scholarly journals LncRNA HOTAIR regulates glucose transporter Glut1 expression and glucose uptake in macrophages during inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Monira Obaid ◽  
S. M. Nashir Udden ◽  
Prasanna Alluri ◽  
Subhrangsu S. Mandal
Keyword(s):  
Immune Response ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Immune Cells ◽  
Glucose Transporter ◽  
Energy Needs ◽  
Glut1 Expression ◽  
Lncrna Hotair ◽  
Upstream Regulators ◽  
Glucose Transporter Glut1

AbstractInflammation plays central roles in the immune response. Inflammatory response normally requires higher energy and therefore is associated with glucose metabolism. Our recent study demonstrates that lncRNA HOTAIR plays key roles in NF-kB activation, cytokine expression, and inflammation. Here, we investigated if HOTAIR plays any role in the regulation of glucose metabolism in immune cells during inflammation. Our results demonstrate that LPS-induced inflammation induces the expression of glucose transporter isoform 1 (Glut1) which controls the glucose uptake in macrophages. LPS-induced Glut1 expression is regulated via NF-kB activation. Importantly, siRNA-mediated knockdown of HOTAIR suppressed the LPS-induced expression of Glut1 suggesting key roles of HOTAIR in LPS-induced Glut1 expression in macrophage. HOTAIR induces NF-kB activation, which in turn increases Glut1 expression in response to LPS. We also found that HOTAIR regulates glucose uptake in macrophages during LPS-induced inflammation and its knockdown decreases LPS-induced increased glucose uptake. HOTAIR also regulates other upstream regulators of glucose metabolism such as PTEN and HIF1α, suggesting its multimodal functions in glucose metabolism. Overall, our study demonstrated that lncRNA HOTAIR plays key roles in LPS-induced Glut1 expression and glucose uptake by activating NF-kB and hence HOTAIR regulates metabolic programming in immune cells potentially to meet the energy needs during the immune response.

scholarly journals Aspirin, a potential GLUT1 inhibitor in a vascular endothelial cell line

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 552-560 ◽  
Author(s):  
Yabo Hu ◽  
Xiaohan Lou ◽  
Ruirui Wang ◽  
Chanjun Sun ◽  
Xiaomeng Liu ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Glucose Transporter 1 ◽  
Glut1 Expression ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms

AbstractRecent epidemiological and preclinical studies have revealed that aspirin possesses antitumor properties; one of the mechanisms results from inhibition of angiogenesis. However, the underlying mechanisms of such action remain to be elucidated, in particular, the effect of aspirin on glucose metabolism of vascular endothelial cells (ECs) has not yet been reported. Herein, we demonstrate that glucose transporter 1 (GLUT1), a main glucose transporter in ECs, can be down-regulated by aspirin. Exposure to 4-mM aspirin significantly decreased GLUT1 at the mRNA and protein level, resulting in impaired glucose uptake capacity in vascular ECs. In addition, we also showed that exposure to 4-mM aspirin led to an inhibition of intracellular ATP and lactate synthesis in vascular ECs, and a down-regulation of the phosphorylation level of NF-κB p65 was observed. Taken together, these findings indicate 4-mM aspirin inhibits glucose uptake and glucose metabolism of vascular ECs through down-regulating GLUT1 expression and suggest that GLUT1 has potential to be a target for aspirin in vascular ECs.

scholarly journals Scavenging ROS Decreases Amyloid-beta Levels via Activation of PI3K/Akt/GLUT1 pathway in N2a/APP695swe Cells

2021 ◽  
Author(s):  
Yan Peng ◽  
Li Zhang ◽  
Fanlin Zhou ◽  
Yangyang Wang ◽  
Shijie Li ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Akt Pathway ◽  
Glucose Transporter 1 ◽  
Abnormal Glucose Metabolism ◽  
Glut1 Expression ◽  
Ros Scavenger ◽  
Underlying Mechanisms ◽  
The Brain

