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Mechanisms of Disease: using genetically altered mice to study concepts of type 2 diabetes

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 164–172 (2008)Cite this article

Abstract

A wide range of genetically engineered murine models of type 2 diabetes have been created to try to understand the site of the primary defect in insulin action, and the relationship between insulin resistance and impaired β-cell function in diabetes. Genetic disruption of various aspects known to be important in diabetes has examined specific facets, including glucose sensing, transcription factors for the insulin gene, the insulin gene itself, insulin and insulin-like growth factor receptors, downstream signaling components and some mutations that increase insulin sensitivity. This article focuses on models that have given insight into insulin resistance and impaired insulin production, especially models that examine molecules involved in the signaling pathway downstream of insulin binding its receptor. These models recapitulate many features of human type 2 diabetes and, although they have emphasized the complexity of this disease, they offer numerous opportunities to characterize particular aspects and eventually fit them together to help delineate the human disease.

Key Points

  • The pathophysiology of type 2 diabetes mellitus includes β-cell dysfunction and insulin resistance

  • Mouse models that have specific gene-deletions are useful for studying disease processes such as diabetes

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Figure 1: Insulin receptor signaling cascades.

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Author information

Authors and Affiliations

  1. D LeRoith is Chief of the Division of Endocrinology, Department of Medicine, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, NY, USA.,

    Derek LeRoith

  2. D Accili is Professor of Medicine and Director, Columbia Diabetes and Endocrinology Research Center, Naomi Berrie Diabetes Center, University College of Physicians and Surgeons, New York.,

    Domenico Accili

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  2. Domenico Accili
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Correspondence to Derek LeRoith.

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LeRoith, D., Accili, D. Mechanisms of Disease: using genetically altered mice to study concepts of type 2 diabetes. Nat Rev Endocrinol 4, 164–172 (2008). https://doi.org/10.1038/ncpendmet0729

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