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Nami Kim  (Kim N) 1 Article
Obesity and Metabolism
Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose Conditions
Jie Sha, Jungsik Na, Jung Ok Lee, Nami Kim, Soo Kyung Lee, Ji Hae Kim, Ji Wook Moon, Su Jin Kim, Hye Jeong Lee, Jong-Il Choi, Sun Hwa Park, Hyeon Soo Kim
Endocrinol Metab. 2014;29(3):363-370.   Published online September 25, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.3.363
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  • 5 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

The role of small GTPase molecules is poorly understood under high glucose conditions.

Methods

We analyzed the expression pattern of Vav3 in skeletal muscle C2C12 cells under high glucose culture condition with reverse transcription-polymerase chain reaction and Western blot analysis. We also measured glucose uptake using isotope-labelled glucose.

Results

We showed that expression of Vav3 (a guanine nucleotide exchange factor for RhoA) increased. mRNA and protein levels in skeletal muscle C2C12 cells under high glucose conditions. The AMP-activated protein kinase (AMPK) activator AMPK agonist 5-aminoimidazole-4-carboxy-amide-1-d-ribofuranoside (AICAR) suppressed high glucose-induced Vav3 induction. In addition, exposure of cells to high glucose concentration increased the phosphorylation of PAK-1, a molecule downstream of RhoA. The phosphorylation of paxillin, a downstream molecule of PAK-1, was also increased by exposure to high glucose. Phosphorylation of these molecules was not observed in the presence of AICAR, indicating that AMPK is involved in the RhoA signal pathway under high glucose conditions. Knock down of Vav3 enhances metformin-mediated glucose uptake. Inhibition of AMPK blocked the increases of Vav3 knock down-induced glucose uptake. Metformin-mediated Glut4 translocation was also increased by Vav3 knock-down, suggesting that Vav3 is involved in metformin-mediated glucose uptake.

Conclusion

These results demonstrate that Vav3 is involved in the process of metformin-mediated glucose regulation.

Citations

Citations to this article as recorded by  
  • A current overview of RhoA, RhoB, and RhoC functions in vascular biology and pathology
    Robert Eckenstaler, Michael Hauke, Ralf A. Benndorf
    Biochemical Pharmacology.2022; 206: 115321.     CrossRef
  • Rho Family GTPases and Rho GEFs in Glucose Homeostasis
    Polly A. Machin, Elpida Tsonou, David C. Hornigold, Heidi C. E. Welch
    Cells.2021; 10(4): 915.     CrossRef
  • Pharmacological Modulators of Small GTPases of Rho Family in Neurodegenerative Diseases
    William Guiler, Addison Koehler, Christi Boykin, Qun Lu
    Frontiers in Cellular Neuroscience.2021;[Epub]     CrossRef
  • Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors
    Nuria Perretta-Tejedor, Javier Fernández-Mateos, Luis García-Ortiz, Manuel A. Gómez-Marcos, José I. Recio-Rodríguez, Cristina Agudo-Conde, Emiliano Rodriguez-Sánchez, Ana I. Morales, Francisco J. López-Hernández, José M. López-Novoa, Rogelio González-Sarm
    Scientific Reports.2017;[Epub]     CrossRef
  • Articles in 'Endocrinology and Metabolism' in 2014
    Won-Young Lee
    Endocrinology and Metabolism.2015; 30(1): 47.     CrossRef

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