Insulin-like Growth Factor Binding protein-I Research Articles

Feeding graded levels of protein to Genetically Improved Farmed Tilapia (GIFT) juveniles reared in inland saline water: Effects on growth and gene expression of IGF[sbnd]I, IGF-IR and IGF-BPI

A 60-day feeding trial was conducted on Genetically Improved Farmed Tilapia (GIFT) juveniles in inland saline water (ISW) of 10 ppt salinity. Seven isoenergetic (400 kcal DE/100 g), isolipidic (6%) and hetero‑nitrogenous (20, 25, 30, 35, 40, 45 and 50% CP) experimental diets were formulated and prepared using purified ingredients. Three hundred and fifteen GIFT juveniles (average body weight 2.68 ± 0.01 g) were distributed in seven experimental groups viz., T20 (20% CP), T25 (25% CP), T30 (30% CP), T35 (35% CP), T40 (40% CP), T45 (45% CP) and T50 (50% CP) in triplicates following a completely randomized design (CRD) with the stocking density of 15 fish/tank (92 cm diameter X 45 cm height) with 200 l water volume. Fishes of different experimental groups were fed with respective experimental diets thrice daily at satiation level. Results indicated that dietary crude protein has significant (p < .05) overall, linear and also quadratic effect on final body weight, percent weight gain (WG%) and feed conversion ratio (FCR) with higher and lower value in T35, T40, T45 and T50 groups, respectively. The protein efficiency ratio (PER) and apparent net protein utilisation (ANPU%) values of fish were decreased with the increasing dietary CP level. The whole body crude protein content was affected linearly as well as quadratically (p < .05) with higher value in T30, T35 and T40 groups, whereas whole body ether extract content of the fish were significantly (p < .05) decreased with the increasing the dietary CP level. Among digestive enzymes, protease and amylase activities were significantly (p < .05) affected due to dietary crude protein linearly as well as quadratically. Though, the expression of insulin like growth factor binding protein I (IGF-BPI) did not show any defined trend, the expression of insulin like growth factor I (IGFI) and Insulin like growth factor I receptor (IGFIR) were highly correlated with WG% (r = 0.92 and r = 0.97, respectively). The expression of IGFIR was also correlated with IGF-I expression (r = 0.93). According to broken-line and second-order polynomial regression analysis in relation to WG% and expression of hepatic IGF-I gene, the optimum dietary crude protein levels of GIFT juveniles reared in inland saline water of 10 ppt salinity were found to be 37.37, 37.72, 40.92 and 38% crude protein with isoenergetic of 400 kcal DE/100 g diet, respectively.

Birth weight effect in twin‐born lambs from mid‐pregnancy shearing is associated with changes in maternal IGF‐I concentration

A number of studies have shown an increase in the birth weight of lambs in response to mid pregnancy shearing. The present study sought to determine whether the birth weight effect of mid‐pregnancy shearing is mediated through changes in maternal insulin‐like growth factor‐I (IGF‐I) and insulin‐like growth factor binding protein‐I (IGFBP‐I) concentrations. Single‐ and twin‐bearing ewes from three genetically divergent IGF‐I lines were either left unshorn or shorn at a mean day 90 of pregnancy (P90). Maternal plasma concentrations of IGF‐I and IGFBP‐I were measured at P89, P108 and P136. Lamb liveweight at birth and weaning weremeasured, andplasmaconcentrations of IGF‐I determined at weaning. Shearing increased the birth weight of twin lambs by over 350 g (P < 0.05) without having any effect on singleton birth weight. The increased birth weight of twin lambs born to shorn ewes was associated with a decline in maternal plasma IGF‐I concentration (P < 0.05) from P108 toP136. Low IGF‐I line ewes had lower (P < 0.001) plasma IGF‐I than high IGF‐I line ewes at each stage measured but higher plasma IGFBP‐I at P89 and P108. Birth weights were higher in lambs born to low IGF‐I line ewes than in those born to high IGF line ewes. These results suggest that the difference in birth weight between twin lambs from shorn and unshorn dams was mediated through a decline in maternal plasma IGF‐I concentrations in late pregnancy. In support of previous studies, there was an inverse relationship between IGF‐I selection line and lamb birth weight.

