Abnormal processing of pro-IGF-II in patients with hepatoma and in some hepatitis B virus antibody-positive asymptomatic individuals.
Hepatomas are a common malignancy in countries with a high prevalence of hepatitis B virus infections. These tumors may present with severe persistent hypoglycemia. We have studied the possible relationship of production of insulin-like growth factor II (IGF-II) by these tumors and the development of hypoglycemia. Mean IGF-II concentration was not significantly higher in 23 patients with hypoglycemia than in nine patients with euglycemia (542 +/- 61 [SE] micrograms/L vs 382 +/- 52 micrograms/L). Serum IGF-I was more suppressed in patients with hypoglycemia (16 +/- 3 micrograms/L) than in patients with euglycemia (57 +/- 18 micrograms/L). Because an increased percentage of IGF-II in serum of patients with hypoglycemia who have other tumors is present as partially processed pro-IGF-II ("big" IGF-II), we passed sera of patients with hypoglycemia and patients with euglycemia with hepatomas through acidic Bio-Gel P-60 columns. We found that 57% +/- 4.6% of the IGF-II in sera from patients with hypoglycemia was present as big IGF-II compared with 22% +/- 3% in patients with euglycemia with hepatomas (not significantly different from that in normal controls). Four of 11 apparently healthy control subjects who were hepatitis B virus positive also had increased percentages of big IGF-II, suggesting that abnormal processing of pro-IGF-II may result from subtle changes in liver function with this infection. It remains to be determined whether these subjects with increased big IGF-II are at increased risk for the development of hepatomas. In conclusion, we have confirmed marked suppression of IGF-I in the sera of patients with hepatoma and hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Daughaday
W H
WH
Department of Medicine, Washington University School of Medicine, MO 63110.
Wu
J C
JC
Lee
S D
SD
Kapadia
M
M
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D002850:Chromatography, Gel; D005260:Female; D006510:Hepatitis B Antibodies / Q000032:analysis*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D008113:Liver Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D011863:Radioimmunoassay; D012016:Reference Values
D006510:Hepatitis B Antibodies; D011498:Protein Precursors; C066038:proinsulin-like growth factor II; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II