Lucy Y.-H. Tseng

The 34 kilodalton insulin-like growth factor binding proteins in human cerebrospinal fluid and the A673 rhabdomyosarcoma cell line are human homologues of the rat BRL-3A binding protein

Three members of a family of insulin-like growth factor binding proteins have been identified by nucleotide sequencing of cDNA clones: the binding subunit of the 150 kDa IGF-binding protein complex in human serum, the 30 kDa IGF binding protein in human amniotic fluid, and a 30 kDa binding protein (BP-3A) isolated from the rat BRL-3A cell line. The present study demonstrates by molecular hybridization and immunoreactivity that the human counterpart of rat BP-3A is a 34 kDa IGF binding protein that is present in human cerebrospinal fluid and is synthesized and secreted by the A673 human rhabdomyosarcoma cell line.

Post-transcriptional regulation of insulin-like growth factor binding protein-2 mRNA in diabetic rat liver

IGFBP-1 and IGFBP-2 mRNAs are increased in the livers of streptozotocin-diabetic rats. A corresponding increase is observed in transcription of the IGFBP-1 but not the IGFBP-2 gene, indicating that the increase in steady-state levels of IGFBP-2 mRNA is a post-transcriptional effect. IGFBP-1 and IGFBP-2 mRNAs also differ in the rapidity of their response to insulin treatment: hepatic IGFBP-1 mRNA is normalized within 1 h, IGFBP-2 mRNA decreases more slowly. These differences suggest that IGFBP-2 may provide more chronic adaptation to metabolic change than IGFBP-1.

Hybrid molecules containing the A-domain of insulin-like growth factor-I and the B-chain of insulin have increased mitogenic activity relative to insulin.

Two synthetic insulin-like compounds consisting of the B-chain of insulin linked via disulfide bonds to A chains corresponding to the A-domain or the A- and D-domains of insulin-like growth factor I (IGF-I) have been evaluated for mitogenic activity and for binding to IGF receptors and IGF carrier proteins. Both compounds are 3- to 5-fold more potent mitogens than insulin, and have a comparably increased affinity for the type I IGF receptor that mediates these mitogenic effects in chick embryo fibroblasts. Neither compound interacts with IGF carrier proteins. These results indicate that the A-domain of IGF-I is importantly involved in its growth-promoting properties.

Rapid Regulation of Insulin-Like Growth Factor Binding Protein-1 Transcription by Insulin in Vivo and in Vitro

Insulin-like growth factor binding protein-1 (IGFBP-1) is distinctive among the IGFBPs in human plasma in its dynamic regulation by metabolic changes [reviewed in 1]. IGFBP-1 levels are increased by acute fasting 2,3 and in diabetes 4,5, and normalized by refeeding and insulin treatment, respectively. IGFBP-1 also is increased by prolonged exercise, growth hormone deficiency and pregnancy 1, and following insulin-induced hypoglycemia 6.

Regulation of Gene Expression of Rat Insulin-Like Growth Factor Binding Proteins 1 and 2

Virtually all of the insulin-like growth factors (IGFs) in extracellular fluids and cell culture medium occur complexed to specific IGF-binding proteins (IGFBPs).1,2 The IGFBPs are a family of proteins that bind IGF-I and IGF-II but are unrelated to IGF receptors. Four IGFBPs have been cloned from human and rat sources,1–8 and partial protein sequence information is available forafifthlGFBP.9–11 OthermembersoftheIGFBPfamilyundoubtedlyexist,12butspecific assignment must await amino acid or nucleotide sequencing.