Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucose uptake by brown adipose tissue, measured following deoxyglucose injection in vivo, was increased by 6- and 11-fold following 2 and 14 days of cold exposure, respectively. To look for the possible mechanism of these modifications, the glucose transporter Glut 4 has been characterized at the protein and mRNA levels in brown adipose tissue, skeletal muscle and white adipose tissue following cold acclimation. Crude membranes were prepared from those tissues, and Glut 4 was studied by Western blot analysis. In brown adipose tissue, the total Glut 4 amount was increased by 52 +/- 7% and by 104 +/- 12% following 2 and 14 days of cold exposure, respectively. By contrast, in white adipose tissue of 14-day-cold-exposed mice the total Glut 4 content was decreased by 42 +/- 5%. However, Glut 4 concentration, expressed per mg of membrane protein, was unchanged in both brown and white adipose tissues following cold exposure, since the membrane protein content increased in brown but decreased in white adipose tissue. No modification in Glut 4 content was observed in skeletal muscle from cold-exposed mice. Total RNA were prepared and analyzed for Glut 4, glyceraldehyde phosphate dehydrogenase (GAPDH) and actin. Glut 4 and GAPDH mRNA were increased 2-fold in brown adipose tissue from cold-exposed mice, while actin mRNA content was unmodified. Glut 4 mRNA content was not changed in white adipose tissue and skeletal muscle from cold-exposed mice. Our results suggest that Glut 4 expression is differently modulated in the three insulin-responsive tissues during cold acclimation.
Mol Cell Endocrinol 1992 Nov
PMID:Effect of cold acclimation on the expression of glucose transporter Glut 4. 130 80

The application of molecular scanning techniques to the detection of potentially pathogenic mutations in candidate genes in patients with non-insulin-dependent diabetes has revealed a number of molecular variants of uncertain pathophysiologic significance. The determination of the significance of such variants requires large-scale population studies of the prevalence of the mutant in affected and control groups. Herein, we describe two adaptations of the technique of single nucleotide primer extension (SNuPE) which allow the simultaneous examination of large numbers of alleles at multiple loci. The usefulness of these adaptations is illustrated by their application to the simultaneous detection of three point mutations, two in the tyrosine kinase domain of the insulin receptor and one in the insulin-responsive glucose transporter (GLUT4) in a highly insulin-resistant NIDDM population. By pooling genomic or amplified DNA and performing the SNuPE reactions with three primers of different length we could readily examine 300 alleles on a single 20 lane gel. Using pooled SNuPE, we also examined a large British Caucasian control population for the prevalence of GLUT4 Ile383, a variant which has previously been reported only in NIDDM. GLUT4 Ile383 was detected in 2/42 of the highly insulin-resistant NIDDM subjects and 4/240 middle-aged blood donors. Family studies and examination of the expressed mutant transporter will be necessary to establish whether this mutation is of functional significance. Pooled and multiplex SNuPE are powerful techniques with wide applicability to population genetic studies of specific mutations.
Hum Mol Genet 1992 Sep
PMID:Rapid and simultaneous detection of multiple mutations by pooled and multiplex single nucleotide primer extension: application to the study of insulin-responsive glucose transporter and insulin receptor mutations in non-insulin-dependent diabetes. 130 12

The in vitro angiogenesis of endothelium obtained from peripheral tissues is stimulated by phorbol esters. The present studies examine the effects of phorbol esters or serum factors on GLUT1 glucose transporter, cytoplasmic actin, and beta-tubulin messenger RNA levels and gene transcription rates in bovine brain capillary endothelial cells grown in tissue culture. Messenger RNA levels were measured by Northern blot analysis and transcription rates were quantified by nuclear run-on assays. Although cytoplasmic actin mRNA levels in cultured brain endothelium were comparable to levels found in isolated capillaries isolated in vivo, there was a profound down-regulation of the GLUT1 glucose transporter mRNA in the cultured endothelium. The GLUT1 mRNA level was increased by exposure to 12-O-tetra-decanoyl-phorbol 13-acetate (TPA). Both serum and TPA enhanced cytoplasmic actin and beta-tubulin mRNA levels in cultured cells; the serum effect on cytoskeletal mRNA persisted through at least 24 h of exposure whereas the TPA stimulation was maximal by 2 h of exposure and lost following 8 h. Both serum and TPA increased cytoplasmic actin mRNA levels approximately 2- to 3-fold greater than the increase in beta-tubulin mRNA levels. GLUT1 and actin transcription rates were measured with the nuclear run-on assay, but no stimulation was observed following 3 h exposure to 200 nM TPA. In conclusion, these studies show that GLUT1 glucose transporter, cytoplasmic actin, and beta-tubulin mRNA levels in bovine brain capillary endothelial cells are regulated by both serum factors and phorbol ester, which activates the protein kinase C pathway, and that the mechanism of the phorbol ester effect is post-transcriptional.
Brain Res Mol Brain Res 1992 Oct
PMID:Enhanced GLUT1 glucose transporter and cytoskeleton gene expression in cultured bovine brain capillary endothelial cells after treatment with phorbol esters and serum. 133 79

The transport of 2-deoxyglucose (dGlc) by cultured rat Sertoli cells was stimulated by L-triiodothyronine (T3) in a time and dose-dependent manner. The lag-time was of about 6 h, the half-maximal dose (ED50) was 0.47 nM, which correlates with the Kd of the nuclear T3 receptor of rat Sertoli cells (Kd = 1-2 nM), and the stimulation was maintained up to 24 h. The effect was specific, as judged by the order of potency of T3 analogs. Cycloheximide prevented the stimulatory effect without affecting the basal uptake. T3 stimulated the uptake of the glucose analog 3-O-methylglucose (MeGlc) with the same order of potency as that of dGlc. The ontogenetic profile of the T3 effect coincides with that of T3 nuclear receptors in rat Sertoli cells. Northern blot analysis demonstrated that Sertoli cells express the erythrocyte/brain glucose transporter isoform (GLUT1) but not the adipose/muscle isoform (GLUT4). T3 treatment (10(-7) M for 24 h) induces an increase of GLUT1 mRNA level comparable to that of glucose analog uptake. These results suggest that thyroid hormone stimulates glucose transport by increasing the synthesis of new glucose transporter units and give further evidence for a direct effect of thyroid hormone in the modulation of Sertoli cell functions.
Mol Cell Endocrinol 1992 Sep
PMID:Thyroid hormone stimulates glucose transport and GLUT1 mRNA in rat Sertoli cells. 144 85

The glucose analogue, 2-deoxy-D-glucose, was used to characterise the glucose transport system in Crithidia luciliae choanomastigotes. Uptake was temperature dependent with a Q10 of 2, and saturable with a Km of 0.22 mM and Vmax of 5.5 nmol min-1 (mg protein)-1 at 23 degrees C. Preloaded cells showed rapid exchange of intracellular 2-deoxy-D-glucose when incubated with extracellular D-glucose or 2-deoxy-D-glucose but little exchange with L-glucose. The substrate specificity of the uptake was studied using a number of D-glucose analogues. 6-Deoxy-D-glucose, 3-fluoro-3-deoxy-D-glucose and 4-fluoro-4-deoxy-D-glucose all competed for the transporter and had significant inhibitory effects on 2-deoxy-D-glucose transport. In contrast, 1-thio-beta-D-glucose, trehalose, 3-O-methyl-D-glucose, arginine, thymidine, L-sorbose and L-glucose were not inhibitory. The results imply the existence of a glucose transporter. The transport was blocked by a number of inhibitors and ionophores, including fluoride, azide, cyanide, dinitrophenol, valinomycin and nigericin. Overall, the uptake, exchange and efflux of 2-deoxy-D-glucose is consistent with transport via facilitated diffusion.
Mol Biochem Parasitol 1992 Nov
PMID:Glucose transport in Crithidia luciliae. 147 88

