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Ian A. Simpson - One of the best experts on this subject based on the ideXlab platform.
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The facilitative glucose transporter GLUT3: 20 years of distinction
American Journal of Physiology-Endocrinology and Metabolism, 2008Co-Authors: Ian A. Simpson, Kelle H. Moley, Donard S. Dwyer, Daniela Malide, Alexander J. Travis, Susan J VannucciAbstract:Glucose metabolism is vital to most mammalian cells, and the passage of glucose across cell membranes is facilitated by a family of integral membrane transporter proteins, the GLUTs. There are currently 14 members of the SLC2 family of GLUTs, several of which have been the focus of this series of reviews. The subject of the present review is GLUT3, which, as implied by its name, was the third glucose transporter to be cloned (Kayano T, Fukumoto H, Eddy RL, Fan YS, Byers MG, Shows TB, Bell GI. J Biol Chem 263: 15245–15248, 1988) and was originally designated as the neuronal GLUT. The overriding question that drove the early work on GLUT3 was why would neurons need a separate glucose transporter isoform? What is it about GLUT3 that specifically suits the needs of the highly metabolic and oxidative neuron with its high glucose demand? More recently, GLUT3 has been studied in other cell types with quite specific requirements for glucose, including sperm, preimplantation embryos, circulating white blood cells, and an array of carcinoma cell lines. The last are sufficiently varied and numerous to warrant a review of their own and will not be discussed here. However, for each of these cases, the same questions apply. Thus, the objective of this review is to discuss the properties and tissue and cellular localization of GLUT3 as well as the features of expression, function, and regulation that distinguish it from the rest of its family and make it uniquely suited as the mediator of glucose delivery to these specific cells.
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supply and demand in cerebral energy metabolism the role of nutrient transporters
Journal of Cerebral Blood Flow and Metabolism, 2007Co-Authors: Ian A. Simpson, Anthony Carruthers, Susan J VannucciAbstract:Glucose is the obligate energetic fuel for the mammalian brain, and most studies of cerebral energy metabolism assume that the majority of cerebral glucose utilization fuels neuronal activity via oxidative metabolism, both in the basal and activated state. Glucose transporter (GLUT) proteins deliver glucose from the circulation to the brain: GLUT1 in the microvascular endothelial cells of the blood—brain barrier (BBB) and glia; GLUT3 in neurons. Lactate, the glycolytic product of glucose metabolism, is transported into and out of neural cells by the monocarboxylate transporters (MCT): MCT1 in the BBB and astrocytes and MCT2 in neurons. The proposal of the astrocyte—neuron lactate shuttle hypothesis suggested that astrocytes play the primary role in cerebral glucose utilization and generate lactate for neuronal energetics, especially during activation. Since the identification of the GLUTs and MCTs in brain, much has been learned about their transport properties, that is capacity and affinity for substrate...
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glucose transporter proteins in brain delivery of glucose to neurons and glia
Glia, 1997Co-Authors: Susan J Vannucci, Fran Maher, Ian A. SimpsonAbstract:Glucose is the principle energy source for the mammalian brain. Delivery of glucose from the blood to the brain requires transport across the endothelial cells of the blood-brain barrier and into the neurons and glia. The facilitative glucose transporter proteins mediate these processes. The primary isoforms in brain are GLUT1, detected at high concentrations as a highly glycosylated form, (55 kDa) in blood-brain barrier, and also as a less glycosylated, 45 kDa form, present in parenchyma, predominantly glia; GLUT3 in neurons; and GLUT5 in microglia. The rest of the transporter family, GLUTs 2, 4, and 7, have also been detected in brain but at lower levels of expression and confined to more discrete regions. All of the transporters probably contribute to cerebral glucose utilization, as part of overall metabolism and metabolic interactions among cells. We discuss the properties, regulation, cell-specific location, and kinetic characteristics of the isoforms, their potential contributions to cerebral metabolism, and several experimental paradigms in which alterations in energetic demand and/or substrate supply affect glucose transporter expression.
