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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.

Authors: Liu, H  Yang, H  Wang, D  Liu, Y  Liu, X  Li, Y  Xie, L  Wang, G 
Citation: Liu H, etal., Eur J Pharmacol. 2009 Jan 14;602(2-3):277-82. Epub 2008 Nov 21.
Pubmed: (View Article at PubMed) PMID:19049803
DOI: Full-text: DOI:10.1016/j.ejphar.2008.11.026

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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RGD Object Information
RGD ID: 2307019
Created: 2009-05-15
Species: All species
Last Modified: 2009-05-15
Status: ACTIVE



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