scholarly journals Nutritional regulation of IGF-II, but not IGF-I, is age dependent in sheep

1999 ◽  
Vol 163 (3) ◽  
pp. 395-402 ◽  
Author(s):  
JM Oldham ◽  
JA Martyn ◽  
KM Hua ◽  
NA MacDonald ◽  
SC Hodgkinson ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Plasma Concentrations ◽  
Age Groups ◽  
Nutritional Regulation ◽  
Igf Binding Proteins ◽  
Ewe Lambs ◽  
Igf I ◽  
Age Dependent ◽  
Igf Binding

In post-natal animals, plasma concentrations of IGF-I are tightly regulated by nutritional status. The current study reports that plasma levels of IGF-II in sheep are also regulated by nutrition, but whether plasma IGF-II is increased, decreased or remains the same, depends on the age of the animal. Ewe lambs, ranging in age from 2 days to 2 years, were fed or fasted for lengths of time between 24 and 72 h. Blood samples were taken at intervals of 24 h throughout the treatment period and immediately before slaughter. Plasma concentrations of IGF-I increased with advancing age in fed animals (P<0.001) and were reduced by fasting in all age groups (P<0.001). Plasma concentrations of IGF-II also increased as animals matured (P<0.001), but did not show an overall effect of the fasting treatment. An interaction between age and nutrition (P<0.001) resulted from a decrease in plasma IGF-II in response to fasting in neonatal animals (P<0.01) and, conversely, increased levels of plasma IGF-II in fasted mature animals (P<0.01 or P<0.001). Fasted sheep of peripubertal age showed no change in plasma levels of IGF-II. The nutritional sensitivity of serum IGF-binding proteins (BPs) also changed with age. The 29 kDa BP, which we presume to be BP1, was elevated by fasting in young animals and reduced slightly in older animals. BP2 was increased to a similar magnitude by fasting at all ages. BP3 was depressed by fasting in young animals and showed little change in adults. In contrast, a 24 kDa BP, which is probably BP4, showed little change in young animals and was reduced substantially in older sheep. In conclusion, the response of plasma IGF-II to fasting suggests that this peptide has functions in mediating nutritional stress which depend on the age of the animal, and also that the role of IGF-II may differ from that of IGF-I in adults.

Differential effects of GH stimulation on fasting and prandial metabolism and plasma IGFs and IGF-binding proteins in lean and obese sheep

1997 ◽  
Vol 154 (2) ◽  
pp. 329-346 ◽  
Author(s):  
J P McCann ◽  
S C Loo ◽  
D L Aalseth ◽  
T Abribat
Keyword(s):  
Binding Proteins ◽  
Binding Capacity ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Daily Injection ◽  
Gh Treatment ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Igf Binding ◽  
Igfbp 3

Abstract The effect of body condition per se on plasma IGFs and IGF-binding proteins (IGFBPs) and the whole-body metabolic responses to recombinant DNA-derived bovine GH (rbGH) in both the fed and the fasted state were determined in lean and dietary obese sheep (n=6/group). Sheep at zero-energy balance and equilibrium body weight were injected s.c. for 12 days with 100 μg/kg rbGH immediately before their morning feeding. Before GH treatment, fasting plasma concentrations of insulin (17·0 ± 1·9 vs 7·5 ± 0·7 μU/ml), IGF-I (345 ± 25 vs 248 ± 10 ng/ml), glucose (52·6 ± 1·1 vs 48·3 ± 0·7 mg/dl), and free fatty acid (FFA) (355 ± 45 vs 229 ± 24 nmol/ml) were greater (P<0·05) and those of GH (1·1 ± 0·2 vs 2·6 ± 0·3 ng/ml) were lower (P<0·05) in obese than in lean sheep. Fasting concentrations of IGF-II and glucagon were not affected (P>0·05) by obesity. GH concentrations were increased equivalently by 6–9 ng/ml in lean and obese sheep during GH treatment. GH caused an immediate and a marked fivefold increase in the fasting insulin level in obese sheep but only minimally affected insulin concentration in lean sheep. The increment in fasting glucose during GH treatment was greater (P<0·05) in obese (8–12 mg/dl) than in lean (2–5 mg/dl) sheep. Frequent measurements in the first 8 h after feeding and injection of excipient (day 0) or the first (day 1), sixth (day 6) and twelfth (day 12) daily injection of GH showed that prandial metabolism in both groups of sheep was affected minimally by GH. However, GH treatment on day 1 (not days 6 or 12) acutely attenuated the feeding-induced suppression of plasma FFA in both groups of sheep and this effect was significantly greater in obese than in lean sheep. Although obese sheep were hyposomatotropic, the basal and GH-induced increases in plasma IGF-I concentrations were greater (P<0·05) in obese than in lean sheep. Plasma IGF-II was unaffected by obesity and was not increased by GH stimulation. Western ligand blotting showed that IGFBP-3 accounted for approximately 50–60% of the plasma IGF-I binding capacity in sheep respectively both before and during GH treatment. Basal plasma levels of IGFBP-2 were lower (P<0·05) and those of IGFBP-3 greater (P<0·05) in obese compared with lean sheep. GH increased the level of IGFBP-3 equally in lean and obese sheep, but suppressed the expression of IGFBP-2 more (P<0·05) in lean than in obese sheep. We concluded that the diabetogenic-like actions of GH in sheep were exaggerated markedly by obesity, and were expressed more during the fasted than the fed states. The effects of GH stimulation on the endocrine pancreas may be selective for β-cells and preferentially enhanced by obesity. GH regulation of IGF-I and the IGFBPs differs in lean and obese sheep. Journal of Endocrinology (1997) 154, 329–346

