Metabolic, enzymatic, and transporter responses in human muscle during three consecutive days of exercise and recovery

2008 ◽  
Vol 295 (4) ◽  
pp. R1238-R1250 ◽  
Author(s):  
Howard J. Green ◽  
Eric Bombardier ◽  
Todd A. Duhamel ◽  
Riley D. Stewart ◽  
A. Ross Tupling ◽  
...  
Keyword(s):  
Enzyme Activities ◽  
Glucose Transporter ◽  
Vastus Lateralis ◽  
Sudden Onset ◽  
Adaptive Responses ◽  
Experimental Protocol ◽  
Tissue Samples ◽  
Glucose Transporter 1 ◽  
Metabolic Properties ◽  
Low Intensity Exercise

This study investigated the responses in substrate- and energy-based properties to repetitive days of prolonged submaximal exercise and recovery. Twelve untrained volunteers (V̇o2peak = 44.8 ± 2.0 ml·kg−1·min−1, mean ± SE) cycled (∼60 V̇o2peak) on three consecutive days followed by 3 days of recovery. Tissue samples were extracted from the vastus lateralis both pre- and postexercise on day 1 (E1), day 3 (E3), and during recovery (R1, R2, R3) and were analyzed for changes in metabolism, substrate, and enzymatic and transporter responses. For the metabolic properties (mmol/kg−1 dry wt), exercise on E1 resulted in reductions ( P < 0.05) in phosphocreatine (PCr; 80 ± 1.9 vs. 41.2 ± 3.0) and increases ( P < 0.05) in inosine monophosphate (IMP; 0.13 ± 0.01 vs. 0.61 ± 0.2) and lactate (3.1 ± 0.4 vs. 19.2 ± 4.3). At E3, both IMP and lactate were lower ( P < 0.05) during exercise. For the transporters, the experimental protocol resulted in a decrease ( P < 0.05) in glucose transporter-1 (GLUT1; 29% by R1), an increase in GLUT4 (29% by E3), and increases ( P < 0.05) for both monocarboxylate transporters (MCT) (for MCT1, 23% by R2 and for MCT4, 18% by R1). Of the mitochondrial and cytosolic enzyme activities examined, cytochrome c oxidase (COX), and hexokinase were both reduced ( P < 0.05) by exercise at E1 and in the case of hexokinase and phosphorylase by exercise on E3. With the exception at COX, which was lower ( P < 0.05) at R1, no differences in enzyme activities existed at rest between E, E3, and recovery days. Results suggest that the glucose and lactate transporters are among the earliest adaptive responses of substrate and metabolic properties studied to the sudden onset of regular low-intensity exercise.

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 MicroRNA-340 Inhibits Bladder Cancer Cell Growth by Downregulating Glucose Transporter-1

2020 ◽  
Author(s):  
Junlong Li ◽  
Gang Xu ◽  
Shouhua Pan
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Gene Networks ◽  
Glucose Transporter ◽  
Inverse Correlation ◽  
Western Blots ◽  
Tissue Samples ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Bladder Cell

Abstract Background: MicroRNA (miRNA)-340 is emerging as a critical regulator for the development and progression of various cancers, such as oral squamous cell carcinoma and prostate cancer. However, little was known about the role of miR-340 in bladder cancer. Methods: Bladder cancer and adjacent non-tumor tissue samples were collected from thirty patients undergoing surgical resection at Shaoxing People's Hospital. The expression of miR-340 and Glut-1 were studied via real-time quantitative PCR (RT-qPCR) or western blots. Bladder cancer T24 cells were transfected with miR-340 mimics to explore cell proliferation and apoptosis via MTT assay, flow cytometer, RT-qPCR and western blots. Results: Compared with that of normal tissues, miR-340 expression was significantly lower, while both mRNA and protein expression of Glut-1 were higher in bladder cancer tissues. The miR-340 could negatively regulate Glut-1 expression in bladder cells. Moreover, bladder cell proliferation could be inhibited by miR-340 and the corresponding antitumor effect could partially reverse by the overexpression of Glut-1. In view of the complexity of gene networks, some other multiple pathways might also confer to miR-340 inducing bladder cell apoptosis, including downregulating PCNA, upregulating Bax and decreasing the phosphorylation levels of PI3K and AKT.Conclusion: This work suggested an inverse correlation between miR-340 and glucose transporter-1 (Glut-1) expression in bladder cancer. miR-340/Glut-1 axis might be a potential and novel therapeutic target for the treatment of bladder cancer. More investigations need to further explore the applications of miR-340 in bladder cancer.

