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Effective glucose metabolism maintains low intracellular glucose in airway epithelial cells after exposure to hyperglycaemia.

Abstract

The airway epithelium maintains differential glucose concentrations between the airway surface liquid (ASL, ~0.4mM) and the blood/interstitium (5-6mM) which is important for defence against infection. Glucose primarily moves from the blood to the ASL via paracellular movement, down its concentration gradient, across the tight junctions. However, there is evidence that glucose can move transcellularly across epithelial cells. Using a Förster Resonance Energy Transfer (FRET) sensor for glucose, we investigated intracellular glucose concentrations in airway epithelial cells and the role of hexokinases in regulating intracellular glucose concentrations in normo- and hyperglycaemic conditions. Our findings indicated that in airway epithelial cells (H441 or primary human epithelial cells HBEC) exposed to 5mM glucose (normoglycaemia), intracellular glucose concentration is in the mM range. Inhibition of facilitative glucose transport (GLUT) with Cytochalasin B reduced intracellular glucose concentration. When cells were exposed to 15mM glucose (hyperglycaemia), intracellular glucose concentration reduced. Airway cells expressed hexokinases 1, 2 and 3. Inhibition with 3-bromopyruvate decreased hexokinase activity by ~25% and elevated intracellular glucose concentration but levels remained in the mM range. Exposure to hyperglycaemia increased glycolysis, glycogen and sorbitol. Thus, glucose enters the airway cell via GLUT transporters and is then rapidly processed by hexokinase-dependent and hexokinase-independent metabolic pathways to maintain low intracellular glucose concentrations. We propose this prevents transcellular transport, aids the removal of glucose from the ASL and that the main route of entry for glucose into the ASL is via the paracellular pathway.

Authors+Show Affiliations

Institute for Infection and Immunity, St George's University of London, London SW17 0RE, United Kingdom.Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE1 7RU UK; Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397 Biberach an der Riβ, Germany.Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397 Biberach an der Riβ, Germany.Institute for Infection and Immunity, St George's University of London, London SW17 0RE, United Kingdom.Institute for Infection and Immunity, St George's University of London, London SW17 0RE, United Kingdom.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31433692

Citation

Bearham, Jade, et al. "Effective Glucose Metabolism Maintains Low Intracellular Glucose in Airway Epithelial Cells After Exposure to Hyperglycaemia." American Journal of Physiology. Cell Physiology, 2019.
Bearham J, Garnett JP, Schroeder V, et al. Effective glucose metabolism maintains low intracellular glucose in airway epithelial cells after exposure to hyperglycaemia. Am J Physiol, Cell Physiol. 2019.
Bearham, J., Garnett, J. P., Schroeder, V., Biggart, M. G., & Baines, D. L. (2019). Effective glucose metabolism maintains low intracellular glucose in airway epithelial cells after exposure to hyperglycaemia. American Journal of Physiology. Cell Physiology, doi:10.1152/ajpcell.00193.2019.
Bearham J, et al. Effective Glucose Metabolism Maintains Low Intracellular Glucose in Airway Epithelial Cells After Exposure to Hyperglycaemia. Am J Physiol, Cell Physiol. 2019 Aug 21; PubMed PMID: 31433692.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effective glucose metabolism maintains low intracellular glucose in airway epithelial cells after exposure to hyperglycaemia. AU - Bearham,Jade, AU - Garnett,James P, AU - Schroeder,Victoria, AU - Biggart,Matthew Gs, AU - Baines,Deborah L, Y1 - 2019/08/21/ PY - 2019/8/22/entrez KW - airway KW - epithelial cell KW - glucose KW - hexokinase KW - metabolism JF - American journal of physiology. Cell physiology JO - Am. J. Physiol., Cell Physiol. N2 - The airway epithelium maintains differential glucose concentrations between the airway surface liquid (ASL, ~0.4mM) and the blood/interstitium (5-6mM) which is important for defence against infection. Glucose primarily moves from the blood to the ASL via paracellular movement, down its concentration gradient, across the tight junctions. However, there is evidence that glucose can move transcellularly across epithelial cells. Using a Förster Resonance Energy Transfer (FRET) sensor for glucose, we investigated intracellular glucose concentrations in airway epithelial cells and the role of hexokinases in regulating intracellular glucose concentrations in normo- and hyperglycaemic conditions. Our findings indicated that in airway epithelial cells (H441 or primary human epithelial cells HBEC) exposed to 5mM glucose (normoglycaemia), intracellular glucose concentration is in the mM range. Inhibition of facilitative glucose transport (GLUT) with Cytochalasin B reduced intracellular glucose concentration. When cells were exposed to 15mM glucose (hyperglycaemia), intracellular glucose concentration reduced. Airway cells expressed hexokinases 1, 2 and 3. Inhibition with 3-bromopyruvate decreased hexokinase activity by ~25% and elevated intracellular glucose concentration but levels remained in the mM range. Exposure to hyperglycaemia increased glycolysis, glycogen and sorbitol. Thus, glucose enters the airway cell via GLUT transporters and is then rapidly processed by hexokinase-dependent and hexokinase-independent metabolic pathways to maintain low intracellular glucose concentrations. We propose this prevents transcellular transport, aids the removal of glucose from the ASL and that the main route of entry for glucose into the ASL is via the paracellular pathway. SN - 1522-1563 UR - https://www.unboundmedicine.com/medline/citation/31433692/Effective_glucose_metabolism_maintains_low_intracellular_glucose_in_airway_epithelial_cells_after_exposure_to_hyperglycaemia L2 - http://www.physiology.org/doi/full/10.1152/ajpcell.00193.2019?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -