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Cells
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Function, Regulation and Trafficking of Facilitative Glucose Transporters
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Function, Regulation and Trafficking of Facilitative Glucose Transporters

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: closed (30 October 2020) | Viewed by 8537

Special Issue Editor

Prof. Dr. Gwyn W. Gould

E-Mail Website
Guest Editor
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK
Interests: insulin-stimulated glucose transport; insulin action; membrane trafficking; Type-2 diabetes; SNARE proteins

Special Issue Information

Dear Colleagues,

The GLUT/SLC2A family of proteins are widely expressed in mammalian cells. There are 14 GLUTs in the human genome which function as glucose and hexose transporters and play key roles in the regulation of metabolism. Structures of GLUTs or their prokaryotic homologs have begun to unlock details of their molecular mechanism and substrate specificities and are enhancing attempts to design novel GLUT-specific inhibitors or delivery mechanisms which offer powerful new insight into many facets of biology.

Superimposed on the basic biology of GLUTs is a drive to understand their regulation. The best studied example is provided by the insulin-responsive glucose transporter GLUT4. This isoform is highly expressed in adipose and muscle cells where it is intracellularly sequestered into vesicles; upon insulin stimulation, these vesicles move (‘translocate’) to the cell surface where they dock and fuse, resulting in increased cell surface GLUT4 levels and increased glucose entry into the cell. Translocation is impaired in Type-2 diabetes making this a key target of research. How different signals like exercise and insulin act to regulate glucose transport in muscle exemplify studies of the trafficking/signalling interface characteristic of this field.

Recently, insulin-stimulated GLUT4 translocation has been observed in certain regions of the brain and in the placental syncytiotrophoblast, and action-potential firing has been shown to recruit GLUT4 to the plasma membrane of hippocampal neurones. Such novel observations make the point that the regulation of GLUT trafficking and activity likely serves to regulate many facets of cell physiology.

This topic will focus on all aspects of GLUT biology, ranging from structure/function analysis, subcellular trafficking, GLUT regulation and the role of transporters in regulating cellular/whole animal physiology. In particular, we welcome contributions of novel GLUT-regulatory networks and mechanisms. We welcome review articles and primary research papers.

Prof. Gwyn W. Gould
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glucose transporter
  • solute carrier family 2
  • glucose metabolism
  • insulin
  • exercise
  • subcellular trafficking of GLUTs
  • signalling/signal transduction
  • brain and nerve glucose transport

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Published Papers (2 papers)

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Research

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16 pages, 3538 KiB  
Article
Tsg101 Is Involved in the Sorting and Re-Distribution of Glucose Transporter-4 to the Sarcolemma Membrane of Cardiac Myocytes
by Kobina Essandoh, Shan Deng, Xiaohong Wang, Yutian Li, Qianqian Li, Xingjiang Mu, Tianqing Peng and Guo-Chang Fan
Cells 2020, 9(9), 1936; https://doi.org/10.3390/cells9091936 - 21 Aug 2020
Cited by 3 | Viewed by 3233
Abstract
Cardiac cells can adapt to pathological stress-induced energy crisis by shifting from fatty acid oxidation to glycolysis. However, the use of glucose-insulin-potassium (GIK) solution in patients undergoing cardiac surgery does not alleviate ischemia/reperfusion (I/R)-induced energy shortage. This indicates that insulin-mediated translocation of glucose [...] Read more.
Cardiac cells can adapt to pathological stress-induced energy crisis by shifting from fatty acid oxidation to glycolysis. However, the use of glucose-insulin-potassium (GIK) solution in patients undergoing cardiac surgery does not alleviate ischemia/reperfusion (I/R)-induced energy shortage. This indicates that insulin-mediated translocation of glucose transporter-4 (Glut-4) is impaired in ischemic hearts. Indeed, cardiac myocytes contain two intracellular populations of Glut-4: an insulin-dependent non-endosomal pool (also referred to as Glut-4 storage vesicles, GSVs) and an insulin-independent endosomal pool. Tumor susceptibility gene 101 (Tsg101) has been implicated in the endosomal recycling of membrane proteins. In this study, we aimed to examine whether Tsg101 regulated the sorting and re-distribution of Glut-4 to the sarcolemma membrane of cardiomyocytes under basal and ischemic conditions, using gain- and loss-of-function approaches. Forced overexpression of Tsg101 in mouse hearts and isolated cardiomyocytes could promote Glut-4 re-distribution to the sarcolemma, leading to enhanced glucose entry and adenosine triphosphate (ATP) generation in I/R hearts which in turn, attenuation of I/R-induced cardiac dysfunction. Conversely, knockdown of Tsg101 in cardiac myocytes exhibited opposite effects. Mechanistically, we identified that Tsg101 could interact and co-localize with Glut-4 in the sarcolemma membrane of cardiomyocytes. Our findings define Tsg101 as a novel regulator of cardiac Glut-4 trafficking, which may provide a new therapeutic strategy for the treatment of ischemic heart disease. Full article
(This article belongs to the Special Issue Function, Regulation and Trafficking of Facilitative Glucose Transporters)
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Review

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21 pages, 2352 KiB  
Review
Anthocyanin Bioactivity in Obesity and Diabetes: The Essential Role of Glucose Transporters in the Gut and Periphery
by Patrick Solverson
Cells 2020, 9(11), 2515; https://doi.org/10.3390/cells9112515 - 20 Nov 2020
Cited by 32 | Viewed by 4785
Abstract
Obesity and type-2 diabetes trends continue to worsen in the United States. Dietary anthocyanins (typically provided by berries and other fruits) are reported to have protective effects against both conditions using a variety of experimental research models including animal and human feeding studies. [...] Read more.
Obesity and type-2 diabetes trends continue to worsen in the United States. Dietary anthocyanins (typically provided by berries and other fruits) are reported to have protective effects against both conditions using a variety of experimental research models including animal and human feeding studies. This review highlights studies that explore the biochemical pathways in both tissue and rodent models which could explain clinical improvements noted with anthocyanin consumption. First, the primary mode of intestinal absorption of anthocyanins is through both sGLT1 and GLUT2 glucose transporters. Stronger binding affinities may allow anthocyanins to be more inhibitive to glucose absorption compared to the reverse, where GLUT2 expression may also be affected. Genetic or chemical inhibition of sGLT1 or GLUT2 demonstrate their essential function in anthocyanin absorption across the enterocyte, where the former interacts with a greater variety of anthocyanins but the latter is the major transporter for specific anthocyanin-glycosides. Once absorbed, anthocyanins positively modulate GLUT4 density and function in both skeletal muscle and adipose tissues via the upregulation of AMPK and restoration of insulin sensitivity. Antioxidant properties and phosphodiesterase inhibition by anthocyanins promote both mitochondrial function and density which could be novel targets for dietary management of obesity and its complications. Full article
(This article belongs to the Special Issue Function, Regulation and Trafficking of Facilitative Glucose Transporters)
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