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Insulin Regulation of Proteostasis and Clinical Implications
Journal article   Open access   Peer reviewed

Insulin Regulation of Proteostasis and Clinical Implications

Haleigh A. James, Brian T. O'Neill and K. Sreekumaran Nair
Cell metabolism, Vol.26(2), pp.310-323
08/01/2017
DOI: 10.1016/j.cmet.2017.06.010
PMCID: PMC8020859
PMID: 28712655
url
https://doi.org/10.1016/j.cmet.2017.06.010View
Published (Version of record) Open Access

Abstract

Maintenance and modification of the cellular proteome are at the core of normal cellular physiology. Although insulin is well known for its control of glucose homeostasis, its critical role in maintaining proteome homeostasis (proteostasis) is less appreciated. Insulin signaling regulates protein synthesis and degradation as well as posttranslational modifications at the tissue level and coordinates proteostasis at the organism level. Here, we review regulation of proteostasis by insulin in postabsorptive, postprandial, and diabetic states. We present the effects of insulin on amino acid flux in skeletal muscle and splanchnic tissues, the regulation of protein quality control, and turnover of mitochondrial protein pools in humans. We also review the current evidence for the mechanistic control of proteostasis by insulin and insulin-like growth factor 1 receptors based on preclinical studies. Finally, we discuss irreversible posttranslational modifications of the proteome in diabetes and how future investigations will provide new insights into mechanisms of diabetic complications.
Cell Biology Endocrinology & Metabolism Life Sciences & Biomedicine Science & Technology

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