title: Familial hyperproinsulinemia: partial characterization of circulating proinsulin-like material.
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.
mesh_terms: D000595:Amino Acid Sequence; D002096:C-Peptide / Q000097:blood; D002869:Chromosome Aberrations / Q000097:blood* / Q000235:genetics; D025063:Chromosome Disorders; D005260:Female; D006801:Humans; D008297:Male; D011384:Proinsulin / Q000097:blood*; D011863:Radioimmunoassay
chemical_list: D002096:C-Peptide; D011384:Proinsulin