Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose Conditions
BackgroundThe role of small GTPase molecules is poorly understood under high glucose conditions.MethodsWe 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 als...
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doaj-1d603bcd1c0945fc8f2c8ce71008df6e2020-11-24T23:51:58ZengAcademya Publishing Co.Endocrinology and Metabolism2093-596X2093-59782014-09-0129336337010.3803/EnM.2014.29.3.36321195Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose ConditionsJie ShaJungsik NaJung Ok LeeNami KimSoo Kyung LeeJi Hae KimJi Wook MoonSu Jin KimHye Jeong LeeJong-Il ChoiSun Hwa ParkHyeon Soo KimBackgroundThe role of small GTPase molecules is poorly understood under high glucose conditions.MethodsWe 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.ResultsWe 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.ConclusionThese results demonstrate that Vav3 is involved in the process of metformin-mediated glucose regulation.http://e-enm.org/Synapse/Data/PDFData/2008ENM/enm-29-363.pdfAMP-activated protein kinasesDiabetesHigh glucoseMetforminVav3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose Conditions Endocrinology and Metabolism AMP-activated protein kinases Diabetes High glucose Metformin Vav3 |
author_facet |
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 |
author_sort |
Jie Sha |
title |
Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose Conditions |
title_short |
Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose Conditions |
title_full |
Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose Conditions |
title_fullStr |
Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose Conditions |
title_full_unstemmed |
Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose Conditions |
title_sort |
vav3, a gef for rhoa, plays a critical role under high glucose conditions |
publisher |
Academya Publishing Co. |
series |
Endocrinology and Metabolism |
issn |
2093-596X 2093-5978 |
publishDate |
2014-09-01 |
description |
BackgroundThe role of small GTPase molecules is poorly understood under high glucose conditions.MethodsWe 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.ResultsWe 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.ConclusionThese results demonstrate that Vav3 is involved in the process of metformin-mediated glucose regulation. |
topic |
AMP-activated protein kinases Diabetes High glucose Metformin Vav3 |
url |
http://e-enm.org/Synapse/Data/PDFData/2008ENM/enm-29-363.pdf |
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