Effects of the permeability enhancers, tetradecylmaltoside and dimethyl-beta-cyclodextrin, on insulin movement across human bronchial epithelial cells (16HBE14o-).
The permeability of human bronchial epithelial cells (16HBE14o(-)) to radiolabelled insulin ([125I]insulin) formulated in the absence or presence of two different saccharide-containing permeability enhancers was investigated. In the absence of either enhancer, mannitol permeability and transepithelial electrical resistance (R(TE)) remained essentially unaffected for the duration of a 2-h experiment. Addition of either 0.125% tetradecylmaltoside (TDM) or 1% dimethyl-beta-cyclodextrin (DMBCD) to the apical surface of cells resulted in increased mannitol permeability and decreased R(TE), suggesting a loosening of cellular tight junctions and a concomitant increase in paracellular movement. Addition of [125I]insulin to the apical side of 16HBE14o(-) cells in the absence or presence of 1% DMBCD resulted in little or no [125I]insulin movement to the basolateral chamber or degradation in the apical chamber. However, in the presence of 0.125% TDM, the amount of intact [125I]insulin remaining in the apical chamber was substantially decreased, while [125I]insulin and 125I-labeled fragments were recovered on the basolateral side of the cells after 2 h. These findings provide evidence that the loosening of the tight junctions between cells achieved with DMBCD is not sufficient to stimulate transepithelial insulin movement, whereas exposure to 0.125% TDM causes an increase in [125I]insulin permeation and degradation.
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D001692:Biological Transport; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D003505:Cyclodextrins / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000493:pharmacokinetics*; D008320:Maltose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008353:Mannitol / Q000378:metabolism; D010539:Permeability; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D047392:beta-Cyclodextrins
D000277:Adjuvants, Pharmaceutic; D003505:Cyclodextrins; D007328:Insulin; D047392:beta-Cyclodextrins; C459187:tetradecyl maltoside; D008353:Mannitol; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D008320:Maltose