scholarly journals IGF-I stimulates chemotaxis of human neuroblasts. Involvement of type 1 IGF receptor, IGF binding proteins, phosphatidylinositol-3 kinase pathway and plasmin system

2000 ◽  
Vol 165 (1) ◽  
pp. 123-131 ◽  
Author(s):  
A Puglianiello ◽  
D Germani ◽  
P Rossi ◽  
S Cianfarani
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Igf Binding Proteins ◽  
Neuroblast Migration ◽  
Igf I ◽  
Igf Binding ◽  
Igf Receptor ◽  
Kinase Pathway

SH-SY5Y human neuroblastoma cells express IGF receptors, IGFs and IGF binding proteins (IGFBPs), and provide a model for studying the role of the IGF system in human neuronal development. We investigated the effect of IGF-I and des(1-3)IGF-I on the motility of SH-SY5Y cells by a cell migration assay based on the assessment of the number of cells which migrated across 8 microm pore size membranes and around an agarose drop. IGF-I and des(1-3)IGF-I stimulated neuroblast chemotaxis in a dose-dependent manner. Treatment of cells with these agents for 24 h resulted in a significant increase (IGF-I by 70% and des(1-3)IGF-I by 90%; P<0. 0001) in cell motility relative to control conditions. Addition of monoclonal antibody against type 1 IGF receptor (alpha-IR3), significantly (P<0.05) reduced the cell motility induced by IGF-I (by 30%) and des(1-3)IGF-I (by 70%). Wortmannin, a specific inhibitor of phosphatidylinositol (PI)-3 kinase intracellular signalling, also reduced the IGF-stimulated cell migration (by over 40%, P<0.01), indicating a key role of the PI-3 kinase pathway in mediating the IGF effect on neuroblast migration. Finally, cell treatment with plasminogen (PLG) markedly enhanced neuroblast migration (by over 200%, P<0.01), whereas incubation with the PLG inhibitor 4-(2-aminoethyl)-benzenesulphonyl fluoride reduced cell motility (by 80%, P<0.01), thus suggesting an involvement of PLG-dependent IGFBP proteolysis in the regulation of neuroblast motility. In conclusion, IGF-I is a potent stimulator of neuroblast migration through the activation of type 1 IGF receptor and the PI-3 kinase intracellular pathway. IGFBPs and the plasmin system seem to play a role in cell motility, although the nature and the extent of their involvement has yet to be elucidated.

scholarly journals The Role of IGF-Binding Proteins in Mediating the Effects of Recombinant Human IGF-I on Insulin Requirements in Type 1 Diabetes Mellitus

2001 ◽  
Vol 86 (8) ◽  
pp. 3686-3691 ◽  
Author(s):  
E. C. Crowne ◽  
J. S. Samra ◽  
T. Cheetham ◽  
C. L. Acerini ◽  
A. Watts ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Binding Protein ◽  
Igf Binding Proteins ◽  
Insulin Requirements ◽  
Free Insulin ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein

To determine the role of IGF-binding proteins in mediating the direct effects of recombinant human IGF-I on insulin requirements in type 1(insulin-dependent) diabetes mellitus, overnight changes in IGF-I, IGF-II, and IGF-binding protein-1, -2, and -3, collected under euglycemic conditions, were compared in nine subjects after double blind, randomized, sc administration of recombinant human IGF-I (40μ g/kg) or placebo at 1800 h. On both nights a somatostatin analog infusion (300 ng/kg·h) suppressed endogenous GH production, and three timed discrete GH pulses (total, 0.029 IU/kg·night) ensured identical GH levels. After recombinant human IGF-I administration, IGF-I levels and the IGF-I/IGF-binding protein-3 ratio increased [mean ± sem:IGF-I, 401 ± 22 ng/ml; placebo, 256 ± 20 ng/ml (P = 0.0002); IGF-I, 0.108 ± 0.006; placebo, 0.074 ± 0.004 (P = 0.0003), respectively], and insulin requirements decreased (IGF-I, 0.12 ± 0.03; placebo, 0.23 ± 0.03 U/kg·min; P = 0.008). The normal within-individual inverse relationships between insulin and IGF-binding protein-1 levels were observed (lag time 2 h: r =− 0.34; P &lt; 0.01). Yet despite reduced free insulin levels (8.5 ± 1.5; placebo, 12.2 ± 1.2 mU/liter; P = 0.03), IGF-binding protein-1 levels were reduced after recombinant human IGF-I administration (53.7 ± 6.8; placebo, 82.2 ± 11.8 ng/ml; P = 0.008). The largest reductions in free insulin levels after recombinant human IGF-I and thus putative improvement in insulin sensitivity occurred in subjects with the smallest increase in the plasma IGF-I/IGF-binding protein-3 ratio (r = 0.7; P = 0.03). Taken together, these data are consistent with the hypothesis that transcapillary movement of IGF-I (perhaps mediated by IGF-binding protein-1), out of the circulation facilitates altered insulin sensitivity. These data have important implications for risk-benefit assessment of recombinant human IGF-I therapy in type 1 diabetes mellitus.

Developmental changes in growth hormone, insulin-like growth factors (IGF-I and IGF-II) and IGF-binding proteins in plasma of young growing pigs

1991 ◽  
Vol 128 (3) ◽  
pp. 439-447 ◽  
Author(s):  
P. C. Owens ◽  
M. A. Conlon ◽  
R. G. Campbell ◽  
R. J. Johnson ◽  
R. King ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Total Concentration ◽  
Plasma Concentrations ◽  
Growing Pigs ◽  
Strong Positive Correlation ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Close Relationship ◽  
Igf Binding ◽  
Plasma Gh

ABSTRACT The relationship between plasma concentrations of normally secreted GH and insulin-like growth factor-I (IGF-I) was investigated in pigs after weaning. Frequent blood sampling for between 12 and 24 h showed that plasma GH was pulsatile in pigs of 10, 20 and 35 kg liveweight. Pulses were brief in duration, low in amplitude and variable in frequency. Basal and average daily plasma concentrations of GH changed significantly with development, increasing by about 50% between 10 and 20 kg liveweight. Concentrations of IGF-I in plasma showed little or no evidence of diurnal periodicity and were not increased by GH pulses. Average daily concentrations of both IGF-I and IGF-II in plasma progressively increased between 10 and 35 kg liveweight, as did the total desaturated IGF-binding protein (IGFBP) activity of plasma. A strong positive correlation was observed between the total concentration of IGFs (IGF-I plus IGF-II) in the circulation and plasma IGFBP activity. The developmental rise in IGFBP activity of plasma was associated with increased labelling with 125I-labelled human IGF-II in ligand blots of binding proteins of apparent molecular masses > 200, 50, 43 and 29 kDa. One class of binding proteins of 34·5 kDa decreased with development. This study of young growing pigs shows that normally secreted endogenous GH exerts no significant immediate control over plasma IGF-I concentrations, and that plasma levels of IGF-I and IGF-II increase with maturation in this species. The close relationship between the concentrations of IGFs and IGFBPs in plasma is consistent with recent evidence indicating that binding proteins partially regulate the levels of IGF-I and IGF-II in blood by controlling their rates of clearance from the circulation. Journal of Endocrinology (1991) 128, 439–447

scholarly journals Metabolic hormones regulate insulin-like growth factor binding protein-1 mRNA levels in primary cultured salmon hepatocytes; lack of inhibition by insulin

2006 ◽  
Vol 191 (2) ◽  
pp. 379-386 ◽  
Author(s):  
A L Pierce ◽  
M Shimizu ◽  
L Felli ◽  
P Swanson ◽  
W W Dickhoff
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Hormonal Regulation ◽  
Growth And Development ◽  
Mrna Levels ◽  
Igf Binding Proteins ◽  
Metabolic Hormones ◽  
Igf I ◽  
Igf Binding

