A human proinsulin variant at arginine 65
Robbins, D.C.; Blix, P.M.; Rubenstein, A.H.; Kanazawa, Y.; Kosaka, K.; Tager, H.S.
Nature 291(5817): 679-681
1981
ISSN/ISBN: 0028-0836 PMID: 7242673 Document Number: 176838
Human diabetes can have several causes among which are the biosynthesis and secretion of mutant insulins with defective function. A patient was described whose diabetes resulted from secretion of an insulin in which leucine substituted for phenylalanine at position B24. Studies showing allelic variation in untranslated and intervening sequences of the human insulin gene (even in normal individuals) have documented a further and unexpected degree of variation in insulin gene structure. The molecular abnormality of hyperproinsulinemia is described in which large amounts of a proinsulin-like peptide are secreted. The circulating proinsulin-like material from patients in 1 of the 2 known families with hyperproinsulinemia is a biosynthetic intermediate of proinsulin conversion in which the C peptide remains joined to the insulin A chain. An amino acid alteration at position 65 (a position normally filled by arginine) apparently blocks conversion of the intermediate to biologically active insulin.