scholarly journals LAT-1 and GLUT-1 Carrier Expression and Its Prognostic Value in Gastroenteropancreatic Neuroendocrine Tumors

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2968
Author(s):  
Miguel Sampedro-Núñez ◽  
Antonio Bouthelier ◽  
Ana Serrano-Somavilla ◽  
Rebeca Martínez-Hernández ◽  
Magdalena Adrados ◽  
...  
Keyword(s):  
Nutrient Uptake ◽  
Neuroendocrine Tumors ◽  
Glucose Transporter ◽  
Tumor Tissue ◽  
Hypoxia Inducible Factor ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Tissue Samples ◽  
Glucose Transporter 1 ◽  
Von Hippel Lindau ◽  
Glut 1

Cancer cells develop mechanisms that increase nutrient uptake, including key nutrient carriers, such as amino acid transporter 1 (LAT-1) and glucose transporter 1 (GLUT-1), regulated by the oxygen-sensing Von Hippel Lindau-hypoxia-inducible factor (VHL-HIF) transcriptional pathway. We aimed to analyze these metabolic players in gastroenteropancreatic neuroendocrine tumors (GEP-NET) and correlate them with tumor malignancy and progression. LAT-1, GLUT-1, and pVHL expression was analyzed in 116 GEP-NETs and 48 peritumoral tissue samples by immunohistochemistry. LAT-1 was stably silenced using specific shRNA in the human NET BON cell line. LAT-1 expression was significantly increased in tumor tissue compared to non-tumor tissue in both gastrointestinal (67% vs. 44%) and pancreatic NETs (54% vs. 31%). Similarly, GLUT-1 was substantially elevated in gastrointestinal (74% vs. 19%) and pancreatic (58% vs. 4%) NETs. In contrast, pVHL expression was decreased (85% vs. 58%) in pancreatic NETs. Tumors with metastases at diagnosis displayed increased LAT-1 and GLUT-1 and decreased pVHL expression (p < 0.001). In accordance with these data, silencing LAT-1 curtailed cell proliferation in BON cells. These findings suggest that specific mechanisms that increase nutrient uptake, such as LAT-1 and GLUT-1, are increased in GEP-NETs, whereas pVHL is decreased. These markers might be related to the proliferation and metastatic capacity of these tumors.

Expression of hypoxia-inducible factor-1α in the brain of rats during chronic hypoxia

2000 ◽  
Vol 89 (5) ◽  
pp. 1937-1942 ◽  
Author(s):  
Juan C. Chávez ◽  
Faton Agani ◽  
Paola Pichiule ◽  
Joseph C. LaManna
Keyword(s):  
Mammalian Cells ◽  
Glucose Transporter ◽  
Hypoxia Inducible Factor ◽  
Arterial Oxygen Tension ◽  
Cell Types ◽  
Arterial Oxygen ◽  
Ependymal Cells ◽  
Mrna Levels ◽  
Adaptive Responses ◽  
Glucose Transporter 1

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates adaptive responses to the lack of oxygen in mammalian cells. HIF-1 consists of two proteins, HIF-1α and HIF-1β. HIF-1α accumulates under hypoxic conditions, whereas HIF-1β is constitutively expressed. HIF-1α and HIF-1β expression were measured during adaptation to hypobaric hypoxia (0.5 atm) in rat cerebral cortex. Western blot analyses indicated that HIF-1α rapidly accumulated during the onset of hypoxia and did not fall for 14 days but fell to normal by 21 days despite the continuous low arterial oxygen tension. Immunostaining showed that neurons, astrocytes, ependymal cells, and possibly endothelial cells were the cell types expressing HIF-1α. Genes with hypoxia-responsive elements were activated under these conditions, as evidenced by elevated vascular endothelial growth factor and glucose transporter-1 mRNA levels. When 21-day-adapted rats were exposed to a more severe hypoxic challenge (8% oxygen), HIF-1α accumulated again. On the basis of these results, we speculate that the vascular remodeling and metabolic changes triggered during prolonged hypoxia are capable of restoring normal tissue oxygen levels.

scholarly journals Diffuse pleural thickening and thoracic contraction: An indistinguishable case from malignant pleural mesothelioma

