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Cellular Mechanisms of Insulin Action

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Principles of Diabetes Mellitus

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Abstract

Insulin is a highly pleiotropic hormone, with predominantly anabolic actions in a variety of tissues. Selectivity of final responses to insulin arises both from cell-specific expression of final effector proteins and by activation of different signaling pathways. We will consider first an overview of mechanisms of insulin action in normal human physiology, introducing the pathways, players, and principles involved, before returning to consider how these elements are modulated in insulin-resistant conditions such as obesity and type 2 diabetes. While the critical initial studies in this area were performed in animal and cell systems and later confirmed in humans, for the consideration of pathophysiology we will concentrate on the literature concerning insulin action in humans. The organizing principles of insulin signaling include the following: (1) presence of phosphorylation/dephosphorylation cascades, (2) phosphorylation of specific sites creates recognition domains that permit the formation of multimolecular complexes, (3) complex formation involves scaffolding or adaptor proteins, (4) these multimolecular complexes often target enzymes to specific intracellular locales where critical substrates reside, and (5) posttranslational modifications other than phosphorylation can effect the behavior of steps 2–4.

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Authors and Affiliations

  1. Department of Medicine-Division of Endocrinology and Metabolism, University of California, San Diego, San Diego, CA, USA

    Theodore P. Ciaraldi

  2. VA San Diego Healthcare System, San Diego, CA, USA

    Theodore P. Ciaraldi

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  1. Theodore P. Ciaraldi
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Correspondence to Theodore P. Ciaraldi .

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Editors and Affiliations

  1. Division of Endocrinology, Gerald J. Friedman Diabetes Institute, Lenox Hill Hospital, Hofstra Northwell School of Medicine, Northwell Health, New York, New York, USA

    Leonid Poretsky

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Ciaraldi, T.P. (2017). Cellular Mechanisms of Insulin Action. In: Poretsky, L. (eds) Principles of Diabetes Mellitus. Springer, Cham. https://doi.org/10.1007/978-3-319-18741-9_5

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  • DOI: https://doi.org/10.1007/978-3-319-18741-9_5

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