scholarly journals GLUT3 expression in cystic change induced by hypoxia in pituitary adenomas

2018 ◽  
Vol 7 (12) ◽  
pp. 1518-1527
Author(s):  
Tao Mei ◽  
Jianhe Zhang ◽  
Liangfeng Wei ◽  
Xingfeng Qi ◽  
Yiming Ma ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Pituitary Adenomas ◽  
Glucose Transporter ◽  
Immunohistochemical Analysis ◽  
High Energy ◽  
Benign Tumors ◽  
Positive Staining ◽  
Cystic Change ◽  
Glucose Transporter 1 ◽  
Glut1 Expression

Tumor cells require large amounts of energy to sustain growth. Through the mediated transport of glucose transporters, the uptake and utilization of glucose by tumor cells are significantly enhanced in the hypoxic microenvironment. Pituitary adenomas are benign tumors with high-energy metabolisms. We aimed to investigate the role of expression of glucose transporter 3 (GLUT3) and glucose transporter 1 (GLUT1) in pituitary adenomas, including effects on size, cystic change and hormone type. Pituitary adenomas from 203 patients were collected from January 2013 to April 2017, and immunohistochemical analysis was used to detect the expression of GLUT3 and GLUT1 in tumor specimens. GLUT3-positive expression in the cystic change group was higher than that in the non-cystic change group (P = 0.018). Proportions of GLUT3-positive staining of microadenomas, macroadenomas, and giant adenomas were 22.7 (5/22), 50.4 (66/131) and 54.0% (27/50), respectively (P = 0.022). In cases of prolactin adenoma, GLUT3-positive staining was predominant in cell membranes (P = 0.000006), while in cases of follicle-stimulating hormone or luteotropic hormone adenoma, we found mainly paranuclear dot-like GLUT3 staining (P = 0.025). In other hormonal adenomas, GLUT3 was only partially expressed, and the intensity of cell membrane or paranuclear punctate staining was weak. In contrast to GLUT3, GLUT1 expression was not associated with pituitary adenomas. Thus, our results indicate that the expression of GLUT3 in pituitary adenomas is closely related to cystic change and hormonal type. This study is the first to report a unique paranuclear dot-like GLUT3 staining pattern in pituitary adenomas.

scholarly journals Glucose transporter GLUT1 expression is an stage-independent predictor of clinical outcome in adrenocortical carcinoma

2009 ◽  
Vol 16 (3) ◽  
pp. 919-928 ◽  
Author(s):  
Wiebke Fenske ◽  
Hans-Ullrich Völker ◽  
Patrick Adam ◽  
Stefanie Hahner ◽  
Sarah Johanssen ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Adrenocortical Carcinoma ◽  
Glucose Transporter ◽  
Disease Free Survival ◽  
Immunohistochemical Analysis ◽  
Radical Resection ◽  
Tissue Microarrays ◽  
Tissue Samples ◽  
Glucose Transporter 1 ◽  
Glut1 Expression

Owing to the rarity of adrenocortical carcinoma (ACC) no prognostic markers have been established beyond stage and resection status. Accelerated glycolysis is a characteristic feature of cancer cells and in a variety of tumour entities key factors in glucose metabolism like glucose transporter 1 and 3 (GLUT1 and -3), transketolase like-1 enzyme (TKTL1) and pyruvate kinase type M2 (M2-PK) are overexpressed and of prognostic value. Therefore, we investigated the role of these factors in ACC. Immunohistochemical analysis was performed on tissue microarrays of paraffin-embedded tissue samples from 167 ACCs, 15 adrenal adenomas and 4 normal adrenal glands. Expression was correlated with baseline parameters and clinical outcome. GLUT1 and -3 were expressed in 33 and 17% of ACC samples respectively, but in none of the benign tumours or normal adrenals glands. By contrast, TKTL1 and M2-PK were detectable in all benign tissues and the vast majority of ACCs. GLUT1 expression was strongly associated with prognosis in univariate and multivariate analysis (P<0.01), whereas GLUT3, TKTL1 and M2-PK did not correlate with clinical outcome. Patients with strong GLUT1 staining showed a considerably higher overall mortality (hazard ratio (HR) 6.34 (95% confidence interval 3.10–12.90) compared with patients with no GLUT1 staining. When analysing patients in their early stages and advanced disease separately, similar results were obtained. HR for survival was 5.31 (1.80–15.62) in patients with metatastic ACC and in patients after radical resection the HR for disease-free survival was 6.10 (2.16–16.94). In conclusion, GLUT1 is a highly promising stage-independent, prognostic marker in ACC.

scholarly journals Glucose transporter 1 (GLUT1) expression is associated with intestinal type of gastric carcinoma

