Source:http://linkedlifedata.com/resource/pubmed/id/18299117
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2008-3-31
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pubmed:abstractText |
We aimed to investigate effects of insulin on function and expression of P-glycoprotein (P-GP) in the blood-brain barrier of streptozotocin (STZ)-induced diabetic rats. Brain-to-plasma concentration ratio of vincristine (VCR) in rats was used as an indicator of in vivo function of P-GP. Western blot and quantitative real time-polymerase chain reaction were used to determine protein levels of P-GP and its mdr1a/mdr1b mRNA levels, respectively, in cerebral cortex of rats. In vitro effects of insulin on function and expression of P-GP in primarily cultured rat brain microvessel endothelial cells (rBMECs) were evaluated using rhodamine 123 (Rho123) uptakes and Western blot, respectively. The results showed that 3- and 5-week insulin treatment alleviated the impaired efflux function, expression and mdr1a/mdr1b mRNA levels of P-GP in cerebral cortex of diabetic rats. The 3- and 5-week insulin treatments also significantly enhanced P-GP levels and mdr1a/mdr1b mRNA levels in the cerebral cortex of normal rats. Addition of insulin to the insulin-deficient diabetic rat serum normalized the impaired function and expression of P-GP in rBMECs cultured in diabetic rat serum. When incubated with normal culture medium containing different levels of insulin, the rBMECs exhibited the enhanced P-GP levels and the reduced Rho123 uptake in a concentration-dependent manner. So we may conclude that appropriate level of insulin plays an important role in maintaining the normal function of BBB through regulating the function and expression of P-GP in the diabetic and normal rats.
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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/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Blood Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/P-glycoprotein 2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Vincristine,
http://linkedlifedata.com/resource/pubmed/chemical/multidrug resistance protein 3
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1873-2968
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
75
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1649-58
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18299117-ATP-Binding Cassette Transporters,
pubmed-meshheading:18299117-Animals,
pubmed-meshheading:18299117-Blood Glucose,
pubmed-meshheading:18299117-Blood-Brain Barrier,
pubmed-meshheading:18299117-Cells, Cultured,
pubmed-meshheading:18299117-Cerebral Cortex,
pubmed-meshheading:18299117-Diabetes Mellitus, Experimental,
pubmed-meshheading:18299117-Endothelial Cells,
pubmed-meshheading:18299117-Hypoglycemic Agents,
pubmed-meshheading:18299117-Insulin,
pubmed-meshheading:18299117-Male,
pubmed-meshheading:18299117-P-Glycoproteins,
pubmed-meshheading:18299117-RNA, Messenger,
pubmed-meshheading:18299117-Rats,
pubmed-meshheading:18299117-Rats, Sprague-Dawley,
pubmed-meshheading:18299117-Vincristine
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pubmed:year |
2008
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pubmed:articleTitle |
Insulin therapy restores impaired function and expression of P-glycoprotein in blood-brain barrier of experimental diabetes.
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pubmed:affiliation |
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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