Secretion of Proinsulin C-Peptide by Pancreatic β Cells and its Circulation in Blood

Abstract

BIOSYNTHETIC studies with human islet cell tumours^1,2, rat^2,3 and codfish⁴ islets, and foetal calf pancreas⁵ have shown that insulin is formed from proinsulin, a single-chain polypeptide precursor. This protein has subsequently been purified from commercial preparations of crystalline insulin⁶, and the amino-acid sequences of porcine⁷ and bovine⁸ proinsulin have been determined. The molecule begins at the N-terminus with the B-chain sequence of insulin, terminates with the insulin A-chain and bears a connecting segment of thirty (bovine) or thirty-three (porcine) amino-acids linking the two chains. Although 30 per cent of the amino-acid sequences of these connecting segments differ, identical pairs of basic amino-acids occur at each end in both species. Limited tryptic digestion in each case liberates desalanyl–insulin, alanyl–arginine, free arginine and the remainder of the connecting segment as an intact peptide^6,7.