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glucose transporter isoforms glut1 and GLUT3 transport dehydroascorbic acid
Journal of Biological Chemistry, 1997Co-Authors: Steven C Rumsey, Guo Wei Xu, Oran Kwon, Charles F Burant, Ian A. Simpson, Mark LevineAbstract:Abstract Dehydroascorbic acid (DHA) is rapidly taken up by cells and reduced to ascorbic acid (AA). Using the Xenopus laevis oocyte expression system we examined transport of DHA and AA via glucose transporter isoforms GLUT1–5 and SGLT1. The apparentK m of DHA transport via GLUT1 and GLUT3 was 1.1 ± 0.2 and 1.7 ± 0.3 mm, respectively. High performance liquid chromatography analysis confirmed 100% reduction of DHA to AA within oocytes. GLUT4 transport of DHA was only 2–4-fold above control and transport kinetics could not be calculated. GLUT2, GLUT5, and SGLT1 did not transport DHA and none of the isoforms transported AA. Radiolabeled sugar transport confirmed transporter function and identity of all cDNA clones was confirmed by restriction fragment mapping. GLUT1 and GLUT3 cDNA were further verified by polymerase chain reaction. DHA transport activity in both GLUT1 and GLUT3 was inhibited by 2-deoxyglucose, d-glucose, and 3-O-methylglucose among other hexoses while fructose and l-glucose showed no inhibition. Inhibition by the endofacial inhibitor, cytochalasin B, was non-competitive and inhibition by the exofacial inhibitor, 4,6-O-ethylidene-α-glucose, was competitive. Expressed mutant constructs of GLUT1 and GLUT3 did not transport DHA. DHA and 2-deoxyglucose uptake by Chinese hamster ovary cells overexpressing either GLUT1 or GLUT3 was increased 2–8-fold over control cells. These studies suggest GLUT1 and GLUT3 isoforms are the specific glucose transporter isoforms which mediate DHA transport and subsequent accumulation of AA.
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The GLUT3 glucose transporter is the predominant isoform in primary cultured neurons: assessment by biosynthetic and photoaffinity labelling
Biochemical Journal, 1994Co-Authors: Fran Maher, Ian A. SimpsonAbstract:Cerebellar granule neurons in primary culture express increasing levels of two glucose transporter isoforms, GLUT1 and GLUT3, as they differentiate in vitro. We have determined the relative abundance of GLUT1 and GLUT3 in these neurons by three different labelling methods. (1) Photoaffinity cell surface labelling of neurons with an impermeant bis-mannose photolabel revealed 6-10-fold more GLUT3 than GLUT1 and dissociation constants (Kd) for the photolabel of 55-68 microM (GLUT3) and 146-169 microM (GLUT1). Binding to both transporters was inhibited by cytochalasin B. (2) Photoaffinity labelling of neuronal membranes with a permeant forskolin derivative showed 5.5-8-fold more GLUT3 than GLUT1, whereas in rat brain membranes containing both neuronal and glial membranes, GLUT3 and GLUT1 were detected in similar proportions. (3) Biosynthetic labelling of neurons with [35S]methionine and [35S]cysteine showed GLUT3 to be 6-10-fold more abundant than GLUT1. Thus GLUT3 is quantitatively the predominant glucose-transport isoform in cultured cerebellar granule neurons.
Anthony Carruthers - One of the best experts on this subject based on the ideXlab platform.
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red wine and green tea flavonoids are cis allosteric activators and competitive inhibitors of glucose transporter 1 glut1 mediated sugar uptake
Journal of Biological Chemistry, 2018Co-Authors: Ogooluwa A Ojelabi, Julie K De Zutter, Kenneth P Lloyd, Anthony CarruthersAbstract:: The antioxidant- and flavonoid-rich contents of red wine and green tea are reported to offer protection against cancer, cardiovascular disease, and diabetes. Some studies, however, show that flavonoids inhibit GLUT1-mediated, facilitative glucose transport, raising the possibility that their interaction with GLUT1 and subsequent downstream effects on carbohydrate metabolism may also impact health. The present study explores the structure-function relationships of flavonoid-GLUT1 interactions. We find that low concentrations of flavonoids act as cis-allosteric activators of sugar uptake, whereas higher concentrations competitively inhibit sugar uptake and noncompetitively inhibit sugar exit. Studies with heterologously expressed human GLUT1, -3, or -4 reveal that quercetin-GLUT1 and -GLUT4 interactions are stronger than quercetin-GLUT3 interactions, that epicatechin gallate (ECG) is more selective for GLUT1, and that epigallocatechin gallate (EGCG) is less GLUT isoform-selective. Docking studies suggest that only one flavonoid can bind to GLUT1 at any instant, but sugar transport and ligand-binding studies indicate that human erythrocyte GLUT1 can bind at least two flavonoid molecules simultaneously. Quercetin and EGCG are each characterized by positive, cooperative binding, whereas ECG shows negative cooperative binding. These findings support recent studies suggesting that GLUT1 forms an oligomeric complex of interacting, allosteric, alternating access transporters. We discuss how modulation of facilitative glucose transporters could contribute to the protective actions of the flavonoids against diabetes and Alzheimer's disease.
