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 elongati on at the C-terminal, is found in the circulation and in different bod y 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 inc reased levels in patient serum, sometimes causing hypoglycemia (nonisl et cell tumor-induced hypoglycemia). We have developed a RIA for a 15- amino acid part of the E-peptide. By using the E(16)-peptide as the la beled ligand, this RIA is unaffected by the presence of IGF-binding pr otein in the samples. Gel chromatography under acid and neutral condit ions revealed that all IGF-IIE was detected without prior separation o f serum. Using recombinant IGF-IIE(21) as standard, we determined norm al levels in 70 males and 61 females between 20-70 yr of age. The aver age was 46.6 +/- 1.1 mu g/L, and the 95% confidence interval was betwe en 21.4-71.9 mu g/L. A significantly higher level was found in males ( 49.0 +/- 1.6 mu g/L) compared to females (44.2 +/- 1.3 mu g/ L). In tw o nonislet cell tumor-induced hypoglycemia patients, levels of immunor eactive (ir) IGF-IIE were 2.5-3 times normal levels. GH-deficient pati ents had normal levels, but daily sc injections of recombinant human I GF-I decreased serum irIGF-IIE by 40%. Insulin-dependent diabetic pati ents undergoing liver venous catheterization had normal basal levels o f irIGF-IIE in peripheral blood. A 180-min insulin infusion decreased the levels significantly in the vena hepatica, but no splanchnic gradi ent was observed.