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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trypanosoma brucei brucei (EATRO-164) contains a tandem array of six genes encoding a glucose transporter, THT1 (trypanosome hexose transporter), followed by five genes encoding a second isoform, THT2. Two distinct clusters containing THT1 and THT2 genes have been identified in the EATRO-164 clone and in most other African trypanosome clones analyzed. Analysis of progeny from crosses between clones of T. b. brucei displaying polymorphism in THT1 copy number per cluster suggests that the two clusters of THT genes are present on homologous chromosomes. In addition, analysis of 30 African trypanosome clones revealed a high degree of polymorphism in THT1 copy number per cluster. Sequence comparison of five THT1 and two and one-half THT2 unit repeats, present within a 20-kb region, provided information about the genesis and evolution of the THT multigene family. The most divergent regions between THT1 and THT2 unit repeats probably arose from insertion of DNA fragments into an ancestral THT region. Genes of each of the different families are almost identical, and there are large regions of identity shared between THT1 and THT2 members. A mosaic copy containing most of a THT1 gene with the 3' extremity of a THT2 gene is found within the cluster. These results suggest that THT1 and THT2 arose by modification (insertion, mutation, or conversion) of duplicated ancestral genes. Functional constraints and homologous recombination may be evoked to explain the maintenance of the conserved sequences of THT1 and THT2.
Mol Biol Evol 1994 Mar
PMID:African trypanosome glucose transporter genes: organization and evolution of a multigene family. 817 Mar 63

In Saccharomyces cerevisiae, TRK1 and TRK2 are required for high- and low-affinity K+ transport. Among suppressors of the K+ transport defect in trk1 delta trk2 delta cells, we have identified members of the sugar transporter gene superfamily. One suppressor encodes the previously identified glucose transporter HXT1, and another encodes a new member of this family, HXT3. The inferred amino acid sequence of HXT3 is 87% identical to that of HXT1, 64% identical to that of HXT2, and 32% identical to that of SNF3. Like HXT1 and HXT2, overexpression of HXT3 in snf3 delta cells confers growth on low-glucose or raffinose media. The function of another new member of the HXT superfamily, HXT4 (previously identified by its ability to suppress the snf3 delta phenotype; L. Bisson, personal communication), was revealed in experiments that deleted all possible combinations of the five members of the glucose transporter gene family. Neither SNF3, HXT1, HXT2, HXT3, nor HXT4 is essential for viability. snf3 delta hxt1 delta hxt2 delta hxt3 delta hxt4 delta cells are unable to grow on media containing high concentrations of glucose (5%) but can grow on low-glucose (0.5%) media, revealing the presence of a sixth transporter that is itself glucose repressible. This transporter may be negatively regulated by SNF3 since expression of SNF3 abolishes growth of hxt1 delta hxt2 delta hxt3 delta hxt4 delta cells on low-glucose medium. HXT1, HXT2, HXT3, and HXT4 can function independently: expression of any one of these genes is sufficient to confer growth on medium containing at least 1% glucose. A synergistic relationship between SNF3 and each of the HXT genes is suggested by the observation that SNF2 hxt1 delta hxt2 delta hxt3 delta hxt4 delta cells and snf3 delta HXT1 HXT2 HXT3 HXT4 cells are unable to grow on raffinose (low fructose) yet SNF3 in combination with any single HXT gene is sufficient for growth on raffinose. HXT1 and HXT3 are differentially regulated. HXT1::lacZ is maximally expressed during exponential growth whereas HXT3::lacZ is maximally expressed after entry into stationary phase.
Mol Cell Biol 1993 Jan
PMID:Roles of multiple glucose transporters in Saccharomyces cerevisiae. 841 58

A tandemly arranged multigene family encoding putative hexose transporters in Trypanosoma brucei has been characterized. It is composed of two 80% homologous groups of genes called THT1 (six copies) and THT2 (five copies). When Xenopus oocytes are microinjected with in vitro-transcribed RNA from a THT1 gene, they express a glucose transporter with properties similar to those of the trypanosome bloodstream-form protein(s). This THT1-encoded transport system for glucose differs from the human erythrocyte-type glucose transporter by its moderate sensitivity to cytochalasin B and its capacity to transport D-fructose. These properties suggest that the trypanosomal transporter may be a good target for antitrypanosomal drugs. mRNA analysis revealed that expression of these genes was life cycle stage dependent. Bloodstream forms express 40-fold more THT1 than THT2. In contrast, procyclic trypanosomes express no detectable THT1 but demonstrate glucose-dependent expression of THT2.
Mol Cell Biol 1993 Feb
PMID:Differential regulation of two distinct families of glucose transporter genes in Trypanosoma brucei. 842 81

