-Gingerol affects glucose metabolism by dual regulation via the ampkα2-mediated as160-rab5 pathway and ampk-mediated insulin sensitizing effects

Jung Ok Lee, Nami Kim, Hye Jeong Lee, Ji Wook Moon, Soo Kyung Lee, Su Jin Kim, Joong Kwan Kim, Sun-Hwa Park, Hyeon Soo Kim

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

[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.

Original languageEnglish
Pages (from-to)1401-1410
Number of pages10
JournalJournal of Cellular Biochemistry
Volume116
Issue number7
DOIs
Publication statusPublished - 2015 Jul 1

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Metabolism
Insulin
Glucose
Phosphorylation
Protein Phosphatase 2
AMP-Activated Protein Kinases
Facilitative Glucose Transport Proteins
gingerol
Substrates
rab GTP-Binding Proteins
GTPase-Activating Proteins
Okadaic Acid
Adenosine Monophosphate
Protein Kinase Inhibitors
Medical problems
Dyslipidemias
Protein Kinases
Muscle Cells
Muscle
Skeletal Muscle

Keywords

  • AMPK
  • DIABETES
  • INSULIN SENSITIZING
  • SIGNAL TRANSDUCTION
  • [6]-GINGEROL

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

-Gingerol affects glucose metabolism by dual regulation via the ampkα2-mediated as160-rab5 pathway and ampk-mediated insulin sensitizing effects. / 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.

In: Journal of Cellular Biochemistry, Vol. 116, No. 7, 01.07.2015, p. 1401-1410.

Research output: Contribution to journalArticle

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. / -Gingerol affects glucose metabolism by dual regulation via the ampkα2-mediated as160-rab5 pathway and ampk-mediated insulin sensitizing effects. In: Journal of Cellular Biochemistry. 2015 ; Vol. 116, No. 7. pp. 1401-1410.
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abstract = "[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.",
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AU - Lee, Jung Ok

AU - Kim, Nami

AU - Lee, Hye Jeong

AU - Moon, Ji Wook

AU - Lee, Soo Kyung

AU - Kim, Su Jin

AU - Kim, Joong Kwan

AU - Park, Sun-Hwa

AU - Kim, Hyeon Soo

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KW - SIGNAL TRANSDUCTION

KW - [6]-GINGEROL

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