scholarly journals Impaired glucose transporter-1 degradation and increased glucose transport and oxidative stress in response to high glucose in chondrocytes from osteoarthritic versus normal human cartilage

2009 ◽  
Vol 11 (3) ◽  
pp. R80 ◽  
Author(s):  
Susana C Rosa ◽  
Juliana Gonçalves ◽  
Fernando Judas ◽  
Ali Mobasheri ◽  
Celeste Lopes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Glucose Transport ◽  
High Glucose ◽  
Glucose Transporter ◽  
Human Cartilage ◽  
Glucose Transporter 1 ◽  
Normal Human ◽  
And Oxidative Stress

Reactive oxygen species downregulate glucose transport system in retinal endothelial cells

2011 ◽  
Vol 300 (4) ◽  
pp. C927-C936 ◽  
Author(s):  
Rosa Fernandes ◽  
Ken-ichi Hosoya ◽  
Paulo Pereira
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Plasma Membrane ◽  
Endothelial Cell ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Cell Damage ◽  
Proteasome Inhibition ◽  
Glucose Transporter 1 ◽  
Retinal Endothelial Cells

Retinal endothelial cells are believed to play an important role in the pathogenesis of diabetic retinopathy. In previous studies, we and others demonstrated that glucose transporter 1 (GLUT1) is downregulated in response to hyperglycemia. Increased oxidative stress is likely to be the event whereby hyperglycemia is transduced into endothelial cell damage. However, the effects of sustained oxidative stress on GLUT1 regulation are not clearly established. The objective of this study is to evaluate the effect of increased oxidative stress on glucose transport and on GLUT1 subcellular distribution in a retinal endothelial cell line and to elucidate the signaling pathways associated with such regulation. Conditionally immortalized rat retinal endothelial cells (TR-iBRB) were incubated with glucose oxidase, which increases the intracellular hydrogen peroxide levels, and GLUT1 regulation was investigated. The data showed that oxidative stress did not alter the total levels of GLUT1 protein, although the levels of mRNA were decreased, and there was a subcellular redistribution of GLUT1, decreasing its content at the plasma membrane. Consistently, the half-life of the protein at the plasma membrane markedly decreased under oxidative stress. The proteasome appears to be involved in GLUT1 regulation in response to oxidative stress, as revealed by an increase in stabilization of the protein present at the plasma membrane and normalization of glucose transport following proteasome inhibition. Indeed, levels of ubiquitinated GLUT1 increase as revealed by immunoprecipitation assays. Furthermore, data indicate that protein kinase B activation is involved in the stabilization of GLUT1 at the plasma membrane. Thus subcellular redistribution of GLUT1 under conditions of oxidative stress is likely to contribute to the disruption of glucose homeostasis in diabetes.

scholarly journals The Formation of an Insulin-responsive Vesicular Cargo Compartment Is an Early Event in 3T3-L1 Adipocyte Differentiation

1999 ◽  
Vol 10 (5) ◽  
pp. 1581-1594 ◽  
Author(s):  
Amr K. El-Jack ◽  
Konstantin V. Kandror ◽  
Paul F. Pilch
Keyword(s):  
Glucose Transport ◽  
Glucose Transporter ◽  
Adipocyte Differentiation ◽  
Receptor Trafficking ◽  
Early Event ◽  
Glucose Transporter 1 ◽  
Glut4 Expression ◽  
Velocity Gradients ◽  
Dependent Inhibition ◽  
Intracellular Glucose

Differentiating 3T3-L1 cells exhibit a dramatic increase in the rate of insulin-stimulated glucose transport during their conversion from proliferating fibroblasts to nonproliferating adipocytes. On day 3 of 3T3-L1 cell differentiation, basal glucose transport and cell surface transferrin binding are markedly diminished. This occurs concomitant with the formation of a distinct insulin-responsive vesicular pool of intracellular glucose transporter 1 (GLUT1) and transferrin receptors as assessed by sucrose velocity gradients. The intracellular distribution of the insulin-responsive aminopeptidase is first readily detectable on day 3, and its gradient profile and response to insulin at this time are identical to that of GLUT1. With further time of differentiation, GLUT4 is expressed and targeted to the same insulin-responsive vesicles as the other three proteins. Our data are consistent with the notion that a distinct insulin-sensitive vesicular cargo compartment forms early during fat call differentiation and its formation precedes GLUT4 expression. The development of this compartment may result from the differentiation-dependent inhibition of constitutive GLUT1 and transferrin receptor trafficking such that there is a large increase in, or the new formation of, a population of postendosomal, insulin-responsive vesicles.

