Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors.
We reported that serum and tumor from a hypoglycemic patient with a fibrosarcoma contained insulin-like growth factor II (IGF-II), mostly in a large molecular form designated "big IGF-II." We now describe two additional patients with non-islet-cell tumor with hypoglycemia (NICTH) whose sera contained big IGF-II. Removal of the tumor eliminated most of the big IGF-II from the sera of two patients. Because specific IGF-binding proteins modify the bioactivity of IGFs, the sizes of the endogenous IGF-binding protein complexes were determined after neutral gel filtration through Saphadex G-200. Normally about 75% of IGFs are carried as a ternary complex of 150 kDa consisting of IGF, a growth hormone (GH)-dependent IGF-binding protein, and an acid-labile complexing component. The three patients with NICTH completely lacked the 150-kDa complex. IGF-II was present as a 60-kDa complex with variable contributions of smaller complexes. In the immediate postoperative period, a 110-kDa complex appeared rather than the expected 150-kDa complex. Abnormal IGF-II binding may be important in NICTH because the 150-kDa complexes cross the capillary membrane poorly. The smaller complexes present in our patients' sera would be expected to enter interstitial fluid readily, and a 4- to 5-fold increase in the fraction of IGFs reaching the target cells would result.
Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110.
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Daughaday
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Kapadia
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002850:Chromatography, Gel; D005260:Female; D005354:Fibrosarcoma / Q000097:blood*; D006393:Hemangiopericytoma / Q000097:blood*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000209:etiology*; D007334:Insulin-Like Growth Factor I / Q000097:blood; D007335:Insulin-Like Growth Factor II / Q000097:blood*; D007890:Leiomyosarcoma / Q000097:blood*; D008297:Male; D011485:Protein Binding; D013002:Somatomedins / Q000097:blood*; D013899:Thoracic Neoplasms / Q000097:blood*
D015415:Biomarkers; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II