Chemical biology probes of mammalian GLUT structure and function

Holman, Geoffrey D.

doi:10.1042/bcj20170677

Cited by 43 publications

(27 citation statements)

References 132 publications

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“…The bis-hexose structure with hydrophobic substitutions in the trailing C4-OH position has affinities for the GLUTs that are 10-fold higher than the parent compound D-glucose. The bis-mannose and bis-glucose photolabels have been used extensively for tracking the kinetics of GLUT movement to and from the plasma membrane in response to insulin (reviewed in [91]).…”

Section: Glut Specificity For Substrates and Inhibitorsmentioning

confidence: 99%

Structure, function and regulation of mammalian glucose transporters of the SLC2 family

Holman

2020

Pflugers Arch - Eur J Physiol

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141

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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 shorttime 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.

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Section: Glut Specificity For Substrates and Inhibitorsmentioning

confidence: 99%

Structure, function and regulation of mammalian glucose transporters of the SLC2 family

Holman

2020

Pflugers Arch - Eur J Physiol

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141

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“…Contribution to the Special Issue on "Glucose transporters in health and disease," edited by Hermann Koepsell and Volker Vallon This article highlights the function of the GLUT family in the liver, muscle, and fat tissue and the specific contribution of GLUTs to systemic glucose homeostasis and energy metabolism in the healthy and diabetic state. Other recent reviews provide excellent and thorough overviews on the structure/ function relationship of GLUTs [32,93,260], insulin signaling [83], and the regulation of the insulin-and contractionresponsive GLUT4 trafficking [100,118]. Table 1 summarizes the tissue-specific function of the GLUTs in metabolism.…”

Section: Introductionmentioning

confidence: 99%

Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease

Chadt

Al-Hasani

2020

Pflugers Arch - Eur J Physiol

345

203

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A family of facilitative glucose transporters (GLUTs) is involved in regulating tissue-specific glucose uptake and metabolism in the liver, skeletal muscle, and adipose tissue to ensure homeostatic control of blood glucose levels. Reduced glucose transport activity results in aberrant use of energy substrates and is associated with insulin resistance and type 2 diabetes. It is well established that GLUT2, the main regulator of hepatic hexose flux, and GLUT4, the workhorse in insulin-and contraction-stimulated glucose uptake in skeletal muscle, are critical contributors in the control of whole-body glycemia. However, the molecular mechanism how insulin controls glucose transport across membranes and its relation to impaired glycemic control in type 2 diabetes remains not sufficiently understood. An array of circulating metabolites and hormone-like molecules and potential supplementary glucose transporters play roles in fine-tuning glucose flux between the different organs in response to an altered energy demand.

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“…As we all know, glucose transporters are the most important regulators of glycolysis [21]. Therefore, we firstly detected glucose transporters expression levels after overexpressing miR-181b.…”

Section: Mir-181b Suppresses the Glucose Metabolism And Proliferationmentioning

confidence: 99%

MiR-181b suppress glioblastoma multiforme growth through inhibition of SP1-mediated glucose metabolism

et al. 2020

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Background: Glucose metabolic reprogramming is a significant hallmark of malignant tumors including GBM. Previous studies suggest that microRNAs play key roles in modulating this process in GBM cells. miR-181b acts as a tumor suppressor miRNA in influencing glioma tumorigenesis. Our previous results showed that miR-181b was down-regulated in glioma cells and tissues. Methods:The extracellular acidification rate (ECAR), colony formation assay and levels of Glut1 and PKM2 were measured to assess the glucose metabolic and proliferation changes in GBM cells overexpressing miR-181b. Immunoblotting and luciferase reporter assay were performed to confirm the expression and role of SP1 as a direct target of miR-181b. ChIP assay was used to figure out the transcriptional regulation of SP1 on Glut1 and PKM2. In vivo study was examined for the role of miR-181b in GBM cells.Results: MiR-181b overexpression significantly reduced the glucose metabolic and colony formation ability of GBM cells. And, SP1 was confirmed as a direct target of miR-181b while upregulation of SP1 could reverse the influence of overexpression of miR-181b. Furthermore, Glut1 and PKM2 could be regulated by SP1. Finally, miR-181b could inhibit the tumor growth in vivo. Conclusions:Our article demonstrated the inhibitory effect of miR-181b on glucose metabolism and proliferation in GBM by suppressing SP1 expression.

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Chemical biology probes of mammalian GLUT structure and function

Cited by 43 publications

References 132 publications

Structure, function and regulation of mammalian glucose transporters of the SLC2 family

Structure, function and regulation of mammalian glucose transporters of the SLC2 family

Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease

MiR-181b suppress glioblastoma multiforme growth through inhibition of SP1-mediated glucose metabolism

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