Characterization of insulin-like growth factor II (IGF-II) and IGF binding proteins in patients with non-islet-cell tumor hypoglycemia.
Insulin-like growth factor II (IGF-II) in serum and tumor extracts from five patients with non-islet-cell tumor hypoglycemia (NICTH) has been characterized. These tumors contained large quantities of IGF-II (2.4-14.2 micrograms/g tissues). The serum IGF-II levels in four of five patients were a little high and the serum IGF-I levels in five patients were low. The serum IGF-II/IGF-I ratios in these patients ranged from 24.1 to 64.2, and the values were significantly greater than those in normal subjects (1.7-7.1). When the sera were gel-filtered on a Sephacryl S-200 column under neutral conditions, the proportion of the free form of IGF-II was not increased. However, in four of five patients, an abnormal IGF-II-IGF binding protein complex was found. When serum IGF binding proteins (IGFBPs) were analyzed by Western ligand blotting, serum IGFBP-2 increased in these patients. When the tumor extracts and sera were gel-filtered on a Biogel P-60 column under acidic conditions, the majority of IGF-II in these sera was a big form of IGF-II. As compared to authentic IGF-II, insulin receptor reactivities and IGF-II receptor reactivities of tumor extracted IGF-II increased in two of three patients. These data indicate that in patients with NICTH, heterogenous IGF-II is produced in respect of size and bioactivities, and that the characteristics of IGF binding protein are altered. Thus, to find IGF-II producing tumors among extrapancreatic tumors associated with hypoglycemia, the quality of IGF-II as well as the quantity should be studied.
Fukuda
I
I
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College, Tokyo, Japan.
Hizuka
N
N
Takano
K
K
Asakawa-Yasumoto
K
K
Shizume
K
K
Demura
H
H
D000368:Aged; D001345:Autoradiography; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D002850:Chromatography, Gel; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000209:etiology; D018971:Insulin-Like Growth Factor Binding Protein 2; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000150:complications / Q000378:metabolism; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000032:analysis; D013002:Somatomedins / Q000378:metabolism*; D014020:Tissue Extracts / Q000737:chemistry
D002352:Carrier Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D011994:Recombinant Proteins; D013002:Somatomedins; D014020:Tissue Extracts; D007335:Insulin-Like Growth Factor II