Visfatin, a novel adipokine, stimulates glucose uptake through the Ca2+-dependent AMPK–p38 MAPK pathway in C2C12 skeletal muscle cells

Jung Ok Lee, Nami Kim, Hye Jeong Lee, Yong Woo Lee, Joong Kwan Kim, Hyung Ip Kim, Soo Kyung Lee, Su Jin Kim, Sun-Hwa Park, Hyeon Soo Kim

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Visfatin is a novel adipocytokine produced by visceral fat. In the present study, visfatin increased AMP-activated protein kinase (AMPK) phosphorylation in mouse C2C12 skeletal muscle cells. It also increased phosphorylation of the insulin receptor, whose knockdown blocked visfatin-induced AMPK phosphorylation and glucose uptake. Visfatin stimulated glucose uptake in differentiated skeletal muscle cells. However, inhibition of AMPKα2 with an inhibitor or with knockdown of AMPKα2 using siRNA blocked visfatin-induced glucose uptake, which indicates that visfatin stimulates glucose uptake through the AMPKα2 pathway. Visfatin increased the intracellular Ca2+ concentration. STO-609, a calmodulindependent protein kinase kinase inhibitor, blocked visfatin-induced AMPK phosphorylation and glucose uptake. Visfatin-mediated activation of p38 MAPK was AMPKα2-dependent. Furthermore, both inhibition and knockdown of p38 MAPK blocked visfatin-induced glucose uptake. Visfatin increased glucose transporter type 4 (GLUT4) mRNA and protein levels. In addition, visfatin stimulated the translocation of GLUT4 to the plasma membrane, and this effect was suppressed by AMPKα2 inhibition. The present results indicate that visfatin plays an important role in glucose metabolism via the Ca2+-mediated AMPK–p38 MAPK pathway.

Original languageEnglish
Pages (from-to)251-262
Number of pages12
JournalJournal of Molecular Endocrinology
Volume54
Issue number3
DOIs
Publication statusPublished - 2015

Fingerprint

Nicotinamide Phosphoribosyltransferase
Adipokines
Muscle Cells
Skeletal Muscle
Glucose
AMP-Activated Protein Kinases
Phosphorylation
Glucose Transporter Type 4
p38 Mitogen-Activated Protein Kinases
Intra-Abdominal Fat
Insulin Receptor

Keywords

  • Adipokine
  • AMPK
  • Calcium
  • Diabetes
  • Glucose transport

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology

Cite this

Visfatin, a novel adipokine, stimulates glucose uptake through the Ca2+-dependent AMPK–p38 MAPK pathway in C2C12 skeletal muscle cells. / Lee, Jung Ok; Kim, Nami; Lee, Hye Jeong; Lee, Yong Woo; Kim, Joong Kwan; Kim, Hyung Ip; Lee, Soo Kyung; Kim, Su Jin; Park, Sun-Hwa; Kim, Hyeon Soo.

In: Journal of Molecular Endocrinology, Vol. 54, No. 3, 2015, p. 251-262.

Research output: Contribution to journalArticle

Lee, Jung Ok ; Kim, Nami ; Lee, Hye Jeong ; Lee, Yong Woo ; Kim, Joong Kwan ; Kim, Hyung Ip ; Lee, Soo Kyung ; Kim, Su Jin ; Park, Sun-Hwa ; Kim, Hyeon Soo. / Visfatin, a novel adipokine, stimulates glucose uptake through the Ca2+-dependent AMPK–p38 MAPK pathway in C2C12 skeletal muscle cells. In: Journal of Molecular Endocrinology. 2015 ; Vol. 54, No. 3. pp. 251-262.
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