2000 ◽  
Vol 15 (4) ◽  
pp. 420 ◽  
Author(s):  
Wan Seop Kim ◽  
Young Youl Kim ◽  
Se Jin Jang ◽  
Kuchan Kimm ◽  
Myeong Ho Jung
Keyword(s):  
Gastric Carcinoma ◽  
Glucose Transporter ◽  
Intestinal Type ◽  
Glucose Transporter 1 ◽  
Glut1 Expression

Glucose transporters control gene expression of aldose reductase, PKCα, and GLUT1 in mesangial cells in vitro

1999 ◽  
Vol 277 (1) ◽  
pp. F97-F104 ◽  
Author(s):  
Douglas N. Henry ◽  
Julia V. Busik ◽  
Frank C. Brosius ◽  
Charles W. Heilig
Keyword(s):  
Aldose Reductase ◽  
Matrix Protein ◽  
Glucose Transporter ◽  
Mesangial Cells ◽  
Organ Damage ◽  
Glucose Transporter 1 ◽  
Protein Levels ◽  
Protein Kinase Cα ◽  
Glut1 Expression

The process linking increased glucose utilization and activation of metabolic pathways leading to end-organ damage from diabetes is not known. We have previously described rat mesangial cells that were transduced to constitutively express the facilitative glucose transporter 1 (GLUT1, MCGT1 cells) or bacterial β-galactosidase (MCLacZ, control cells). Glucose transport was rate limiting for extracellular matrix production in the MCGT1 cells. In the present work, we investigated the effect of GLUT1 overexpression in mesangial cells on aldose reductase (AR), protein kinase Cα (PKCα), and native GLUT1 transcript levels, to determine whether changes in GLUT1 alone could regulate their expression in the absence of high extracellular glucose concentrations. MCGT1 cells grown in normal (8 mM) or elevated (20 mM) glucose had elevated abundance of AR, PKCα, and the native GLUT1 transcripts compared with control cells. AR protein levels, AR activity, sorbitol production, and PKCα protein content were also greater in the MCGT1 cells than in control cells grown in the same media. This is the first report of the concomitant activation of AR, PKCα, and GLUT1 genes by enhanced GLUT1 expression. We conclude that increased GLUT1 expression leads to a positive feedback of greater GLUT1 expression, increased AR expression and activity with polyol accumulation, and increased total and active PKCα protein levels, which leads to detrimental stimulation of matrix protein synthesis by diabetic mesangial cells.

Acute fasting decreases the expression of GLUT1 and glucose utilisation involved in mouse oocyte maturation and cumulus cell expansion

2012 ◽  
Vol 24 (5) ◽  
pp. 733 ◽  
Author(s):  
Yingying Han ◽  
Jun Yan ◽  
Jinlian Zhou ◽  
Zhen Teng ◽  
Fenghua Bian ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
High Glucose ◽  
Cell Expansion ◽  
Glucose Transporter ◽  
Cumulus Cell ◽  
Glucose Consumption ◽  
Glucose Transporter 1 ◽  
Glucose Utilisation ◽  
Glut1 Expression

Acute fasting impairs meiotic resumption and glucose consumption in mouse cumulus cell and oocyte complexes (COCs). This study examines the effects of acute fasting on the regulation of glucose transporter 1 (GLUT1) expression and glucose consumption in oocyte maturation. Our results indicate that the restriction of glucose utilisation by 2-deoxyglucose (2-DG) mimicked the inhibitory effects of acute fasting on oocyte meiotic resumption and cumulus cell expansion, effects that were rescued by high glucose concentrations in the culture medium. GLUT1 protein levels were higher in cumulus cells compared with oocytes, and GLUT1 expression in COCs increased with FSH treatment in vitro. However, under acute fasting conditions, GLUT1 expression in COCs decreased and the response to FSH disappeared. Exposure to high glucose conditions (27.5 mM and 55 mM), significantly increased both glucose consumption and GLUT1 levels in COCs. Inhibition of GLUT1 function using an anti-GLUT1 antibody significantly inhibited FSH-induced oocyte meiotic resumption. Taken together, these results suggest that acute fasting decreases GLUT1 expression and glucose utilisation, inhibiting the processes of oocyte maturation and cumulus cell expansion.

scholarly journals Subtype-dependent difference of glucose transporter 1 and hexokinase II expression in craniopharyngioma: an immunohistochemical study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naoto Mukada ◽  
Masahiko Tosaka ◽  
Nozomi Matsumura ◽  
Rei Yamaguchi ◽  
Masanori Aihara ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Transporter ◽  
Immunohistochemical Analysis ◽  
Braf V600e ◽  
Beta Catenin ◽  
Hexokinase Ii ◽  
Glucose Transporter 1 ◽  
Positive Group ◽  
Glut 1 ◽  
Positive Rate