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wzb117 2 fluoro 6 m hydroxybenzoyloxy phenyl m hydroxybenzoate inhibits glut1 mediated sugar transport by binding reversibly at the exofacial sugar binding site
Journal of Biological Chemistry, 2016Co-Authors: Ogooluwa A Ojelabi, Julie K De Zutter, Kenneth P Lloyd, Andrew H Simon, Anthony CarruthersAbstract:Abstract WZB117 (2-fluoro-6-(m-hydroxybenzoyloxy) phenyl m-hydroxybenzoate) inhibits passive sugar transport in human erythrocytes and cancer cell lines and, by limiting glycolysis, inhibits tumor growth in mice. This study explores how WZB117 inhibits the erythrocyte sugar transporter glucose transport protein 1 (GLUT1) and examines the transporter isoform specificity of inhibition. WZB117 reversibly and competitively inhibits erythrocyte 3-O-methylglucose (3MG) uptake with Ki(app) = 6 μm but is a noncompetitive inhibitor of sugar exit. Cytochalasin B (CB) is a reversible, noncompetitive inhibitor of 3MG uptake with Ki(app) = 0.3 μm but is a competitive inhibitor of sugar exit indicating that WZB117 and CB bind at exofacial and endofacial sugar binding sites, respectively. WZB117 inhibition of GLUTs expressed in HEK293 cells follows the order of potency: insulin-regulated GLUT4 ≫ GLUT1 ≈ neuronal GLUT3. This may explain WZB117-induced murine lipodystrophy. Molecular docking suggests the following. 1) The WZB117 binding envelopes of exofacial GLUT1 and GLUT4 conformers differ significantly. 2) GLUT1 and GLUT4 exofacial conformers present multiple, adjacent glucose binding sites that overlap with WZB117 binding envelopes. 3) The GLUT1 exofacial conformer lacks a CB binding site. 4) The inward GLUT1 conformer presents overlapping endofacial WZB117, d-glucose, and CB binding envelopes. Interrogating the GLUT1 mechanism using WZB117 reveals that subsaturating WZB117 and CB stimulate erythrocyte 3MG uptake. Extracellular WZB117 does not affect CB binding to GLUT1, but intracellular WZB117 inhibits CB binding. These findings are incompatible with the alternating conformer carrier for glucose transport but are consistent with either a multisubunit, allosteric transporter, or a transporter in which each subunit presents multiple, interacting ligand binding sites.
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sequence determinants of glut1 oligomerization analysis by homology scanning mutagenesis
Journal of Biological Chemistry, 2013Co-Authors: Julie K De Zutter, Kara B Levine, Di Deng, Anthony CarruthersAbstract:Abstract The human blood-brain barrier glucose transport protein (GLUT1) forms homodimers and homotetramers in detergent micelles and in cell membranes, where the GLUT1 oligomeric state determines GLUT1 transport behavior. GLUT1 and the neuronal glucose transporter GLUT3 do not form heterocomplexes in human embryonic kidney 293 (HEK293) cells as judged by co-immunoprecipitation assays. Using homology-scanning mutagenesis in which GLUT1 domains are substituted with equivalent GLUT3 domains and vice versa, we show that GLUT1 transmembrane helix 9 (TM9) is necessary for optimal association of GLUT1-GLUT3 chimeras with parental GLUT1 in HEK cells. GLUT1 TMs 2, 5, 8, and 11 also contribute to a less abundant heterocomplex. Cell surface GLUT1 and GLUT3 containing GLUT1 TM9 are 4-fold more catalytically active than GLUT3 and GLUT1 containing GLUT3 TM9. GLUT1 and GLUT3 display allosteric transport behavior. Size exclusion chromatography of detergent solubilized, purified GLUT1 resolves GLUT1/lipid/detergent micelles as 6- and 10-nm Stokes radius particles, which correspond to GLUT1 dimers and tetramers, respectively. Studies with GLUTs expressed in and solubilized from HEK cells show that HEK cell GLUT1 resolves as 6- and 10-nm Stokes radius particles, whereas GLUT3 resolves as a 6-nm particle. Substitution of GLUT3 TM9 with GLUT1 TM9 causes chimeric GLUT3 to resolve as 6- and 10-nm Stokes radius particles. Substitution of GLUT1 TM9 with GLUT3 TM9 causes chimeric GLUT1 to resolve as a mixture of 6- and 4-nm particles. We discuss these findings in the context of determinants of GLUT oligomeric structure and transport function.
