Cited by 476Metabolism, Diabetes, and CancerIon Transport and Channel RegulationDiabetes Treatment and Management

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The glucose transporter families SGLT and GLUT: molecular basis of normal and aberrant function

Scheepers, A, Joost, HG, Schurmann, A·2004·Journal of Parenteral and Enteral Nutrition

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Abstract

Glucose enters eucaryotic cells via 2 different types of membrane associated carrier proteins, the Na+‐coupled glucose transporters (SGLT) and glucose transporter facilitators (GLUT). Three members of the SGLT family function as sugar transporters (SGLT1 and SGLT2) or sensors (SGLT3). The human GLUT family consists of 14 members, of which 11 have been shown to catalyze sugar transport. The individual isotypes exhibit different substrate specificity, kinetic characteristics, and expression profiles, thereby allowing a tissue‐specific adaptation of glucose uptake through regulation of their gene expression. Furthermore, some transporters (eg, GLUT4 and GLUT8) are regulated by their subcellular distribution. In addition to catalyzing glucose entry into cells, some isotypes (eg, GLUT2) seem to be involved in the mechanisms of glucosensing of pancreatic beta‐cells, neuronal, or other cells, thereby playing a major role in the hormonal and neural control. Targeted disruption in mice has helped to elucidate the physiologic function of some isotypes (GLUT1, GLUT2, GLUT4). Furthermore, several congenital defects of sugar metabolism are caused by aberrant transporter genes (eg, the glucose‐galactose malabsorption syndrome, SGLT1; the glucose transporter 1 deficiency syndrome; and the Fanconi‐Bickel syndrome, GLUT2). In addition, a malfunction of glucose transporter expression or regulation (GLUT4) appears to contribute to the insulin resistance syndrome.

