Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of facilitative glucose transporter (GLUT) isoforms in human astrocytic tumors was examined. Reverse transcriptase-polymerase chain reaction of a surgically biopsied glioblastoma was carried out using the degenerative oligonucleotide primers corresponding to the sequences of the human facilitative glucose transporter family, and polymerase chain reaction products were hybridized with human GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5 cDNA probes. The results showed that a biopsied glioblastoma expressed GLUT1, GLUT3, and GLUT4 glucose transporter genes. Northern blot analysis of total RNA (10 micrograms) from a biopsied glioblastoma showed the transcripts of only GLUT1 and GLUT3, suggesting that the expression of insulin-responsive glucose transporter GLUT4 mRNA is relatively low. Immunoblot analysis of biopsied glioblastoma tissues by polyclonal antibodies against the C-terminal synthetic peptides of GLUT1, GLUT3, and GLUT4 showed a single band of each polypeptide. However, elevated expression of GLUT1 and GLUT3 glucose transporters was not observed in the glioblastoma. Astrocytic tumor tissues (n = 14) were also examined immunohistochemically. Reactive products for GLUT1 were observed in the luminal surface of capillaries in all cases, whereas tumor cells were positive for GLUT1 in only two of 14 cases. GLUT3 was positive in astrocytic tumor cells in all cases. Three of 14 cases expressed the GLUT4 protein, which was localized in the cytoplasm of tumor cells. These results suggest that the facilitative glucose transport may be altered in astrocytic tumor cells and thus display a significant change in glucose metabolism.
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PMID:Expression of facilitative glucose transporter isoforms in human brain tumors. 824 60

Insulin-response glucose transporter GLUT4 is a member of the glucose transporter family (GLUT) and is present exclusively in muscle and adipose tissue. It is a target of insulin action in humans and rodents. To clarify the molecular structure of bovine GLUT4, its GLUT4 cDNA was cloned by the RT-PCR method. Several cDNA clones corresponding to the different regions of GLUT4 were obtained by amplifying reverse-transcriptase products of RNA extracted from Holstein cattle skeletal muscle. Nucleotide sequence analysis of the cDNA clones revealed that bovine GLUT4 cDNA was composed of 2,656 base pairs with a coding region for a 509 amino acid protein. The deduced amino acid sequence was 64% and 92% identical with bovine GLUT1 (GLUT ubiquitously expressed in all tissues) and rat GLUT4, respectively. Although the amino acid sequence of the GLUT4 COOH-terminal region is highly conserved among the species so far reported, one amino acid (Asp) of the region was replaced by His in bovine GLUT4. The tissue distribution of GLUT4 was also examined by Northern blot analysis using a probe prepared from the bovine cDNA. GLUT4 mRNA was detected in skeletal muscle, heart, and adipose tissue, but not in liver, kidney, lung, brain, or spleen. Such a distribution is essentially the same as in humans and rodents, suggesting that GLUT4 is an insulin-responsive glucose transporter in cattle.
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PMID:Molecular cloning and mRNA expression of the bovine insulin-responsive glucose transporter (GLUT4). 902 64

While previous work has demonstrated that monosaccharides can be absorbed from bile, studies of sugar transport by the biliary, epithelia (i.e., cholangiocytes) are lacking. Using a novel model of polarized rat cholangiocytes in primary culture, designated normal rat cholangiocytes (NRC), we examined directly the uptake and transcellular transport of a nonmetabolizable monosaccharide, methyl alpha-D-glucopyranoside (AMG). When the apical or basolateral domain of cholangiocytes was exposed to radiolabeled AMG or sucrose (control), only apical absorption of AMG was evident. This apical uptake was time dependent, saturable, and significantly inhibited (> or = 90%) by removal of Na+ or in the presence of phlorizin (0.1 mM), a competitive inhibitor of the Na(+)-glucose cotransporter. The transcellular flux of AMG was also polar (i.e., apical to basolateral). Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of the transcript for the specific Na(+)-glucose cotransporter SGLT1 in NRC and in freshly isolated cholangiocytes but not in purified hepatocytes; in contrast, the transcript for SGLT2 was absent in all liver samples. In situ RT-PCR on frozen sections of normal rat liver showed that SGLT1 was expressed exclusively in cholangiocytes. Immunoblot analysis using a specific polyclonal antibody for the facilitative glucose transporter GLUT1 demonstrated it to be present in vesicles derived from NRC enriched in basolateral plasma membrane domains. Our data are consistent with the concept that SGLT1 is present on the apical domain of biliary epithelia and, in conjunction with GLUT1 on the basolateral domain, accounts for glucose absorption from bile.
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PMID:Kinetic and molecular identification of sodium-dependent glucose transporter in normal rat cholangiocytes. 917 27

The principal goal of the present study was to test the hypothesis that cytokines modulate glucose transport in skeletal muscle by increasing nitric oxide production. Cultured L6 skeletal muscle cells were incubated in the presence of tumour necrosis factor-alpha, interferon-gamma or lipopolysaccharide (LPS) alone or in combination for 24 h. Neither cytokines nor LPS alone induced NO production, as measured by nitrite concentrations in the medium. However, when used in combination, the two cytokines significantly stimulated NO production, and this effect was synergistically enhanced by the presence of LPS. Reverse transcriptase-PCR (RT-PCR) analysis revealed that NO release was associated with the induction of inducible (macrophage-type) NO synthase (iNOS). The increase in iNOS expression was confirmed at the protein level by Western-blot analysis and NADPH/diaphorase histochemical staining. Cytokines and LPS markedly increased basal glucose transport in L6 myocytes. Insulin also stimulated basal glucose transport, but significantly less in cells chronically exposed to cytokines/LPS. The sensitivity of L6 muscle cells to insulin-stimulated glucose transport was also significantly decreased by cytokines/LPS treatment. The NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME) inhibited nitrite production in cytokine/LPS-treated cells, and this prevented the increase in basal glucose transport and restored muscle cell responsiveness to insulin. Cytokines/LPS exposure significantly increased GLUT1 transporter protein levels but decreased GLUT4 expression in L6 cells. l-NAME treatment prevented the increase in GLUT1 protein content but failed to restore GLUT4 transporter levels. These results demonstrate that cytokines and LPS affect glucose transport and insulin action by inducing iNOS expression and NO production in skeletal muscle cells. The data further indicate that cytokines and LPS increase the expression of the GLUT1 transporter protein by an NO-dependent mechanism.
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PMID:Cytokines modulate glucose transport in skeletal muscle by inducing the expression of inducible nitric oxide synthase. 923 Jan 32

Glucose utilisation by cancer cells is greatly enhanced when compared with that by normal tissue. Glucose is taken up by cells and then phosphorylated to glucose-6-phosphate. Facilitative hexose uptake is achieved by five transmembrane transporters, termed glut1-5, which are protein products of their respective GLUT genes. Glut types differ in their kinetics, which are tailored to the requirements of the cell type they serve, although more than one glut may be expressed by a particular cell type. Herein are reviewed the results from approximately 30 studies which examined glut expression in human cancer tissue. These studies measured GLUT messenger RNA (mRNA) either using the reverse-transcriptase polymerase chain reaction or by Northern blot analysis, or detected glut proteins using the appropriate antibodies. Tumour tissue is frequently associated with the abnormal and/or over-expression of gluts, especially glut1. Some tumour cells express specific GLUT mRNA but not the respective protein. Some studies have reported associations between glut expression and proliferative indices, whilst others suggest that glut may be of prognostic significance, especially in lung cancer.
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PMID:Facilitative glucose transporter expression in human cancer tissue. 1079 74