The nucleotide sequence of the melB gene coding for the Na+ (Li+)/melibiose symporter of Salmonella typhimurium LT2 was determined, and its amino acid sequence was deduced. It consists of 1428 bp, corresponding to a protein of 476 amino acid residues (calculated molecular weight 52,800). The amino acid sequence is homologous to that of the melibiose permease of Escherichia coli K12, with 85% identical residues. All, except one, of the amino acid residues that have been reported to be important for cation or substrate recognition in the melibiose permease of E. coli are conserved in the melibiose permease of S. typhimurium. In addition, part of the sequence resembles the lactose permease of Streptococcus thermophilus, the animal glucose transporter (GLUT1), the plasmid-coded raffinose permease (RafB), and the NADH-ubiquinone oxidoreductase chain 4 (Nuo4) of Aspergillus amstelodami.
Mol Gen Genet 1992 Jul
PMID:Cloning and sequencing of the melB gene encoding the melibiose permease of Salmonella typhimurium LT2. 149 87

7-(2-Aminoethyl)aminocarbonyl-7-desacetylforskolin (7-AEC-Fsk) and 6-(2-aminoethyl)aminocarbonylforskolin (6-AEC-Fsk) were synthesized and tested for their ability to activate adenylyl cyclase and inhibit the high affinity binding of [3H]forskolin to bovine brain membranes. Forskolin and 7-AEC-Fsk were equipotent in activating adenylyl cyclase, with EC50 values of about 4 microM, whereas 6-AEC-Fsk had an EC50 of about 2 microM. 6-AEC-Fsk and 7-AEC-Fsk stimulated adenylyl cyclase about 7-fold over basal levels at 100 microM, whereas forskolin produced a 5-fold stimulation. Forskolin and 6-AEC-Fsk inhibited the binding of [3H]forskolin to bovine brain membranes with Kd values of 41 nM and 28 nM, respectively, whereas 7-AEC-Fsk had a Kd of 83 nM. The 3-(3-iodo-4-hydroxyphenyl)propionamide derivative of 6-AEC-Fsk (6-I-HPP-Fsk) was more potent than forskolin in inhibiting [3H]forskolin binding to bovine brain membranes, with a Kd of 14 nM. 6-AEC-Fsk was reacted with 125I-labeled Bolton-Hunter reagent to produce 6-125I-HPP-Fsk with a specific activity of 2175 Ci/mmol. 6-125I-HPP-Fsk bound to bovine brain membranes with a Kd of 13 nM and a Bmax of 3.8 pmol/mg of protein. Forskolin inhibited the binding of 6-125I-HPP-Fsk to bovine brain membranes with a Kd of 31 nM, whereas 1,9-dideoxyforskolin only slightly inhibited the binding at 10 microM. The binding of 6-125I-HPP-Fsk was not inhibited by agents that inhibit forskolin binding to the glucose transporter, such as D-glucose or cytochalasin B. There was no displaceable binding of 6-125I-HPP-Fsk to red blood cell membranes, which contain a large concentration of the glucose transporter. Pretreatment of bovine brain membranes with an alkylating derivative of forskolin, 7-bromoacetyl-7-desacetylforskolin (BrAcFsk), led to an irreversible decrease in the binding of [3H]forskolin and 6-125I-HPP-Fsk. The time dependence and concentration dependence for the BrAcFsk-induced decrease in [3H]forskolin binding sites were identical to those observed for the decrease in 6-125I-HPP-Fsk binding sites. 6-125I-HPP-Fsk binding was determined in human platelet membranes in the presence of Mg2+ alone and in combination with guanosine 5'-O-(3-thio)triphosphate (GTP gamma S) or AIF4-. The presence of GTP gamma S or AIF4- increased the binding of 6-125I-HPP-Fsk by 4.5-fold and 4-fold, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Pharmacol 1992 Feb
PMID:Interaction of aminoalkylcarbamates of forskolin with adenylyl cyclase: synthesis of an iodinated derivative of forskolin with high affinity for adenylyl cyclase. 153 12

