scholarly journals Effects of intravenous insulin-like growth factor-I and insulin administration on insulin-like growth factor-binding proteins in the ovine fetus

2001 ◽  
Vol 171 (1) ◽  
pp. 143-151 ◽  
Author(s):  
WH Shen ◽  
X Yang ◽  
DW Boyle ◽  
WH Lee ◽  
EA Liechty
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Intravenous Infusion ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Intravenous Insulin ◽  
Igf I ◽  
Ovine Fetus ◽  
Igfbp 3

The insulin-like growth factors (IGF) are important anabolic hormones in the mammalian fetus; their anabolic actions are potentially modulated by alterations in the IGF-binding proteins (IGFBP). We have previously shown that the nutritional state of the fetus affects both IGF-I and the IGFBP concentrations. The present study was designed to determine the effect of alterations in insulin and IGF-I circulating concentrations on the IGFBPs. Because both insulin and IGF-I elicit decreases in glucose and amino acid concentrations, the concentrations of these substrates were clamped during the hormone infusions. Sixteen ovine fetuses were chronically catheterized at approximately 115 days of gestation, and experimental procedures performed at approximately 130 days of gestation. Insulin, IGF-I or both were infused for an 8-h period. Baseline concentrations of hormones and binding proteins were obtained, and concentrations were also obtained at the end of the infusion. Hepatic IGFBP-1 mRNA expression was also determined. Intravenous infusion of IGF-I significantly increased IGF-I concentrations in plasma in the ovine fetus. Intravenous infusion of insulin inhibited hepatic IGFBP-1 gene expression when amino acids and glucose were clamped. In contrast, intravenous infusion of recombinant human IGF-I (rhIGF-I) enhanced hepatic IGFBP-1 gene expression. Neither insulin nor rhIGF-I treatment had an effect on hepatic IGFBP-3 gene expression. Insulin did not alter plasma IGFBP-1 significantly, but it increased IGFBP-3 in plasma. rhIGF-I increased both IGFBP-1 and IGFBP-3 protein levels in plasma. The responses of IGFBP-1 and IGFBP-3 to increased plasma IGF-I and insulin may serve to protect the fetus from exaggerated anabolic effects and to blunt the hypoglycemic potential of circulating IGFs and insulin.

Measurement of Human Igf-II Using Sephacryl Extraction: A Rapid and Reliable Assay Method

1996 ◽  
Vol 33 (3) ◽  
pp. 201-208 ◽  
Author(s):  
Barbara H Mason ◽  
Michele A Tatnell ◽  
Ian M Holdaway
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Complete Removal ◽  
Assay Method ◽  
Insulin Like Growth Factor ◽  
Serum Concentrations ◽  
Igf Binding Proteins ◽  
Factor Ii ◽  
Igf I ◽  
Igfbp 3

Measurement of insulin-like growth factor II (IGF-II) in human serum is complicated by the presence of IGF binding proteins and usually involves cumbersome extraction procedures followed by radioimmunoassay. We have utilized an extraction process developed for measuring insulin-like growth factor II in ovine serum using Sephacryl HR100, and have applied this to the extraction of human samples followed by radioimmunoassay for human IGF-II. The assay yielded 98% recovery of unlabelled IGF-II, parallelism between dilutions of eluate and the standard curve, complete removal of binding proteins and near-complete removal of IGF-I, and intra- and interassay coefficients of variation of 5% and 9%, respectively. The normal range for serum IGF-II in women was 490–1056 μg/L, and IGF-II levels were positively correlated with serum concentrations of insulin-like growth factor binding protein-3 (IGFBP-3) but not with IGF-I levels. Mean serum concentrations of IGF-II were reduced below normal in a number of hypopituitary patients and children with short stature and IGF-II concentrations in these subjects correlated positively with IGF-I and IGFBP-3. In acromegalic patients IGF-II levels were usually normal and were negatively correlated with IGF-I concentrations. From our experience with the above results the present assay appears particularly suitable for clinical measurements and research projects where high sample throughput is required.

