TROXERUTIN IMPROVES INSULIN SIGNALING IN TNFα TREATED 3T3-L1 ADIPOCYTESAbstract
Chronic low-grade inflammation of adipose tissue is associated with obesity and insulin resistance (IR). The aim of this study is to determine the effect of troxerutin (TX) on insulin signaling in tumor necrosis factor α (TNFα) treated 3T3-L1 adipocytes. Differentiated 3T3-L1 adipocytes were pre-treated with TX, elastatinal (ELAS) or sodium salicylate (SAL) before exposure to recombinant human TNFα (20 ng/mL) for 24 h. Glucose uptake was measured by 2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxyglucose (2-NBDG) assay. The protein expression of insulin receptor-β (IR-β), insulin receptor substrate-1 (IRS-1), phosphatidyl inositol 3 kinase (PI3K) association with IRS-1, protein kinase B (Akt) and glucose transporter 4 (GLUT4) were studied. The mRNA and protein expression of caveolin-1 and suppressor of cytokine signaling 3 (SOCS3) were also analyzed. TNFα treated 3T3-L1 adipocytes displayed decreased tyrosine phosphorylation of IR-β and IRS-1. Further, the association of p85 subunit of PI3K with IRS-1, subsequent Akt phosphorylation and GLUT4 activation were also reduced. TX pre-treatment enhanced tyrosine phosphorylation of IR-β, IRS-1, IRS1-PI3K association and Akt and GLUT4 expression. These changes were higher as compared to ELAS and SAL. The expression of SOCS3 was downregulated, while that of caveolin-1 was upregulated by TX. These findings suggest that TX activates the IRS-PI3K-Akt pathway of insulin signaling, enhances caveolin-1 expression, suppresses SOCS3, promotes glucose uptake and improves insulin sensitivity in TNFα treated 3T3-L1 cells. Thus, TX could be a potential therapeutic agent for the management of IR.
R. Vidhya, U. Ajay Krishnan and C. V. Anuradha *
Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, Tamil Nadu, India.
23 October 2020
11 February 2021
24 May 2021
01 October 2021