Irisin, a novel myokine, regulates glucose uptake in skeletal muscle cells via AMPK

Hye Jeong Lee, Jung Ok Lee, Nami Kim, Joong Kwan Kim, Hyung Ip Kim, Yong Woo Lee, Su Jin Kim, Jongil Choi, Yoonji Oh, Jeong Hyun Kim, Suyeon Hwang, Sun-Hwa Park, Hyeon Soo Kim

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Abstract

Irisin is a novel myokine produced by skeletal muscle. However, its metabolic role is poorly understood. In the present study, irisin induced glucose uptake in differentiated skeletal muscle cells. It increased AMP-activated protein kinase (AMPK) phosphorylation and the inhibition of AMPK blocked glucose uptake. It also increased reactive oxygen species (ROS) generation. N-acetyl cysteine, a ROS scavenger, blocked irisin-induced AMPK phosphorylation. Moreover, irisin activated p38 MAPK in an AMPK-dependent manner. The inhibition and knockdown of p38 MAPK blocked irisin-induced glucose uptake. A colorimetric absorbance assay showed that irisin stimulated the translocation of glucose transporter type 4 to the plasma membrane and that this effect was suppressed in cells pretreated with a p38 MAPK inhibitor or p38 MAPK small interfering RNA. In primary cultured myoblast cells, irisin increased the concentration of intracellular calcium. STO-609, a calcium/calmodulin-dependent protein kinase kinase inhibitor, blocked irisin-induced AMPK phosphorylation, implying that calcium is involved in irisin-mediated signaling. Our results suggest that irisin plays an important role in glucose metabolism via the ROS-mediated AMPK pathway in skeletal muscle cells.

Original languageEnglish
Pages (from-to)873-881
Number of pages9
JournalMolecular Endocrinology
Volume29
Issue number6
DOIs
Publication statusPublished - 2015 Jun 1

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ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Lee, H. J., Lee, J. O., Kim, N., Kim, J. K., Kim, H. I., Lee, Y. W., Kim, S. J., Choi, J., Oh, Y., Kim, J. H., Hwang, S., Park, S-H., & Kim, H. S. (2015). Irisin, a novel myokine, regulates glucose uptake in skeletal muscle cells via AMPK. Molecular Endocrinology, 29(6), 873-881. https://doi.org/10.1210/me.2014-1353