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Search Results: 1 - 10 of 52339 matches for " S odium linked glucose transporter protein (SGLT) "
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In Silico Molecular Modelling and Docking of Quercetin - γ - Cyclodextrin Inclusion Complex on SGLT of Vibrio parahaemolyticus
Sushama Vaishnav (HOTA),Kulkarni G.K,Perumal P
International Journal of Pharmaceutical and Phytopharmacological Research , 2013,
Abstract: Quercetin glucosides are transported across intestinal epithelium by active transport. Is not significantly transported by sodiumlinked glucose transporter 1 (SGLT1) and shows lesser intestinal absorption than its glucosides. Quercetin complexes withcyclodextrins have been described to increase its solubility. It has long been assumed that cyclodextrins improve its intestinalabsorption by releasing it near intestinal epithelium and making quercetin available for passive diffusion. In silico molecularmodeling and docking studies provide an accurate and cost effective method to understand these interactions. X-ray crystalstructure of sodium dependent glucose transporter isolated from Vibrio parahaemolyticus was used asa model for dockingstudies. The test ligands including quercetin-γ-cyclodextrin, quercetin-3,4'-glucoside, quercetin-3-glucoside, and quercetin weredocked in predicted active site of Vibrio parahaemolyticus sodium linked glucose transporter (vSGLT). Validation of potentialmean force method used for docking was performed by docking glucose, a natural ligand of vSGLT. It was found that quercetinglucosides and quercetin-γ-cyclodextrin docked analogously with predicted active site of vSGLT and their docking scores werecomparable. Quercetin docked at a different location with less docking score. Theresults point towards possible mimicking ofglucose moieties by γ-cyclodextrin in mechanism of active transport of quercetin and its glycosides by SGLT.
The Role of Glucose Transporters in Brain Disease: Diabetes and Alzheimer’s Disease
Kaushik Shah,Shanal DeSilva,Thomas Abbruscato
International Journal of Molecular Sciences , 2012, DOI: 10.3390/ijms131012629
Abstract: The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and Alzheimer’s diseases. However, the preceding mechanism to altered glucose metabolism has not been well understood. Glucose enters the brain via glucose transporters primarily present at the blood-brain barrier. Any changes in glucose transporter function and expression dramatically affects brain glucose homeostasis and function. In the brains of both diabetic and Alzheimer’s disease patients, changes in glucose transporter function and expression have been observed, but a possible link between the altered glucose transporter function and disease progress is missing. Future recognition of the role of new glucose transporter isoforms in the brain may provide a better understanding of brain glucose metabolism in normal and disease states. Elucidation of clinical pathological mechanisms related to glucose transport and metabolism may provide common links to the etiology of these two diseases. Considering these facts, in this review we provide a current understanding of the vital roles of a variety of glucose transporters in the normal, diabetic and Alzheimer’s disease brain.
Biología molecular de los transportadores de glucosa: clasificación, estructura y distribución
Bermúdez,Valmore; Bermúdez,Fernando; Arraiz,Nailet; Leal,Elliuz; Linares,Sergia; Mengual,Edgardo; Valdelamar,Lisney; Rodríguez,Moisés; Seyfi,Hamid; Amell,Anilsa; Carrillo,Marisol; Silva,Carlos; Acosta,Alejandro; A?ez,Johnny; Andara,Carla; Angulo,Verónica; Martins,Gabriela;
Archivos Venezolanos de Farmacología y Terapéutica , 2007,
Abstract: hexoses like glucose, galactose and fructose serve as basic fuel molecules for eucaryotic cells. these molecules are unable to diffuse across cellular membranes, and require transporter proteins for entry into and exit from cells. three distinct groups of hexose transporters have been identified and classified based on their dependence on cellular energy and its chemistry structure. each of the transporters has different affinities for glucose and the other hexoses, which largely dictates their function. the hexose transporters are large integral membrane proteins. based on the deduced amino acid sequences of their cloned cdnas, they have similar structures, consisting of 12 or 14 membrane-spanning regions with cytoplasmic c-terminal and n-terminal tails. also, they all appear to be glycosylated on one of the extracellular loops. transport of sugars across membranes appears to result from a series of conformational changes which "flips" the transporter between alternate states with the substrate binding site either facing the extracellular or cytoplasmic side of the membrane. transport in either direction is thus possible, depending on relative substrate concentrations on either side of the membrane. the original protein, glut1, was identified in molecular term?s 12 years ago. in the subsequent 15 years, a family of related transporters was identified (gluts 1-14). the impact of these discoveries is better realized when we list a sample of the processes that utilize different members of the glut family: control of glycemia; insulin dependent glucose utilization; transport pathways in brain neurons and glia; mechanisms of glucose and fructose uptake in the intestinal track; reabsorption of glucose in kidney tubules and jejunum; maturation of transporters during lactation and weaning; sensing of glucose levels by the pancreas and the liver; control of glucose uptake in high fat feeding; glucose uptake in response to exercise, adaptive response of energy metabolism to