Pharmacokinetics and pharmacodynamics of growth hormone in patients on chronic haemodialysis compared with matched healthy subjects: an open, nonrandomized, parallel‐group trial

BackgroundGH may be beneficial in treating patients with end-stage renal disease (ESRD). However, the efficacy and safety of GH could be compromised by the potential for accumulation in the circulation.ObjectiveThe objective was to investigate the pharmacokinetics and safety of GH treatment in ESRD patients.DesignThis was an open, nonrandomized, single-centre parallel-group study lasting 8–9 days.SubjectsEleven adult ESRD patients and 10 matched healthy individuals received recombinant human GH (50 µg/kg/day for 7 days) by subcutaneous injection; there were two dose reductions (25%) from Day 5/7. ESRD patients underwent dialysis four times.MeasurementsSerum concentrations of GH, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-I (IGFBP-I), IGFBP-III and GHBP were measured. The primary end-point was GH exposure [area-under-the-curve (AUC) calculated from the 24-h profile] on Days 7–8.ResultsGH AUC0–24 h was greater for patients (387·91 ± 134·13 µg h/l) than healthy subjects (225·35 ± 59·63 µg h/l) and the 90% confidence interval (CI) for the estimated patient : healthy subject ratio (1·40–2·07) was not within the acceptance interval (0·67–1·50). GH AUC18–24 h for patients and healthy subjects (3·03 ± 2·71 µg h/l and 6·37 ± 4·21 µg h/l) returned approximately to baseline (2·86 ± 3·91 µg h/l and 1·09 ± 1·43 µg h/l); terminal half-life (t1/2,z) was shorter for patients (2·28 ± 00·43 h vs. 3·23 ± 00·75 h). No major safety issues were identified.ConclusionsResults demonstrate a difference between patients and healthy subjects regarding GH AUC0–24 h. However, GH concentrations for both groups were comparable to baseline by 20–22 h, thus GH was not retained in the circulation of ESRD patients.

Maternal Interleukin-6: Marker of Fetal Growth and Adiposity

Fetal overgrowth and higher adiposity are hallmarks of pregnancy with maternal obesity and poor glucose tolerance, two conditions associated with decreased maternal insulin sensitivity. In non-pregnant individuals, adipokines, vasoactive peptides, and components of the immune system crosstalk with metabolic factors to generate signals triggering obesity and impaired insulin action. We have investigated circulating maternal and fetal cytokines and growth-factors as potential biochemical markers of fetal adiposity. Mothers and neonates were classified into three tertiles (T1-T3) using total neonatal fat mass as the outcome with 309 +/- 25 g in T1, 478 +/- 40 g in T2, and 529 +/- 39 g in T3. Umbilical cord endothelin-1 (ET-1), C-peptide, and leptin were higher in T3 and T2 versus T1. Only cord leptin was strongly associated with fetal fat mass (P < .01), whereas neonatal lean body mass was negatively correlated with maternal insulin-like growth factor binding protein-I (IGFBP-I) (r = -0.53, P < .04). This study shows an association between increased fetal adiposity and maternal systemic interleukin-6 (IL-6). No such correlation was found with factors circulating in cord blood, suggesting that the stimuli favoring fetal fat accretion derive from maternal or placental sources rather than from the fetus.

Insulin-like growth factor binding protein-I levels are strongly associated with insulin sensitivity and obesity in early pubertal children.

In conditions associated with insulin resistance, insulin-like growth factor binding protein-I (IGFBP-I) levels have been shown to correlate inversely with insulin levels. Puberty is associated with insulin resistance and thus provides a model for comparing the relationship of IGFBP-I to both insulin levels and measures of insulin sensitivity. Our study population consisted of 104 healthy pubertal children, age 9.8-14.6 yr. Each subject had his/her insulin sensitivity (Si) assessed by the modified minimal model of Bergman, which employs a frequently sampled i.v. glucose tolerance test. Results showed that IGFBP-I levels were significantly higher in boys than in pubertally matched girls (P < 0.01). There was a strong positive correlation between IGFBP-I levels and Si (r = 0.65, P < 0.0001) and a weaker negative correlation with fasting insulin levels (r = -0.38, P < 0.0001). An inverse relationship was also found between IGFBP-I levels and body mass index (r = -0.46, P < 0.0001) and with IGF-I levels (girls only, r = -0.41, P < 0.003). Consequently, insulin sensitivity, obesity, and IGF-I are important predictors of IGFBP-I levels in pubertal children. It is possible that insulin-mediated suppression of IGFBP-I in obese children may increase free IGF-I levels and thus contribute to somatic growth. The same mechanism may operate in pubertal children, where insulin resistance and growth acceleration occur simultaneously.