AbstractPapillary craniopharyngiomas are characterized by the BRAF V600E mutation. Enhancement of glucose metabolism may be involved in the downstream of the BRAF V600E mutation in many types of tumors. Glucose metabolism was investigated in craniopharyngioma using immunohistochemical analysis. The study included 29 cases of craniopharyngioma (18 adamantinomatous type [ACP], 11 papillary type [PCP]). Immunohistochemical analysis was performed with anti-glucose transporter-1 (GLUT-1), anti-hexokinase-II (HK-II), anti-BRAF V600E, and anti-beta-catenin antibodies. Expressions of GLUT-1 and HK-II were evaluated using a semiquantitative 4-tiered scale as 0, 1+, 2+, 3+, and divided into negative (0 or 1+) or positive (2+ or 3+) group. GLUT-1 expression level was significantly higher in PCPs than ACPs (0, 1+, 2+, 3+ = 2, 12, 4, 0 cases in ACP, respectively, 0, 1+, 2+, 3+ = 0, 2, 5, 4 in PCP, p = 0.001), and most PCPs were classified into positive group (positive rate, 22.2% [4/18] in ACP, 81.8% [9/11] in PCP; p = 0.003). HK-II expression was also conspicuous in PCPs (0, 1+, 2+, 3+ = 7, 9, 2, 0 cases in ACP, 0, 3, 3, 5 in PCP; p = 0.001), and most of them divided into positive group (positive rate, 11.1% [2/18] in ACP, 72.7% [8/11] in PCP; p = 0.001). Expression patterns of BRAF V600E and beta-catenin reflected the clinicopathological subtypes. Both GLUT-1 and HK-II expressions were prominent in PCP. Glucose metabolism might be more enhanced in PCP than ACP. PCP may use the glucose metabolic system downstream of the BRAF V600E mutant protein.

scholarly journals MON-009 GLUT1-Mediated Glycolysis Facilitates GnRH-Induced Secretion of Luteinizing Hormone

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Dequina Nicholas ◽  
Vashti Knight ◽  
Karen Tonsfeldt ◽  
Tomohiro Terasaka ◽  
Olivia Molinar-Inglis ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
High Energy ◽  
Receptor Expression ◽  
Flux Analysis ◽  
Energy Availability ◽  
Hpg Axis ◽  
Glucose Transporter 1 ◽  
Lh Surge ◽  
Glut1 Expression ◽  
Lh Secretion

Abstract Reproduction requires intensive energy expenditure, and energy availability impacts the function of the reproductive endocrine HPG-axis. Accordingly, the reproductive axis is suppressed during hypoglycemia. Circulating blood glucose can directly interact with gonadotropes within the highly vascular pituitary. Therefore, it is possible that gonadotropes may sense energy availability via the presence of glucose in the circulation and integrate this status with input from GnRH neurons to regulate hormone production. Gonadotropes dominantly express glucose transporter 1 (GLUT1) and increase glucose uptake in response to GnRH. Thus, we hypothesized that gonadotropes engage glycolysis in response to GnRH stimulation due to the high energy demand of protein synthesis required for LH production. We developed an approach to sort and successfully culture primary gonadotropes from wild type mice. Using this approach, we performed extracellular flux analysis and found that gonadotropes respond to GnRH by inducing GLUT1-mediated glycolysis that is independent of mitochondrial respiration. Knock-down of GLUT1 expression in the LβT2 gonadotrope cell line, glucose restriction, or treatment with the competitive inhibitor of glycolysis, 2-DG, diminished GnRH-induced LH secretion, indicating GLUT1 expression is necessary for maximal GnRH-induced LH secretion. We confirmed this observation in primary female mouse gonadotropes by limiting glucose availability which resulted in diminished basal LH and FSH secretion. Lastly, GLUT1 expression in the pituitary correlates with GnRH receptor expression and is increased during the LH surge in a mouse model. These results implicate glucose uptake through GLUT1 as permissive for gonadotrope secretion of LH and therefore reproductive function, especially the LH surge. We conclude that GLUT1-mediated glucose uptake is an important rate-limiting step in gonadotropin synthesis and operation of the HPG-axis.

scholarly journals Glucose transporter‑1 inhibition overcomes imatinib resistance in gastrointestinal stromal tumor cells

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Takafumi Shima ◽  
Kohei Taniguchi ◽  
Yoshihisa Tokumaru ◽  
Yosuke Inomata ◽  
Jun Arima ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Tumor Cells ◽  
Glucose Transporter ◽  
Stromal Tumor ◽  
Imatinib Resistance ◽  
Glucose Transporter 1

scholarly journals Stromal Expression of Hypoxia Regulated Proteins Is an Adverse Prognostic Factor in Colorectal Carcinomas