Biología molecular de los transportadores de glucosa: clasificación, estructura y distribución
Valmore Bermúdez,Fernando Bermúdez,Nailet Arraiz,Elliuz Leal
Archivos Venezolanos de Farmacología y Terapéutica , 2007,
Abstract: Hexosas como la glucosa, galactosa y fructosa cumplen funciones importantes en las células eucarióticas. Estas moléculas son incapaces de difundir directamente a través de las membranas celulares por lo que requieren proteínas transportadoras especializadas para entrar al interior celular. Dichas biomoléculas pertenecen a un grupo de transportadores constituida por 2 familias de proteínas: la familia de los Glut′s (del inglés Glucose Transporters) y la familia de los co-transportadores de sodio y glucosa. Según la información obtenida de la secuencia de aminoácidos por medio de librerías de cADN todos poseen una estructura básica similar: 12 (Gluts) o 14 (SGLT) dominios trasmembrana. Igualmente todos parecen estar glicosilados en alguna de sus asas extracelulares. En los últimos siete a os ha habido un explosivo incremento en la información sobre estos transportadores, de hecho, hasta hace diez a os solo se conocían 6 transportadores pero esta familia ha crecido rápidamente hasta llegar a 14 miembros para los Gluts y 6 miembros para los SGLT′s. El impacto de estos descubrimientos se hace notar cuando se analizan los procesos en los que se involucran estas proteínas: Control de la glicemia basal y post-prandial; mecanismos de absorción de la glucosa y fructosa en el intestino delgado; absorción de fructosa en los espermatozoides; reabsorción de glucosa a nivel tubular renal y yeyuno; maduración de la expresión de Glut′s en la mama en lactación; incorporación de glucosa al músculo durante el ejercicio; mecanismo sensor en la secreción de insulina y respuestas adaptativa del metabolismo energético durante estados de estrés, etc. Hexoses like glucose, galactose and fructose serve as basic fuel molecules for eucaryotic cells. These molecules are unable to diffuse across cellular membranes, and require transporter proteins for entry into and exit from cells. Three distinct groups of hexose transporters have been identified and classified based on their dependence on cellular energy and its chemistry structure. Each of the transporters has different affinities for glucose and the other hexoses, which largely dictates their function. The hexose transporters are large integral membrane proteins. Based on the deduced amino acid sequences of their cloned cDNAs, they have similar structures, consisting of 12 or 14 membrane-spanning regions with cytoplasmic C-terminal and N-terminal tails. Also, they all appear to be glycosylated on one of the extracellular loops. Transport of sugars across membranes appears to result from a series of conformational changes which "fl
Characterization of the Interaction Between the Small Regulatory Peptide SgrT and the EIICBGlc of the Glucose-Phosphotransferase System of E. coli K-12
Anne Kosfeld,Knut Jahreis
Metabolites , 2012, DOI: 10.3390/metabo2040756
Abstract: Escherichia coli is a widely used microorganism in biotechnological processes. An obvious goal for current scientific and technical research in this field is the search for new tools to optimize productivity. Usually glucose is the preferred carbon source in biotechnological applications. In E. coli, glucose is taken up by the phospho enolpyruvate-dependent glucose phosphotransferase system (PTS). The regulation of the ptsG gene for the glucose transporter is very complex and involves several regulatory proteins. Recently, a novel posttranscriptional regulation system has been identified which consists of a small regulatory RNA SgrS and a small regulatory polypeptide called SgrT. During the accumulation of glucose-6-phosphate or fructose-6-phosphate, SgrS is involved in downregulation of ptsG mRNA stability, whereas SgrT inhibits glucose transport activity by a yet unknown mechanism. The function of SgrS has been studied intensively. In contrast, the knowledge about the function of SgrT is still limited. Therefore, in this paper, we focused our interest on the regulation of glucose transport activity by SgrT. We identified the SgrT target sequence within the glucose transporter and characterized the interaction in great detail. Finally, we suggest a novel experimental approach to regulate artificially carbohydrate uptake in E. coli to minimize metabolic overflow in biotechnological applications.
