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rdf:type |
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lifeskim:mentions |
umls-concept:C0002520,
umls-concept:C0015744,
umls-concept:C0021641,
umls-concept:C0021655,
umls-concept:C0037083,
umls-concept:C0205160,
umls-concept:C0441712,
umls-concept:C1136240,
umls-concept:C1522538,
umls-concept:C1704259,
umls-concept:C1704336,
umls-concept:C1705987,
umls-concept:C1710082,
umls-concept:C2911691
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pubmed:issue |
41
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pubmed:dateCreated |
2001-10-8
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pubmed:abstractText |
Amino acids have emerged as potent modulators of the mTOR/p70 S6 kinase pathway. The involvement of this pathway in the regulation of insulin-stimulated glucose transport was investigated in the present study. Acute exposure (1 h) to a balanced mixture of amino acids reduced insulin-stimulated glucose transport by as much as 55% in L6 muscle cells. The effect of amino acids was fully prevented by the specific mTOR inhibitor rapamycin. Time course analysis of insulin receptor substrate 1 (IRS-1)-associated phosphatidylinositol (PI) 3-kinase activity revealed that incubation with amino acids speeds up its time-dependent deactivation, leading to a dramatic suppression (-70%) of its activity after 30 min of insulin stimulation as compared with its maximal activation (5 min of stimulation). This accelerated deactivation of PI 3-kinase activity in amino acid-treated cells was associated with a concomitant and sustained increase in the phosphorylation of p70 S6 kinase. In marked contrast, inhibition of mTOR by rapamycin maintained PI 3-kinase maximally activated for up to 30 min. The marked inhibition of insulin-mediated PI 3-kinase activity by amino acids was linked to a rapamycin-sensitive increase in serine/threonine phosphorylation of IRS-1 and a decreased binding of the p85 subunit of PI 3-kinase to IRS-1. Furthermore, amino acids were required for the degradation of IRS-1 during long term insulin treatment. These results identify the mTOR/p70 S6 kinase signaling pathway as a novel modulator of insulin-stimulated glucose transport in skeletal muscle cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
38052-60
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11498541-Amino Acids,
pubmed-meshheading:11498541-Biological Transport,
pubmed-meshheading:11498541-Cell Line,
pubmed-meshheading:11498541-Enzyme Activation,
pubmed-meshheading:11498541-Feedback,
pubmed-meshheading:11498541-Glucose,
pubmed-meshheading:11498541-Hydrolysis,
pubmed-meshheading:11498541-Insulin,
pubmed-meshheading:11498541-Insulin Receptor Substrate Proteins,
pubmed-meshheading:11498541-Insulin Resistance,
pubmed-meshheading:11498541-Muscle, Skeletal,
pubmed-meshheading:11498541-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11498541-Phosphoproteins,
pubmed-meshheading:11498541-Phosphorylation,
pubmed-meshheading:11498541-Protein Kinases,
pubmed-meshheading:11498541-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11498541-Proto-Oncogene Proteins,
pubmed-meshheading:11498541-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:11498541-Ribosomal Protein S6 Kinases,
pubmed-meshheading:11498541-Signal Transduction,
pubmed-meshheading:11498541-TOR Serine-Threonine Kinases,
pubmed-meshheading:11498541-Tyrosine
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pubmed:year |
2001
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pubmed:articleTitle |
Amino acid and insulin signaling via the mTOR/p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells.
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pubmed:affiliation |
Department of Physiology and Lipid Research Unit, Laval University Hospital Research Center, Ste-Foy, Québec G1V 4G2, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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