Amino acids and leucine allow insulin activation of the PKB/mTOR pathway in normal adipocytes treated with wortmannin and in adipocytes from db/db mice

@article{Hinault2004AminoAA,
  title={Amino acids and leucine allow insulin activation of the PKB/mTOR pathway in normal adipocytes treated with wortmannin and in adipocytes from db/db mice},
  author={C Hinault and Isabelle Mothe-Satney and Nadine Gautier and John C. Lawrence and E Van Obberghen},
  journal={The FASEB Journal},
  year={2004},
  volume={18}
}
Amino acids are nutrients responsible for mammalian target of rapamycin (mTOR) regulation in mammalian cells. The mTOR protein is mainly known for its role in regulating cell growth, notably via protein synthesis. In addition to amino acids, mTOR is regulated by insulin via a phosphatidylinositol 3‐kinase (PI 3‐kinase)‐dependent pathway. mTOR mediates crosstalk between amino acids and insulin signaling. We show that in freshly isolated rat adipocytes, insulin stimulates the phosphorylation of… 
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TLDR
A mathematical representation of the effects of insulin and essential amino acid (EAA) on phosphorylation of protein kinase B (Akt), mammalian target of rapamycin (mTOR) and eukaryotic initiation factor 4E binding protein 1 (4EBP1), the latter being critical for initiation of protein synthesis is developed.
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TLDR
Current research indicates that mTOR integrates input from multiple upstream pathways, including insulin, growth factors, nutrients, mitogens and energy, which adds to the intricacies of mTOR as a master switch in cell signaling.
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References

SHOWING 1-10 OF 44 REFERENCES
Amino acid and insulin signaling via the mTOR/p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells.
TLDR
The mTOR/p70 S6 kinase signaling pathway is identified as a novel modulator of insulin-stimulated glucose transport in skeletal muscle cells.
Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway.
TLDR
The findings support the conclusion that insulin activates mTOR by promoting phosphorylation of the protein via a signaling pathway that contains PKB.
Bidirectional modulation of insulin action by amino acids.
TLDR
Data support the hypothesis that amino acids act as specific positive signals for maintenance of protein stores, while inhibiting other actions of insulin at multiple levels and indicate crosstalk between hormonal and nutritional signals.
Amino Acid Sufficiency and mTOR Regulate p70 S6 Kinase and eIF-4E BP1 through a Common Effector Mechanism*
TLDR
The present study identifies the operation of a signal tranduction pathway in mammalian cells that provides a checkpoint control, linking amino acid sufficiency to the control of peptide chain initiation, indicating that mTOR is required for the response to amino acids.
Role of leucine in the regulation of mTOR by amino acids: revelations from structure-activity studies.
  • C. Lynch
  • Biology, Medicine
    The Journal of nutrition
  • 2001
TLDR
An overview is presented of the mTOR signaling pathway and its regulation by amino acids, particularly L-leucine, and there is evidence that the mechanism of mTOR activation may be different from cells where mainly leucine is regulatory.
Mammalian Target of Rapamycin Pathway Regulates Insulin Signaling via Subcellular Redistribution of Insulin Receptor Substrate 1 and Integrates Nutritional Signals and Metabolic Signals of Insulin
TLDR
A novel function of mTOR is identified that integrates nutritional signals and metabolic signals of insulin and that the pathway also negatively regulates insulin-stimulated glucose transport, probably through the redistribution of IRS-1.
Regulation of amino acid–sensitive TOR signaling by leucine analogues in adipocytes
TLDR
The structure‐activity relationships of a putative L‐leucine recognition site in adipocytes (LeuRA) that regulates TOR activity were analyzed by examining the effects of leucine analogues on the rapamycin‐sensitive phosphorylation of the translational repressor, eIF‐4E binding protein‐I (4E‐BP1), an index of TOR activity.
Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation.
TLDR
The findings demonstrate that mTOR is a direct target for PKB and support the conclusion that regulation of phosphorylation of Ser(2448) is a point of convergence for the counteracting regulatory effects of growth factors and amino acid levels.
A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells.
TLDR
It is demonstrated that interleukin-3 stimulation induces a wortmannin-sensitive increase in mTOR kinase activity in a myeloid progenitor cell line, and that the activation status of the PI3K-AKT pathway in cancer cells may be an important determinant of cellular sensitivity to the cytostatic effect of rapamycin.
Branched-chain amino acids are essential in the regulation of PHAS-I and p70 S6 kinase by pancreatic beta-cells. A possible role in protein translation and mitogenic signaling.
TLDR
It is demonstrated that essential amino acids, in particular branched-chain amino acids (leucine, valine, and isoleucine), are largely responsible for mediating this effect of phosphorylation of PHAS-I, and proposed that amino acids may be essential for other beta-cell growth factors in addition to insulin and IGF-I to activate this signaling pathway.
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