Source:http://linkedlifedata.com/resource/pubmed/id/11342532
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
29
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| pubmed:dateCreated |
2001-7-16
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| pubmed:abstractText |
We previously isolated dephostatin from Streptomyces as a novel inhibitor of CD45-associated protein-tyrosine phosphatase. We prepared Et-3,4-dephostatin as a stable analogue and found it to inhibit PTP-1B and SHPTP-1 protein-tyrosine phosphatases selectively but not to inhibit CD45 and leukocyte common antigen-related phosphatase ones effectively. Et-3,4-dephostatin increased the tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 with or without insulin in differentiated 3T3-L1 mouse adipocytes. The increase of tyrosine phosphorylation by Et-3,4-dephostatin was more prominent in 6-h than in 30-min incubation. It also increased phosphorylation and activation of Akt with or without insulin. Et-3,4-dephostatin also enhanced translocation of glucose transporter 4 from the cytoplasm to the membrane and 2-deoxy-glucose transport. Et-3,4-dephostatin-induced glucose uptake was inhibited by SB203580, a p38 inhibitor, but not by PD98059, a MEK inhibitor, or by cycloheximide as insulin-induced uptake. Interestingly, although LY294002, a phosphatidylinositol 3-kinase inhibitor, inhibited the insulin-induced glucose uptake completely, it only partially inhibited the Et-3,4-dephostatin-induced uptake. It also blocked insulin-induced glucose transporter 4 translocation but not the Et-3,4-dephostatin-induced one. The increase in c-Cbl tyrosine phosphorylation caused by Et-3,4-dephostatin was stronger than that in insulin receptor phosphorylation. These observations indicate that a phosphatidylinositol 3-kinase-independent pathway involving c-Cbl is more important in Et-3,4-dephostatin-induced glucose uptake than in insulin-induced uptake. Et-3,4-dephostatin showed an in vivo antidiabetic effect in terms of reducing the high blood glucose level in KK-A(y) mice after oral administration. Thus, Et-3,4-dephostatin potentiated insulin-related signal transductions in cultured mouse adipocytes and showed an antidiabetic effect in mice.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Catecholamines,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyglucose,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroso Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
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/Tyrosine
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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 | |
| pubmed:issnType |
Print
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| pubmed:day |
20
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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 |
27511-8
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:11342532-3T3 Cells,
pubmed-meshheading:11342532-Adipocytes,
pubmed-meshheading:11342532-Animals,
pubmed-meshheading:11342532-Catecholamines,
pubmed-meshheading:11342532-Chromones,
pubmed-meshheading:11342532-Deoxyglucose,
pubmed-meshheading:11342532-Enzyme Activation,
pubmed-meshheading:11342532-Enzyme Inhibitors,
pubmed-meshheading:11342532-Hypoglycemic Agents,
pubmed-meshheading:11342532-Insulin,
pubmed-meshheading:11342532-Mice,
pubmed-meshheading:11342532-Morpholines,
pubmed-meshheading:11342532-Nitroso Compounds,
pubmed-meshheading:11342532-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11342532-Protein Tyrosine Phosphatases,
pubmed-meshheading:11342532-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11342532-Proto-Oncogene Proteins,
pubmed-meshheading:11342532-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:11342532-Signal Transduction,
pubmed-meshheading:11342532-Tyrosine
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| pubmed:year |
2001
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| pubmed:articleTitle |
Potentiation of insulin-related signal transduction by a novel protein-tyrosine phosphatase inhibitor, Et-3,4-dephostatin, on cultured 3T3-L1 adipocytes.
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| pubmed:affiliation |
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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