Interaction between insulin-like growth factor-I and insulin-like growth factor-binding proteins in TC-1 stromal cells

1996 ◽  
Vol 149 (3) ◽  
pp. 519-529 ◽  
Author(s):  
P Grellier ◽  
D Feliers ◽  
D Yee ◽  
K Woodruff ◽  
S L Abboud
Keyword(s):  
Growth Factor ◽  
Stromal Cells ◽  
Binding Proteins ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Mediated Effects ◽  
Igf I ◽  
Igfbp 3

Abstract IGF-I and -II play an important role in regulating bone formation. Bone marrow stromal cells, particularly those with osteoblast-like features, may act in concert with osteoblasts to increase IGF-I and -II levels in the bone microenvironment. Local bioavailability of IGFs, however, is modulated by IGF binding proteins (IGFBPs). We have previously demonstrated that murine TC-1 stromal cells constitutively secrete IGF-I and IGFBPs. In the present study, we determined the phenotype of these cells and used them as a model to explore the effect of IGFBPs on IGF-I-induced mitogenesis. The effect of IGF-I on IGFBPs expressed by TC-1 was also determined. When grown under conditions that promote osteogenic differentiation, TC-1 cells showed high alkaline phosphatase activity and mRNA levels, weakly expressed osteocalcin mRNA, and formed mineralized bone-like nodules. TC-1 cells expressed IGF-I and IGF-II mRNAs, while other stromal phenotypes preferentially expressed IGF-I. IGF-I stimulated TC-1 DNA synthesis in a dose-dependent manner and this effect was inhibited by recombinant IGFBP-1 and -4. Since IGF-I may regulate IGFBP production, the effect of IGF-I on IGFBPs expressed by TC-1 cells was determined. IGF-I increased the abundance of IGFBP-3, -4 and -5 in TC-1 conditioned medium; this correlated with induction of IGFBP-3 mRNA, but not with that of IGFBP-4 or -5 mRNAs. The findings demonstrate that most stromal cells express IGF-I which may act in an autocrine and/or paracrine fashion. The local effects of IGF-I, however, may be blocked by IGFBP-1 or -4. IGF-I regulates the relative abundance of IGFBPs in stromal cells which, in turn, may influence IGF-I-mediated effects on bone remodeling. Journal of Endocrinology (1996) 149, 519–529

Insulin-like growth factor-I (IGF-I) and IGF-binding proteins both decline in the rat during late pregnancy

1990 ◽  
Vol 127 (3) ◽  
pp. 383-390 ◽  
Author(s):  
S. E. Gargosky ◽  
P. E. Walton ◽  
P. C. Owens ◽  
J. C. Wallace ◽  
F. J. Ballard
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Late Pregnancy ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Pregnant Rats ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Igfbp 3

ABSTRACT Insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding proteins (IGFBP) were examined in rat serum during pregnancy and lactation. IGF-I concentrations determined after acid column chromatography of serum were low during the last third of pregnancy. IGF-II was undetectable in pregnant and non-pregnant rats. IGF-binding protein (IGFBP) concentrations, measured as high molecular mass activity in the IGF-I RIA and the IGF-II RRA of acid column fractions, paralleled the changes observed with IGF-I. Western ligand blot analysis of serum from non-pregnant rats revealed a 40–50 kDa IGFBP aligning with IGFBP-3, a smaller 28–30 kDa doublet and 24 kDa IGFBP. Serum from rats in late pregnancy lacked IGFBP-3, whereas the smaller IGFBP persisted during late pregnancy. IGFBP-3 reappeared in postpartum animals. The fall in serum IGF-I is consistent with a maternal catabolic state during late pregnancy which may maximize substrate availability for the developing fetus. Journal of Endocrinology (1990) 127, 383–390

Changes in hepatic insulin-like growth factor-binding proteins -1, -2 and -3 mRNA levels in rats with altered thyroid status

1994 ◽  
Vol 140 (2) ◽  
pp. 251-255 ◽  
Author(s):  
J Rodriguez-Arnao ◽  
J Miell ◽  
M Thomas ◽  
A M McGregor ◽  
R J M Ross
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Binding Proteins ◽  
Major Effect ◽  
Control Group ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Thyroid Status ◽  
Igf Binding Proteins ◽  
Igfbp 3

