Studies on the Conversion of Proinsulin to Insulin

This is the authors' abstract. We don't add key points for this paper.

A chymotryptic-like fragment of the rat proinsulin connecting peptide (C-peptide) has been isolated from whole rat pancreas. Amino acid analysis and partial sequence determination showed the fragment to contain the NH2-terminal 22 residues of C-peptide I. A radioactive fragment of similar electrophoretic mobility was also isolated from rat pancreatic islets which had been incubated with [3H]-leucine. Stepwise Edman degradation of the radioactive fragment showed the positions of its leucine residues to be identical with those of the unlabeled material. Homogenization of [3H]leucine-labeled rat C-peptide with whole pancreas and extraction under conditions used for the isolation of the fragment did not result in cleavage of the C-peptide to the fragment. Furthermore, the fractional ratio of fragment to C-peptide (normally about 0.2) did not increase when rat islets were incubated with [3H]leucine for 1 hour and then incubated with unlabeled leucine for 1, 2, or 3 hours. Treatment of a mixture of [3H]leucine-labeled proinsulin and proinsulin intermediates with high amounts of trypsin resulted in the release of the C-peptide fragment as well as desglutamine (residue 31) C-peptide. It is concluded that a chymotrypsin-like cleavage in the C-peptide region of proinsulin or in one of its intermediates occurs normally during the conversion of proinsulin to insulin in the rat.