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[6]‐Gingerol Affects Glucose Metabolism by Dual Regulation via the AMPKα2‐Mediated AS160–Rab5 Pathway and AMPK‐Mediated Insulin Sensitizing Effects
Author(s) -
Lee Jung Ok,
Kim Nami,
Lee Hye Jeong,
Moon Ji Wook,
Lee Soo Kyung,
Kim Su Jin,
Kim Joong Kwan,
Park Sun Hwa,
Kim Hyeon Soo
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25100
Subject(s) - ampk , glut4 , chemistry , protein phosphatase 2 , protein kinase a , glucose transporter , phosphorylation , glucose uptake , protein kinase b , microbiology and biotechnology , medicine , endocrinology , biochemistry , insulin , biology , phosphatase
[6]‐Gingerol has been used to control diabetes and dyslipidemia; however, its metabolic role is poorly understood. In this study, [6]‐gingerol increased adenosine monophosphate (AMP)‐activated protein kinase (AMPK) phosphorylation in mouse skeletal muscle C2C12 cells. Stimulation of glucose uptake by [6]‐gingerol was dependent on AMPKα2. Moreover, both Inhibition and knockdown of AMPKα2 blocked [6]‐gingerol‐induced glucose uptake. [6]‐Gingerol significantly decreased the activity of protein phosphatase 2A (PP2A). Inhibition of PP2A activity with okadaic acid enhanced the phosphorylation of AMPKα2. Moreover, the interaction between AMPKα2 and PP2A was increased by [6]‐gingerol, suggesting that PP2A mediates the effect of [6]‐gingerol on AMPK phosphorylation. In addition, [6]‐gingerol increased the phosphorylation of Akt‐substrate 160 (AS160), which is a Rab GTPase‐activating protein. Inhibition of AMPKα2 blocked [6]‐gingerol‐induced AS160 phosphorylation. [6]‐gingerol increased the Rab5, and AMPKα2 knockdown blocked [6]‐gingerol‐induced expression of Rab5, indicating AMPK play as an upstream of Rab5. It also increased glucose transporter 4 (GLUT4) mRNA and protein expression and stimulated GLUT4 translocation. Furthermore, insulin‐mediated glucose uptake and Akt phosphorylation were further potentiated by [6]‐gingerol treatment. This potentiation was not observed in the presence of AMPK inhibitor compound C. In summary, our results suggest that [6]‐gingerol plays an important role in glucose metabolism via the AMPKα2‐mediated AS160–Rab5 pathway and through potentiation of insulin‐mediated glucose regulation. J. Cell. Biochem. 116: 1401–1410, 2015. © 2015 Wiley Periodicals, Inc.