PROTEIN-KINASE-C ACTIVATION INCREASES TRANSEPITHELIAL TRANSPORT OF BIOLOGICALLY-ACTIVE INSULIN

Protein kinase C activation leads to tight junctional leakiness and, c onsequently, to increased transepithelial (paracellular) solute flux a cross epithelial barriers, This leakiness is shown here to result in a s much as a 20-fold increase in the transepithelial flux of insulin. U sing an epithelial/fibroblast coculture model, this transepithelially transported insulin is shown to be biologically active. The 3T3 fibrob lasts situated on one side of the epithelial barrier exhibited increas ed insulin binding and resulting DNA synthesis when the epithelial jun ctions were made leaky to insulin on the opposite side of the epitheli al barrier, The dramatically enhanced permeability of macromolecules a cross epithelial cell layers undergoing protein kinase C activation ma y play a significant role in epithelial cancer, immunology, and drug d elivery.