Abstract Dysregulated glucose metabolism in the brain is considered to be the underlying cause of Alzheimer's disease (AD). Abnormal glucose metabolism in AD is associated with decreased glucose transporter 1 (GLUT1) and GLUT3 in the brain, but the underlying mechanisms remains unclear. Here, we reported that GLUT1 expression was decreased in N2a/APP695swe cells and GLUT3 expression was not significantly changed. Flow Cytometry analysis showed a significant increase of intracellular ROS content in N2a/APP695swe cells and GLUT1 expression was upregulated after treatment with the ROS scavenger N-acetyl-L-Cysteine (NAC). Cellular glucose uptake and ATP levels were reduced following decreased GLUT1 expression and increased after upregulating GLUT1. Western blot analyses showed that phosphorylation of PI3K/Akt pathway decreased in N2a/APP695swe cells. Aβ levels decreased after upregulation of GLUT1 expression and increased after downregulation of GLUT1. After NAC treatment, PI3K/Akt pathway phosphorylation levels and GLUT1 expression were upregulated, glucose uptake and ATP contents were increased, and Aβ levels were decreased. After adding PI3K/Akt pathway inhibitor LY29004, GLUT1 expression was reduced and Aβ levels were increased. Besides, the increased glucose uptake and ATP contents by the Akt activator SC79 were hindered with the GLUT1 inhibitor WZB117. Aβ levels decreased after SC79 treatment and increased after WZB117 treatment. Overall, our data suggest that ROS reduced GLUT1 expression by inhibiting PI3K/Akt pathway activity resulting in impaired glucose metabolism and scavenging ROS prevents Aβ via activation of PI3K/Akt/GLUT1 pathway in N2a/APP695swe cells.

Differential glycolytic and glycogenogenic transduction pathways in male and female bovine embryos produced in vitro

2012 ◽  
Vol 24 (2) ◽  
pp. 344 ◽  
Author(s):  
M. Garcia-Herreros ◽  
I. M. Aparicio ◽  
D. Rath ◽  
T. Fair ◽  
P. Lonergan
Keyword(s):  
Glucose Metabolism ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Glycogen Synthase ◽  
Bovine Embryos ◽  
High Concentration ◽  
Glucose Transporter 1 ◽  
Male And Female ◽  
Glut 1

Previous studies have shown that developmental kinetic rates following IVF are lower in female than in male blastocysts and that this may be related to differences in glucose metabolism. In addition, an inhibition of phosphatidylinositol 3-kinase (PI3-K) inhibits glucose uptake in murine blastocysts. Therefore, the aim of this study was to identify and compare the expression of proteins involved in glucose metabolism (hexokinase-I, HK-I; phosphofructokinase-1, PFK-1; pyruvate kinase1/2, PK1/2; glyceraldehyde-3-phosphate dehydrogenase, GAPDH; glucose transporter-1, GLUT-1; and glycogen synthase kinase-3, GSK-3) in male and female bovine blastocysts to determine whether PI3-K has a role in the regulation of the expression of these proteins. Hexokinase-I, PFK-1, PK1/2, GAPDH and GLUT-1 were present in bovine embryos. Protein expression of these proteins and GSK-3 was significantly higher in male compared with female blastocysts. Inhibition of PI3-K with LY294002 significantly decreased the expression of HK-I, PFK-1, GAPDH, GSK-3 A/B and GLUT-1. Results showed that the expression of glycolytic proteins HK-I, PFK-1, GAPDH and PK1/2, and the transporters GLUT-1 and GSK-3 is regulated by PI3-K in bovine blastocysts. Moreover, the differential protein expression observed between male and female blastocysts might explain the faster developmental kinetics seen in males, as the expression of main proteins involved in glycolysis and glycogenogenesis was significantly higher in male than female bovine embryos and also could explain the sensitivity of male embryos to a high concentration of glucose, as a positive correlation between GLUT-1 expression and glucose uptake in embryos has been demonstrated.

scholarly journals Alterations in Glucose Metabolism During the Transition to Heart Failure: The Contribution of UCP-2

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 552 ◽  
Author(s):  
Hanna Sarah Kutsche ◽  
Rolf Schreckenberg ◽  
Martin Weber ◽  
Christine Hirschhäuser ◽  
Susanne Rohrbach ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Contractile Function ◽  
Uncoupling Protein ◽  
Left Ventricular ◽  
Mitochondrial Uncoupling ◽  
Glut 4

