Immunoreactive proinsulin-like growth factor-II levels in healthy subjects, patients with growth hormone deficiency, and patients with type 1 diabetes: effects of insulin-like growth factor-I and insulin.
Proinsulin-like growth factor-II (IGF-IIE), with an E-peptide elongation at the C-terminal, is found in the circulation and in different body fluids with mol wt between 10-16 kilodaltons compared to native 7.4-kilodalton IGF-II. Some tumors overexpress IGF-II and IGF-IIE with increased levels in patients serum, sometimes causing hypoglycemia (nonislet cell tumor-induced hypoglycemia). We have developed a RIA for a 15-amino acid part of the E-peptide. By using the E16-peptide as the labeled ligand, this RIA is unaffected by the presence of IGF-binding protein in the samples. Gel chromatography under acid and neutral conditions revealed that all IGF-IIE was detected without prior separation of serum. Using recombinant IGF-IIE21 as standard, we determined normal levels in 70 males and 67 females between 20-70 yr of age. The average was 46.6 +/- 1.1 micrograms/L, and the 95% confidence interval was between 21.4-71.9 micrograms/L. A significantly higher level was found in males (49.0 +/- 1.6 micrograms/L) compared to females (44.2 +/- 1.3 micrograms/L). In two nonislet cell tumor-induced hypoglycemia patients, levels of immunoreactive (ir) IGF-IIE were 2.5-3 times normal levels. GH-deficient patients had normal levels, but daily sc injections of recombinant human IGF-I decreased serum irIGF-IIE by 40%. Insulin-dependent diabetic patients undergoing liver venous catheterization had normal basal levels of irIGF-IIE in peripheral blood. A 180-min insulin infusion decreased the levels significantly in the vena hepatica, but no splanchnic gradient was observed.
Tally
M
M
Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Eriksson
U
U
Thorén
M
M
Brismar
K
K
Hall
K
K
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D013006:Growth Hormone / Q000172:deficiency*; D006503:Hepatic Veins; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000209:etiology; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000150:complications; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism*; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D012727:Sex Characteristics
D001786:Blood Glucose; D007328:Insulin; D011498:Protein Precursors; D011994:Recombinant Proteins; C066038:proinsulin-like growth factor II; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone