Abstract: AIM: To investigate the expression and transport function of P-glycoprotein ( P-gp ) at the blood-brain barrier ( BBB) in insulin resistance ( IR) rats.METHODS: The rats were fed with high-fat diet to induce insulin resistance.At 6 weeks after the induction, the oral glucose tolerance test ( OGTT) and insulin tolerance test ( ITT) were carried out, and the insulin sensitivity index ( ISI) was determined, all of which were used to evaluate IR.The rats were sacrificed for observing the integrity of the BBB by electron microscopy, and Evans blue was used to examine the permeability of the BBB.The levels of P-gp protein were determined by Western blot, the mRNA levels of mdr1a mdr1b were examined by RT-PCR, and Rhodamine 123 ( Rh123) accumulation tests were used to evaluate the transport function of P-gp at the BBB in the rats.RESULTS: The rats fed with high-fat diet displayed overweigh, abnormal glucose tolerance, significant increase in their fasting serum insulin ( FINS) and significant decrease in insulin sensitivity, compared with those of control rats, at 6 weeks after the induction.The data of Evans blue test and electron microscopy showed that no significant changes of the permeability and integrity of BBB were found in IR rats. The data of Rh123 accumulation test suggested that the transport function of P-gp at the BBB was impaired in the IR rats.The data of Western blot and RT-PCR showed that the levels of P-gp protein and mRNA levels of mdr1a were decreased significantly at the BBB in the IR rats.CONCLUSION: IR impairs the transport function of P-gp, which that results from the down-regulation of its expression at the BBB.

Key words: P-glycoprotein, blood-brain barrier, insulin resistance