Insulin-Like Growth Factor Binding Protein-I Levels Are Strongly Associated with Insulin Sensitivity and Obesity in Early Pubertal Children

Insulin-Like Growth Factor Binding Protein-I Levels Are Strongly Associated with Insulin Sensitivity and Obesity in Early Pubertal Children

Hypoxia response element (hre) in the insulin-like growth factor binding protein-i (igfbp-1) gene is functional: Potential relevance to hypoxia

Hypoxia response element (hre) in the insulin-like growth factor binding protein-i (igfbp-1) gene is functional: Potential relevance to hypoxia

Characterization of insulin-like growth factor binding protein-1 kinases from human hepatoma cells.

The phosphorylation of insulin-like growth factor binding protein-I (IGFBP-1) alters its binding affinity for insulin-like growth factor I (IGF-I) and thus regulates the bioavailability of IGF-I for binding to the IGF-I receptor. The kinase(s) responsible for the phosphorylation of IGFBP-1 has not been identified. This study was designed to characterize the IGFBP-1 kinase activity in HepG2 human hepatoma cells, a cell line that secretes IGFBP-1 primarily as phosphorylated isoforms. IGFBP-1 kinase activity was partially purified from detergent extracts of the cells by phosphocellulose chromatography and gel filtration. Two kinases of approximate M(r) 150,000 (peak I kinase) and M(r) 50,000 (peak II kinase) were identified. Each kinase phosphorylated IGFBP-1 at serine residues that were phosphorylated by intact HepG2 cells. The kinases were distinct based on their differential sensitivity to inhibition by heparin (IC50 = 2.5 and 16.5 micrograms/ml, peak I and II kinase, respectively) and inhibition by the isoquinoline sulfonamide CKI-7 (IC50 = 50 microM and 100 microM, peak I and II kinase, respectively). In addition, a tenfold molar excess of nonradioactive GTP relative to [gamma-32P]ATP lowered the incorporation of 32P into IGFBP-1 by 80% when the reaction was catalyzed by the peak I kinase, whereas GTP had no effect on the reaction catalyzed by the peak II kinase. In the presence of polylysine, IGFBP-1 was radiolabeled by the partially purified kinase activity when [gamma-32P]GTP served as the phosphate donor indicating the presence of casein kinase II activity. Furthermore, IGFBP-1 was phosphorylated by purified casein kinase I and casein kinase II at sites phosphorylated by the peak I and II kinases. Our data suggest that at least two kinases could be responsible for the phosphorylation of IGFBP-1 in intact HepG2 cells and that the kinases are related to the casein kinase family of protein kinases.

Relations between sex hormones, sex hormone binding globulin, insulin‐like growth factor‐I and insulin‐like growth factor binding protein‐I in post‐menopausal breast cancer patients

Clinical EndocrinologyVolume 43, Issue 6 p. 772-772 Relations between sex hormones, sex hormone binding globulin, insulin-like growth factor-I and insulin-like growth factor binding protein-I in post-menopausal breast cancer patients First published: December 1995 https://doi.org/10.1111/j.1365-2265.1995.tb00555.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume43, Issue6December 1995Pages 772-772 RelatedInformation

Altered regulation of insulin-like growth factor binding protein-I in patients with polycystic ovary syndrome

Altered regulation of insulin-like growth factor binding protein-I in patients with polycystic ovary syndrome

Altered Regulation of Insulin-Like Growth Factor Binding Protein-I in Patients With Polycystic Ovary Syndrome

