AMPK, a metabolic sensor, is involved in isoeugenol-induced glucose uptake in muscle cells

Nami Kim, Jung Ok Lee, Hye Jeong Lee, Yong Woo Lee, Hyung Ip Kim, Su Jin Kim, Sun-Hwa Park, Chul Su Lee, Sun Woo Ryoo, Geum Sook Hwang, Hyeon Soo Kim

    Research output: Contribution to journalArticlepeer-review

    18 Citations (Scopus)

    Abstract

    Isoeugenol exerts various beneficial effects on human health. However, the mechanisms underlying these effects are poorly understood. In this study, we observed that isoeugenol activated AMP-activated protein kinase (AMPK) and increased glucose uptake in rat L6 myotubes. Isoeugenol-induced increase in intracellular calcium concentration and glucose uptake was inhibited by STO-609, an inhibitor of calcium/calmodulin-dependent protein kinase kinase (CaMKK). Isoeugenol also increased the phosphorylation of protein kinase C-α (PKCα). Chelation of calcium with BAPTA-AM blocked isoeugenol-induced AMPK phosphorylation and glucose uptake. Isoeugenol stimulated p38MAPK phosphorylation that was inhibited after pretreatment with compound C, an AMPK inhibitor. Isoeugenol also increased glucose transporter type 4 (GLUT4) expression and its translocation to the plasma membrane. GLUT4 translocation was not observed after the inhibition of AMPK and CaMKK. In addition, isoeugenol activated the Akt substrate 160 (AS160) pathway, which is downstream of the p38MAPK pathway. Knockdown of the gene encoding AS160 inhibited isoeugenol-induced glucose uptake. Together, these results indicate that isoeugenol exerts beneficial health effects by activating the AMPK/p38MAPK/AS160 pathways in skeletal muscle.

    Original languageEnglish
    Pages (from-to)105-114
    Number of pages10
    JournalJournal of Endocrinology
    Volume228
    Issue number2
    DOIs
    Publication statusPublished - 2016 Feb 1

    Bibliographical note

    Funding Information:
    This study was supported by the National Research Foundation of Korea, which is funded by the Korean government (NRF-2013R1A2A2A05004796).

    Publisher Copyright:
    © 2016 The authors.

    Keywords

    • AMPK
    • Glucose uptake
    • Isoeugenol
    • p38 MAPK

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Endocrinology

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