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Skeletal Muscle Metabolism in Exercise and Diabetes pp 73–85Cite as

Insulin Signaling and Glucose Transport in Insulin Resistant Skeletal Muscle

Special Reference to GLUT4 Transgenic and GLUT4 Knockout Mice

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 441))

Abstract

Glucose homeostasis is impaired in patients with non-insulin dependent diabetes mellitus (NIDDM) and this defect is due in part, to defects in glucose transport in skeletal muscle. Intense interest is now focused on whether reduced insulin-mediated glucose transport in muscle from NIDDM patients results from alterations in the insulin signal transduction pathway or from alterations in traffic and/or translocation of GLUT4 to the plasma membrane. Recently, potential targets for impaired traffic/translocation of GLUT4 have been reported to include defective phosphorylation of IRS-1 and reduced PI-3 kinase activity. In addition to insulin signaling defects, impaired glucose transport may result from a defect(s) in the activation or functional capacity of GLUT4. Because GLUT4 is dysregulated in skeletal muscle from NIDDM patients, it is an attractive target for gene therapy. Overexpression of GLUT4 in muscle results in increased glucose uptake and metabolism, and protects against the development of insulin resistance in transgenic mice. Genetic ablation of GLUT4 results in impaired insulin tolerance and defects in glucose metabolism in skeletal muscle. Because impaired muscle glucose transport leads to reduced whole body glucose uptake and hyperglycemia, understanding the molecular regulation of glucose transport in skeletal muscle is necessary to develop effective strategies to prevent or reduce the incidence of NIDDM.

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Authors and Affiliations

  1. Department of Clinical Physiology, Karolinska Hospital, S-171 76, Stockholm, Sweden

    Dana Galuska, Jeff Ryder, Yuichi Kawano & Juleen R. Zierath Ph.D.

  2. Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, 10461-1602, USA

    Maureen J. Charron

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  1. Copenhagen Muscle Research Centre, University of Copenhagen, Copenhagen, Denmark

    Erik A. Richter , Bente Kiens , Henrik Galbo  & Bengt Saltin , ,  & 

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Galuska, D., Ryder, J., Kawano, Y., Charron, M.J., Zierath, J.R. (1998). Insulin Signaling and Glucose Transport in Insulin Resistant Skeletal Muscle. In: Richter, E.A., Kiens, B., Galbo, H., Saltin, B. (eds) Skeletal Muscle Metabolism in Exercise and Diabetes. Advances in Experimental Medicine and Biology, vol 441. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1928-1_7

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