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Background
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“This task is accomplished either by sodium coupled glucose transporters (SGLTs) or by glucose facilitative transporters, the GLUT family (33).”
BackgroundMethodInfluential
Growth Hormone Inhibition of Glucose Uptake in Adipocytes Occurs without Affecting GLUT4 Translocation through an Insulin Receptor Substrate-2-Phosphatidylinositol 3-Kinase-dependent Pathway
Sasaki-Suzuki, N., Arai, K., Ogata, T., Kasahara, K., Sakoda, H., Chida, K., Asano, T., Pessin, J. E., Hakuno, F., & Takahashi, S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808282200 · Cited by 31
Respiratory syncytial virus co-opts hypoxia-inducible factor-1α-mediated glycolysis to favor the production of infectious virus
Chen, L., Cai, J.-X., Zhang, J., Tang, Y., Chen, J., Xiong, S., Li, Y.-L., Zhang, H., Liu, Z., & Li, M. (2023) · mBio · doi:10.1128/mbio.02110-23 · Cited by 31
“Among them, class I Gluts, including Glut1, Glut2, Glut3, and Glut4, are mainly responsible for transporting glucose (25–27).”
Background
The potential role of GLUT4 transporters and insulin receptors in the hypoglycaemic activity of Ficus lutea acetone leaf extract
Olaokun, O. O., McGaw, L. J., Awouafack, M. D., et al. (2014) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-14-269 · Cited by 30
“The 3T3-L1 pre-adipocytes predominantly express the GLUT1 glucose transporter over GLUT4 [37]; the differentiated C2C12 myocytes and the primary cells the GLUT4 transporter and the H-4-II-E hepatoma cells the GLUT2 glucose transporter [38].”
Background
Adult presentation of arterial tortuosity syndrome in a 51‐year‐old woman with a novel homozygous c.1411+1G>A mutation in the SLC2A10 gene
Castori, M., Ritelli, M., Zoppi, N., Molisso, L., Chiarelli, N., Zaccagna, F., Grammatico, P., & Colombi, M. (2012) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.35266 · Cited by 32
Efficacy of flavonoids on biomarkers of type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials
Liu, F., Sirisena, S., & Ng, K. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.2009761 · Cited by 29
“2000; Scheepers, Joost, and Schurmann 2004; Minokoshi, Kahn, and Kahn 2003; Kwon et al.”
Effect of highly branched α-glucans synthesized by dual glycosyltransferases on the glucose release rate
Hong, M.-G., Yoo, S., & Lee, B.-H. (2021) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2021.119016 · Cited by 29
The effect of metformin treatment in vivo on acute and long-term energy metabolism and progesterone production in vitro by granulosa cells from women with polycystic ovary syndrome
Maruthini, D., Harris, S. E., Barth, J. H., Balen, A. H., Campbell, B. K., & Picton, H. M. (2014) · Human Reproduction · doi:10.1093/humrep/deu187 · Cited by 29
“The rate-limiting factor in insulin-mediated glucose uptake is the transfer of GLUTs to the plasma membrane (Girard et al., 1992; Takata, 1996; Scheepers et al., 2004).”
Background
High Glucose Condition Suppresses Neurosphere Formation by Human Periodontal Ligament‐Derived Mesenchymal Stem Cells
Sawangmake, C., Pavasant, P., Chansiripornchai, P., & Osathanon, T. (2013) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24735 · Cited by 29
“…expression in undifferentiated and neurogenic differentiated hPDLSCs was observed correlating to previous publications illustrating the expression of GLUT4 in insulin‐responsive tissues, for example, adipocytes and myocytes [Wood and Trayhurn, 2003; Scheepers et al., 2004; Leto and Saltiel, 2012].”
BackgroundResult
Lysosomal localization of GLUT8 in the testis – the EXXXLL motif of GLUT8 is sufficient for its intracellular sorting via AP1‐ and AP2‐mediated interaction
Diril, M. K., Schmidt, S., Krauss, M., et al. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.07089.x · Cited by 28
Self-citation
PKC and MAPKs Pathways Mediate EGF-induced Stimulation of 2-Deoxyglucose Uptake in Mouse Embryonic Stem Cells
Heo, J. S., & Han, H. J. (2006) · Cellular Physiology and Biochemistry · doi:10.1159/000092076 · Cited by 28
Fuel/Energy Sources of Spermatozoa
Sengupta, P., Durairajanayagam, D., & Agarwal, A. K. (2020) · Springer eBooks · doi:10.1007/978-3-030-32300-4_26 · Cited by 31
“The pharmacological profile of SGLT2 inhibitors: Focus on mechanistic aspects and pharmacogenomics”
Kaur, P., Behera, B. S., Singh, S., & Munshi, A. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174169 · Cited by 27
GLUT4 in Mouse Endometrial Epithelium: Roles in Embryonic Development and Implantation
Long, Y., Wang, Y.-C., Yuan, D., Dai, X., Liao, L., Zhang, X., Zhang, L., Ma, Y.-D., Lei, Y., Cui, Z., et al. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.674924 · Cited by 27
FDG-PET reveals improved cardiac regeneration and attenuated adverse remodelling following Sitagliptin + G-CSF therapy after acute myocardial infarction
Groß, L., Paintmayer, L., Lehner, S., et al. (2015) · European Heart Journal - Cardiovascular Imaging · doi:10.1093/ehjci/jev237 · Cited by 27
Transendothelial glucose transport is not restricted by extracellular hyperglycaemia
Tumova, S., Kerimi, A., Porter, K. E., & Williamson, G. (2016) · Vascular Pharmacology · doi:10.1016/j.vph.2016.11.001 · Cited by 31
“Glucose transporters (GLUTs) of the SLC2A family are transmembrane proteins classified in three groups (reviewed in [26-28].”
Background
GLP-1-Based Strategies: A Physiological Analysis of Differential Mode of Action
Burcelin, R., Gourdy, P., & Dalle, S. (2014) · Physiology · doi:10.1152/physiol.00009.2013 · Cited by 26
Diabetes and Sperm DNA Damage: Efficacy of Antioxidants
Laleethambika, N., Venugopal, A., Manojkumar, C., Muruganandam, I., Giridharan, B., Ravimanickam, T., & Vellingiri, B. (2018) · SN Comprehensive Clinical Medicine · doi:10.1007/s42399-018-0012-9 · Cited by 28
“Oxidative phosphorylation and anaerobic glycolysis are the two primary metabolic pathways required in energy production [42].”
Background
Stroma-derived HGF drives metabolic adaptation of colorectal cancer to angiogenesis inhibitors
Mira, A., Morello, V., Céspedes, M. V., Perera, T. P. S., Comoglio, P. M., Mangues, R., & Michieli, P. (2017) · Oncotarget · doi:10.18632/oncotarget.16942 · Cited by 26
“GLUT1 is the prototype of facilitated glucose transporters and is frequently overexpressed in tumors [37].”
Background
Expression of glucose transporters SLC2A1, SLC2A8, and SLC2A12 in different chicken muscles during ontogenesis
Coudert, E., Praud, C., Dupont, J., et al. (2018) · Journal of Animal Science · doi:10.1093/jas/skx084 · Cited by 26
“This pathway dominates in skeletal muscle, contributing largely to glucose homeostasis (Scheepers et al., 2004) although recent findings suggest that other isoforms such as GLUT1, GLUT12 (Rogers et al., 2002; Stuart et al., 2009; Purcell et al., 2011), and GLUT8 (de Laat et al., 2015) might also…”
Background
Long-Term Chronic Intermittent Hypobaric Hypoxia Induces Glucose Transporter (GLUT4) Translocation Through AMP-Activated Protein Kinase (AMPK) in the Soleus Muscle in Lean Rats
Siqués, P., Brito, J., Flores, K., Ordenes, S., Arriaza, K., Pena, E., Lèon‐Velarde, F., de Pablo, Á. L. L., González, M. C., & Arribas, S. M. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00799 · Cited by 26
“Cellular glucose uptake is mainly accomplished via facilitated transport mediated by a family of GLUTs: GLUT1 is responsible for basal glucose uptake, and GLUT4 is an insulinregulated GLUT; both transporters are present in skeletal muscles (Scheepers et al., 2004).”
Background
Metabolic Transporters in the Peripheral Nerve—What, Where, and Why?
Rawat, A. K., & Morrison, B. M. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01150-2 · Cited by 26
“There are 14 members of the GLUT family [16], expressed by different cell types in the nervous system [17].”
Background
Neurodevelopment Is Dependent on Maternal Diet: Placenta and Brain Glucose Transporters GLUT1 and GLUT3
Daida, T., Shin, B., Cepeda, C., & Devaskar, S. U. (2024) · Nutrients · doi:10.3390/nu16142363 · Cited by 30
“The human GLUT family consists of 14 members, and they are categorized into three classes according to sequence similarity [31,32].”
Background
The impact of prolonged hyperinsulinaemia on glucose transport in equine skeletal muscle and digital lamellae
de Laat, M. A., Clement, C. K., Sillence, M. N., McGowan, C. M., Pollitt, C. C., & Lacombe, V. A. (2014) · Equine Veterinary Journal · doi:10.1111/evj.12320 · Cited by 26
Glucose Transport and Metabolism in Sertoli Cell: Relevance for Male Fertility
Dias, T. R., Martins, A. D., dos Reis, V. M. S. F., Socorro, S., Silva, B. M., Alves, M. G., & Oliveira, P. F. (2014) · Current Chemical Biology · doi:10.2174/2212796807999131128125510 · Cited by 25
Sodium transport through the cerebral sodium–glucose transporter exacerbates neuron damage during cerebral ischaemia
Yamazaki, Y., Harada, S., Wada, T., et al. (2016) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.12571 · Cited by 25
“Although SGLT-1, SGLT-3, SGLT-4 and SGLT-6 have been identified in brain tissues, the roles of cerebral SGLT remain poorly understood.([11,12]) Previous reports show that the specific SGLT family inhibitor phlorizin ameliorates the development of focal and global cerebral ischaemia.”
Background
Sodium–glucose transporter as a novel therapeutic target in disease
Yamazaki, Y., Harada, S., & Tokuyama, S. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.01.003 · Cited by 25
Sodium glucose cotransporters inhibitors in type 1 diabetes
Dellepiane, S., Nasr, M. B., Assi, E., Usuelli, V., Letizia, T., D’Addio, F., Zuccotti, G., & Fiorina, P. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.04.018 · Cited by 26
Homeorhetic adaptation to lactation: comparative transcriptome analysis of mammary, liver, and adipose tissue during the transition from pregnancy to lactation in rats
PATEL, O. V., Casey, T., Dover, H. E., & Plaut, K. I. (2010) · Functional & Integrative Genomics · doi:10.1007/s10142-010-0193-0 · Cited by 24
“Glucose is conveyed into the cells either discretely by facilitative transporters (GLUT) or coupled to other ions, such as sodium by sodium-coupled glucose transporters (SGLT) (Manolescu et al. 2007; Scheepers et al. 2004; Wood and Trayhurn 2003).”
Background
Glucagon‐like peptide‐2: A potential role in equine insulin dysregulation
de Laat, M. A., Fitzgerald, D. M., Sillence, M. N., & Spence, R. J. (2018) · Equine Veterinary Journal · doi:10.1111/evj.12825 · Cited by 24
“Glucose uptake is facilitated by sodium-glucose cotransporters (SGLTs) expressed on intestinal epithelial cells [12].”
Background
GLUT1 inhibition by BAY-876 induces metabolic changes and cell death in human colorectal cancer cells
Hayashi, M., Nakamura, K., Harada, S., Tanaka, M. H., Kobayashi, A., Saito, H., Tsuji, T., Yamamoto, D., Moriyama, H., Kinoshita, J., et al. (2025) · BMC Cancer · doi:10.1186/s12885-025-14141-9 · Cited by 32
“There are two classes of glucose transporters: sodium-dependent glucose transporter (SGLT) and facilitative glucose transporter (GLUT) [12].”