The cardiac expression of the mitochondrial uncoupling protein (UCP)-2 is increased in patients with heart failure. However, the underlying causes as well as the possible consequences of these alterations during the transition from hypertrophy to heart failure are still unclear. To investigate the role of UCP-2 mechanistically, expression of UCP-2 was silenced by small interfering RNA in adult rat ventricular cardiomyocytes. We demonstrate that a downregulation of UCP-2 by siRNA in cardiomyocytes preserves contractile function in the presence of angiotensin II. Furthermore, silencing of UCP-2 was associated with an upregulation of glucose transporter type (Glut)-4, increased glucose uptake, and reduced intracellular lactate levels, indicating improvement of the oxidative glucose metabolism. To study this adaptation in vivo, spontaneously hypertensive rats served as a model for cardiac hypertrophy due to pressure overload. During compensatory hypertrophy, we found low UCP-2 levels with an upregulation of Glut-4, while the decompensatory state with impaired function was associated with an increase of UCP-2 and reduced Glut-4 expression. By blocking the aldosterone receptor with spironolactone, both cardiac function as well as UCP-2 and Glut-4 expression levels of the compensated phase could be preserved. Furthermore, we were able to confirm this by left ventricular (LV) biopsies of patients with end-stage heart failure. The results of this study show that UCP-2 seems to impact the cardiac glucose metabolism during the transition from hypertrophy to failure by affecting glucose uptake through Glut-4. We suggest that the failing heart could benefit from low UCP-2 levels by improving the efficiency of glucose oxidation. For this reason, UCP-2 inhibition might be a promising therapeutic strategy to prevent the development of heart failure.

scholarly journals Glucose uptake inhibition decreases expressions of receptor activator of nuclear factor-kappa B ligand (RANKL) and osteocalcin in osteocytic MLO-Y4-A2 cells

2018 ◽  
Vol 314 (2) ◽  
pp. E115-E123 ◽  
Author(s):  
Ayumu Takeno ◽  
Ippei Kanazawa ◽  
Masakazu Notsu ◽  
Ken-ichiro Tanaka ◽  
Toshitsugu Sugimoto
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
P38 Mapk ◽  
Glucose Transporter ◽  
Mek Inhibitor ◽  
Long Bone ◽  
Uptake Inhibition ◽  
Glucose Transporter 1 ◽  
P38 Inhibitor ◽  
Glucose Levels

Bone and glucose metabolism are closely associated with each other. Both osteoblast and osteoclast functions are important for the action of osteocalcin, which plays pivotal roles as an endocrine hormone regulating glucose metabolism. However, it is unknown whether osteocytes are involved in the interaction between bone and glucose metabolism. We used MLO-Y4-A2, a murine long bone-derived osteocytic cell line, to investigate effects of glucose uptake inhibition on expressions of osteocalcin and bone-remodeling modulators in osteocytes. We found that glucose transporter 1 (GLUT1) is expressed in MLO-Y4-A2 cells and that treatment with phloretin, a GLUT inhibitor, significantly inhibited glucose uptake. Real-time PCR and Western blot showed that phloretin significantly and dose-dependently decreased the expressions of RANKL and osteocalcin, whereas osteoprotegerin or sclerostin was not affected. Moreover, phloretin activated AMP-activated protein kinase (AMPK), an intracellular energy sensor. Coincubation of ara-A, an AMPK inhibitor, with phloretin canceled the phloretin-induced decrease in osteocalcin expression, but not RANKL. In contrast, phloretin suppressed phosphorylation of ERK1/2, JNK, and p38 MAPK, and treatments with the p38 inhibitor SB203580 and the MEK inhibitor PD98059, but not the JNK inhibitor SP600125, significantly decreased expressions of RANKL and osteocalcin. These results indicate that glucose uptake by GLUT1 is required for RANKL and osteocalcin expressions in osteocytes, and that inhibition of glucose uptake decreases their expressions through AMPK, ERK1/2, and p38 MAPK pathways. These findings suggest that lowering glucose uptake into osteocytes may contribute to maintain blood glucose levels by decreasing osteocalcin expression and RANKL-induced bone resorption.

Effect of oocyte vitrification on glucose transport in mouse metaphase II oocytes

Reproduction ◽  
2021 ◽  
Vol 161 (5) ◽  
pp. 549-559
Author(s):  
Yufei Wang ◽  
Haoya Chang ◽  
Qifu He ◽  
Yaxing Xue ◽  
Kang Zhang ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Energy Levels ◽  
Oocyte Vitrification ◽  
Abnormal Glucose Metabolism ◽  
Cell Embryo ◽  
Irreversible Effect ◽  
Metaphase Ii Oocytes

