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PredicateObject
rdf:type
lifeskim:mentions
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1879-0712
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
602
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
277-82
pubmed:dateRevised
2011-11-17
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
pubmed:year
2009
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.
pubmed:affiliation
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't