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role of monosaccharide transport proteins in carbohydrate assimilation distribution metabolism and homeostasis
Comprehensive Physiology, 2012Co-Authors: Anthony J Cura, Anthony CarruthersAbstract:The facilitated diffusion of glucose, galactose, fructose, urate, myoinositol, and dehydroascorbic acid in mammals is catalyzed by a family of 14 monosaccharide transport proteins called GLUTs. These transporters may be divided into three classes according to sequence similarity and function/substrate specificity. GLUT1 appears to be highly expressed in glycolytically active cells and has been coopted in vitamin C auxotrophs to maintain the redox state of the blood through transport of dehydroascorbate. Several GLUTs are definitive glucose/galactose transporters, GLUT2 and GLUT5 are physiologically important fructose transporters, GLUT9 appears to be a urate transporter while GLUT13 is a proton/myoinositol cotransporter. The physiologic substrates of some GLUTs remain to be established. The GLUTs are expressed in a tissue specific manner where affinity, specificity, and capacity for substrate transport are paramount for tissue function. Although great strides have been made in characterizing GLUT-catalyzed monosaccharide transport and mapping GLUT membrane topography and determinants of substrate specificity, a unifying model for GLUT structure and function remains elusive. The GLUTs play a major role in carbohydrate homeostasis and the redistribution of sugar-derived carbons among the various organ systems. This is accomplished through a multiplicity of GLUT-dependent glucose sensing and effector mechanisms that regulate monosaccharide ingestion, absorption, distribution, cellular transport and metabolism, and recovery/retention. Glucose transport and metabolism have coevolved in mammals to support cerebral glucose utilization. © 2012 American Physiological Society. Compr Physiol 2:863-914, 2012.
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supply and demand in cerebral energy metabolism the role of nutrient transporters
Journal of Cerebral Blood Flow and Metabolism, 2007Co-Authors: Ian A. Simpson, Anthony Carruthers, Susan J VannucciAbstract:Glucose is the obligate energetic fuel for the mammalian brain, and most studies of cerebral energy metabolism assume that the majority of cerebral glucose utilization fuels neuronal activity via oxidative metabolism, both in the basal and activated state. Glucose transporter (GLUT) proteins deliver glucose from the circulation to the brain: GLUT1 in the microvascular endothelial cells of the blood—brain barrier (BBB) and glia; GLUT3 in neurons. Lactate, the glycolytic product of glucose metabolism, is transported into and out of neural cells by the monocarboxylate transporters (MCT): MCT1 in the BBB and astrocytes and MCT2 in neurons. The proposal of the astrocyte—neuron lactate shuttle hypothesis suggested that astrocytes play the primary role in cerebral glucose utilization and generate lactate for neuronal energetics, especially during activation. Since the identification of the GLUTs and MCTs in brain, much has been learned about their transport properties, that is capacity and affinity for substrate...
Mark Levine - One of the best experts on this subject based on the ideXlab platform.
