Insulin-like growth factors and their binding proteins in pleural fluid

1997 ◽  
pp. 467-473 ◽  
Author(s):  
Y Le Bouc ◽  
A Bellocq ◽  
C Philippe ◽  
L Perin ◽  
M Garabedian ◽  
...  
Keyword(s):  
Growth Factors ◽  
Pleural Fluid ◽  
Binding Proteins ◽  
Specific Binding ◽  
Gel Filtration ◽  
Specific Protein ◽  
Hydroxyvitamin D ◽  
Igf I ◽  
Acid Gel ◽  
Insulin Like Growth Factors

We investigated the expression and potential regulatory role of insulin-like growth factors (IGFs) and their specific binding proteins (BPs) in tuberculous and nontuberculous pleuritis. By using a radioimmunoassay after acid gel filtration chromatography, we found that mean concentrations of IGF-I were 211.9 +/- 20.2 microg/l and 203.2 +/- 31.1 microg/l in pleural fluid of 14 patients with tuberculous pleuritis and 9 patients with malignant pleuritis respectively. These values were near those in serum of the same patients (221.3 +/- 19.5 microg/l and 204.6 +/- 21.0 microg/l respectively). By using a specific protein-binding assay, we found that mean concentrations of IGF-II were 345.3 +/- 61.0 microg/l and 167.6 +/- 22.7 microg/l in tuberculous and malignant pleural effusions respectively. These values were significantly lower than those in serum of the same patients (628.3 +/- 79.0 microg/l, P<0.025 and 532.0 +/- 85.9 microg/l, P<0.025 respectively). Because bioavailability and bioactivity of IGFs may be regulated by their binding to IGFBPs, we studied IGFBP patterns in the pleural fluid of 6 patients with tuberculous pleuritis. As assessed by Western ligand blotting the levels of IGFBP-1 and IGFBP-2 were increased whereas those of IGFBP-3 were decreased in pleural fluid in comparison with serum. The decrease in IGFPB-3 levels reflected increased proteolysis, as assessed by Western immunoblotting. In spite of this presence of IGFBPs, IGFs could be responsible for the local biosynthesis of 1.25-dihydroxyvitamin D (1,25-(OH)2D) since pleural fluid levels of both IGF-I and IGF-II significantly correlated with those of 1,25-(OH)2D. These results indicate that IGFs are detectable in pleural fluid and may contribute to control the activity of 25-hydroxyvitamin D-1alpha hydroxylase in tuberculous pleuritis.

scholarly journals Proteolytic conversion of insulin-like growth factors to an acidic form(s)

1984 ◽  
Vol 223 (1) ◽  
pp. 97-103 ◽  
Author(s):  
A D Kuffer ◽  
A C Herington
Keyword(s):  
Growth Factors ◽  
Human Serum ◽  
Gel Filtration ◽  
Amino Acid Sequences ◽  
Full Spectrum ◽  
Acidic Form ◽  
Igf I ◽  
Acid Gel ◽  
Insulin Like Growth Factors

The relative amounts of the various forms of bioassayable insulin-like growth factors (IGF) isolated from human serum or serum fraction Cohn IV-1 depend on the purification procedure. With acid gel filtration or acid/ethanol extraction as the initial step, IGF-II (pI approximately 6.5) was the most abundant (40-70%) followed by somatomedin A (pI approximately 7.4; 15-23%), an acidic form of insulin-like activity (ILA pI 4.8) (13-21%) and IGF-I (pI approximately 8.5; 5-27%). If, however, pH 5.5 ion-exchange chromatography on SP-Sephadex was used prior to acid gel filtration, the acidic pI 4.8 form was the major (greater than 90%) species recovered and was accompanied by a quantitative loss of the other IGF species. This suggested a possible conversion of IGF-I, somatomedin A and/or IGF-II to the acidic ILA pI 4.8 form(s) during the SP-Sephadex procedure. Further experiments indicated that differences in the yields of ILA pI 4.8 were not due simply to differences in the initial pH conditions of the various methods (i.e. acid versus neutral), although exposure to pH 9.7 (a pH experienced during elution of IGF activity from the SP-Sephadex) did appear to play a role. The involvement of the carrier protein in the conversion process was tested by subjecting carrier-free IGF-I and IGF-II to the SP-Sephadex procedure. No conversion of the free forms to ILA pI 4.8 occurred. To examine the possible role of proteinase in the conversion of IGFs to ILA pI 4.8, SP-Sephadex chromatography was performed in the presence of a broad spectrum proteinase inhibitor. The IGF distribution pattern obtained closely resembled the ‘normal’ pattern seen with acid gel filtration, indicating that proteinase inactivation had prevented conversion to ILA pI 4.8. These data suggest that proteolytic conversion of IGF-I, somatomedin A and IGF-II to more acidic ILA pI 4.8 form(s) (i) occurs during SP-Sephadex chromatography, (ii) is not prevented simply by prior acid exposure, and (iii) takes place only when IGF-I and -II are in their high-Mr carrier-bound forms. Since IGF-I and IGF-II, although homologous, have unique amino acid sequences, the conversion of both IGFs implies that at least two acidic ILA forms exist. Nevertheless, because ILA pI 4.8 retains the full spectrum of IGF bioactivities in vitro, and significant quantities are present in normal human serum (21%), it would suggest that proteolytic conversion of IGF-I, somatomedin A and IGF-II to ILA pI 4.8 in vivo may be a physiologically significant event.

