Change in P-glycoprotein and caveolin protein expression in brain striatum capillaries in New Zealand obese mice with type 2 diabetes.
OBJECTIVE
To investigate the expression of P-gp and caveolins in brain striatum capillaries in inbred mice with type 2 diabetes.


METHODS
Inbred mice with type 2 diabetes (male New Zealand obese; NZO) were compared with related mice without diabetes (female NZO and New Zealand White). Protein expression of P-gp and caveolins in capillaries of the brain striatum was examined by immunohistochemical analysis. P-gp efflux pump activity in the blood-brain barrier (BBB) was measured by in vivo brain microdialysis. Regulation of P-gp and caveolin expression was examined in cultured adult rat brain endothelial cells (ARBEC).


RESULTS
In capillaries in the brain striatum, expression of P-gp and caveolins was higher and lower, respectively, in mice with type 2 diabetes compared with non-diabetic mice. Brain extracellular concentrations of intravenously injected rhodamine 123 were more than 50-60% lower in type 2 diabetic mice. Insulin and PMA treatments significantly increased P-gp expression, whereas the same treatments decreased caveolin expression in ARBEC.


CONCLUSIONS
Protein expression of P-gp and caveolins can be regulated in animals with type 2 diabetes. These changes may be important in modulating P-gp activity in the BBB in type 2 diabetes.
Wu
Kuo-Chen
KC
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Pan
Huei-Ju
HJ
Yin
Hsiang-Shu
HS
Chen
Mei-Ru
MR
Lu
Shao-Chun
SC
Lin
Chun-Jung
CJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002196:Capillaries / Q000378:metabolism*; D022461:Caveolins / Q000378:metabolism*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000098:blood supply / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008820:Mice, Obese; D051381:Rats; D012015:Reference Standards; D015854:Up-Regulation
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D022461:Caveolins; D051246:Glucose Transport Proteins, Facilitative