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, Jongil Choi, Sun-Hwa Park, Hyeon Soo Kim

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)363-370
Number of pages8
JournalEndocrinology and Metabolism
Volume29
Issue number3
DOIs
Publication statusPublished - 2014

Fingerprint

Glucose
Metformin
AMP-Activated Protein Kinases
Phosphorylation
Amides
Muscle Cells
Skeletal Muscle
Paxillin
Guanine Nucleotide Exchange Factors
Monomeric GTP-Binding Proteins
Isotopes
Reverse Transcription
Signal Transduction
Western Blotting
Polymerase Chain Reaction
Messenger RNA

Keywords

  • AMP-activated protein kinases
  • Diabetes
  • High glucose
  • Metformin
  • Vav3

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Vav3, a GEF for RhoA, plays a critical role under high glucose conditions. / Sha, Jie; Na, Jungsik; Lee, Jung Ok; Kim, Nami; Lee, Soo Kyung; Kim, Ji Hae; Moon, Ji Wook; Kim, Su Jin; Lee, Hye Jeong; Choi, Jongil; Park, Sun-Hwa; Kim, Hyeon Soo.

In: Endocrinology and Metabolism, Vol. 29, No. 3, 2014, p. 363-370.

Research output: Contribution to journalArticle

Sha, J, Na, J, Lee, JO, Kim, N, Lee, SK, Kim, JH, Moon, JW, Kim, SJ, Lee, HJ, Choi, J, Park, S-H & Kim, HS 2014, 'Vav3, a GEF for RhoA, plays a critical role under high glucose conditions', Endocrinology and Metabolism, vol. 29, no. 3, pp. 363-370. https://doi.org/10.3803/EnM.2014.29.3.363
Sha, Jie ; Na, Jungsik ; Lee, Jung Ok ; Kim, Nami ; Lee, Soo Kyung ; Kim, Ji Hae ; Moon, Ji Wook ; Kim, Su Jin ; Lee, Hye Jeong ; Choi, Jongil ; Park, Sun-Hwa ; Kim, Hyeon Soo. / Vav3, a GEF for RhoA, plays a critical role under high glucose conditions. In: Endocrinology and Metabolism. 2014 ; Vol. 29, No. 3. pp. 363-370.
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AU - Sha, Jie

AU - Na, Jungsik

AU - Lee, Jung Ok

AU - Kim, Nami

AU - Lee, Soo Kyung

AU - Kim, Ji Hae

AU - Moon, Ji Wook

AU - Kim, Su Jin

AU - Lee, Hye Jeong

AU - Choi, Jongil

AU - Park, Sun-Hwa

AU - Kim, Hyeon Soo

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - AMP-activated protein kinases

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