Insulin cleavage pattern

The cleavage pattern noted for the various peptides in Table I is consistent in requiring strongly hydrophobic residues on either side of the bond to be cleaved. Cathepsin D is able to act as an aminopeptidase on several small Leu- and Phe-peptides. This agrees with the known slow release of Phe from the NH2-terminus of the B chain of insulin and from position 25 in the peptide Phe25-Ala3Q. 

Studies on characterizing the enzymatic barrier at each delivery site have investigated the pattern of cleavage of enkephalins, substance P, insulin and proinsulin, and have demonstrated the presence of both exo- and endo-peptidases in the various epithelial tissues. What distinguishes one route from another is probably the relative proportion of these proteases, as well as their subcellular distribution. 

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