Mechanism of insulin uptake in rat alveolar type II and type I-like epithelial cells.

The mechanism underlying the handling of protein and peptide drugs such as insulin in alveolar epithelial cells is still unclear. We therefore examined fluorescein isothiocyanate-labeled (FITC)-insulin uptake in rat primary cultured alveolar type II epithelial cells and in transdifferentiated type I-like cells. FITC-insulin uptake in these cells was much higher than those of FITC-immunoglobulin (IgG), transferrin, and dextran. FITC-insulin uptake was time- and concentration-dependent, and was almost completely inhibited by metabolic inhibitors in both cells, while bafilomycin A(1) inhibited the uptake only in type II cells. Inhibitors of clathrin- and caveolae-mediated endocytosis did not affect FITC-insulin uptake in either type of cell. Dynasore, a dynamin GTPase inhibitor, potently inhibited FITC-insulin uptake in type II cells. These results suggest that the characteristics of insulin uptake in type II and type I cells are different, and dynamin-dependent endocytosis that utilizes neither clathrin nor caveolae is involved in type II cells, while a dynamin-independent pathway is mainly involved in type I cells.