Original Article

Metformin induces Rab4 through AMPK and modulates GLUT4 translocation in skeletal muscle cells†

  1. Jung Ok Lee1,
  2. Soo Kyung Lee1,
  3. Jin Hee Jung1,
  4. Ji Hae Kim1,
  5. Ga Young You1,
  6. Su Jin Kim1,
  7. Sun Hwa Park1,
  8. Kyung-Ok Uhm2,
  9. Hyeon Soo Kim1,*

Article first published online: 25 JAN 2011

DOI: 10.1002/jcp.22410

Issue

Journal of Cellular Physiology

Journal of Cellular Physiology

Volume 226, Issue 4, pages 974–981, April 2011

Additional Information

How to Cite

Lee, J. O., Lee, S. K., Jung, J. H., Kim, J. H., You, G. Y., Kim, S. J., Park, S. H., Uhm, K.-O. and Kim, H. S. (2011), Metformin induces Rab4 through AMPK and modulates GLUT4 translocation in skeletal muscle cells. J. Cell. Physiol., 226: 974–981. doi: 10.1002/jcp.22410

Author Information

  1. 1

    Department of Anatomy, Korea University College of Medicine, Seoul, Korea

  2. 2

    Department of Alzheimer's Disease Research, National Institute for Geriatrics and Gerontology, Morioka, Aichi, Japan

*126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-701, Korea.

  1. †

    The authors confirm that there are no conflicts of interest.

Publication History

  1. Issue published online: 25 JAN 2011
  2. Article first published online: 25 JAN 2011
  3. Accepted manuscript online: 20 SEP 2010 12:00AM EST
  4. Manuscript Accepted: 19 AUG 2010
  5. Manuscript Received: 19 APR 2010

Funded by

  • Korea University College of Medicine
  • Korea Science and Engineering Foundation (KOSEF). Grant Number: R01-2008-000-11180-0
Corrected by:

Errata: Erratum: Metformin induces Rab4 through AMPK and modulates GLUT4 translocation in skeletal muscle cells. J. O. Lee, S. K. Lee, J. H. Jung, J. H. Kim, G. Y. You, S. J. Kim, S. H. Park, K.-O. Uhm, H. S. Kim

Vol. 227, Issue 6, 2804, Article first published online: 24 FEB 2012

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (318K)

Abstract

Metformin is a major oral anti-diabetic drug and is known as an insulin sensitizer. However, the mechanism by which metformin acts is unclear. In this study, we found that AICAR, an AMPK activator, and metformin increased the expression of Rab4 mRNA and protein levels in skeletal muscle C2C12 cells. The promoter activity of Rab4 was increased by metformin in an AMPK-dependent manner. Metformin stimulated the phosphorylation of AS160, Akt substrate, and Rab GTPase activating protein (GAP), and also increased the phosphorylation of PKC-zeta, which is a critical molecule for glucose uptake. Knockdown of AMPK blocked the metformin-induced phosphorylation of AS160/PKC-zeta. In addition, a colorimetric absorbance assay showed that insulin-induced translocation of GLUT4 was suppressed in Rab4 knockdown cells. Moreover, Rab4 interacted with PKC-zeta but not with GLUT4. The C-terminal-deleted Rab4 mutant, Rab4ΔCT, showed diffuse sub-cellular localization, while wild-type Rab4 localized exclusively to the perinuclear membrane. Unlike Rab4ΔCT, wild-type Rab4 co-localized with PKC-zeta. Together, these results demonstrate that metformin induces Rab4 expression via AMPK-AS160-PKC-zeta and modulates insulin-mediated GLUT4 translocation. J. Cell. Physiol. 226: 974–981, 2011. © 2010 Wiley-Liss, Inc.

View Full Article (HTML) Get PDF (318K)