Hesperidin ameliorates insulin resistance by regulating the IRS1‐GLUT2 pathway via TLR4 in HepG2 cells

• Published in: Phytotherapy research 2019-06, Vol.33 (6), p.1697-1705
• Main Authors: Xuguang, Hu, Aofei, Tian, Tao, Liu, Longyan, Zhou, Weijian, Bei, Jiao, Guo
• Format: Article
• Language: English
• Subjects: Animals; Cell culture; Deoxyglucose; Glucose; Glucose - metabolism; Glucose oxidase; Glucose transporter; glucose transporter 2; Glucose Transporter Type 2 - metabolism; GLUT2 protein; Hep G2 Cells; Hepatocellular carcinoma; Hesperidin; Hesperidin - pharmacology; Humans; Insulin; Insulin - metabolism; Insulin receptor substrate 1; Insulin Receptor Substrate Proteins - metabolism; Insulin resistance; Insulin Resistance - physiology; Interleukins; Lipopolysaccharides; NF-kappa B - metabolism; nuclear factor kappa B; Peroxidase; Protein expression; Proteins; Receptors; Signal Transduction - drug effects; Substrates; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; toll‐like receptor 4; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Western blotting
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.6358

The aim of this study was to evaluate the effect and mechanism of hesperidin (HES) on insulin resistance (IR) in the human hepatocellular carcinoma cell line (HepG2 cells). HepG2 cells were induced with lipopolysaccharide (LPS) as a model of IR and treated with HES at three dosages. Next, the levels of interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α), the glucose content, and glucose uptake were evaluated by enzyme‐linked immunosorbent assay, glucose oxidase‐peroxidase method (GOD‐POD), or (2‐(N‐(7‐nitrobenz‐2‐oxa‐1, 3‐diazol‐4‐yl)amino)‐2‐deoxyglucose) (2‐NBDG). Moreover, the protein expression of toll‐like receptors 4 (TLR4), insulin receptor substrate 1 (IRS1), nuclear factor kappa B (NF‐κB), and glucose transporter 2 (GLUT2) in HepG2 cells treated with HES were assessed via western blotting analysis. In addition, GLUT2 protein expression exposed to HES was detected following treatment with TLR4 inhibitor (HTA125). Our results demonstrated that HES decreased the levels of TNF‐α and IL‐6, attenuated the glucose content in culture medium and increased glucose uptake in insulin‐resistant HepG2 cells in vitro. Moreover, HES upregulated the expression of IRS1 and GLUT2 protein and downregulated the protein expression of TLR4 and NF‐κB in insulin‐resistant HepG2 cells. The expression of GLUT2 protein had no significant changes when treated with HES after blockade of TLR4. HES attenuated IR in LPS‐inducedinsulin‐resistant HepG2 cells. Therefore, regulating the IRS1‐GLUT2 pathway via TLR4 represents a potential mechanism of HES on IR in HepG2 cells.