng
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Aim:To examine the insulin sensitizing effects of a novel α-methyl-α-phenoxylpropionate derivative YY20 in insulin-sensitive cell lines.Methods:Theperoxisome proliferator-activated receptor γ(PPARγ)agonist bioactivities of YY20were detected by a preadipocyte differentiation assay.RT-PCR and Westernblotting analysis were used to detect the expression of the target gene or protein.The effects of YY20 on insulin-mediated glucose consumption were determined inthe HepG2 human hepatocellular carcinoma line.Results:YY20 could enhancethe differentiation of preadipocytes to adipocytes and upregulate the gene ex-pression of PPARγ_2,as well as the protein expression of insulin receptor sub-strate-1(IRS-1),glucose transporter-4(GLUT4),and adiponectin(ACRP30).Theeffects on GLUT4 and ACRP30 could be reversed by the PPARγ inhibitor SR-202.Furthermore,YY20 efficiently reduced glucose consumptions in HepG2 cells after24 h culture,and the effects were related to insulin and YY20 concentrations.Conclusion:YY20,a potential insulin-sensitizing agent like rosiglitazone,couldenhance glucose consumption in HepG2 cells in a concentration-and insulin-dependent manner.It may improve the insulin resistance associated with type 2diabetes. 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 YY20were 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 HepG2 human hepatocellular carcinoma line. Results: YY20 could enhance the differentiation of preadipocytes to adipocytes and upregulate the gene ex-pression 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. Fermentmore, YY20 efficiently reduced glucose consumptions in HepG2 cells after 24 h culture, and the effects were related to insulin and YY20 concentrations. CON clusion: YY20, a potential insulin-sensitizing agent like rosiglitazone, couldenhance glucose consumption in HepG2 cells in a concentration-and insulin-dependent manner. It may improve the insulin resistance associated with type 2 diabetes.
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