Insulin-like growth factor (IGF-I) action is influenced by circulating as well as tissue levels of its binding proteins. Because serum IGF binding protein-1 (IGFBP-1) levels have been found to be decreased in patients with polycystic ovary syndrome (PCOS), we tested the hypothesis that regulation of IGFBP-1 secretion may be different in patients with PCOS compared with normal women. We studied 15 normal ovulatory women and 15 women with PCOS of similar age (21 +/- 1 and 22 +/- 1 years, respectively). All subjects were studied after an overnight fast between days 5-8 after spontaneous or progestin-induced menses. Perturbations included the administration of insulin intravenously, maintenance of a euglycemic clamp, and, in a subsequent cycle, the administration of a long-acting somatostatin analogue (octreotide, 100 micrograms) given subcutaneously. Blood samples were collected before treatment, every 15 minutes for 6 hours after insulin, and every 30 minutes for 3 hours after octreotide administration. Serum levels of IGF-I, IGFBP-1, IGFBP-3, and insulin were measured by specific immunoassays. Compared with the controls, patients with PCOS had significantly higher insulin levels, similar IGF-I and IGFBP-3 levels, and significantly lower IGFBP-1. Insulin did not change serum IGF-I levels in either group, although a significant decrease in IGFBP-1 levels occurred in normal women but not in patients with PCOS. Octreotide treatment also did not change serum IGF-I levels in either group, but serum insulin levels decreased significantly and IGFBP-1 levels increased significantly in both groups; this response was significantly greater in controls. Our data are compatible with the notion that regulation of IGFBP-1 is altered in women with PCOS and that several factors may be involved.

Regulation of insulin-like growth factor binding protein-I during the 24-hour metabolic clock and in response to hypoinsulinemia induced by fasting and sandostatin in normal women

Regulation of insulin-like growth factor binding protein-I during the 24-hour metabolic clock and in response to hypoinsulinemia induced by fasting and sandostatin in normal women

Regulation of Insulin-Like Growth Factor Binding Protein-I During the 24-Hour Metabolic Clock and in Response to Hypoinsulinemia Induced by Fasting and Sandostatin in Normal Women

To establish the relation of insulin-like growth factor-I (IGF-I) and IGF-binding protein-1 (IGFBP-1) with 24-hour metabolic excursions in normal healthy women and in response to acute interruption of metabolic homeostasis by hypoinsulinemia. Hourly blood samples during the 24-hour metabolic clock were obtained from seven normally cycling women. Uniform dietary composition (50% carbohydrate, 35% fat, and 15% protein) and timing of meals (8 AM, 12 PM, and 6 PM) were prescribed. Daytime hypoinsulinemia was induced by omitting meals and by Sandostatin (100 micrograms) administration. Changes in serum levels of glucose, insulin, cortisol, IGF-I, and IGFBP-1 were measured. The diurnal pattern of serum IGFBP-1 levels during the 24-hour metabolic clock was characterized by a rapid fall during the feeding phase of the day and a progressive 3.5-fold rise during nocturnal fasting; IGF-I levels were unchanged. Changes in IGFBP-1 levels were in parallel to those of cortisol and were inversely related to increases in glucose (80%) and insulin (tenfold) levels after each meal and to their decline during nocturnal fasting. Daytime fasting and administration of Sandostatin were accompanied by rapid and sustained increases in IGFBP-1 when insulin levels declined to 54 +/- 20 pmol/L. With constant levels of IGF-I, the diurnal rhythm of IGFBP-1 may subserve a physiologic function by coordinating insulin and IGF-I action with substrate availability. Fluctuations of insulin levels during the 24-hour metabolic clock in normal women appear to serve as a signal, with an inhibitory effect on IGFBP-1 production when levels are above 70 pmol/L and a stimulatory effect at levels below 70 pmol/L. These findings provide a basis for future investigations in women with nutritionally related reproductive disorders.