IGF-binding proteins (IGFBPs) modulate the effects of the IGFs, major stimulators of vertebrate growth and development. In mammals, IGFBP-1 inhibits the actions of IGF-I. Rapid increases in circulating IGFBP-1 occur during catabolic states. Insulin and glucocorticoids are the primary regulators of circulating IGFBP-1 in mammals. Insulin inhibits and glucocorticoids stimulate hepatocyte IGFBP-1 gene expression and production. A 22 kDa IGFBP in salmon blood also increases during catabolic states and has recently been identified as an IGFBP-1 homolog. We examined the hormonal regulation of salmon IGFBP-1 mRNA levels and protein secretion in primary cultured salmon hepatocytes. The glucocorticoid agonist dexamethasone progressively increased hepatocyte IGFBP-1 mRNA levels (eightfold) and medium IGFBP-1 immunoreactivity over concentrations comparable with stressed circulating cortisol levels (10−9–10−6 M). GH progressively reduced IGFBP-1 mRNA levels (0.3-fold) and medium IGFBP-1 immunoreactivity over physiological concentrations (5 × 10−11–5 × 10−9 M). Unexpectedly, insulin slightly increased hepatocyte IGFBP-1 mRNA (1.4-fold) and did not change medium IGFBP-1 immunoreactivity over physiological concentrations and above (10−9–10−6 M). Triiodothyronine had no effect on hepatocyte IGFBP-1 mRNA, whereas glucagon increased IGFBP-1 mRNA (2.2-fold) at supraphysiological concentrations (10−6 M). This study suggests that the major inhibitory role of insulin in the regulation of liver IGFBP-1 production in mammals is not found in salmon. However, regulation of salmon liver IGFBP-1 production by other metabolic hormones is similar to what is found in mammals.

Ontogenic and nutritional changes in circulating insulin-like growth factor (IGF)-I, IGF-II and IGF-binding proteins in growing ewe and ram lambs

1997 ◽  
Vol 155 (1) ◽  
pp. 47-54 ◽  
Author(s):  
KL Gatford ◽  
KJ Quinn ◽  
PE Walton ◽  
PA Grant ◽  
BJ Hosking ◽  
...  
Keyword(s):  
Sex Differences ◽  
Feed Intake ◽  
Plasma Concentrations ◽  
Endocrine System ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Before And After ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

The ontogeny of the IGF endocrine system was investigated in 15 young lambs before and after weaning at 62 days of age. Before weaning, plasma IGF-I concentrations were higher in rams than ewes, and plasma concentrations of IGF-II and IGF-binding protein-3 (IGFBP-3) also tended to be higher in rams than in ewes. Feed intake of ewes and rams was restricted after weaning to remove sex differences in feed intake. Plasma concentrations of IGF-I and IGFBP-3 did not differ between rams and ewes at 100 days of age, but plasma IGF-II was higher in rams than in ewes at this time. Since circulating concentrations of GH were higher in rams than in ewes at 100 days of age, this implies that the restricted feed intake blocked the IGF-I and IGFBP-3 responses to GH. We conclude that sex differences in circulating IGF-I and IGFBP-3 concentrations in the growing lamb alter with age, and are not present when nutrition is restricted.

Systemic infusion of IGF-I or LR(3)IGF-I stimulates visceral organ growth and proliferation of gut tissues in suckling rats

1997 ◽  
Vol 272 (3) ◽  
pp. G522-G533 ◽  
Author(s):  
C. B. Steeb ◽  
C. A. Shoubridge ◽  
D. R. Tivey ◽  
L. C. Read
Keyword(s):  
Growth Parameters ◽  
Body Weight Gain ◽  
Age Groups ◽  
Igf Binding Proteins ◽  
Suckling Rats ◽  
Igf I ◽  
Enhanced Expression ◽  
Igf Binding ◽  
Muscularis Externa ◽  
Igfbp 3

This study describes developmental changes in gastrointestinal response to insulin-like growth factor I (IGF-I) peptide administration. Neonatal rats were infused with IGF-I or long [Arg3]IGF-I (LR(3)IGF-I) for 6.5 days starting on day 6 or 12 postpartum. Peptides were delivered by mini osmotic pumps at 0, 2, 5, or 12.5 microg x g(-1) x day(-1). IGF-I infusion increased plasma IGF-I levels in both age groups but stimulated body weight gain only in the older rats. Infusion of LR(3)IGF-I did not change plasma IGF-I levels. Both peptides enhanced expression of IGF-binding proteins (IGFBP) 1 and 2 and induced IGFBP-3 in the older rats. For both age groups, weights of the kidney and spleen increased by up to 85 and 76%, respectively. IGF-I treatment also stimulated gut weight and length by up to 60 and 32%, respectively, but dose dependency was observed only in the older rats. LR(3)IGF-I was more potent for all growth parameters in both age groups. Histological observations included thickening of the mucosa and muscularis externa after infusion of IGF-I peptides. Thymidine labeling in the younger rats indicated that proliferative activity increased proportionately with crypt cell growth. These results show that IGF-I peptides selectively stimulate growth of gastrointestinal tissues in suckling rats and that the proximal gut was the most peptide-responsive region.

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