GLUT1 expression in malignant tumors and its use as an immunodiagnostic marker
Carvalho, Kátia C.;Cunha, Isabela W.;Rocha, Rafael M.;Ayala, Fernanda R.;Cajaíba, Mariana M.;Begnami, Maria D.;Vilela, Rafael S.;Paiva, Geise R.;Andrade, Rodrigo G.;Soares, Fernando A.;
Clinics , 2011, DOI: 10.1590/S1807-59322011000600008
Abstract: objective: to analyze glucose transporter 1 expression patterns in malignant tumors of various cell types and evaluate their diagnostic value by immunohistochemistry. introduction: glucose is the major source of energy for cells, and glucose transporter 1 is the most common glucose transporter in humans. glucose transporter 1 is aberrantly expressed in several tumor types. studies have implicated glucose transporter 1 expression as a prognostic and diagnostic marker in tumors, primarily in conjunction with positron emission tomography scan data. methods: immunohistochemistry for glucose transporter 1 was performed in tissue microarray slides, comprising 1955 samples of malignant neoplasm from different cell types. results: sarcomas, lymphomas, melanomas and hepatoblastomas did not express glucose transporter 1. fortyseven per cent of prostate adenocarcinomas were positive, as were 29% of thyroid, 10% of gastric and 5% of breast adenocarcinomas. thirty-six per cent of squamous cell carcinomas of the head and neck were positive, as were 42% of uterine cervix squamous cell carcinomas. glioblastomas and retinoblastomas showed membranous glucose transporter 1 staining in 18.6% and 9.4% of all cases, respectively. squamous cell carcinomas displayed membranous expression, whereas adenocarcinomas showed cytoplasmic glucose transporter 1 expression. conclusion: glucose transporter 1 showed variable expression in various tumor types. its absence in sarcomas, melanomas, hepatoblastomas and lymphomas suggests that other glucose transporters mediate the glycolytic pathway in these tumors. the data suggest that glucose transporter 1 is a valuable immunohistochemical marker that can be used to identify patients for evaluation by positron emission tomography scan. the function of cytoplasmic glucose transporter 1 in adenocarcinomas must be further examined.
Value of Glut-1 and Koc Markers in the Differential Diagnosis of Reactive Mesothelial Hyperplasia, Malignant Mesothelioma and Pulmonary Adenocarcinoma
?zlem ü?ER,Adile Ferda DA?LI,Ahmet KILI?ARSLAN,G?khan ARTA?
Türk Patoloji Dergisi , 2013, DOI: 10.5146/tjpath.2013.01158
Abstract: Objective: Malignant mesothelioma (MM) is a primary malignant tumor developing from mesothelial cells lining the serosal surfaces and particularly the pleura, and has a very poor prognosis. It may display a variety of histological patterns and has a wide spectrum of cytomorphological characteristics, causing problems in its diff erential diagnosis from lung adenocarcinomas and sometimes from benign mesothelial proliferations. Immunohistochemical examination is the most useful method for this distinction. In our study, we aimed to determine the value of glucose transporter isoform-1 (GLUT-1) and K homology domain-containing protein (KOC) markers in the diff erential diagnosis of reactive mesothelial hyperplasia, malignant mesothelioma and lung adenocarcinoma.Material and Method: Our study included 30 samples of malignant mesothelioma, 30 samples of pulmonary adenocarcinoma and 30 samples of reactive mesothelial hyperplasia selected from the archives of the F rat University Hospital's Pathology Department Laboratory. The samples were applied GLUT-1 and KOC markers by immunohistochemistry and the place of these markers in the diff erential diagnosis was examined.Results: GLUT-1 was found positive in 80% of malignant mesothelioma cases, 83.3% of adenocarcinoma cases and 6.6% of reactive mesothelial hyperplasia cases. KOC was positive in 83.3% of malignant mesothelioma cases, 76.6% of adenocarcinoma cases and 46.6% of reactive mesothelial hyperplasia cases. There was no statistically significant diff erence between malignant mesothelioma and lung adenocarcinoma cases in terms of the diffuseness and intensity of staining with GLUT-1, whereas a significant diff erence was established when these groups were compared with reactive mesothelial hyperplasia cases. However, the KOC staining diffuseness and intensity results were similar to those obtained with GLUT-1.Conclusion: In conclusion, GLUT-1 and KOC markers do not diff erentiate malignant mesotheliomas from pulmonary adenocarcinomas but can be useful in diff erentiating reactive mesothelial hyperplasia from malignant mesothelioma and lung adenocarcinoma.