scholarly journals The Fast Lane of Hypoxic Adaptation: Glucose Transport Is Modulated via A HIF-Hydroxylase-AMPK-Axis in Jejunum Epithelium

2019 ◽  
Vol 20 (20) ◽  
pp. 4993 ◽  
Author(s):  
Dengler ◽  
Gäbel
Keyword(s):  
Glucose Transport ◽  
Glucose Transporter ◽  
Ussing Chamber ◽  
Transepithelial Transport ◽  
Adaptation To Hypoxia ◽  
Regulation Mechanism ◽  
Short Term ◽  
Glucose Transporter 1 ◽  
Functional Changes ◽  
Short Term Adaptation

The intestinal epithelium is able to adapt to varying blood flow and, thus, oxygen availability. Still, the adaptation fails under pathologic situations. A better understanding of the mechanisms underlying the epithelial adaptation to hypoxia could help to improve the therapeutic approach. We hypothesized that the short-term adaptation to hypoxia is mediated via AMP-activated protein kinase (AMPK) and that it is coupled to the long-term adaptation by a common regulation mechanism, the HIF-hydroxylase enzymes. Further, we hypothesized the transepithelial transport of glucose to be part of this short-term adaptation. We conducted Ussing chamber studies using isolated lagomorph jejunum epithelium and cell culture experiments with CaCo-2 cells. The epithelia and cells were incubated under 100% and 21% O2, respectively, with the panhydroxylase inhibitor dimethyloxalylglycine (DMOG) or under 1% O2. We showed an activation of AMPK under hypoxia and after incubation with DMOG by Western blot. This could be related to functional effects like an impairment of Na+-coupled glucose transport. Inhibitor studies revealed a recruitment of glucose transporter 1 under hypoxia, but not after incubation with DMOG. Summing up, we showed an influence of hydroxylase enzymes on AMPK activity and similarities between hypoxia and the effects of hydroxylase inhibition on functional changes.

Role of vasoactive peptides in high glucose-induced increased expression of Gαq/11 proteins and associated signaling in vascular smooth muscle cellsThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 331-340 ◽  
Author(s):  
Magda Descorbeth ◽  
Madhu B. Anand-Srivastava
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
High Glucose ◽  
Ang Ii ◽  
Vasoactive Peptides ◽  
Enhanced Production ◽  
Enhanced Expression ◽  
Health And Disease ◽  
And Oxidative Stress

We have recently shown that A10 vascular smooth muscle cells (VSMCs) exposed to high glucose exhibited enhanced expression of Gαq and PLCβ proteins. Since high glucose has been reported to increase the levels of vasoactive peptides and oxidative stress, the present study was undertaken to investigate the implication of angiotensin II (Ang II), endothelin (ET)-1, and oxidative stress in the high glucose-induced enhanced expression of Gαq/11 and PLCβ proteins and associated signaling in A10 VSMCs. The levels of Gαq, Gα11, PLCβ-1, and PLCβ-2 proteins, as determined by Western blotting, were significantly higher in A10 VSMCs exposed to high glucose than in control cells. The elevated levels were restored to control values by the antioxidant diphenyleneiodonium (DPI), as well as by the antagonist of Ang II AT1 receptor losartan and the antagonists of ETA and ETB receptors BQ123 and BQ788, respectively. In addition, ET-1-stimulated production of inositol trisphosphate (IP3), which was enhanced by high glucose, was also restored toward control levels by DPI. Furthermore, the enhanced production of superoxide anion (O2–), increased NADPH oxidase activity, and enhanced expression of p22phox and p47phox proteins induced by high glucose were restored to control levels by losartan, BQ123, and BQ788. These results suggest that through increased oxidative stress, high glucose-induced enhanced levels of endogenous Ang II and ET-1 may contribute to the increased levels of Gαq/11 and mediated signaling in A10 VSMCs.

Sign in / Sign up

Export Citation Format

Share Document