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

Published

Journal Article (Review)

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.

Full Text

Duke Authors

Cited Authors

  • Um, SH; D'Alessio, D; Thomas, G

Published Date

  • June 2006

Published In

Volume / Issue

  • 3 / 6

Start / End Page

  • 393 - 402

PubMed ID

  • 16753575

Pubmed Central ID

  • 16753575

International Standard Serial Number (ISSN)

  • 1550-4131

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2006.05.003

Language

  • eng

Conference Location

  • United States