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Signal transduction

Lipid rafts and insulin action

Nature volume 407, pages 147–148 (2000)Cite this article

One of the greatest medical breakthroughs of the twentieth century was the demonstration in 1922 of insulin's ability to alleviate some of the symptoms of diabetes, including high levels of glucose in the blood. Insulin has received special attention ever since: the amino-acid sequence of the insulin protein was the first to be decoded, and the insulin gene was one of the first to be cloned. Tremendous effort has also gone into understanding how insulin works. We know that it stimulates muscle and fat cells to remove glucose from the blood, by encouraging an intracellular glucose transporter, called GLUT4, to move to the plasma membrane of these cells. But we know few of the details of how insulin does this, beyond the fact that a particular cellular signalling pathway involving lipids is necessary, but may not on its own be sufficient1. On page 202 of this issue, Baumann and colleagues2 offer a possible solution: they describe a second insulin-stimulated signalling pathway in human cells that may also be required to stimulate glucose uptake.

If this pathway is blocked, so too is the insulin-dependent regulation of GLUT4 (refs 3, 4). And adipocytes (fat cells) from mice lacking insulin-receptor substrate (IRS)-1, a linking or ‘adaptor’ protein that is phosphorylated by the insulin receptor and which recruits PI(3)K, show the expected drop in insulin-mediated glucose uptake5. These and many other findings converged a few years ago to suggest that figuring out how insulin signals to GLUT4 was simply a matter of identifying the downstream elements in this PI(3)K pathway.

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Figure 1: Pathways for glucose uptake in muscle and fat cells.

References

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Authors and Affiliations

  1. the Program in Molecular Medicine and the Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School , 373 Plantation Street, Worcester, 01605, Massachusetts, USA

    Michael P. Czech

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  1. Michael P. Czech
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Correspondence to Michael P. Czech.

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Czech, M. Lipid rafts and insulin action. Nature 407, 147–148 (2000). https://doi.org/10.1038/35025183

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