Oocyte vitrification has significantly improved the survival rate and become the mainstream method for cryopreserving oocytes. Previous studies have demonstrated that the ultrastructure, mitochondrial function, DNA methylation, and histone modification exhibit an irreversible effect after oocyte vitrification. However, little is known about the effects of oocyte vitrification on glucose transport and metabolism. This study aims to determine whether mouse oocyte vitrification causes abnormal glucose metabolism and identify a strategy to correct abnormal glucose metabolism. Furthermore, this study further investigates the effects of oocyte vitrification on glucose uptake, and glucose metabolism, and energy levels. The results indicated that vitrification significantly reduced the glucose transport activity, NADPH, glutathione, and ATP levels, and increased reactive oxygen species levels in oocytes (P  < 0.01). Vitrification also reduced the expression of glucose transporter isoform 1 (GLUT1) (P  < 0.01). Adding a GLUT1 inhibitor reduced the glucose uptake capacity of oocytes. Furthermore, the inclusion of vitamin C into thawing and culture solutions restored abnormal glucose transportation and metabolism and improved the survival, two-cell embryo, and blastocyst rates of the vitrified groups via parthenogenesis (P  < 0.05). Overall, this method may improve the quality and efficiency of oocyte vitrification.

scholarly journals Liver Plays a Major Role in FGF-21 Mediated Glucose Homeostasis

2018 ◽  
Vol 45 (4) ◽  
pp. 1423-1433 ◽  
Author(s):  
Mingyao Liu ◽  
Hongwei Cao ◽  
Yuting Hou ◽  
Guopeng Sun ◽  
Deshan Li ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Plasma Glucose ◽  
Glycogen Synthesis ◽  
Glycogen Storage ◽  
Glucose Absorption ◽  
Liver Cells ◽  
Dependent Manner ◽  
Diabetic Mice ◽  
Glut1 Expression

Background/Aims: The liver is a vital organ in vertebrates and has a wide range of functions, including glucose absorption, glycogen storage and glucose production. Fibroblast growth factor (FGF)-21 is a metabolic regulator that is primarily produced by the liver. In this paper, we studied the effect of FGF-21 on glucose metabolism in the liver. Methods: The glucose uptake of cells was detected by 2-Deoxy-d-[3H] glucose; the synergy between insulin and FGF-21 was evaluated. The mRNA expression of GLUT1-4, G6Pase and PEPCK was detected by real-time PCR. Glycogen synthesis was examined by the anthrone method. Blood samples to monitor glucose in db/db diabetic mice were obtained by tail snip. Glucose metabolism in the liver and adipose tissues was observed by fluorescence microscopy. Results: In this study, FGF-21 stimulated glucose uptake by liver cells in both a dose and time-dependent manner, and at the same time, FGF-21 specifically stimulated GLUT1 expression in the liver cells. Furthermore, FGF-21 demonstrated a synergistic effect with insulin on glucose absorption, which is in accordance with enhanced GLUT-1 and -4 expression. Treatment with FGF-21 increased glycogen storage in liver cells. Consistent with in vitro results, FGF-21 lowered the plasma glucose level and stimulated GLUT1 expression and glycogen synthesis in db/db diabetic mice. Simultaneously, FGF-21 inhibited the gene expression of G6Pase and PEPCK. Conclusion: Our results suggest that FGF-21 clears up plasma glucose by stimulating glucose absorption in the liver of diabetic animals and decreases glucose release from the liver by inhibiting gluconeogenesis. Overall, these data indicate that the liver is an important target organ of FGF-21 to regulate glucose metabolism.

The regulation of glucose transporter (GLUT1) expression by the RNA binding protein HuR

2006 ◽  
Vol 99 (2) ◽  
pp. 565-574 ◽  
Author(s):  
Kira R. Gantt ◽  
Joy Cherry ◽  
Melissa Richardson ◽  
Vesna Karschner ◽  
Ulus Atasoy ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Glut1 Expression ◽  
Glucose Transporter Glut1 ◽  
Transporter Glut1

scholarly journals Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1

2020 ◽  
Vol 11 (14) ◽  
pp. 3737-3744 ◽  
Author(s):  
Alexandra Brito ◽  
Patrícia M. R. Pereira ◽  
Diana Soares da Costa ◽  
Rui L. Reis ◽  
Rein V. Ulijn ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Self Assembly ◽  
Cancer Metabolism ◽  
Glucose Transporter ◽  
Glucose Transporter Glut1 ◽  
Transporter Glut1

We report on aromatic N-glucosides that inhibit selectively the cancer metabolism via two coexistent mechanisms: by deprivation of the glucose uptake through blocking of GLUT1 and by formation of sequestering nanonet through biocatalytic self-assembly.

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