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Gingerenone A Sensitizes the Insulin Receptor and Increases Glucose Uptake by Inhibiting the Activity of p70 S6 Kinase
Author(s) -
Chen Junhong,
Sun Jing,
Prinz Richard A.,
Li Yi,
Xu Xiulong
Publication year - 2018
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201800709
Subject(s) - glut4 , p70 s6 kinase 1 , insulin receptor , glucose transporter , glucose uptake , irs1 , insulin resistance , insulin , insulin receptor substrate , medicine , protein kinase b , endocrinology , 3t3 l1 , tyrosine phosphorylation , downregulation and upregulation , biology , phosphorylation , chemistry , biochemistry , adipocyte , adipose tissue , gene
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 AKT S473 and S6K1 T389 but decreases S6 S235/236 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.