Guanosine 5′-O-(3-Thiotriphosphate) (GTPγS) Stimulation of GLUT4 Translocation is Tyrosine Kinase-dependent

Elmendorf, Jeffrey S.; Chen, Dong; Pessin, Jeffrey E.

doi:10.1074/jbc.273.21.13289

Cited by 68 publications

(57 citation statements)

References 50 publications

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“…The protein expression level of pol η was examined by Western blot analysis with anti-human or anti-mouse pol η antibodies from Biorbyt. The harvested SVF cells from mice adipose tissue, 3T3L1 transfectants, and MEF cells were cultured and differentiated into adipocytes (56), and then examined for SA-β-gal staining and Oil Red O staining.…”

Section: Methodsmentioning

confidence: 99%

Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities

Chen

Harris

Hatahet

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Obesity and the metabolic syndrome have evolved to be major health issues throughout the world. Whether loss of genome integrity contributes to this epidemic is an open question. DNA polymerase η (pol η), encoded by the xeroderma pigmentosum (XP-V) gene, plays an essential role in preventing cutaneous cancer caused by UV radiation-induced DNA damage. Herein, we demonstrate that pol η deficiency in mice (pol η −/− ) causes obesity with visceral fat accumulation, hepatic steatosis, hyperleptinemia, hyperinsulinemia, and glucose intolerance. In comparison to WT mice, adipose tissue from pol η −/− mice exhibits increased DNA damage and a greater DNA damage response, indicated by upregulation and/or phosphorylation of ataxia telangiectasia mutated (ATM), phosphorylated H 2 AX (γH 2 AX), and poly[ADP-ribose] polymerase 1 (PARP-1). Concomitantly, increased cellular senescence in the adipose tissue from pol η −/− mice was observed and measured by up-regulation of senescence markers, including p53, p16 Ink4a , p21, senescence-associated (SA) β-gal activity, and SA secretion of proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) as early as 4 wk of age. Treatment of pol η −/− mice with a p53 inhibitor, pifithrin-α, reduced adipocyte senescence and attenuated the metabolic abnormalities. Furthermore, elevation of adipocyte DNA damage with a high-fat diet or sodium arsenite exacerbated adipocyte senescence and metabolic abnormalities in pol η −/− mice. In contrast, reduction of adipose DNA damage with N-acetylcysteine or metformin ameliorated cellular senescence and metabolic abnormalities. These studies indicate that elevated DNA damage is a root cause of adipocyte senescence, which plays a determining role in the development of obesity and insulin resistance.T he human genome is constantly challenged by exogenous and endogenous DNA damaging agents. To ensure genome integrity, human cells have faithful DNA replication machinery and DNA repair systems that are coordinated by DNA damage response networks. In response to different extents or types of DNA lesions, the DNA damage response activates appropriate cellular responses, including transient or permanent (senescence) cell cycle arrest, or apoptosis, to minimize the detrimental effects of DNA lesions (1). Reduction or deficiency in DNA repair/replication enzyme activity is well documented to increase vulnerability for the development of cancer, neurodegenerative diseases, and aging (2). In addition, defective DNA repair enzymes are associated with the metabolic symptom; for example, DNA glycosylase (Neil1)-and OGG1-deficient mice are obese (3-5), and nucleotide excision repair protein ERCC1-XPF deficiency causes lipodystrophy (6). Furthermore, DNA damage response protein ataxia telangiectasia mutated (ATM) suppresses JNK activity through p53 signaling and mediates an antioxidant action that has been suggested to be relevant to the metabolic syndrome (7). Nucleotide excision repair XP-A protein may affect metabolism by altering mitochondrial...

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Section: Methodsmentioning

confidence: 99%

Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities

Chen

Harris

Hatahet

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…These data support a model in which a proportion of the intracellular GLUT4 protein is partitioned into a specialized intracellular insulin-sensitive storage compartment that represents the primary site for insulin action. The remaining GLUT4 protein is present in various other intracellular compartments some of which are probably responsive to other stimuli such as GTPγ S or exercise/contraction in skeletal muscle and others that are constitutively undergoing recycling [59][60][61][62]. However, the mechanisms responsible for increased translocation remain unresolved.…”

Section: Regulated Glut4 Traffickingmentioning

confidence: 99%

An adipocentric view of signaling and intracellular trafficking

Mora

Pessin

2002

Diabetes Metabolism Res

Self Cite

149

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SummaryAdipocytes have traditionally been considered to be the primary site for whole body energy storage mainly in the form of triglycerides and fatty acids. This occurs through the ability of insulin to markedly stimulate both glucose uptake and lipogenesis. Conventional wisdom held that defects in fuel partitioning into adipocytes either because of increased adipose tissue mass and/or increased lipolysis and circulating free fatty acids resulted in dyslipidemia, obesity, insulin resistance and perhaps diabetes. However, it has become increasingly apparent that loss of adipose tissue (lipodystrophies) in both animal models and humans also leads to metabolic disorders that result in severe states of insulin resistance and potential diabetes. These apparently opposite functions can be resolved by the establishment of adipocytes not only as a fuel storage depot but also as a critical endocrine organ that secretes a variety of signaling molecules into the circulation. Although the molecular function of these adipocyte-derived signals are poorly understood, they play a central role in the maintenance of energy homeostasis by regulating insulin secretion, insulin action, glucose and lipid metabolism, energy balance, host defense and reproduction. The diversity of these secretory factors include enzymes (lipoprotein lipase (LPL) and adipsin), growth factors [vascular endothelial growth factor (VEGF)], cytokines (tumor necrosis factor-α, interleukin 6) and several other hormones involved in fatty acid and glucose metabolism (leptin, Acrp30, resistin and acylation stimulation protein). Despite the large number of molecules secreted by adipocytes, our understanding of the pathways and mechanisms controlling intracellular trafficking and exocytosis in adipocytes is poorly understood. In this article, we will review the current knowledge of the trafficking and secretion processes that take place in adipocytes, focusing our attention on two of the best characterized adipokine molecules (leptin and adiponectin) and on one of the most intensively studied regulated membrane proteins, the GLUT4 glucose transporter.

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“…Differentiation media was replaced with 3FC media (differentiation media excluding PPAR␥ agonist and dexamethasone) for a further 7 days. 3T3L1 fibroblasts were differentiated to adipocytes as previously described (26).…”

Section: -[12-mentioning

confidence: 99%

Interferon γ Attenuates Insulin Signaling, Lipid Storage, and Differentiation in Human Adipocytes via Activation of the JAK/STAT Pathway

McGillicuddy

Chiquoine

Hinkle

et al. 2009

Journal of Biological Chemistry

220

189

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Guanosine 5′-O-(3-Thiotriphosphate) (GTPγS) Stimulation of GLUT4 Translocation is Tyrosine Kinase-dependent

Cited by 68 publications

References 50 publications

Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities

Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities

An adipocentric view of signaling and intracellular trafficking

Interferon γ Attenuates Insulin Signaling, Lipid Storage, and Differentiation in Human Adipocytes via Activation of the JAK/STAT Pathway

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