Change in P-glycoprotein and caveolin protein expression in brain striatum capillaries in New Zealand obese mice with type 2 diabetes.

Aims: To investigate the expression of P-gp and caveolins in brain striatum capillaries in inbred mice with type 2 diabetes.

Main 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).

Key Findings: 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.

Significance: 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.