2007 ◽  
Vol 29 (3) ◽  
pp. 229-240
Author(s):  
Arjen H. G. Cleven ◽  
Manon van Engeland ◽  
Bradly G. Wouters ◽  
Adriaan P. de Bruïne
Keyword(s):  
Prognostic Factor ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Glucose Transporter ◽  
Tumor Biology ◽  
Tumor Hypoxia ◽  
Epithelial Tumor ◽  
Glucose Transporter 1 ◽  
Colorectal Adenocarcinomas ◽  
Hypoxia Markers

Background: Hypoxia modifies the phenotype of tumors in a way that promotes tumor aggressiveness and resistance towards chemotherapy and radiotherapy. However, the expression and influence of hypoxia-regulated proteins on tumor biology are not well characterized in colorectal tumors. We studied the role of protein expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, carbonic anhydrase 9 (CA9) and glucose transporter 1 (GLUT1) in patients with colorectal adenocarcinomas. Methods: Expression of HIF-1α, HIF-2α, CA9 and GLUT1 was quantified by immunohistochemistry in 133 colorectal adenocarcinomas. The expression of hypoxia markers was correlated with clinicopathological variables and overall patient survival. Results: Expression of these hypoxia markers was detected in the epithelial compartment of the tumor cells as well as in tumor-associated stromal cells. Although tumor cells frequently showed expression of one or more of the investigated hypoxia markers, no correlation among these markers or with clinical response was found. However, within the tumor stroma, positive correlations between the hypoxia markers HIF-2α, CA9 and GLUT1 were observed. Furthermore expression of HIF-2α and CA9 in tumor-associated stroma were both associated with a significantly reduced overall survival. In the Cox proportional hazard model, stromal HIF-2α expression was an independent prognostic factor for survival. Conclusion: These observations show, that expression of hypoxia regulated proteins in tumor-associated stromal cells, as opposed to their expression in epithelial tumor cells, is associated with poor outcome in colorectal cancer. This study suggests that tumor hypoxia may influence tumor-associated stromal cells in a way that ultimately contributes to patient prognosis.

Utility of Glucose Transporter 1 in the Distinction of Benign and Malignant Thoracic and Abdominal Mesothelial Lesions

2012 ◽  
Vol 136 (7) ◽  
pp. 804-809 ◽  
Author(s):  
Stephen M. Lagana ◽  
Robert N. Taub ◽  
Alain C. Borczuk
Keyword(s):  
Malignant Mesothelioma ◽  
Predictive Value ◽  
Glucose Transporter ◽  
High Specificity ◽  
Tissue Microarrays ◽  
Lower Sensitivity ◽  
Positive Staining ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Reactive Hyperplasia

Context.—Malignant mesothelioma, of either peritoneum or pleura, is an uncommon cancer. The diagnosis is often difficult to make, in part because of the overlapping morphology of reactive and malignant mesothelial cells. Glucose transporter 1 (GLUT-1) is a glucose transporter typically found on erythrocytes, which is aberrantly expressed in various carcinomas. It has recently been reported as specific and sensitive in discriminating malignant pleural mesothelioma from reactive hyperplasia. The application of GLUT-1 staining in peritoneal mesothelioma has not been fully explored. Objective.—To determine if GLUT-1 staining is helpful in distinguishing abdominal mesotheliomas from benign, reactive mesothelial lesions and to further study its utility in the thorax. Design.—Tissue microarrays containing 135 abdominal malignant mesotheliomas and 30 malignant pleural mesotheliomas were stained with an antibody to GLUT-1, as were 56 reactive mesothelial lesions. Results.—The overall sensitivity and specificity for GLUT-1 in mesothelioma was 53% and 98%, respectively. The sensitivity in epithelioid malignant mesothelioma was 49% and in sarcomatoid/biphasic malignant mesothelioma, 66%. In the thorax, the sensitivity was 50% and in the abdomen it was 54%. The positive predictive value of GLUT-1 immunoreactivity was 98% and the negative predictive value was 40%. Conclusion.—Glucose transporter 1 staining of thoracic mesotheliomas showed high specificity but lower sensitivity than previously reported. Abdominal malignant mesotheliomas showed similar results. Because of low sensitivity, only positive staining is informative. In both sites, the utility of the stain was limited by nonspecific staining (eg, in necrotic areas) as well as bright labeling of erythrocytes and occasional lymphoid elements. Despite these limitations, GLUT-1 can help differentiate malignant mesothelioma from reactive benign mesothelium.

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