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Physiological Reviews Jul 2013Glucose is an important fuel for contracting muscle, and normal glucose metabolism is vital for health. Glucose enters the muscle cell via facilitated diffusion through... (Review)
Review
Glucose is an important fuel for contracting muscle, and normal glucose metabolism is vital for health. Glucose enters the muscle cell via facilitated diffusion through the GLUT4 glucose transporter which translocates from intracellular storage depots to the plasma membrane and T-tubules upon muscle contraction. Here we discuss the current understanding of how exercise-induced muscle glucose uptake is regulated. We briefly discuss the role of glucose supply and metabolism and concentrate on GLUT4 translocation and the molecular signaling that sets this in motion during muscle contractions. Contraction-induced molecular signaling is complex and involves a variety of signaling molecules including AMPK, Ca(2+), and NOS in the proximal part of the signaling cascade as well as GTPases, Rab, and SNARE proteins and cytoskeletal components in the distal part. While acute regulation of muscle glucose uptake relies on GLUT4 translocation, glucose uptake also depends on muscle GLUT4 expression which is increased following exercise. AMPK and CaMKII are key signaling kinases that appear to regulate GLUT4 expression via the HDAC4/5-MEF2 axis and MEF2-GEF interactions resulting in nuclear export of HDAC4/5 in turn leading to histone hyperacetylation on the GLUT4 promoter and increased GLUT4 transcription. Exercise training is the most potent stimulus to increase skeletal muscle GLUT4 expression, an effect that may partly contribute to improved insulin action and glucose disposal and enhanced muscle glycogen storage following exercise training in health and disease.
Topics: Biological Transport; Exercise; Glucose; Glucose Transporter Type 4; Humans; Muscle, Skeletal; Sarcolemma
PubMed: 23899560
DOI: 10.1152/physrev.00038.2012 -
American Journal of Physiology.... Feb 2010The ability to take up and metabolize glucose at the cellular level is a property shared by the vast majority of existing organisms. Most mammalian cells import glucose... (Review)
Review
The ability to take up and metabolize glucose at the cellular level is a property shared by the vast majority of existing organisms. Most mammalian cells import glucose by a process of facilitative diffusion mediated by members of the Glut (SLC2A) family of membrane transport proteins. Fourteen Glut proteins are expressed in the human and they include transporters for substrates other than glucose, including fructose, myoinositol, and urate. The primary physiological substrates for at least half of the 14 Glut proteins are either uncertain or unknown. The well-established glucose transporter isoforms, Gluts 1-4, are known to have distinct regulatory and/or kinetic properties that reflect their specific roles in cellular and whole body glucose homeostasis. Separate review articles on many of the Glut proteins have recently appeared in this journal. Here, we provide a very brief summary of the known properties of the 14 Glut proteins and suggest some avenues of future investigation in this area.
Topics: Glucose; Glucose Transport Proteins, Facilitative; Humans; Membrane Transport Proteins
PubMed: 20009031
DOI: 10.1152/ajpendo.00712.2009 -
Trends in Molecular Medicine Nov 2020Keratinocytes and skin immune cells are actively metabolizing nutrients present in their microenvironment. This is particularly important in common chronic inflammatory... (Review)
Review
Keratinocytes and skin immune cells are actively metabolizing nutrients present in their microenvironment. This is particularly important in common chronic inflammatory skin diseases such as psoriasis and atopic dermatitis, characterized by hyperproliferation of keratinocytes and expansion of inflammatory cells, thus suggesting increased cell nutritional requirements. Proliferating inflammatory cells and keratinocytes express high levels of glucose transporter (GLUT)1, l-type amino acid transporter (LAT)1, and cationic amino acid transporters (CATs). Main metabolic regulators such as hypoxia-inducible factor (HIF)-1α, MYC, and mechanistic target of rapamycin (mTOR) control immune cell activation, proliferation, and cytokine release. Here, we provide an updated perspective regarding the potential role of nutrient transporters and metabolic pathways that could be common to immune cells and keratinocytes, to control psoriasis and atopic dermatitis.
