Insulin-like growth factor (IGF)-binding proteins inhibit the biological activities of IGF-1 and IGF-2 but not des-(1-3)-IGF-1

Abstract

(1) Many cell types secrete insulin-like growth factor (IGF)-binding proteins that can be expected to sequester free IGF and modify the biological activities of the growth factors. (2) A binding protein purified from bovine kidney (MDBK) cells potently inhibited the ability of IGF-2 to stimulate DNA synthesis or protein accumulation as well as to reduce rates of protein breakdown in chick embryo fibroblasts. The binding protein did not influence the biological activities of des-(1-3)-IGF-1, while effects on IGF-1 were intermediate. Since the chick embryo fibroblasts contain only the type 1 IGF receptor, the MDBK-cell binding protein must have reduced the accessibility of IGF-2 and IGF-1 to that receptor. Binding to the type 2 receptor on L6 myoblasts was also inhibited. (3) Inhibiting effects on both protein breakdown responsiveness to IGF and IGF binding to cell receptors were also observed with human amniotic fluid binding protein, although here IGF-1 and IGF-2 were equipotent. These results contrast with stimulatory responses on different IGF-1 actions of the same binding protein reported previously [Elgin, Busby & Clemmons (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 3254-3258]. (4) The biological potencies of IGF-1, IGF-2 and des-(1-3)-IGF-1 correlate inversely with their binding to proteins released into the medium by cells, so that the enhanced potency of des-(1-3)-IGF-1 is a consequence of it not binding to purified binding proteins or those released by cultured cells.

Increased weight gain, nitrogen retention and muscle protein synthesis following treatment of diabetic rats with insulin-like growth factor (IGF)-I and des(1–3)IGF-I

“…Our second experiment extended these findings by the inclusion of a 2.5-fold higher dose of IGF-I as well as a low dose of the truncated IGF-I analogue, des(l-3)IGF-I, that has been shown to be more potent than IGF-I in cellculture growth studies [20][21][22]. The second experiment was also different because at the beginning of the 7-day treatment period the animals were not insulin-maintained.…”

“…It should be stressed, however, that the responses produced by des(l-3)IGF-I or the higher dose of IGF-I were not significantly greater than those obtained with the lower IGF-I dose. Hence any conclusion that des(l-3)IGF-I is more potent than IGF-I in diabetic rats, as in cultured muscle cells [20][21][22], must await more complete doseresponse studies.…”

Purification, amino acid sequence and characterisation of kangaroo IGF-I

“…Binding of IGFs to receptors (RRA) in rat L6 myoblasts and S. crassicaudata transformed lung fibroblasts was measured as described by Ross et al (1989). Briefly, radioligand and unlabelled growth factors were added to cell monolayers and incubated for 16 h at 4 C. The monolayers were washed and the bound radioactivity measured.…”

Elevated insulin-like growth factor (IGF) binding protein (IGFBP)-2 and IGFBP-4 expression of leukemic T-cells is affected by autocrine/paracrine IGF-II action but not by IGF type I receptor expression

“…Cellular responses to IGFs are mediated by way of the IGF receptors and are affected by at least seven IGF binding proteins (IGFBP-1 to -6 (2); IGFBP-7 (3)). IGFBPs modulate IGF actions by altering their half-lives and by competing with IGF receptors (1,4). IGF receptor expression, cell cycle and other growth factors can affect the tissue-specific production of IGFs and IGFBPs.…”