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intestinal dehydroascorbic acid dha transport mediated by the facilitative sugar transporters glut2 and glut8
Journal of Biological Chemistry, 2013Co-Authors: Christopher Corpe, Jin Wang, Hadi Alhasani, Mark LevineAbstract:Intestinal vitamin C (Asc) absorption was believed to be mediated by the Na+-dependent ascorbic acid transporter SVCT1. However, Asc transport across the intestines of SVCT1 knock-out mice is normal indicating that alternative ascorbic acid transport mechanisms exist. To investigate these mechanisms, rodents were gavaged with Asc or its oxidized form dehydroascorbic acid (DHA), and plasma Asc concentrations were measured. Asc concentrations doubled following DHA but not Asc gavage. We hypothesized that the transporters responsible were facilitated glucose transporters (GLUTs). Using Xenopus oocyte expression, we investigated whether facilitative glucose transporters GLUT2 and GLUT5–12 transported DHA. Only GLUT2 and GLUT8, known to be expressed in intestines, transported DHA with apparent transport affinities (Km) of 2.33 and 3.23 mm and maximal transport rates (Vmax) of 25.9 and 10.1 pmol/min/oocyte, respectively. Maximal rates for DHA transport mediated by GLUT2 and GLUT8 in oocytes were lower than maximal rates for 2-deoxy-d-glucose (Vmax of 224 and 32 pmol/min/oocyte for GLUT2 and GLUT8, respectively) and fructose (Vmax of 406 and 116 pmol/min/oocyte for GLUT2 and GLUT8, respectively). These findings may be explained by differences in the exofacial binding of substrates, as shown by inhibition studies with ethylidine glucose. DHA transport activity in GLUT2- and GLUT8-expressing oocytes was inhibited by glucose, fructose, and by the flavonoids phloretin and quercetin. These studies indicate intestinal DHA transport may be mediated by the facilitative sugar transporters GLUT2 and GLUT8. Furthermore, dietary sugars and flavonoids in fruits and vegetables may modulate Asc bioavailability via inhibition of small intestinal GLUT2 and GLUT8.
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glucose transporter isoforms glut1 and GLUT3 transport dehydroascorbic acid
Journal of Biological Chemistry, 1997Co-Authors: Steven C Rumsey, Guo Wei Xu, Oran Kwon, Charles F Burant, Ian A. Simpson, Mark LevineAbstract:Abstract Dehydroascorbic acid (DHA) is rapidly taken up by cells and reduced to ascorbic acid (AA). Using the Xenopus laevis oocyte expression system we examined transport of DHA and AA via glucose transporter isoforms GLUT1–5 and SGLT1. The apparentK m of DHA transport via GLUT1 and GLUT3 was 1.1 ± 0.2 and 1.7 ± 0.3 mm, respectively. High performance liquid chromatography analysis confirmed 100% reduction of DHA to AA within oocytes. GLUT4 transport of DHA was only 2–4-fold above control and transport kinetics could not be calculated. GLUT2, GLUT5, and SGLT1 did not transport DHA and none of the isoforms transported AA. Radiolabeled sugar transport confirmed transporter function and identity of all cDNA clones was confirmed by restriction fragment mapping. GLUT1 and GLUT3 cDNA were further verified by polymerase chain reaction. DHA transport activity in both GLUT1 and GLUT3 was inhibited by 2-deoxyglucose, d-glucose, and 3-O-methylglucose among other hexoses while fructose and l-glucose showed no inhibition. Inhibition by the endofacial inhibitor, cytochalasin B, was non-competitive and inhibition by the exofacial inhibitor, 4,6-O-ethylidene-α-glucose, was competitive. Expressed mutant constructs of GLUT1 and GLUT3 did not transport DHA. DHA and 2-deoxyglucose uptake by Chinese hamster ovary cells overexpressing either GLUT1 or GLUT3 was increased 2–8-fold over control cells. These studies suggest GLUT1 and GLUT3 isoforms are the specific glucose transporter isoforms which mediate DHA transport and subsequent accumulation of AA.
Charles F Burant - One of the best experts on this subject based on the ideXlab platform.
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glucose transporter isoforms glut1 and GLUT3 transport dehydroascorbic acid
Journal of Biological Chemistry, 1997Co-Authors: Steven C Rumsey, Guo Wei Xu, Oran Kwon, Charles F Burant, Ian A. Simpson, Mark LevineAbstract:Abstract Dehydroascorbic acid (DHA) is rapidly taken up by cells and reduced to ascorbic acid (AA). Using the Xenopus laevis oocyte expression system we examined transport of DHA and AA via glucose transporter isoforms GLUT1–5 and SGLT1. The apparentK m of DHA transport via GLUT1 and GLUT3 was 1.1 ± 0.2 and 1.7 ± 0.3 mm, respectively. High performance liquid chromatography analysis confirmed 100% reduction of DHA to AA within oocytes. GLUT4 transport of DHA was only 2–4-fold above control and transport kinetics could not be calculated. GLUT2, GLUT5, and SGLT1 did not transport DHA and none of the isoforms transported AA. Radiolabeled sugar transport confirmed transporter function and identity of all cDNA clones was confirmed by restriction fragment mapping. GLUT1 and GLUT3 cDNA were further verified by polymerase chain reaction. DHA transport activity in both GLUT1 and GLUT3 was inhibited by 2-deoxyglucose, d-glucose, and 3-O-methylglucose among other hexoses while fructose and l-glucose showed no inhibition. Inhibition by the endofacial inhibitor, cytochalasin B, was non-competitive and inhibition by the exofacial inhibitor, 4,6-O-ethylidene-α-glucose, was competitive. Expressed mutant constructs of GLUT1 and GLUT3 did not transport DHA. DHA and 2-deoxyglucose uptake by Chinese hamster ovary cells overexpressing either GLUT1 or GLUT3 was increased 2–8-fold over control cells. These studies suggest GLUT1 and GLUT3 isoforms are the specific glucose transporter isoforms which mediate DHA transport and subsequent accumulation of AA.
