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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
27
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pubmed:dateCreated |
2000-8-16
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pubmed:abstractText |
The effects of a high concentration of glucose on the insulin receptor-down signaling were investigated in human hepatoma (HepG2) cells in vitro to delineate the molecular mechanism of insulin resistance under glucose toxicity. Treatment of the cells with high concentrations of glucose (15-33 mm) caused phosphorylation of serine residues of the insulin receptor substrate 1 (IRS-1), leading to reduced electrophoretic mobility of it. The phosphorylation of IRS-1 with high glucose treatment was blocked only by protein kinase C (PKC) inhibitors. The high glucose treatment attenuated insulin-induced association of IRS-1 and phosphatidylinositol 3-kinase and insulin-stimulated phosphorylation of Akt. A metabolic effect of insulin, stimulation of glycogen synthesis, was also inhibited by the treatment. In contrast, insulin-induced association of Shc and Grb2 was not inhibited. Treatment of the cells with high glucose promoted the translocation of PKCepsilon and PKCdelta from the cytosol to the plasma membrane but not that of other PKC isoforms. Finally, PKCepsilon and PKCdelta directly phosphorylated IRS-1 under cell-free conditions. We conclude that a high concentration of glucose causes phosphorylation of IRS-1, leading to selective attenuation of metabolic signaling of insulin. PKCepsilon and PKCdelta are involved in the down-regulation of insulin signaling, and they may lie in a pathway regulating the phosphorylation of IRS-1.
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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/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Vesicular...,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen,
http://linkedlifedata.com/resource/pubmed/chemical/IRS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoamino Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
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/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/SHC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Shc Signaling Adaptor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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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 |
7
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
20880-6
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10764799-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:10764799-Adaptor Proteins, Vesicular Transport,
pubmed-meshheading:10764799-Carcinoma, Hepatocellular,
pubmed-meshheading:10764799-Down-Regulation,
pubmed-meshheading:10764799-GRB2 Adaptor Protein,
pubmed-meshheading:10764799-Glucose,
pubmed-meshheading:10764799-Glycogen,
pubmed-meshheading:10764799-Humans,
pubmed-meshheading:10764799-Insulin Receptor Substrate Proteins,
pubmed-meshheading:10764799-Isoenzymes,
pubmed-meshheading:10764799-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:10764799-Phosphoamino Acids,
pubmed-meshheading:10764799-Phosphoproteins,
pubmed-meshheading:10764799-Phosphorylation,
pubmed-meshheading:10764799-Protein Kinase C,
pubmed-meshheading:10764799-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10764799-Proteins,
pubmed-meshheading:10764799-Proto-Oncogene Proteins,
pubmed-meshheading:10764799-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:10764799-Receptor, Insulin,
pubmed-meshheading:10764799-Shc Signaling Adaptor Proteins,
pubmed-meshheading:10764799-Signal Transduction,
pubmed-meshheading:10764799-Tumor Cells, Cultured
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pubmed:year |
2000
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pubmed:articleTitle |
Selective attenuation of metabolic branch of insulin receptor down-signaling by high glucose in a hepatoma cell line, HepG2 cells.
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pubmed:affiliation |
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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