Topics: Amino Acids; Animals; Biological Transport; Dermatitis; Disease Susceptibility; Glucose; Homeostasis; Humans; Keratinocytes; Membrane Transport Proteins; Metabolic Networks and Pathways; Signal Transduction; Skin; Skin Physiological Phenomena; TOR Serine-Threonine Kinases
PubMed: 32371170
DOI: 10.1016/j.molmed.2020.04.004 -
Pflugers Archiv : European Journal of... Sep 2020The SLC2 genes code for a family of GLUT proteins that are part of the major facilitator superfamily (MFS) of membrane transporters. Crystal structures have recently... (Review)
Review
The SLC2 genes code for a family of GLUT proteins that are part of the major facilitator superfamily (MFS) of membrane transporters. Crystal structures have recently revealed how the unique protein fold of these proteins enables the catalysis of transport. The proteins have 12 transmembrane spans built from a replicated trimer substructure. This enables 4 trimer substructures to move relative to each other, and thereby alternately opening and closing a cleft to either the internal or the external side of the membrane. The physiological substrate for the GLUTs is usually a hexose but substrates for GLUTs can include urate, dehydro-ascorbate and myo-inositol. The GLUT proteins have varied physiological functions that are related to their principal substrates, the cell type in which the GLUTs are expressed and the extent to which the proteins are associated with subcellular compartments. Some of the GLUT proteins translocate between subcellular compartments and this facilitates the control of their function over long- and short-time scales. The control of GLUT function is necessary for a regulated supply of metabolites (mainly glucose) to tissues. Pathophysiological abnormalities in GLUT proteins are responsible for, or associated with, clinical problems including type 2 diabetes and cancer and a range of tissue disorders, related to tissue-specific GLUT protein profiles. The availability of GLUT crystal structures has facilitated the search for inhibitors and substrates and that are specific for each GLUT and that can be used therapeutically. Recent studies are starting to unravel the drug targetable properties of each of the GLUT proteins.
Topics: Animals; Catalytic Domain; Enzyme Stability; Glucose; Glucose Transport Proteins, Facilitative; Humans; Protein Transport
PubMed: 32591905
DOI: 10.1007/s00424-020-02411-3 -
The FEBS Journal May 2021This review aims to serve as an introduction to the solute carrier proteins (SLC) superfamily of transporter proteins and their roles in human cells. The SLC superfamily... (Review)
Review
This review aims to serve as an introduction to the solute carrier proteins (SLC) superfamily of transporter proteins and their roles in human cells. The SLC superfamily currently includes 458 transport proteins in 65 families that carry a wide variety of substances across cellular membranes. While members of this superfamily are found throughout cellular organelles, this review focuses on transporters expressed at the plasma membrane. At the cell surface, SLC proteins may be viewed as gatekeepers of the cellular milieu, dynamically responding to different metabolic states. With altered metabolism being one of the hallmarks of cancer, we also briefly review the roles that surface SLC proteins play in the development and progression of cancer through their influence on regulating metabolism and environmental conditions.
Topics: Biological Transport; Cell Membrane; Humans; Membrane Transport Proteins; Neoplasms; Solute Carrier Proteins
PubMed: 32810346
DOI: 10.1111/febs.15531 -
Nature Nov 2010Sugar efflux transporters are essential for the maintenance of animal blood glucose levels, plant nectar production, and plant seed and pollen development. Despite broad...
Sugar efflux transporters are essential for the maintenance of animal blood glucose levels, plant nectar production, and plant seed and pollen development. Despite broad biological importance, the identity of sugar efflux transporters has remained elusive. Using optical glucose sensors, we identified a new class of sugar transporters, named SWEETs, and show that at least six out of seventeen Arabidopsis, two out of over twenty rice and two out of seven homologues in Caenorhabditis elegans, and the single copy human protein, mediate glucose transport. Arabidopsis SWEET8 is essential for pollen viability, and the rice homologues SWEET11 and SWEET14 are specifically exploited by bacterial pathogens for virulence by means of direct binding of a bacterial effector to the SWEET promoter. Bacterial symbionts and fungal and bacterial pathogens induce the expression of different SWEET genes, indicating that the sugar efflux function of SWEET transporters is probably targeted by pathogens and symbionts for nutritional gain. The metazoan homologues may be involved in sugar efflux from intestinal, liver, epididymis and mammary cells.
