Gingerenone A Sensitizes the Insulin Receptor and Increases Glucose Uptake by Inhibiting the Activity of p70 S6 Kinase
Year: 2018
Type: article
Abstract: Scope The bioactive constituents in ginger extract are responsible for anti‐hyperglycemic effects and the underlying mechanisms are incompletely understood. Gingerenone A (Gin A) has been identified as an inhibitor of p70 S6 (S6K1), a kinase that plays a critical role in the pathogenesis of insulin resistance. This study aims to evaluate if Gin A can sensitize the insulin receptor by inhibiting S6K1 activity. Methods and results Western blot analysis reveals that Gin A induces phosphatidylinositide‐3 kinase (PI3K) feedback activation in murine 3T3‐L1 adipocytes and rat L6 myotubes, as evidenced by increased AKTS473 and S6K1T389 but decreases S6S235/236 and insulin receptor substrate 1 (IRS‐1)S1101 phosphorylation. Western blot and immunoprecipitation analysis reveal that Gin A increases insulin receptor tyrosine phosphorylation in L6 myotubes and IRS‐1 binding to the PI3K in 3T3‐L1 adipocytes. Confocal microscopy reveals that Gin A enhances insulin‐induced translocation of glucose transporter 4 (GLUT4) into the cell membrane in L6 cells. 2‐NBDG (2‐N‐(Nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl)amino)‐2‐deoxyglucose) Fluorescent assay reveals that Gin A enhances insulin‐stimulated glucose uptake in 3T3‐L1 adipocytes and L6 myotubes. Conclusions Gin A overcomes insulin resistance and increases glucose uptake by inhibiting S6K1 activity. Gin A or other plant‐derived S6K1 inhibitors could be developed as novel antidiabetic agents.
Authors: Junhong Chen, Jing Sun, Richard A. Prinz, Yi Li, Xiulong Xu
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
Awards: G2548043017, G6467878648
OpenAlex ID: W2896774774