rdf:type |
|
lifeskim:mentions |
umls-concept:C0021641,
umls-concept:C0033634,
umls-concept:C0044602,
umls-concept:C0079904,
umls-concept:C0225336,
umls-concept:C0242643,
umls-concept:C0285761,
umls-concept:C0851285,
umls-concept:C1150481,
umls-concept:C1368105,
umls-concept:C1451005,
umls-concept:C1704259,
umls-concept:C1705325,
umls-concept:C1705987,
umls-concept:C1882598,
umls-concept:C2350570
|
pubmed:issue |
2-3
|
pubmed:dateCreated |
2009-1-12
|
pubmed:abstractText |
Our previous study showed that insulin restored impaired function and expression of P-glycoprotein in diabetic blood-brain barrier, and further study showed that insulin up-regulated P-glycoprotein expression and function in normal blood-brain barrier, so insulin might be one of the factors that regulated the function and expression of P-glycoprotein in blood-brain barrier of diabetes. In this study, the intracellular pathways that insulin regulated the P-glycoprotein were investigated using primarily cultured rat brain microvessel endothelial cells model. The rat brain microvessel endothelial cells were incubated in normal culture medium containing 50 mU/l insulin and different concentrations of inhibitors for 72 h. The P-glycoprotein function and expression in the rat brain microvessel endothelial cells were assessed using the uptake of P-glycoprotein substrate rhodamine 123 and western blot assay, respectively. It was found that treatment of 50 mU/l insulin significantly increased P-glycoprotein function and expression in rat brain microvessel endothelial cells. This induced effect was blocked by insulin receptor antibody, insulin receptor tyrosine kinase inhibitor I-OMe-AG538, PKC inhibitor chelerythrine and NF-kappaB inhibitor pyrrolidine dithiocarbamate ammonium (PDTC). But this induced effect was not inhibited by phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor LY294002. These results indicated that insulin regulated P-glycoprotein function and expression through signal transduction pathways involving activation of PKC/NF-kappaB but not PI3K/Akt pathway.
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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/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1879-0712
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pubmed:author |
|
pubmed:issnType |
Electronic
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pubmed:day |
14
|
pubmed:volume |
602
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
277-82
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19049803-Animals,
pubmed-meshheading:19049803-Antibodies,
pubmed-meshheading:19049803-Blood-Brain Barrier,
pubmed-meshheading:19049803-Brain,
pubmed-meshheading:19049803-Endothelial Cells,
pubmed-meshheading:19049803-Enzyme Inhibitors,
pubmed-meshheading:19049803-Gene Expression Regulation,
pubmed-meshheading:19049803-Insulin,
pubmed-meshheading:19049803-Microvessels,
pubmed-meshheading:19049803-NF-kappa B,
pubmed-meshheading:19049803-P-Glycoprotein,
pubmed-meshheading:19049803-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:19049803-Protein Kinase C,
pubmed-meshheading:19049803-Protein-Tyrosine Kinases,
pubmed-meshheading:19049803-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:19049803-Rats,
pubmed-meshheading:19049803-Receptor, Insulin,
pubmed-meshheading:19049803-Signal Transduction
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pubmed:year |
2009
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pubmed:articleTitle |
Insulin regulates P-glycoprotein in rat brain microvessel endothelial cells via an insulin receptor-mediated PKC/NF-kappaB pathway but not a PI3K/Akt pathway.
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pubmed:affiliation |
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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