Topics: Animals; Arabidopsis; Arabidopsis Proteins; Biological Transport; Gene Expression Profiling; Gene Expression Regulation, Plant; Glucose; HEK293 Cells; Host-Pathogen Interactions; Humans; Membrane Transport Proteins; Models, Biological; Oryza; RNA, Messenger; Saccharomyces cerevisiae; Xenopus
PubMed: 21107422
DOI: 10.1038/nature09606 -
Biomedicine & Pharmacotherapy =... Feb 2023Endothelial metabolism is a promising target for vascular functional regulation and disease therapy. Glucose is the primary fuel for endothelial metabolism, supporting... (Review)
Review
Endothelial metabolism is a promising target for vascular functional regulation and disease therapy. Glucose is the primary fuel for endothelial metabolism, supporting ATP generation and endothelial cell survival. Multiple studies have discussed the role of endothelial glucose catabolism, such as glycolysis and oxidative phosphorylation, in vascular functional remodeling. However, the role of the first gatekeepers of endothelial glucose utilization, glucose transporters, in the vasculature has long been neglected. Here, this review summarizes glucose transporter studies in vascular research. We mainly focus on GLUT1 and GLUT3 because they are the most critical glucose transporters responsible for most endothelial glucose uptake. Some interesting topics are also discussed, intending to provide directions for endothelial glucose transporter research in the future.
Topics: Glucose; Glucose Transport Proteins, Facilitative; Biological Transport; Glycolysis; Biology
PubMed: 36565587
DOI: 10.1016/j.biopha.2022.114151 -
F1000Research 2020Deficient glucose transport and glucose disposal are key pathologies leading to impaired glucose tolerance and risk of type 2 diabetes. The cloning and identification... (Review)
Review
Deficient glucose transport and glucose disposal are key pathologies leading to impaired glucose tolerance and risk of type 2 diabetes. The cloning and identification of the family of facilitative glucose transporters have helped to identify that underlying mechanisms behind impaired glucose disposal, particularly in muscle and adipose tissue. There is much more than just transporter protein concentration that is needed to regulate whole body glucose uptake and disposal. The purpose of this review is to discuss recent findings in whole body glucose disposal. We hypothesize that impaired glucose uptake and disposal is a consequence of mismatched energy input and energy output. Decreasing the former while increasing the latter is key to normalizing glucose homeostasis.
Topics: Adipose Tissue; Biological Transport; Diabetes Mellitus, Type 2; Glucose; Humans; Monosaccharide Transport Proteins
PubMed: 32595948
DOI: 10.12688/f1000research.22237.1 -
Biochimica Et Biophysica Acta.... Feb 2020While efficient glucose transport is essential for all cells, in the case of the human placenta, glucose transport requirements are two-fold; provision of glucose for... (Review)
Review
While efficient glucose transport is essential for all cells, in the case of the human placenta, glucose transport requirements are two-fold; provision of glucose for the growing fetus in addition to the supply of glucose required the changing metabolic needs of the placenta itself. The rapidly evolving environment of placental cells over gestation has significant consequences for the development of glucose transport systems. The two-fold transport requirement of the placenta means also that changes in expression will have effects not only for the placenta but also for fetal growth and metabolism. This review will examine the localization, function and evolution of placental glucose transport systems as they are altered with fetal development and the transport and metabolic changes observed in pregnancy pathologies.
Topics: Biological Transport; Female; Fetal Development; Glucose; Glucose Transport Proteins, Facilitative; Humans; Placenta; Pregnancy
PubMed: 30593896
DOI: 10.1016/j.bbadis.2018.12.010 -
Nutrients May 2022Several types of specialized glucose transporters (GLUTs) provide constant glucose transport from the maternal circulation to the developing fetus through the placental... (Review)
Review
Several types of specialized glucose transporters (GLUTs) provide constant glucose transport from the maternal circulation to the developing fetus through the placental barrier from the early stages of pregnancy. GLUT1 is a prominent protein isoform that regulates placental glucose transfer via glucose-facilitated diffusion. The GLUT1 membrane protein density and permeability of the syncytial basal membrane (BM) are the main factors limiting the rate of glucose diffusion in the fetomaternal compartment in physiological conditions. Besides GLUT1, the GLUT3 and GLUT4 isoforms are widely expressed across the human placenta. Numerous medical conditions and molecules, such as hormones, adipokines, and xenobiotics, alter the GLUT's mRNA and protein expression. Diabetes upregulates the BM GLUT's density and promotes fetomaternal glucose transport, leading to excessive fetal growth. However, most studies have found no between-group differences in GLUTs' placental expression in macrosomic and normal control pregnancies. The fetomaternal GLUTs expression may also be influenced by several other conditions, such as chronic hypoxia, preeclampsia, and intrahepatic cholestasis of pregnancy.
Topics: Biological Transport; Female; Glucose; Glucose Transport Proteins, Facilitative; Humans; Placenta; Pregnancy; Protein Isoforms
PubMed: 35631166
DOI: 10.3390/nu14102025