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

Research output: Contribution to journalArticle

47 Citations (Scopus)

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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AMP-Activated Protein Kinases
Muscle Cells
Skeletal Muscle
p38 Mitogen-Activated Protein Kinases
Glucose
Reactive Oxygen Species
Phosphorylation
Calcium-Calmodulin-Dependent Protein Kinase Kinase
Glucose Transporter Type 4
Calcium
Myoblasts
Small Interfering RNA
Cysteine
Cultured Cells
Cell Membrane

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Irisin, a novel myokine, regulates glucose uptake in skeletal muscle cells via AMPK. / Lee, Hye Jeong; Lee, Jung Ok; Kim, Nami; Kim, Joong Kwan; Kim, Hyung Ip; Lee, Yong Woo; Kim, Su Jin; Choi, Jongil; Oh, Yoonji; Kim, Jeong Hyun; Hwang, Suyeon; Park, Sun-Hwa; Kim, Hyeon Soo.

In: Molecular Endocrinology, Vol. 29, No. 6, 01.06.2015, p. 873-881.

Research output: Contribution to journalArticle

Lee, HJ, Lee, JO, Kim, N, Kim, JK, Kim, HI, Lee, YW, Kim, SJ, Choi, J, Oh, Y, Kim, JH, Hwang, S, Park, S-H & Kim, HS 2015, 'Irisin, a novel myokine, regulates glucose uptake in skeletal muscle cells via AMPK', Molecular Endocrinology, vol. 29, no. 6, pp. 873-881. https://doi.org/10.1210/me.2014-1353
Lee, Hye Jeong ; Lee, Jung Ok ; Kim, Nami ; Kim, Joong Kwan ; Kim, Hyung Ip ; Lee, Yong Woo ; Kim, Su Jin ; Choi, Jongil ; Oh, Yoonji ; Kim, Jeong Hyun ; Hwang, Suyeon ; Park, Sun-Hwa ; Kim, Hyeon Soo. / Irisin, a novel myokine, regulates glucose uptake in skeletal muscle cells via AMPK. In: Molecular Endocrinology. 2015 ; Vol. 29, No. 6. pp. 873-881.
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