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    •   OpenBU
    • School of Medicine
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    • Department of Medicine
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    AMPK Exerts Dual Regulatory Effects on the PI3K Pathway

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    Copyright 2010 Tao et al; licensee BioMed Central Ltd.
    Date Issued
    2010-2-18
    Related DOI
    10.1186/1750-2187-5-1
    Author
    Tao, Rong
    Gong, Jun
    Luo, Xixi
    Zang, Mengwei
    Guo, Wen
    Wen, Rong
    Luo, Zhijun
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    Permanent Link
    https://hdl.handle.net/2144/2937
    Citation
    Tao, Rong, Jun Gong, Xixi Luo, Mengwei Zang, Wen Guo, Rong Wen, Zhijun Luo. "AMPK exerts dual regulatory effects on the PI3K pathway" Journal of Molecular Signaling 5:1. (2010)
    Abstract
    BACKGROUND AMP-activated protein kinase (AMPK) is a fuel-sensing enzyme that is activated when cells experience energy deficiency and conversely suppressed in surfeit of energy supply. AMPK activation improves insulin sensitivity via multiple mechanisms, among which AMPK suppresses mTOR/S6K-mediated negative feedback regulation of insulin signaling. RESULTS In the present study we further investigated the mechanism of AMPK-regulated insulin signaling. Our results showed that 5-aminoimidazole-4-carboxamide-1 ribonucleoside (AICAR) greatly enhanced the ability of insulin to stimulate the insulin receptor substrate-1 (IRS1)-associated PI3K activity in differentiated 3T3-F442a adipocytes, leading to increased Akt phosphorylation at S473, whereas insulin-stimulated activation of mTOR was diminished. In 3T3-F442a preadipocytes, these effects were attenuated by expression of a dominant negative mutant of AMPK α1 subunit. The enhancing effect of ACIAR on Akt phosphorylation was also observed when the cells were treated with EGF, suggesting that it is regulated at a step beyond IR/IRS1. Indeed, when the cells were chronically treated with AICAR in the absence of insulin, Akt phosphorylation was progressively increased. This event was associated with an increase in levels of phosphatidylinositol -3,4,5-trisphosphate (PIP3) and blocked by Wortmannin. We then expressed the dominant negative mutant of PTEN (C124S) and found that the inhibition of endogenous PTEN per se did not affect phosphorylation of Akt at basal levels or upon treatment with AICAR or insulin. Thus, this result suggests that AMPK activation of Akt is not mediated by regulating phosphatase and tensin homologue (PTEN). CONCLUSION Our present study demonstrates that AMPK exerts dual effects on the PI3K pathway, stimulating PI3K/Akt and inhibiting mTOR/S6K.
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    Copyright 2010 Tao et al; licensee BioMed Central Ltd.
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    • MED: Medicine Papers [229]
    • MED: Biochemistry Papers [22]

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