The trace element vanadium is a potent insulinomimetic agent in vitro. Oral administration of vanadate to rats made diabetic by streptozotocin (45 mg/kg i.v.) caused a 65% fall in plasma glucose levels without modifying low insulinemia. We studied whether the hypoglycemic effect of vanadate was associated with altered expression of genes involved in key steps of hepatic glucose metabolism. Glucokinase (GK) and L-type pyruvate kinase (L-PK) mRNA levels were decreased respectively by 90% and 70% in fed diabetic rats, in close correlation with changes in enzyme activities. Eighteen days of vanadate treatment partially restored GK mRNA and activity (40% of control levels), and totally restored L-PK parameters. In contrast to the glycolytic enzymes, mRNA levels and activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK) were increased (15- and 2-fold, respectively) in fed diabetic rats. Vanadate treatment normalized both PEPCK mRNA and activity in diabetic rat liver. The 2-fold increase in liver glucose transporter (GLUT2) mRNA and protein, produced by diabetes, was also corrected by this treatment. In conclusion, oral vanadate given to diabetic rats induces a shift of the predominating gluconeogenic flux, with subsequent high hepatic glucose production, into a glycolytic flux by pretranslational regulatory mechanisms.
Mol Cell Endocrinol 1993 Feb
PMID:Vanadate treatment of diabetic rats reverses the impaired expression of genes involved in hepatic glucose metabolism: effects on glycolytic and gluconeogenic enzymes, and on glucose transporter GLUT2. 847 58

Glucokinase and GLUT-2 high Km glucose transporter gene expression were studied in pancreas and liver from 2 day old neonatal and 16 day old rats. In pancreas tissue the glucokinase gene was transcribed into a 2.8 kb and a 4.4 kb mRNA species. However, while the 2.8 kb transcript was expressed already in pancreas from 2 day old neonatal rats, distinct expression of the 4.4 kb transcript occurred only in the pancreas from 16 day old rats. GLUT-2 glucose transporter was expressed already in the pancreas from 2 day old neonatal rats, albeit to a lesser extent than in the pancreas from 16 day old rats. Liver glucokinase gene was not expressed in 2 day old neonatal rats but in 16 day old neonatal rats, whereas the GLUT-2 glucose transporter gene was expressed both in the liver from 2 day old neonatal and 16 day old rats. The differences between glucokinase gene expression in neonatal pancreas and neonatal liver provide an indication for a different function of this enzyme in the two tissues. The immature insulin secretory response to glucose in neonatal pancreas may be related to a deficient glucokinase and probably also to a reduced GLUT-2 glucose transporter gene expression.
Biochem Mol Biol Int 1993 Jan
PMID:Differential regulation of glucokinase and GLUT-2 glucose transporter gene expression in pancreas and liver from neonatal and 16 day old rats. 849 May 62

Insulin stimulates glucose transport in muscle and adipose tissue by triggering the translocation of the glucose transporter GLUT-4 from intracellular vesicles to the cell surface. In the present study we have attempted to characterize the intracellular GLUT-4 compartment using vesicle immunoadsorption. Silver staining of this fraction indicates that this compartment contains numerous polypeptides that exhibit a marked change in mobility upon treatment with reducing agents. The polypeptide composition of GLUT-4-containing vesicles isolated from a variety of insulin-sensitive cell types, including heart, adipose tissue, skeletal muscle and 3T3-L1 adipocytes, is similar. In addition, the polypeptide composition of the GLUT-4 compartment isolated from CHO cells transfected with GLUT-4 resembles that observed in insulin-sensitive cells. Two major proteins in this vesicle fraction isolated from all cell types are the transferrin receptor (TfR) and the mannose 6-phosphate/IGF II receptor (MPR). Furthermore, vesicles immunoadsorbed from adipocytes, with antibodies specific for GLUT-4 and the TfR, also show conservation in their overall polypeptide composition. Protein micro sequencing of a major 80 kDa polypeptide enriched in the GLUT-4 compartment isolated from skeletal muscle revealed this protein to be rat transferrin. These data indicate that there is a close relationship between the intracellular GLUT-4 compartment and the endosomal system. Future studies will be required to determine if it is possible to isolate subcompartments within this system to determine if GLUT-4 is targeted to a specialized secretory compartment in insulin-sensitive cells or simply a subdomain within recycling endosomes.
Mol Membr Biol
PMID:Characterization of the intracellular GLUT-4 compartment. 852 Jun 27