Authors: Scheepers, A., Joost, H., & Schurmann, A.
Affiliations: German Institute of Human Nutrition (DE)
Venue: Journal of Parenteral and Enteral Nutrition
Publisher: Wiley
Published: 2004-09
Volume: 28
Issue: 5
Pages: 364-371
ISSN: 0148-6071 (ISSN-L)
1941-2444
DOI: 10.1177/0148607104028005364
OpenAlex: W1993812967
Cited by: 476
References: 0
Citations by year: 2026: 7 · 2025: 17 · 2024: 16 · 2023: 16 · 2022: 27 · 2021: 26 · 2020: 27 · 2019: 24 · 2018: 29 · 2017: 22 · 2016: 23 · 2015: 29 · 2014: 34 · 2013: 28 · 2012: 28
FWCI: 3.76
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Parenteral and Enteral Nutrition (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: glucose transporters, GLUT family, SGLT1, SGLT2, GLUT1, GLUT2, GLUT4, GLUT8, glucose transport, sugar transporters, glucose detection, pancreatic beta cells, GLUT1 deficiency syndrome, Fanconi-Bickel syndrome, insulin resistance, gene expression regulation
MeSH terms: Animals, Biological Transport, Active, Gene Expression Regulation, Glucose, Humans, Monosaccharide Transport Proteins, Signal Transduction, Protein Isoforms, Mice

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The glucose transporter families SGLT and GLUT: molecular basis of normal and aberrant function

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