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Protein Kinase C Activation Increases Transepithelial Transport of Biologically Active Insulin¹

The Lankenau Medical Research Center, Wynnewood, Pennsylvania 19096 [J. M. M., K. V. L.], and Rosemont College, Rosemont, Pennsylvania 19010 [N. G.]

Protein kinase C activation leads to tight junctional leakiness and, consequently, to increased transepithelial (paracellular) solute flux across epithelial barriers. This leakiness is shown here to result in as much as a 20-fold increase in the transepithelial flux of insulin. Using an epithelial/fibroblast coculture model, this transepithelially transported insulin is shown to be biologically active. The 3T3 fibroblasts situated on one side of the epithelial barrier exhibited increased insulin binding and resulting DNA synthesis when the epithelial junctions were made leaky to insulin on the opposite side of the epithelial barrier. The dramatically enhanced permeability of macromolecules across epithelial cell layers undergoing protein kinase C activation may play a significant role in epithelial cancer, immunology, and drug delivery.

¹ Supported by NIH Grant CA48121.

² To whom requests for reprints should be addressed, at The Lankenau Medical Research Center, 100 Lancaster Avenue, Wynnewood, PA 19096. Phone: (610) 645-2703; Fax: (610) 645-2205; E-mail: jmmulin@ix.netcom.com.

Received 1/14/98. Accepted 3/ 3/98.

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