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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1979 Jun;76(6):2881–2885. doi: 10.1073/pnas.76.6.2881

Familial hyperproinsulinemia: partial characterization of circulating proinsulin-like material.

K H Gabbay, R M Bergenstal, J Wolff, M E Mako, A H Rubenstein
PMCID: PMC383713  PMID: 288074

Abstract

Familial hyperproinsulinemia is an autosomal dominant defect that is associated with strikingly elevated levels of serum proinsulin-like material. Our studies show that trypsin converts familial hyperproinsulinemia proinsulin to insulin more slowly than it converts a 131I-labeled porcine proinsulin marker. Molar yields of insulin indicated that the material may be an intermediate proinsulin. Studies with two human C-peptide antisera that differ in their relative immunoreactivity with human C-peptide and proinsulin showed that the two antisera reacted equally with familial hyperproinsulinemia proinsulin, suggesting that it is a partially cleaved proinsulin intermediate. Sulfitolysis of highly purified material to break the inter- and intra-chain disulfide bridges and subsequent adsorption on a specific B-chain antibody covalently bound to Sepharose beads showed that the C-peptide was still connected to the B-chain. These data indicate that familial hyperproinsulinemia proinsulin is normally cleaved at the C-peptide-A-chain linkage site. A structural abnormality appears to underlie familial hyperproinsulinemia proinsulin, which impairs its cleavage at the B-chain-C-peptide linkage site.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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