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Type 2 diabetes — who is conducting the orchestra?

Nature Genetics volume 20, pages 223–225 (1998)Cite this article

In this issue, Davide Lauro and colleagues4 describe a new transgenic model in which insulin signalling is severely impaired in muscle and adipose tissue, leading to a moderate defect in insulin action in these tissues. Insulin signalling in liver remains intact, and the mice do not develop overt diabetes; a finding consistent with lack of overt hyperglycaemia in mice sporting either a severe depletion –greater than 90% – of insulin receptor (IR; ref. 5) or a dominant IR (ref. 6), in muscle. These data challenge the generally accepted belief that deficient insulin signalling in skeletal muscle is a major contributor to type 2 diabetes. Lauro et al. propose that the impairment of hepatic insulin action in type 2 diabetes is intrinsic and possibly genetically determined.

Is the hepatic defect primary or secondary?

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Figure 1: Reciprocal relationship between insulin secretion and insulin action.
Figure 2: Alternative models for the pathogenesis of type 2 diabetes mellitus.

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Authors and Affiliations

  1. Endocrine Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, 02215, Massachusetts, USA

    Barbara B Kahn

  2. Department of Medicine, Diabetes Research Center, Albert Einstein College of Medicine, The Bronx, 10461, New York, USA

    Luciano Rossetti

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  1. Barbara B Kahn
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  2. Luciano Rossetti
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Kahn, B., Rossetti, L. Type 2 diabetes — who is conducting the orchestra?. Nat Genet 20, 223–225 (1998). https://doi.org/10.1038/3018

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