Cited by 690PI3K/AKT/mTOR signaling in cancerMetabolism, Diabetes, and CancerMuscle metabolism and nutrition

Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1

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Um, Sung Hee, D'Alessio, David, Thomas, George·2006·Cell Metabolism

Abstract

Nutrient overload leads to obesity, insulin resistance, and often type 2 diabetes. Whereas increased fat intake is commonly cited as the major factor in diet-induced dysmetabolic states, increased protein consumption also contributes, through elevated circulating amino acids. Recent studies have revealed that ribosomal protein S6 kinase 1, S6K1, an effector of mTOR, is sensitive to both insulin and nutrients, including amino acids. Although S6K1 is an effector of growth, recent reports show that amino acids also negatively affect insulin signaling through mTOR/S6K1 phosphorylation of IRS1. Moreover, rather than signaling through the class 1 PI3K pathway, amino acids appear to mediate mTOR activation through class 3 PI3K, or hVps34. Consistent with this, infusion of amino acids into humans leads to S6K1 activation, inhibition of insulin-induced class 1 PI3K activation, and insulin resistance. Thus, S6K1 may mediate deleterious effects, like insulin resistance, and potentially type 2 diabetes in the face of nutrient excess.

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Crossref · 10.1016/j.cmet.2006.05.003

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  • mTORC1 activation of S6 kinase blocks insulin signaling.

    “Insulin is a critical mediator of adaptive immune effector function against respiratory infections172, and mTORC1 activation of S6 kinase blocks insulin signaling173,174.”

    From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [174]

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Authors
Um, S. H., D'Alessio, D., & Thomas, G.
Affiliations
University of Cincinnati (US)
Corresponding author
Thomas, George
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2006-06
Volume
3
Issue
6
Pages
393-402
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2166307667
Cited by
690
References
105
Citations by year
2026: 13 · 2025: 22 · 2024: 24 · 2023: 25 · 2022: 32 · 2021: 26 · 2020: 33 · 2019: 33 · 2018: 33 · 2017: 27 · 2016: 26 · 2015: 37 · 2014: 42 · 2013: 43 · 2012: 56
FWCI
3.10
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords
nutrient overload, insulin resistance, ribosomal protein S6 kinase 1, S6K1, mTOR signaling, amino acids, type 2 diabetes, obesity, IRS-1 phosphorylation, Vps34, dietary protein
MeSH terms
Adipose Tissue, Amino Acids, Animals, Glucose, Homeostasis, Humans, Insulin, Insulin Resistance, Muscles, Nutritional Status, Signal Transduction, Phosphatidylinositol 3-Kinases, Ribosomal Protein S6 Kinases, 90-kDa

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