{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T10:32:01Z","timestamp":1761129121117},"reference-count":12,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,8,1]]},"abstract":"<jats:p>Hepatitis C-associated osteosclerosis (HCAO) is a rare syndrome of adult-onset osteosclerosis. An understanding of the factor(s) leading to the stimulation of bone formation in these patients may provide novel anabolic approaches for the treatment of osteoporosis. We have demonstrated that HCAO patients have a specific increase in circulating big IGF-II (IGF-IIE) and IGF-binding protein-2 (IGFBP-2) levels, and that IGF-IIE and IGFBP-2 circulate together in a bioavailable, 50-kDa complex. Patients with nonislet cell tumor hypoglycemia (NICTH) also have increased circulating IGF-IIE and IGFBP-2 levels. However, HCAO patients do not exhibit hypoglycemia, nor do NICTH patients exhibit obvious osteosclerosis. Thus, to better understand the reason(s) for the differing clinical manifestations of the IGF-IIE excess in the two syndromes, we characterized IGF-IIE in HCAO and NICTH sera using recently developed antibodies (Ab) recognizing either the full-length IGF-IIE 89-amino acid C-terminal extension peptide (IIE138\u2013156 Ab) or specific cleavage forms of IGF-IIE (IIE78\u201388 Ab and IIE89\u2013101 Ab). The predominant IGF-IIE form in HCAO serum migrated on SDS-PAGE as a single band at approximately 18 kDa that reacted with the IIE89\u2013101 Ab. On the other hand, the predominant form in NICTH serum migrated as a doublet of 14 and 16 kDa that reacted with the IIE78\u201388 Ab. There results are consistent with differential processing of the IGF-IIE precursor at predicted cleavage sites producing IGF-IIE1\u2013104 and IGF-IIE1\u201388 in HCAO and NICTH, respectively. As these two forms may have differing biological activities and\/or targeting properties, our findings may explain at least in part the different manifestations of IGF-IIE overproduction in the two syndromes.<\/jats:p>","DOI":"10.1210\/jcem.87.8.8783","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:08:23Z","timestamp":1389200903000},"page":"3867-3870","source":"Crossref","is-referenced-by-count":24,"title":["Use of Site-Specific Antibodies to Characterize the Circulating Form of Big Insulin-Like Growth Factor II in Patients with Hepatitis C-Associated Osteosclerosis"],"prefix":"10.1210","volume":"87","author":[{"given":"Sundeep","family":"Khosla","sequence":"first","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic and Mayo Foundation (S.K., C.A.C.), Rochester, Minnesota 55905"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. John","family":"Ballard","sequence":"additional","affiliation":[{"name":"GroPep Ltd. 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