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Metabolism

A transporter on the move

Nature Reviews Endocrinology volume 20, page 127 (2024)Cite this article

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Glucose is a hydrophilic molecule that is transported in the blood and is vital for energy homeostasis across most tissues. However, glucose cannot readily diffuse through the lipid bilayers of cells and so glucose needs a transporter. The glucose transporters were first described in the 1980s. Today, 13 different glucose transporters have been identified, each with their own specific properties, and are expressed in various tissues.

In 1988 and 1989, David E. James and colleagues published two seminal papers describing what is now known as glucose transporter 4 (GLUT4). Briefly, using isolated rat adipocytes, James and colleagues (1988) first showed that a glucose transport protein must exist, which translocates from the intracellular compartment to the plasma membrane upon stimulation with insulin. James and colleagues subsequently cloned the transporter, which was reported in a paper published in Nature in 1989. This discovery led to the description of a key feature of glucose homeostasis: insulin-stimulated GLUT4 translocation in skeletal muscle and adipose tissue.

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References

Original articles:

  • James, D. E., Brown, R., Navarro, J. & Pilch, P. F. Insulin-regulatable tissues express a unique insulin-sensitive glucose transport protein. Nature 333, 183–185 (1988)

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  • James, D. E., Strube, M. & Mueckler, M. Molecular cloning and characterization of an insulin-regulatable glucose transporter. Nature 338, 83–87 (1989)

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  • Hoffman, N. J. et al. Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates. Cell Metab. 22, 922–935 (2015)

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  • Needham, E. J. et al. Personalized phosphoproteomics identifies functional signaling. Nat. Biotechnol. 40, 576–584 (2022)

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  • Fazakerley, D. J. et al. Phosphoproteomics reveals rewiring of the insulin signaling network and multi-nodal defects in insulin resistance. Nat. Commun. 14, 923 (2023)

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Acknowledgements

The author acknowledges the support of Erik A. Richter and Lykke Sylow (University of Copenhagen) during the preparation of this manuscript. The author acknowledges the support of grants from the Independent Research Fund Denmark 2030-00007A and Lundbeck Foundation R380-2021-1451 to S.H.R.

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  1. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Steffen H. Raun

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  1. Steffen H. Raun
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Correspondence to Steffen H. Raun.

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Raun, S.H. A transporter on the move. Nat Rev Endocrinol 20, 127 (2024). https://doi.org/10.1038/s41574-023-00944-y

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