Glucose uptake by all cells in the organism by glucose transport proteins is among the most. Practiceslocalization and gene expression of glucose transporters. Distribution of glucose transporters in renal diseases. The oxidation of glucose represents a major source of metabolic energy for mammaliancells. The reduction of glucose in the blood results from the action of insulin. Mcgraw,2 and ning wu1,6, 1van andel research institute, grand rapids, mi 49503, usa. Gregor madeja,1, linfeng sunb,1, nieng yanb,2, and h.
The role of skeletal muscle in glucose transport, glucose. The glut or slc2a family are a protein family that is found in most mammalian cells. Functional properties and genomics of glucose transporters. Glucose uptake in muscle occurs by a system of facilitated diffusion involving at least two distinct glucose transporters, glut1 and glut4.
With the increasing prevalence of diabetes worldwide, the world health organization predicts diabetesrelated deaths will double between 2005 to 2030. Glucose transporters in cancer from tumor cells to the. Molecular basis of the glucose transport mechanism in plants balaji selvam, yachi yu, liqing chen, and diwakar shukla. Glucose transporters gluts at the bloodbrain barrier maintain the continuous high glucose and energy demands of the brain. Molecular basis of the glucose transport mechanism in plants. Department of chemical and biomolecular engineering, university of illinois at urbanachampaign, urbana, illinois 61801, united states department of plant biology, university of illinois at urbanachampaign, urbana, illinois 61801, united states. There are two mechanisms for glucose transport across cell membranes. Sequence and structure of a human glucose transporter. What we know about facilitative glucose transporters.
Glucose transporters manage the traffic of glucose across the cells outer membrane. Phosphorylation of txnip by akt mediates acute influx of. Degree of sglt1 phosphorylation is associated with but. Glucose enters the beta cells of the pancreas through the glucose transporter glut2 and this. The gluts transport glucose across the plasma membrane by means of a facilitated diffusion. In the intestine and renal proximal tubule, glucose is transported against a concentration gradient by a secondary active transport mechanism in which glucose is cotransported with sodium ions. Pdf differential subcellular distribution of glucose. Review modulation of glucose transporter protein by. Regulation of amino acid and glucose transporters in. Substantial evidence indicates that increased glucose uptake in malignant cells is associated with dysregulated expression of glucose transporter proteins, especially glucose transporter 1 glut1. Adipocytes and myocytes contain glut4 glucose transporters, which contain twelve membrane. The facilitative glucose transporter family solute carriers slc2a, protein symbol. Renal gluconeogenesis prevents hypoglycemia by releasing glucose into the blood stream.
In this study, the regulation of glucose transporters by glucose was examined in cultured baecs and bsmcs, and in human arterial smooth muscle. Glucose transporters in the 21st century bernard thorens1 and mike mueckler2 1department of physiology and center for integrative genomics, university of lausanne, lausanne, switzerland. The amino acid sequence of the glucose transport protein from human hepg2 hepatoma cells was deduced from analysis of a complementary dna clone. Glucose transporter an overview sciencedirect topics. Glucose enters the beta cells of the pancreas through the glucose transporter glut2 and this is a major signal leading to. Inhibition of glucose transporters and glutaminase. Hostderived glucose and its transporter in the obligate. Regulation of glucose transport by hypoxia jinzhong zhang, phd,alireza behrooz, phd, and faramarz ismailbeigi, md, phd transport of glucose into most mammalian cells and tissues is ratecontrolling for its metabolism.
Both bind the fungal metabolite and inhibitor of glucos transport. Glucose transport into animal cells is adapted to their metabolic rate and often controls rates of glucose use. Similarly, brain tissues from glioblastoma patients also display reduction of glt1 and mislocalization of glast. Insulin stimulates glucose transport by promoting translocation of intracellular vesicles that contain the glut4 and glut1 glucose transporters to the plasma membrane. Stroet, 1,7 aylin binici, lena knauer,2 silke brand, axel choidas,3 carsten strohmann,2 slava ziegler,1 and herbert waldmann1,2 8. Glucose transport and glucose transporters in muscle and. The localization, expression and regulation of the glut family are tissue and often cellspecific.
The cellular localization of the glucose transporters was directly examined by immunofluorescence staining. The latter is regulated by a family of facilitated glucose transporters among which glucose transporter protein glut4 is best characterized for its role in insulin responsive glucose import. We would like to show you a description here but the site wont allow us. However, because the plasma membrane is impermeable to polar molecules such as glucose, the cellular uptake of this important nutrient is accomplished by membraneassociated carrier proteins that bind and transfer it across the lipid bilayer. Little is known, however, about glucose transporters and their regulation in thevascular system. Department of chemical and biomolecular engineering, university of illinois at urbanachampaign, urbana, illinois 61801, united states department of plant biology, university of illinois at urbanachampaign, urbana, illinois. Subcellular localization and trafficking of the glut4. Functional architecture of mfs dglucose transporters. Glucose transporter protein, insulin, type 2 diabetes mellitus, flavonoids, glucose uptake. Functional localization of glucose transporter 2 in rat liver article pdf available in journal of histochemistry and cytochemistry 4411. Molecular and cellular regulation of glucose transporter.
Regulation of glut4 glucose transporter trafficking. Since the discovery of the lysosome, much insight has been obtained into the role of this organelle in the catabolism of a wide variety of macromolecules. Glucose homeostasis is also due, in part, to reabsorption and excretion of hexose in the kidney. Insulin or igfi had no effect on the expression of the three glucose transporter isoforms, even in the absence of glucose.
They also act as therapeutic targets and provide routes of entry for drug delivery to the brain and central nervous system for treatment of neurological and neurovascular conditions and brain tumours. Without directly affecting glucose transport in other cell types, which of the following would be most likely to selectively increase glucose. Cell reports report phosphorylation of txnip by akt mediates acute in. Compromised glutamate transport in human glioma cells. The protein family of glucose transport facilitators. Knockout of naglucose transporter sglt2 attenuates.
Pdf a family of seven facilitative glucose transporters glut15, 7 and 8 mediates the cellular uptake of glucose. Cell chemical biology article inhibition of glucose transporters and glutaminase synergistically impairs tumor cell growth elena s. Introduction diabetes mellitus dm is a metabolic disease marked by a high level of blood glucose due to finsu ficient or inefficient insulin secretory response. First, the transporter has an opening facing the outside of the cell, and it picks up a molecule of glucose. Structural and mechanistic investigations of the glucose transporters dong deng and nieng yan state key laboratory of biomembrane and membrane biotechnology, center for structural biology, tsinghuapeking center for life sciences, school of life sciences and school of medicine, tsinghua university, beijing 84, china. However, a previous immunohistochemical analysis of glut1 expression in 154 malignant. The main sugar that the body makes from the food in the diet. Hyperglycemia has been implicated in the pathogenesis of both micro and macrovascular complications in diabetes. Atpase pump is utilised to transport glucose into cells against its concentration gradient.
Molecular biology of mammalian glucose transporters. However, subcellular fractionation, photolabelling and immunocytochemical studies have shown that the pool of glut4 present. Functional architecture of mfs d glucose transporters m. The upregulation of gluts has been reported in numerous cancer types as a result of perturbation of gene expression or protein relocalization or stabilization. Distribution of glucose transporters in renal diseases leszek szablewski abstract kidneys play an important role in glucose homeostasis.
Many mammalian tissues, such as the brain,have a constitutively high glucose requirement. A blank chart for each day of the week to record blood glucose levels and medicine use. Structural analysis of the purified human erythrocyte glucose transporter by fast atom bombardment mapping and gas phase edman degradation confirmed the identity of the clone and demonstrated that the hepg2 and erythrocyte transporters. Development of a novel class of glucose transporter inhibitors. Glucose is carried through the bloodstream to provide energy to all cells in the body. Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Glucose transport is acutely stimulated by hypoxic conditions, and the response is mediated by enhanced function of the. Hostderived glucose and its transporter in the obligate intracellular pathogen toxoplasma gondii are dispensable by glutaminolysis martin blumea, dayana rodriguezcontrerasb, scott landfearb, tobias fleigec, dominique soldatifavrec, richard luciusa, and nishith guptaa,1 adepartment of molecular parasitology, humboldt university, philippstrasse, 10115, berlin, germany.
Platt,4 hermann koepsell,5 robyn cunard,3,1 kumar sharma,1,3 scott c. However, in glioma cells, essentially all glast protein was found in cell nuclei rather than the plasma membrane. The ratelimiting step in the uptake and metabolism of d glucose by insulin target cells is thought to be glucose transport mediated by glucose transporters primarily the glut4 isoform localized to the plasma membrane. Localization of glucose transporter 10 to hair cells cuticular plate in the mouse inner ear bei chen, zhengzhou university yunfeng wang, fudan university manying geng, zhengzhou university xi erick lin, emory university wenxue tang, zhengzhou university journal title. The body produces it from protein, fat and, in largest part, carbohydrate. New glut isoforms are continually being discovered and. In all other cells, glucose transport is mediated by one or more of the members of the closely related glut family of glucose. Glucose transporters accomplish the movement of glucose from the extracellular space deriving from the bloodstream into cells. Reckzeh,1,2 george karageorgis,1,4 melanie schwalfenberg,1 javier ceballos,1,5 jessica nowacki,1,6 marcus c. It has been proposed that the enhanced metabolic activity of tumor cells is accompanied by an increased expression of facilitative hexose transporters gluts. The tuberous sclerosis complex regulates trafficking of. Knockout of na glucose transporter sglt2 attenuates hyperglycemia and glomerular hyper. Pdf facilitative glucose transporters in ruminants j. Genomic localization and organization of human glucose transporters.
Localization of glucose transporter 10 to hair cells. Glucose transporter isoforms differ in properties such as their maximal rates of glucose transport, their ability to bind glucose, and the regulation of their activity by various hormones. Solute carriers of the glucose transporter glut family mediate the first step for cellular glucose usage. Skeletal muscle is the primary tissue responsible for insulindependent glucose uptake in vivo. However, equivalent human data regarding glucose transporter abundance along the gastrointestinal tract are rare although there is a rising incidence of metabolic disorders based on disturbed glucose absorption in western societies. This form of glucose transport takes place across the lumenal membrane of cells lining the small intestine and the proximal tubules of the kidneys. Madaj,1 jennifer wen,2 kelsey veldkamp,3 matthew hollowell,3 bin zheng,4 lewis c. Pdf immunohistochemical localization and quantification of. Expression and cellular localization of glucose transporters glut1. Cells cannot use glucose without the help of insulin glucose is a simple sugar a monosaccharide. Then it shifts shape, and opens towards the inside, releasing glucose into the cell. The ratelimiting step in muscle glucose use is the transmembrane transport of glucose mediated by glucose transporter glut 4 ref. Because glucose is a vital source of energy for all life, these transporters are present in all phyla. Cellspecific localization of glucose transporter proteins in.
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