4-Hydroxyisoleucine improves insulin resistance in HepG2 cells by decreasing TNF-α and regulating the expression of insulin signal transduction proteins

Molecular Medicine Reports
Feng GaoFurong Lu

Abstract

Previous studies have indicated that 4‑hydroxyisoleucine (4‑HIL) improves insulin resistance, however, the underlying mechanisms remain to be elucidated. In the present study, the molecular mechanisms underlying how 4‑HIL improves insulin resistance in hepatocytes were examined. HepG2 cells were co‑cultured with insulin and a high glucose concentration to obtain insulin‑resistant (IR) HepG2 cells. Insulin sensitivity was determined by measuring the glucose uptake rate. The IR HepG2 cells were treated with different concentrations of 4‑HIL to determine its effect on IR Hep2 cells. The levels of tumor necrosis factor‑α (TNF‑α) were measured by an enzyme‑linked immunosorbent assay and protein levels of TNF‑α converting enzyme (TACE)/tissue inhibitor of metalloproteinase 3 (TIMP3), insulin receptor substrate (IRS)‑1, IRS‑2, phosphorylated (p)‑IRS‑1 (Ser307) and glucose transporter type 4 (GLUT4) were measured by western blot analysis. The results of the present study demonstrated that insulin‑induced glucose uptake was reduced in IR HepG2 cells; however, this reduction was reversed by 4‑HIL in a dose‑dependent manner. 4‑HIL achieved this effect by downregulating the expression of TNF‑α and TACE, and upregulating the expression of T...Continue Reading

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Citations

Nov 24, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anaguiven Avalos-SorianoTeresa Garcia-Gasca
Jan 26, 2017·International Journal of Obesity : Journal of the International Association for the Study of Obesity·J LatorreF J Ortega
Mar 8, 2017·Molecular Nutrition & Food Research·Kalyan C Nagulapalli VenkataAnupam Bishayee
May 7, 2016·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Mohammad Ishraq Zafar, Feng Gao

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Methods Mentioned

BETA
electrophoresis

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