FIGURE 11.

Pathways of conversion of proinsulin to insulin and C-peptide in the beta cell. The pathway shown on the right is predominant normally because PC1/3 acts somewhat earlier than PC2, forming a preferred intermediate for PC2 cleavage, the des-31,32-proinsulin intermediate. In the absence of PC1/3, only ∼10–15% of the proinsulin is processed to insulin. The B chain/C-peptide junction is a better convertase substrate because it is more accessible and has an upstream basic residue (lysine) at the P4 position (B29). The C-peptide/A chain site lacks a P4 basic residue. (See Refs. 79 and 84 for further discussion.)