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GLUT3 glucose transporter isoform in rat testis: localization, effect of diabetes mellitus, and comparison to human testis
American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 1994Co-Authors: Charles F Burant, Nicholas O. DavidsonAbstract:Facilitative hexose transporter expression was compared in rat and human testes. In rat testis, only GLUT1 and GLUT3 proteins were expressed. By contrast, human testis expressed GLUT1 and GLUT3 in addition to GLUT5. Immunocytochemical studies showed that GLUT3 was expressed in all cells of the seminiferous epithelium of rat testis, including sperm. In human testis, GLUT3 was expressed exclusively in cells juxtaposed to the lumen of the seminiferous tubule and ejaculate sperm, a pattern of expression that was identical to that of GLUT5. Induction of insulinopenic diabetes mellitus in the rat did not alter the levels or the distribution of GLUT3 protein or mRNA in the testis. Moreover insulin treatment of the diabetic rats did not produce changes in GLUT3 mRNA or protein levels. The results show that rat and human testis express the high-affinity glucose transporter GLUT3, which allows for the efficient uptake of glucose. In addition, the testis may be protected from changes in glucose transporter expression in experimental diabetes.
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human facilitative glucose transporters isolation functional characterization and gene localization of cdnas encoding an isoform glut5 expressed in small intestine kidney muscle and adipose tissue and an unusual glucose transporter pseudogene like se
Journal of Biological Chemistry, 1990Co-Authors: Toshiaki Kayano, Hirofumi Fukumoto, Susumu Seino, Roger L Eddy, Charles F Burant, Thomas B Shows, M. G. Byers, Gwyn W. Gould, Graeme I BellAbstract:Abstract Two novel facilitative glucose transporter-like cDNAs have been isolated from human small intestine and fetal skeletal muscle cDNA libraries by low stringency cross-hybridization with a fragment of the human erythrocyte/GLUT1 facilitative glucose transporter cDNA. One encodes a 501-amino acid facilitative glucose transporter, designated as the small intestine/GLUT5 isoform, having 41.7, 40.0, 38.7, and 41.6% identity with the previously described human erythrocyte/GLUT1, liver/GLUT2, brain/GLUT3, and muscle-fat/GLUT4 isoforms, respectively. GLUT5 mRNA is expressed at highest levels in small intestine and at much lower levels in kidney, skeletal muscle, and adipose tissue. Expression of in vitro synthesized human GLUT5 mRNA in Xenopus laevis oocytes indicates that the GLUT5 protein is a cytochalasin B-sensitive glucose carrier. The gene encoding the GLUT5 protein is located on the short arm of human chromosome 1. The second facilitative transporter-like cDNA sequence, designated GLUT6, is part of an 11-kilobase transcript that is expressed in all tissues examined. The sequence of a partial-length GLUT6 cDNA having an insert of 3.4 kilobase pairs revealed a region of 1.5 kilobase pairs that has 79.6% identity with the human brain/GLUT3 facilitative glucose transporter cDNA. However, because of the presence of multiple stop codons and frame shifts, this sequence cannot encode a functional glucose transporter protein. The region of facilitative glucose transporter nucleotide sequence homology in the GLUT6 transcript may have arisen by insertion of a reverse-transcribed GLUT3 transcript into the untranslated region of another gene. The GLUT6 gene is located on the long arm of human chromosome 5.
