Glucose transport in lymphocytes
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INVITED REVIEW
Glucose transport in lymphocytes Florian Lang 1,2 Karl S. Lang 7
&
Yogesh Singh 3 & Madhuri S. Salker 4 & Ke Ma 1 & Aleksandra A. Pandyra 5,6 & Philipp A. Lang 5 &
Received: 11 March 2020 / Revised: 29 May 2020 / Accepted: 3 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Glucose uptake into lymphocytes is accomplished by non-concentrative glucose carriers of the GLUT family (GLUT1, GLUT3, GLUT4, GLUT6) and/or by the Na+-coupled glucose carrier SGLT1. The latter accumulates glucose against glucose gradients and is still effective at very low extracellular glucose concentrations. Signaling involved in SGLT1 expression and activity includes protein kinase A (PKA), protein kinase C (PKC), serum- and glucocorticoid-inducible kinase (SGK1), AMP-activated kinase (AMPK), and Janus kinases (JAK2 and JAK3). Glucose taken up is partially stored as glycogen. In hypoxic environments, such as in tumors as well as infected and inflamed tissues, lymphocytes depend on energy production from glycogen-dependent glycolysis. The lack of SGLT1 may compromise glycogen storage and thus lymphocyte survival and function in hypoxic tissues. Accordingly, in mice, genetic knockout of sglt1 compromised bacterial clearance following Listeria monocytogenes infection leading to an invariably lethal course of the disease. Whether the effect was due to the lack of sglt1 in lymphocytes or in other cell types still remains to be determined. Clearly, additional experimental effort is required to define the role of glucose transport by GLUTs and particularly by SGLT1 for lymphocyte survival and function, as well as orchestration of the host defense against tumors and bacterial infections. Keywords Cytotoxic T lymphocytes . Jurkat T cells . GLUT . SGLT1 . Energy depletion . Janus kinases . Cancer . Bacterial infection
Introduction This article is part of the special issue on Glucose Transporters in Health and Disease in Pflügers Archiv—European Journal of Physiology * Florian Lang [email protected] 1
Department of Physiology, Eberhard Karl University, Tubingen, Germany
2
Department of Physiology, University of Tübingen, Wilhelmstr. 56, 72076 Tubingen, Germany
3
Institute of Medical Genetics and Applied Genomics, Eberhard Karl University, Tubingen, Germany
4
Research Institute of Women’s Health, Eberhard Karl University, Tubingen, Germany
5
Department of Molecular Medicine II, Heinrich Heine University Düsseldorf, Dusseldorf, Germany
6
Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Dusseldorf, Germany
7
Department of Immunology, University of Essen, Essen, Germany
Glucose transport across the cell membrane can be accomplished by non-concentrative glucose carriers of the GLUT family [33], which mediate passive transport but are unable to operate against a chemical glucose gradient [52, 64]. In contrast, Na+-coupled glucose carriers of the SGLT family accomplish uphill transport of glucose driven by Na+ entry down its electrochemica
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