2020 ◽  
Vol 8 ◽  
pp. 2050313X2094871
Author(s):  
Yuji Tada ◽  
Masatoshi Tagawa ◽  
Toshikazu Yusa ◽  
Mari Yatomi ◽  
Iwao Shimomura ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Glucose Transporter ◽  
Asbestos Exposure ◽  
Correct Diagnosis ◽  
Diagnostic Methods ◽  
High Concentration ◽  
Tissue Samples ◽  
Glucose Transporter 1 ◽  
Pleural Thickening ◽  
Diffuse Pleural Thickening

The differential diagnosis of reactive mesothelial hyperplasia and mesothelioma is difficult. We present a rare case of diffuse pleural thickening with thoracic contraction that was indistinguishable from mesothelioma. A 66-year-old woman with no history of asbestos exposure visited our hospital with a complaint of dyspnea. The clinical findings included circumferential pleural thickening on chest computed tomography image and a high concentration of hyaluronic acid in the pleural fluid. Pleural biopsies obtained by thoracoscopy under local anesthesia were pathologically consistent with mesothelioma, but the patient refused to take any kind of mesothelioma treatments. Four months later, she consented to a surgical pleural biopsy under general anesthesia to obtain larger tissue samples, which included typical proliferating polygonal cells positive for CAM5.2, calretinin, WT-1, D2-40, CK5/6, epithelial membrane antigen, and glucose transporter-1 and negative for carcinoembryonic antigen, BerEP4, and MOC31. The analysis was consistent with diagnosis of epithelioid mesothelioma. Fluorescence in situ hybridization, however, showed the presence of p16 gene, and the expression of BRCA1-associated protein-1 was detected by immunohistochemistry. Our final diagnosis was diffuse pleural thickening unrelated to asbestos exposure. Differential diagnosis of diffuse pleural thickening and malignant mesothelioma is thus difficult and routine immunohistochemical examinations are often insufficient for accurate diagnosis. Multiple diagnostic methods are required for correct diagnosis in a clinically marginal case.

Enzyme activities of FT and ST muscle fibers in heavy-resistance trained athletes

1989 ◽  
Vol 67 (1) ◽  
pp. 83-87 ◽  
Author(s):  
P. A. Tesch ◽  
A. Thorsson ◽  
B. Essen-Gustavsson
Keyword(s):  
Resistance Training ◽  
Enzyme Activities ◽  
Citrate Synthase ◽  
Fiber Type ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Fiber Types ◽  
Tissue Samples ◽  
Fiber Area ◽  
Freeze Dried

Tissue samples were obtained from the vastus lateralis muscle of elite olympic weight and power lifters (OL/PL, n = 6), bodybuilders (BB, n = 7), and sedentary men (n = 7). Enzyme activities of citrate synthase (CS), lactate dehydrogenase (LD), 3-OH-acyl-CoA-dehydrogenase (HAD), and myokinase (MK) were assayed on freeze-dried dissected pools of slow-twitch (ST) and fast-twitch (FT) fiber fragments by fluorometric means. Histochemical analyses were carried out to assess fiber type composition and fiber area. CS and HAD activities were lower (P less than 0.05), and LD and MK were higher (P less than 0.05) in FT than ST fibers in the entire subject pool (n = 20). CS of FT fibers and HAD of ST fibers were lower in athletes (P less than 0.05–0.01) compared with nonathletes, whereas LD of both fiber types was higher (P less than 0.05–0.001) in athletes. CS activity of ST fibers and MK activity of FT fibers were higher (P less than 0.05) in BB compared with OL/PL. FT and ST fiber area was greater (P less than 0.05) in athletes than in nonathletes. BB displayed greater (P less than 0.05) fiber size than OL/PL. FT/ST area was greater (P less than 0.05) in OL/PL than BB. It is suggested that long-term heavy-resistance training results in specific metabolic adaptations of FT and ST fiber types. These changes appear to be influenced by the type of resistance training.

HIF1-α-Mediated Gene Expression Induced by Vitamin B1 Deficiency

2013 ◽  
Vol 83 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Rebecca L. Sweet ◽  
Jason A. Zastre
Keyword(s):  
Gene Expression ◽  
Thiamine Deficiency ◽  
Glucose Transporter ◽  
Neuroblastoma Cell ◽  
Hypoxia Inducible Factor ◽  
Clinical Manifestations ◽  
Vitamin B1 ◽  
Low Oxygen ◽  
Glucose Transporter 1 ◽  
Metabolic Intermediates

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.

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