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


BIOSYNTHETIC studies with human islet cell tumours1,2, rat2,3 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 peptide6,7.

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RUBENSTEIN, A., CLARK, J., MELANI, F. et al. Secretion of Proinsulin C-Peptide by Pancreatic β Cells and its Circulation in Blood. Nature 224, 697–699 (1969).

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