A defect in glucose sensing of the pancreatic beta-cells has been observed in several animal models of type II diabetes and has been correlated with a reduced gene expression of the glucose transporter type 2 (Glut2). In a transgenic mouse model, expression of Glut2 antisense RNA in pancreatic beta-cells has recently been shown to be associated with an impaired glucose-induced insulin secretion and the development of diabetes. To identify factors that may be involved in the specific decrease of Glut2 in the beta-cells of the diabetic animal, an attempt was made to localize the cis-elements and trans-acting factors involved in the control of Glut2 expression in the endocrine pancreas. It was demonstrated by transient transfection studies that only 338 base pairs (bp) of the murine Glut2 proximal promoter are needed for reporter gene expression in pancreatic islet-derived cell lines, whereas no activity was detected in nonpancreatic cells. Three cis-elements, GTI, GTII, and GTIII, have been identified by DNAse I footprinting and gel retardation experiments within these 338 bp. GTI and GTIII bind distinct but ubiquitously expressed trans-acting factors. On the other hand, nuclear proteins specifically expressed in pancreatic cell lines interact with GTII, and their relative abundance correlates with endogenous Glut2 expression. These GTII-binding factors correspond to nuclear proteins of 180 and 90 kilodaltons as defined by Southwestern analysis. The 180-kilodalton factor is present in pancreatic beta-cell lines but not in an alpha-cell line. Mutation of the GTI or GTIII cis-elements decreases transcriptional activity directed by the 338-bp promoter, whereas mutation of GTII increases gene transcription. Thus negative and positive regulatory sequences are identified within the proximal 338 bp of the GLUT2 promoter and may participate in the islet-specific expression of the gene by binding beta-cell specific trans-acting factors.
Mol Endocrinol 1995 Oct
PMID:Pancreatic-specific expression of the glucose transporter type 2 gene: identification of cis-elements and islet-specific trans-acting factors. 854 49

Vertebrate cells that are transformed by oncogenes such as v-src or are stimulated by mitogens have increased rates of glucose uptake. In rodent cells, the mechanisms whereby glucose transport is up-regulated are well understood. Stimulation of glucose transport involves an elevation in mRNA encoding the GLUT1 glucose transporter that is controlled at the levels of both transcription and mRNA stability. Cloning and sequencing of chicken GLUT1 cDNA showed that it shares 95% amino acid sequence similarity to mammalian GLUT1s. Nevertheless, unlike mammalian GLUT1 mRNA, it was not induced by v-src, serum addition, or treatment with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate in chicken embryo fibroblasts. Rather, the induction of glucose transport in chicken embryo fibroblasts by v-src, serum, and 12-O-tetradecanoylphorbol 13-acetate was associated with induction of GLUT3 mRNA level and GLUT3 transcription. Rat fibroblasts were also found to express both GLUT1 and GLUT3 isoforms, but v-src induced GLUT1 and not GLUT3. This suggests that animal cells require both a basal and an upregulatable glucose transporter and that these functions have been subsumed by different GLUT isoforms in avian and mammalian cells.
Mol Biol Cell 1995 Nov
PMID:Characterization of the avian GLUT1 glucose transporter: differential regulation of GLUT1 and GLUT3 in chicken embryo fibroblasts. 858 57

In order to elucidate the implication of GLUT2 in the impaired glucose metabolism caused by ethanol, we examined if ethanol affects GLUT2 glucose transporter mRNA expression in the liver. After the adult rats were fed with and/or without ethanol for 1 or 4 weeks, hepatocytes were isolated and total RNA was extracted from them. The levels of GLUT2 mRNA in hepatocytes isolated from 1 week-ethanol fed rats estimated by Northern blot analysis did not change compared to those of untreated rats, those levels in hepatocytes from 4 weeks-ethanol fed rats decreased markedly. Studies were also performed using primary rat hepatocyte cultures in vitro. We found that ethanol, when added to cultured hepatocytes, resulted in a substantial reduction in the levels of GLUT2 mRNA and this effect was only observed after 24 hr exposure of ethanol. Thus, ethanol seems to have a direct inhibitory effect on GLUT2mRNA in the liver, which may eventually cause the impaired glucose tolerance.
Biochem Mol Biol Int 1995 Nov
PMID:Ethanol decreases the levels of GLUT2 glucose transporter mRNA in hepatocytes. 858 40

Diseases involving glucose metabolism disorders are more and more prevalent. Therefore the question of glucose transporter gene expression is being addressed in experimental and clinical studies. Radioactive probes are generally used to assess glucose transporter mRNA levels, but these probes are short-lived, costly and harmful to the environment. Alternative methods that do not present these disadvantages, for example digoxigenin (DIG) labelled probes, might prove to be very interesting for the study of glucose transporter mRNA. The aim of the present work was to compare DIG-labelled cRNA probes to 32P-labelled cRNA probes in order to see whether or not the non-radioactive method can be used to assess glucose transporter gene expression. This work shows that DIG-labelled glucose transporter (GLUT1 and GLUT4) cRNAs are suitable probes for the assessment of these gene expressions. We have found that the DIG system offers a much higher sensitivity than the 32P system for both GLUT1 and GLUT4 mRNA detection. This represents a decisive advantage in human studies where tissue quantity is a limiting factor. In addition, stability, safety, time saving and cost reduction are other considerations that make DIG-labelled GLUT1 and GLUT4 cRNAs very attractive.
Cell Mol Biol (Noisy-le-grand) 1995 Nov
PMID:Sensitive northern blot hybridization using digoxigenin RNA probes for the mRNA detection of two glucose transporter isoforms. 859 77


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