Glucose transporter isoform expression was studied in the skeletal muscle-like cell line, C2C12. Northern and Western blot analysis showed that the insulin-responsive muscle/fat glucose transporter isoform, GLUT 4, was expressed in these cells at very low levels, whereas the erythrocyte isoform, GLUT 1, was expressed at readily detectable levels. Insulin did not stimulate glucose transport in this cultured muscle cell line. The C2C12 cells were then transfected separately with either GLUT 1 or GLUT 4, and stable cell lines expressing high levels of mRNA and protein were isolated. GLUT 1-transfected cells exhibited a 3-fold increase in the amount of the GLUT 1 transporter protein which was accompanied by a 2- to 3-fold increase in the glucose uptake rate. However, despite at least a 10-fold increase in GLUT 4 mRNA and protein detected after GLUT 4 cDNA transfection, the glucose uptake of these cells was unchanged and remained insulin-insensitive. By laser confocal immunofluorescence imaging, it was established that the transfected GLUT 4 protein was localized almost entirely in cytoplasmic compartments. In contrast, the GLUT 1 isoform was detected both at the plasma membrane as well as in intracellular compartments. These results suggest that acute insulin stimulation of glucose transport is not solely dependent on the presence of the insulin receptor and the GLUT 4 protein, and that the presence of some additional protein(s) must be required.
Mol Endocrinol 1992 Mar
PMID:Expression of the glucose transporter isoform GLUT 4 is insufficient to confer insulin-regulatable hexose uptake to cultured muscle cells. 158 10

In most strains of Kluyveromyces lactis, respiratory function is not required for growth on glucose. However, some natural variant strains are unable to grow when respiration is blocked by specific inhibitors (Rag- phenotype). This phenotype is due to an allelic variation of the chromosomal gene RAG1. The sensitive variants have a recessive allele rag1. The RAG1 gene has been cloned by complementation of a rag1 strain from a genomic bank derived from a Rag+ strain. The nucleotide sequence of the cloned gene indicated that the RAG1 product was a sugar transporter protein. The amino acid sequence deduced from the gene structure contained the 12 hydrophobic segments typical of a transmembrane protein, and showed a high degree of homology with the GAL2 (galactose permease) and HXT2 (a high-affinity glucose transporter) proteins of Saccharomyces cerevisiae. In a rag1 null mutant, as in the natural rag1 variant, uptake of glucose at high external glucose concentrations was impaired. The RAG1 protein appears to correspond to a low-affinity glucose transporter. Transcription of the RAG1 gene, which was undetectable when cells were grown in glycerol, was induced by glucose. It is concluded that respiration-dependent growth on glucose of the Rag- variant strains is due to a defect in this inducible glucose transport system.
Mol Gen Genet 1992 May
PMID:Glucose transport in the yeast Kluyveromyces lactis. I. Properties of an inducible low-affinity glucose transporter gene. 160 78

In rat adipocytes, the insulin stimulation of the rate of glucose uptake is due, at least partially, to the recruitment of glucose transporter proteins from an intracellular compartment to the plasma membrane. Vanadate is a known insulin mimetic agent and causes an increase in the rate of glucose transport in rat adipocytes similar to that seen with insulin. The objective of the present study was to determine whether vanadate exerts its effect through the recruitment of glucose transporters to the plasma membrane. We report that under conditions where vanadate stimulates the rate of 2-deoxyglucose uptake to the same extent as insulin, the concentration of GLUT-4 in the plasma membrane was increased similarly by both insulin and vanadate, and its concentration was decreased in the low density microsomal fraction. These results suggest that vanadate induces the recruitment of GLUT-4 to the plasma membrane. The effects of vanadate and insulin on the stimulation of 2-deoxyglucose uptake and recruitment of GLUT-4 were not additive. This is the first report of an effect of vanadate on the intracellular distribution of the glucose transporter.
Mol Cell Biochem 1992 Feb 12
PMID:Vanadate induces the recruitment of GLUT-4 glucose transporter to the plasma membrane of rat adipocytes. 162 80


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