Increased IGFBP-1 Levels Relating to Low IGF-I in Diabetic Children

It is known that retarded growth is caused by low IGF-I due to poor metabolic control in children with insulin-dependent diabetes mellitus (IDDM). Our study aims to clarify whether increased levels of insulin-like growth factor binding protein-I (IGFBP-1) reflect low IGF-I production. Nine prepubertal and 25 adolescent IDDM patients were studied in a fasting condition, early on the same morning. IGF-I, IGFBP-1, IGFBP-3, free insulin (IRI), blood glucose and other metabolic parameters were assayed. IGF-I levels were low, with high IGFBP-1 and low IGFBP-3, in IDDM according to pubertal stages. IGFBP-1 showed inverse correlation with IGF-I in adolescent IDDM. Since both IGFBP-1 and IGF-I showed closer correlation with fasting blood glucose than hemoglobin (Hb) Alc levels, the co-factors may be involved in fasting metabolic disturbance rather than overall hyperglycemia. IGFBP-1 showed inverse correlation with fasting free IRI whose levels themselves were not so low, while free fatty acids were not so high and correlated positively with IGFBP-1. These findings indicate that attention should be paid to hepatic insulin deficiency and overnight hypoglycemia in the treatment of IDDM.

Enhanced Expression of Insulin-Like Growth Factor-Binding Protein-I in the Fasted Rat: The Effects of Insulin and Growth Hormone Administration*

The effect of fasting on insulin-like growth factor-binding protein-1 (IGFBP-1) expression was examined in the rat. Food deprivation for a period of 24 h resulted in a 9.5 +/- 2.0-fold increase in hepatic IGFBP-1 mRNA abundance (P less than 0.001). An increase in circulating IGFBP-1 in sera from fasted rats was demonstrated by immunoblotting, and an increased abundance of a 30-kDa IGFBP in sera from fasted rats was apparent when [125I]IGF-I was used in ligand blotting experiments. Refeeding resulted in a prompt decline in hepatic IGFBP-1 mRNA. Administration of insulin (0.5-4 U, ip) to fasted rats resulted in profound hypoglycemia, but either increased or had no significant effect on hepatic IGFBP-1 mRNA abundance. In contrast, administration of human GH (hGH; 100 micrograms, ip) resulted in a prompt decline in hepatic IGFBP-1 mRNA, followed by a late rebound in IGFBP-1 mRNA to levels greater than those in fasted controls. Furthermore, hepatic IGFBP-1 mRNA levels were significantly lower in hGH-treated (100 micrograms every 8 h) food-deprived rats than in saline-treated food-deprived rats (2.25 +/- 1.55- vs. 8.99 +/- 3.80-fold increase; P less than 0.005). Similar changes were observed when serum IGFBP-1 was quantitated by immunoblotting. The effects of GH could not be explained by secondary hyperinsulinism, since no significant increase in insulin levels was observed in GH-treated rats. From these observations we conclude the enhanced expression of IGFBP-1 in the food-deprived rat may be a consequence of GH deficiency rather than insulin deficiency.

RELATIONSHIP BETWEEN THE PUBERTAL FALL INSEX HORMONE BINDING GLOBULIN AND INSULIN‐LIKE GROWTH FACTOR BINDING PROTEIN‐I. A SYNCHRONIZED APPROACH TO PUBERTAL DEVELOPMENT?

In a cross-sectional study of 69 normal adolescents we have found sex hormone-binding globulin (SHBG) levels to fall in both males and females throughout the pubertal period. Multiple regression analysis revealed a close negative correlation with insulin in both sexes. Weaker correlations were also found between SHBG and circulating androgen concentrations, in both males and females. Similar results were also obtained for a second circulating binding protein of primarily hepatic origin. This low molecular weight insulin-like growth factor (IGF) binding protein I (IBP-I) is one of two distinct classes of IGF binding proteins which bind IGF-I and IGF-II. IGF-I in turn mediates, at least in part, the actions of growth hormone. IBP-I also fell throughout puberty, correlating with the increasing insulin levels. In addition IBP-I correlated with androgen levels in both sexes. These similarities between SHBG and IBP-I, together with a strong correlation across puberty between the levels of the two binding proteins themselves (r = 0.737, P less than 0.001), suggest common mechanisms of control over the circulating levels of these two binding proteins. The association with insulin raises the possibility of a synchronized modulation of the actions of sex steroids and IGFs by nutritional intake. Thus pubertal growth and sexual development may occur over the same time with both modulated according to nutritional intake, linked through pancreatic insulin release, to hepatic production of SHBG and IBP-I.