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A proteolysis study of human monoarginyl-insulin ([Arg(A0)]-HI) and diarginyl-insulin ([Arg(B31)-Arg(B32)]-HI) within hepatic endosomes was undertaken to determine whether the endosomal compartment represents a physiological site for the removal of Arg residues and conversion of Arg-extended insulins into fully processed human insulin.

Endosomal proteolysis of internalised [ArgA0]-human insulin at neutral pH generates the mature insulin peptide in rat liver in vivo