Nidaa Mikail - One of the best experts on this subject based on the ideXlab platform.
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differences in alimentary glucose absorption and intestinal disposal of blood glucose after roux en y gastric bypass vs sleeve gastrectomy
Gastroenterology, 2016Co-Authors: Jeanbaptiste Cavin, Robert Ducroc, Konstantinos Arapis, Eglantine Voitellier, Laura Gillard, Muriel Hourseau, Francoise Cluzeaud, Anne Couvelard, Rachida Lebtahi, Nidaa MikailAbstract:Background & Aims Bariatric procedures, such as Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG), are the most effective approaches to resolve type 2 diabetes in obese individuals. Alimentary glucose absorption and intestinal disposal of blood glucose have not been directly compared between individuals or animals that underwent RYGB vs VSG. We evaluated in rats and humans how the gut epithelium adapts after surgery and the consequences on alimentary glucose absorption and intestinal disposal of blood glucose. Methods Obese male rats underwent RYGB, VSG, or sham (control) operations. We collected intestine segments from all rats; we performed histologic analyses and measured levels of messenger RNAs encoding the sugar transporters SGLT1, GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5. Glucose transport and consumption were assayed using ex vivo jejunal loops. Histologic analyses were also performed on Roux limb sections from patients who underwent RYGB 1−5 years after surgery. Roux limb glucose consumption was assayed after surgery by positron emission and computed tomography imaging. Results In rats and humans that underwent RYGB, the Roux limb became hyperplasic, with an increased number of incretin-producing cells compared with the corresponding jejunal segment of controls. Furthermore, expression of sugar transporters and hypoxia-related genes increased and the nonintestinal glucose transporter GLUT1 appeared at the basolateral membrane of enterocytes. Ingested and circulating glucose was trapped within the intestinal epithelial cells of rats and humans that underwent RYGB. By contrast, there was no hyperplasia of the intestine after VSG, but the intestinal absorption of alimentary glucose was reduced and density of endocrine cells secreting glucagon-like peptide-1 increased. Conclusions The intestine adapts differently to RYGB vs VSG. RYGB increases intestinal glucose disposal and VSG delays glucose absorption; both contribute to observed improvements in glycemia.
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Differences in Alimentary Glucose 1 Absorption and Intestinal Disposal of Blood Glucose Following Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy
Gastroenterology, 2015Co-Authors: Jeanbaptiste Cavin, Robert Ducroc, Konstantinos Arapis, Eglantine Voitellier, Laura Gillard, Muriel Hourseau, Francoise Cluzeaud, Anne Couvelard, Rachida Lebtahi, Nidaa MikailAbstract:Background & Aims: Bariatric surgeries, such as Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG), are the most effective approaches to resolve type 2 diabetes in obese individuals. Alimentary glucose absorption and intestinal disposal of blood glucose have not been directly compared between individuals or animals that underwent RYGB vs VSG. We evaluated in rats and humans how the gut epithelium adapts following surgery and the consequences on alimentary glucose absorption and intestinal disposal of blood glucose. Methods: Obese male rats underwent RYGB, VSG, or sham (control) surgeries. We collected intestine segments from all rats; we performed histologic analyses and measured levels of mRNAs encoding the sugar transporters SGLT1, GLUT1, GLUT2, GLUT3, GLUT4 and GLUT5. Glucose transport and consumption were assayed using ex vivo jejunal loops. Histologic analyses were also performed on Roux limb sections from patients who underwent RYGB, 1–5 years after surgery. Roux limb glucose consumption was assayed following surgery by positron emission and computed tomography imaging. Results: In rats and humans that underwent RYGB, the Roux limb became hyperplasic, with an increased number of incretin-producing cells, compared with the corresponding jejunal segment of controls. Furthermore, expression of sugar transporters and hypoxia-related genes increased and the non-intestinal glucose transporter GLUT1 appeared at the basolateral membrane of enterocytes. Ingested and circulating glucose was trapped within the intestinal epithelial cells of rats and humans that underwent RYGB. By contrast, there was no hyperplasia of the intestine after VSG, but the intestinal absorption of alimentary glucose was reduced and density of endocrine cells secreting glucagon-like peptide-1 (GLP1) increased. Conclusions: The intestine adapts differently to RYGB vs VSG. RYGB increases intestinal glucose disposal, whereas VSG delays glucose absorption; both contribute to observed improvements in glycemia.