HCMEC/D3 P-gp protein expression and activity is upregulated by exposure to hyperglycemic conditions, cigarette smoke extract and both combined. a P-gp expression in the membrane fraction was significantly upregulated following 12 h exposure to HG (p < 0.05), CSE (p < 0.01) and HG + CSE (p < 0.05) when compared to the corresponding controls. b Effect on membrane P-gp expression persisted at 24 h exposure under all tested conditions. However, a significant increase in efflux activity was observed only in endothelial cultures exposed to HG + CSE. (p < 0.05; n = 4 biological replicates). *p < 0.05, **p < 0.01, ***p < 0.001 vs. control.