Abstract
Human diabetes can have several causes among which are the biosynthesis and secretion of mutant insulins with defective function. We recently described a patient whose diabetes resulted from secretion of an insulin in which leucine substituted for phenylalanine at position B24 (refs 1–4). 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 structure5,6. We now describe the molecular abnormality of hyperproinsulinaemia in which large amounts of a proinsulin-like peptide are secreted7–10. The circulating proinsulin-like material from patients in one of the two known families with hyperproinsulinaemia9,10 turns out to be a biosynthetic intermediate of proinsulin conversion in which the C peptide remains joined to the insulin A chain (see refs 11–13 for reviews of proinsulin biosynthesis and conversion). An amino acid alteration at position 65 (a position normally filled by arginine) apparently blocks conversion of the intermediate to biologically active insulin.
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Robbins, D., Blix, P., Rubenstein, A. et al. A human proinsulin variant at arginine 65. Nature 291, 679–681 (1981). https://doi.org/10.1038/291679a0
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DOI: https://doi.org/10.1038/291679a0
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