title: Indication of transcytotic movement of insulin across human bronchial epithelial cells.
abstract: This study was performed to evaluate insulin permeability across human bronchial epithelial cell lines and investigate if insulin is transported via the paracellular or transcellular pathway. The movement of insulin across two bronchial epithelial cells, 16HBE14o- and Calu-3, was studied in the presence or absence of octylmaltoside. Mannitol and propanolol have been used as paracellular and transcellular marker, respectively, and transepithelial electrical resistance (TEER) was determined to investigate the tight junctional integrity of the monolayers. The possible endocytotic mechanism of insulin across these two cell lines was studied by confocal laser scanning microscopy after incubating the cells with fluorescent-labeled insulin. The TEER values for both cell monolayers were >400 Omega cm2 at confluency. There was a decrease in the TEER values when octylmaltoside was added to the apical side of transwells. Similarly, the apparent permeability coefficient (P(app)) values of insulin, mannitol and propanolol, showed an increase with the rise in the concentration of octylmaltoside. In the absence of octylmaltoside, the P(app) values for insulin and the markers were in the following order: propanolol > mannitol > insulin. Confocal microscopic studies revealed that the uptake of insulin by the bronchial epithelial cells perhaps occurs via translocation across the cell. The data presented in this study demonstrate that insulin perhaps moves across the bronchial cells via both paracellular and transcellular pathways.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, Texas Tech University, 1300 Coulter Drive, Amarillo, TX 79106, USA.
authors.forename: Alamdar
authors.initials: A
authors.lastname: Hussain
authors.forename: Fakhrul
authors.initials: F
authors.lastname: Ahsan
mesh_terms: D001692:Biological Transport; D001980:Bronchi / Q000166:cytology* / Q000378:metabolism; D002461:Cell Line, Transformed; D017097:Electric Impedance; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007328:Insulin / Q000493:pharmacokinetics*; D018613:Microscopy, Confocal; D010539:Permeability
chemical_list: D007328:Insulin