Single Step Nanoplasmonic Immunoassay for the Measurement of Protein Biomarkers
Shradha Prabhulkar,Adam de la Zerda,Amit Paranjape,Richard M. Awdeh
Biosensors , 2013, DOI: 10.3390/bios3010077
Abstract: A nanoplasmonic biosensor for highly-sensitive, single-step detection of protein biomarkers is presented. The principle is based on the utilization of the optical scattering properties of gold nanorods (GNRs) conjugated to bio-recognition molecules. The nanoplasmonic properties of the GNRs were utilized to detect proteins using near-infrared light interferometry. We show that the antibody-conjugated GNRs can specifically bind to our model analyte, Glucose Transporter-1 (Glut-1). The signal intensity of back-scattered light from the GNRs bound after incubation, correlated well to the Glut-1 concentration as per the calibration curve. The detection range using this nanoplasmonic immunoassay ranges from 10 ng/mL to 1 ug/mL for Glut-1. The minimal detectable concentration based on the lowest discernable concentration from zero is 10 ng/mL. This nanoplasmonic immunoassay can act as a simple, selective, sensitive strategy for effective disease diagnosis. It offers advantages such as wide detection range, increased speed of analysis (due to fewer incubation/washing steps), and no label development as compared to traditional immunoassay techniques. Our future goal is to incorporate this detection strategy onto a microfluidic platform to be used as a point-of-care diagnostic tool.
Antidiabetic effects of Tangnaikang on obese Zucker rats and the mechanism
Xiang-yu GUO
Zhong Xi Yi Jie He Xue Bao , 2010,
Abstract: Objective: To observe the effects of Tangnaikang (TNK), a compound traditional Chinese herbal medicine, on glucose metabolism and insulin resistance in obese Zucker rats. Methods: Twelve male obese Zucker rats, 6 weeks old, were randomly divided into control group and TNK group (3.24 g/kg) after being fed for 2 weeks. All rats received high-fat diet and 4-week treatment. Body weight and blood glucose were tested every week. Oral glucose tolerance test (OGTT) was performed and fasting insulin level was tested on days 0, 14 and 28. Triglyceride, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and free fatty acids (FFA) were tested on day 28. Glucose infusion rate (GIR) was tested by hyperinsulinemic-euglycemic clamp from day 29. The protein expressions of protein kinase B (Akt), phospho-Akt (p-Akt) (Thr308) and glucose transporter protein 4 (GLUT4) in skeletal muscle and GLUT4 in adipose tissue were measured after hyperinsulinemic-euglycemic clamp test.Results: Compared with the control group, the fed blood glucose level and glucose level of OGTT at 120 min had a significant decline in TNK group on day 28, and TNK caused no alteration of the fasting serum insulin, and the GIR increased significantly in hyperinsulinemic-euglycemic clamp study. Furthermore, TNK increased Akt and p-Akt (Thr308) protein expressions in skeletal muscle and decreased the protein expression of GLUT4 in white adipose tissue. Body weight, and triglyceride, cholesterol, LDL-C and FFA contents were slightly decreased in the TNK group, but there were no statistically significant effects.Conclusion: TNK increases the protein expressions of Akt and p-Akt (Thr308) of the signal transduction pathway to influence the translocation of GLUT4 in skeletal muscle and improves glucose metabolism by reducing insulin resistance.
Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer
Kenneth J. O'Byrne,Anne-Marie Baird,Lisa Kilmartin,Jennifer Leonard,Calen Sacevich,Steven G. Gray
Cancers , 2011, DOI: 10.3390/cancers3021550
Abstract: Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin receptor in non-small cell lung cancer (NSCLC) is associated with an increased risk of metastasis and decreased survival. The uptake of glucose into cells is carried out via glucose transporters or GLUTs. Of these, GLUT-4 is essential for insulin-stimulated glucose uptake. Following treatment with the epigenetic targeting agents histone deacetylase inhibitors (HDACi), GLUT-3 and GLUT-4 expression were found to be induced in NSCLC cell lines, with minimal responses in transformed normal human bronchial epithelial cells (HBECs). Similar results for GLUT-4 were observed in cells derived from liver, muscle, kidney and pre-adipocytes. Bioinformatic analysis of the promoter for GLUT-4 indicates that it may also be regulated by several chromatin binding factors or complexes including CTCF, SP1 and SMYD3. Chromatin immunoprecipitation studies demonstrate that the promoter for GLUT-4 is dynamically remodeled in response to HDACi. Overall, these results may have value within the clinical setting as (a) it may be possible to use this to enhance fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) imaging sensitivity; (b) it may be possible to target NSCLC through the use of HDACi and insulin mediated uptake of the metabolic targeting drugs such as 2-deoxyglucose (2-DG); or (c) enhance or sensitize NSCLC to chemotherapy.
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