In vivo proteolysis of serum insulin-like growth factor (IGF) binding protein-3 results in increased availability of IGF to target cells.

Abstract. Serum insulin-like growth factor (IGF) and IGF-binding protein (IGF-bp) levels were studied in 92 constitutionally short children and adolescents (height < mean for age −2 sd) and in 13 subjects after completion of growth. IGF levels increased with age in a manner similar to that in normal subjects, but at lower levels (P < 0.001). The values were 0.41 ± 0.03 sem U/ml in 1 to 5 year old children, 0.72 ± 0.03 U/ml in 6-to 16 year old prepubescent children and 0.95 ± 0.05 U/ml during puberty. IGF-bp levels developed in a similar way, the values being 0.45 ± 0.06, 0.61 ± 0.04 and 0.85 ± 0.06 U/ml, respectively, for the three periods considered. Both IGF and IGF-bp levels in each of the three groups were significantly lower than those in normal subjects at the same stage of development. After fusion of the epiphyses, IGF and IGF-bp levels were within the normal range. A longitudinal study was undertaken in 15 subjects, showing increases in height corresponding with increases in IGF levels. For all the subjects studied during their growth period, there was a correlation between height age and IGF levels (r = 0.64, P < 0.001). All the subjects exhibited a normal rise in GH levels following stimulation. Although the possibility of quantitative or qualitative disorders of GH biosynthesis cannot be excluded in some of the cases, our data are compatible with the hypothesis that the growth retardation observed in constitutionally short children results, at least in part, from insufficient IGF production during post-natal growth.

Download Full-text

Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.86.17.6778 ◽

1989 ◽

Vol 86 (17) ◽

pp. 6778-6782 ◽

Cited By ~ 68

Author(s):

W H Daughaday ◽

M Kapadia

Keyword(s):

Growth Factor ◽

Islet Cell ◽

Molecular Form ◽

Binding Protein ◽

Islet Cell Tumor ◽

Target Cells ◽

Insulin Like Growth Factor ◽

Factor Ii ◽

Igf Binding ◽

Igf Binding Protein

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.

Download Full-text