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.

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 GnRH increases glucose transporter-1 expression and stimulates glucose uptake in the gonadotroph

2011 ◽  
Vol 212 (2) ◽  
pp. 139-147 ◽  
Author(s):  
Valerie M Harris ◽  
Sachin V Bendre ◽  
Francina Gonzalez De Los Santos ◽  
Alemu Fite ◽  
Ahmad El-Yaman El-Dandachli ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Mrna Expression ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Subcellular Location ◽  
Pcr Analysis ◽  
Glucose Transporter 1 ◽  
Glut1 Protein ◽  
Main Regulator ◽  
Exogenous Treatment

GnRH is the main regulator of the hypothalamic–pituitary–gonadal (H–P–G) axis. GnRH stimulates the pituitary gonadotroph to synthesize and secrete gonadotrophins (LH and FSH), and this effect of GnRH is dependent on the availability of glucose and other nutrients. Little is known about whether GnRH regulates glucose metabolism in the gonadotroph. This study examined the regulation of glucose transporters (Gluts) by GnRH in the LβT2 gonadotroph cell line. Using real-time PCR analysis, the expression ofGlut1, -2, -4, and -8 was detected, butGlut1mRNA expression level was more abundant than the mRNA expression levels ofGlut2, -4, and -8. After the treatment of LβT2 cells with GnRH,Glut1mRNA expression was markedly induced, but there was no GnRH-induction ofGlut2, -4, or -8 mRNA expression in LβT2 cells. The effect of GnRH onGlut1mRNA expression is partly mediated by ERK activation. GnRH increased GLUT1 protein and stimulated GLUT1 translocation to the cell surface of LβT2 cells. Glucose uptake assays were performed in LβT2 cells and showed that GnRH stimulates glucose uptake in the gonadotroph. Finally, exogenous treatment of mice with GnRH increased the expression ofGlut1but not the expression ofGlut2, -4, or -8 in the pituitary. Therefore, regulation of glucose metabolism by GnRH via changes inGlutsexpression and subcellular location in the pituitary gonadotroph reveals a novel response of the gonadotroph to GnRH.

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.

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.

Abstract 112: A Pathological Role of Endothelial p53 in the Regulation of Endothelial Function and Glucose Metabolism

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Masataka YOKOYAMA ◽  
Yoshio KOBAYASHI ◽  
Tohru MINAMINO
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Cell ◽  
Glucose Metabolism ◽  
Endothelial Function ◽  
Mitochondrial Biogenesis ◽  
Glucose Transporter ◽  
Diabetic Patients ◽  
Glucose Transporter 1 ◽  
P53 Activation

Cellular senescence is a state of irreversible growth arrest induced by various stresses such as oncogenic stimuli. This response is controlled by negative regulators of the cell cycle like the p53 tumor suppressor protein. Accumulating evidence has suggested a role of p53 activation in various age-associated conditions including atherosclerosis, heart failure and diabetes. Here we show that endothelial p53 activation plays a pathological role in the regulation of endothelial function and glucose metabolism under diabetic conditions. Endothelial expression of p53 was markedly up-regulated in a streptozotocin-induced diabetes model. Endothelial function such as acetylcholine-dependent vasodilatation was markedly impaired in this model. Although hyperglycemia was not altered, impairment of endothelial function was significantly improved in mice with endothelial cell-specific p53 deficiency. In same way, p53 was markedly activated in ischemic vessels, and endothelial p53 deficiency enhanced ischemia-induced angiogenesis. Mechanistically, endothelial p53 up-regulated the expression of PTEN that negatively regulated the Akt-eNOS pathway, and therefore disruption of p53 improved endothelial dysfunction. We also found that endothelial p53 was markedly activated, and the Akt-eNOS pathway was attenuated in a diet-induced obesity model. Disruption of endothelial p53 activation improved dietary inactivation of eNOS that up-regulated the expression of PGC-1α in skeletal muscle, thereby increasing mitochondrial biogenesis and oxygen consumption. Inhibition of endothelial p53 also improved dietary impairment of glucose transport into skeletal muscle by up-regulating endothelial expression of glucose transporter 1. Consequently, mice with endothelial cell-specific p53 deficiency fed a high-calorie diet showed improvement of insulin sensitivity and less fat accumulation compared with control littermates. These results indicate that endothelial p53 negatively regulates endothelium-dependent vasodilatation, ischemia-induced angiogenesis, and mitochondrial biogenesis by inhibiting the Akt-eNOS pathway and suggest that inhibition of endothelial p53 could be a novel therapeutic target in diabetic patients.

Sign in / Sign up

Export Citation Format

Share Document