Abstract Changes in thyroid status have a major effect on the GH/insulin-like growth factor (IGF) axis. The majority of IGF in the circulation is bound to specific IGF-binding proteins (IGFBPs) of which six have been cloned and sequenced. We have studied changes in hepatic gene expression of IGFBP-1, -2 and -3, in male Wistar rats rendered hyperthyroid (thyroxine, 200 μg/kg per day) or hypothyroid (propylthiouracil, 0·1% daily). Littermates of the same age were used as controls (n=6 in each group). Thyroxine was measured by radioimmunoassay, and hepatic IGFBP-1, -2 and -3 mRNA levels by Northern blot analysis using specific rat cDNA probes with a 28S ribosomal probe as a loading control. Mean± s.e.m. thyroxine levels were 247·0±44·5 (hyperthyroid group), <9·0 (hypothyroid group) and 76·0 ± 4·5 nmol/l (control group). IGFBP-1 and -2 mRNA levels in the hypothyroid animals compared with the controls were significantly increased, but similar levels of expression were found in thyrotoxic and control rats. IGFBP-3 mRNA levels in hypothyroid animals were decreased, and increased in thyrotoxic animals. Thus, in the adult rat, hypothyroidism is associated with increased hepatic IGFBP-1 and -2 gene expression, but decreased IGFBP-3 gene expression, while in thyrotoxicosis there are normal IGFBP-1 and -2 mRNA levels but increased IGFBP-3 gene expression. These results suggest that there is specific and different transcriptional regulation for IGFBP-1, -2 and -3 in hypoand hyperthyroid rats. Journal of Endocrinology (1994) 140, 251–255

scholarly journals Insulin-like growth factor (IGF)-II binding to IGF-binding proteins and IGF receptors is modified by deletion of the N-terminal hexapeptide or substitution of arginine for glutamate-6 in IGF-II

1993 ◽  
Vol 293 (3) ◽  
pp. 713-719 ◽  
Author(s):  
G L Francis ◽  
S E Aplin ◽  
S J Milner ◽  
K A McNeil ◽  
F J Ballard ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Biological Activities ◽  
Biological Properties ◽  
Hepatoma Cells ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Anabolic Response ◽  
Igf I ◽  
Igf Binding

Recombinant insulin-like growth factor-II (IGF-II) and two structural analogues, des(1-6)IGF-II and [Arg6]-IGF-II, were produced to investigate the role of N-terminal residues in binding to IGF-binding proteins (IGFBPs) and hence the biological properties of the modified peptides. The growth factors were modelled on two previously characterized variants of IGF-I, des(1-3)IGF-I and [Arg3]-IGF-I, which both show substantially decreased binding to IGFBPs and were expressed as fusion proteins in Escherichia coli. The biological activities of the corresponding analogues of IGF-I and IGF-II were compared in rat L6 myoblasts and H35B hepatoma cells. In the L6-myoblast protein-synthesis assay, the IGF-II analogues, des(1-6)IGF-II and [Arg6]-IGF-II, were slightly more potent than IGF-II but about 10-fold less potent than IGF-I and 100-fold less potent than the respective IGF-I analogues, des(1-3)IGF-I and [Arg3]IGF-I. In H35 hepatoma cells the anabolic response measured was the inhibition of protein breakdown, and the potency order was insulin >>> [Arg3]-IGF-I > des(1-3)IGF-I > [Arg6]-IGF-II > des(1-6)IGF-II > IGF-I > IGF-II. Binding of the IGFs and their analogues to the type 1 IGF receptor in L6 myoblasts and to the insulin receptor in H35 hepatoma cells did not fully explain the observed anabolic potency differences. Moreover, binding of all four analogues to the IGFBPs secreted by L6 myoblasts and H35B hepatoma cells was greatly decreased compared with the parent IGF. We conclude that the observed anabolic response to each IGF was determined by their relative binding to the competing cell receptor and IGFBP binding sites present.

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