THE INVOLVEMENT OF CYTOSOLIC CHYMOTRYPSIN-LIKE, TRYPSIN-LIKE, AND CUCUMSIN-LIKE ACTIVITIES IN DEGRADATION OF INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I BY EPITHELIAL TISSUES

Using specific substrates, benzyloxycarbonyl-Gly-Gly- Leu-p-nitroanili de, benzyloxycarbonyl-Gly- Gly-Arg-2-naphthylamide and benzyloxycarbon yl-leu-leu-Glu-2-naphthyl cytosolic chymotrypsin-like, trypsin-like an d cucumsin-like activities were determined, respectively, in rat epith elial tissues and differentiated human Caco-2 cells. The cytosolic fra ctions of rat colonic, rectal, nasal, and alveolar epithelial cells an d differentiated human Caco-2 cells contained these three distinct enz yme activities. However, effects of enzyme inhibitors revealed that th ese three distinctive activities were not extensively involved in cyto solic or homogenate degradation of insulin and insulin-like growth fac tor I (IGF-I). It is concluded that proteasome-like activities may not significantly limit nonparenteral absorption of peptide and protein d rugs such as insulin and IGF-I.