Regulation of binding proteins for insulin-like growth factors (IGF) in humans. Increased expression of IGF binding protein 2 during IGF I treatment of healthy adults and in patients with extrapancreatic tumor hypoglycemia.

Abstract

Insulin-like growth factors (IGFs) in blood form two complexes with specific binding proteins (BPs): a large, growth hormone (GH)-dependent complex with restricted capillary permeability, and a smaller complex, inversely related to GH, with high turnover of its IGF pool and free capillary permeability. The distribution of BPs and of IGFs I and II between these complexes was studied in sera from healthy adults treated with IGF I or/and GH and from patients with extrapancreatic tumor hypoglycemia. Like GH, IGF I administration raises IGF I and two glycosylation variants of IGFBP-3 in the large complex, but unlike GH drastically reduces IGF II. During IGF I infusion, IGFBP-3 appears in the small complex whose IGFBP-2 and IGF I increase three-to fivefold and fivefold, respectively. GH treatment, associated with elevated insulin levels, suppresses IGFBP-2 and inhibits its increase owing to infused IGF I. The small complex of tumor sera contains increased amounts of IGFBP-2 and -3, and two-to threefold elevated IGF IL Conclusions: low GH and/or insulin during IGF I infusion and in extrapancreatic tumor hypoglycemia enhance expression of IGFBP-2 and favor partition of IGFBP-3 into the small complex. Free capillary passage and high turnover of its increased IGF I or II pools may contribute to compensate for suppressed insulin secretion during IGF I infusion or to development of tumor hypoglycemia. (J. Clin. Invest. 1990. 86:952-961.) Key words: IGF binding proteins-IGF I treatment * extrapancreatic tumor hypoglycemia Introduction Insulin-like growth factors (IGFs)' are synthesized and released by many tissues and cell types (1, 2). The liver contributes most of the IGFs in the circulation (1, 3). IGFs are always found in association with specific high-affinity binding proteins (2). As is true for IGFs, the highest concentrations of IGF

Increased levels of circulating free insulin-like growth factors in patients with non-islet cell tumour hypoglycaemia

“…In NICTH, the secretion of GH is suppressed [3], and this results in a reduction in the levels of the GH dependent peptides ALS, IGFBP-3 and IGF-I, and thus ternary complex formation [4,12]. Levels of IGFBP-2, the second most abundant IGFBP, and IGFBP-1 are, on the other hand, increased [5,13]. Whereas the mechanisms regulating IGFBP-2 are still unclear [14], the increase in levels of IGFBP-1 is secondary to the hypoinsulinaemia [15].…”

Normal expression of type 1 insulin‐like growth factor receptor by human osteoarthritic chondrocytes with increased expression and synthesis of insulin‐like growth factor binding proteins

“…In general, each cell type secretes a distinct pattern of binding proteins and changes in their secretion are associated with changes in certain cell functions. In various pathologic states, the level of one or more of these IGFBP has been found to disrupt the normal metabolism through sequestration of the IGF (34,35).…”

Development of neuropeptide drugs that cross the blood-brain barrier

“…Delivery of peptides to the brain can be affected by a number of processes. Peptide drugs can bind to carrier proteins within the blood (1) or can enter the blood cells (2). These processes are in equilibrium, and the release of peptides from these two compartments is dependant on the "off" and "on" rates of the carrier protein.…”

“…Insulin-like growth factor (IGF)-1, a 70-amino acid peptide, has a number of different binding sites within plasma and each has differing binding constants. 1 The level of one IGF binding protein has been shown to be regulated by IGF levels, as well as disease state 2 .…”