scholarly journals Receptors and Binding Proteins for Insulin and Insulin-Like Growth Factors in the Placenta of Healthy Mothers and Mothers with Insulin-Dependent Diabetes Mellitus

2009 ◽  
Vol 28 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Milena Weber ◽  
Ivona Baričević-Jones ◽  
Romana Masnikosa ◽  
Dejan Filimonović ◽  
Željko Miković ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factors ◽  
Binding Proteins ◽  
Gel Filtration ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Igf System ◽  
Igf I ◽  
Insulin Dependent ◽  
Insulin Like Growth Factors

Receptors and Binding Proteins for Insulin and Insulin-Like Growth Factors in the Placenta of Healthy Mothers and Mothers with Insulin-Dependent Diabetes Mellitus The IGF system of human placenta consists of insulin-like growth factors (IGF)-I and -II, their receptors (IGF-1R and IGF-2R), and binding proteins (IGFBP-1 to -6). Due to many structural and metabolic similarities with insulin, the IGF system cannot be examined separately from insulin and its receptor (IR). In this study gel filtration was used to detect solubilized membrane proteins of the placenta obtained from healthy mothers and mothers with IDDM. In order to detect placental membrane proteins that bind IGF molecules (and insulin), the solubilized membranes were incubated with each of the three 125I-labelled ligands: 125I-IGF-I, 125I-IGF-II and 125I-insulin prior to gel filtration chromatography. The biochemical evidence of the presence of receptors for insulin and IGFs, as well as that of IGFBP-1 were obtained by immunoblotting. Herein we demonstrated that, considering IGF and insulin receptor content, the placental tissue obtained from mothers with IDDM was not different from that obtained from healthy mothers. However, the concentration of IGFBP-1 differed between the examined placentas. IDDM in mothers caused an increase in the amount of IGFBP-1 in their placentas and, consequently, the amount of the labelled ligand bound to it. The redistribution of IGFs between the receptors and IGFBP-1 may be involved in regulatory mechanisms in the placenta of mothers with IDDM.

scholarly journals Studies on Insulin-like Growth Factors (IGF-I, -II) and There Binding Proteins in Normal Human Pregnancy

1990 ◽  
Vol 66 (7) ◽  
pp. 688-699 ◽  
Author(s):  
Toru FUNAKOSHI ◽  
Yasuo UEDA ◽  
Akio KOBAYASHI ◽  
Hajime MORIKAWA ◽  
Mastuto MOCHIZUKI
Keyword(s):  
Growth Factors ◽  
Binding Proteins ◽  
Human Pregnancy ◽  
Igf I ◽  
Normal Human ◽  
Insulin Like Growth Factors

scholarly journals GH/IGF e neoplasia: o que há de novo nesta associação

2005 ◽  
Vol 49 (5) ◽  
pp. 833-842 ◽  
Author(s):  
Angela M. Spinola e Castro ◽  
Gil Guerra-Júnior
Keyword(s):  
Growth Factors ◽  
Binding Proteins ◽  
De Novo ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Ciclo Celular ◽  
Igf Binding ◽  
Insulin Like Growth Factors

Estudos in vitro e em animais sugerem que os membros do sistema insulin-like growth factors (IGFs), incluindo IGF-I, IGF-II, receptores de IGF-I e IGF-II (IGF-IR e IGF-IIR), e as IGF-binding proteins (IGFBPs) podem ter um importante envolvimento no desenvolvimento e na progressão de neoplasias. Mais especificamente, as IGFs promovem a progressão do ciclo celular e inibem a apoptose tanto por ação direta com outros fatores de crescimento como por ação indireta interagindo com outros sistemas moleculares intracelulares envolvidos na promoção e/ou progressão do câncer. Além disso, inúmeros estudos epidemiológicos têm sugerido que concentrações elevadas das IGFs, independente das alterações nas IGFBPs, podem estar associadas a um aumento no risco de desenvolver determinadas neoplasias. Esta revisão tem como objetivo apresentar o envolvimento do sistema IGF na regulação tumoral, os principais estudos epidemiológicos realizados e o risco de desenvolvimento de neoplasia em pacientes (com ou sem história pessoal de neoplasia prévia) que receberam hormônio de crescimento (rhGH). É importante salientar que o uso clínico de rhGH, nas indicações aprovadas internacionalmente, é seguro e não existem evidências, até o momento, da associação com o desenvolvimento de neoplasias.

scholarly journals The effect of intermittent umbilical cord occlusion on insulin-like growth factors and their binding proteins in preterm and near-term ovine fetuses

2000 ◽  
Vol 166 (3) ◽  
pp. 565-577 ◽  
Author(s):  
LR Green ◽  
Y Kawagoe ◽  
DJ Hill ◽  
BS Richardson ◽  
VK Han
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Umbilical Cord ◽  
Fetal Growth ◽  
Binding Proteins ◽  
Negative Impact ◽  
Mrna Levels ◽  
Igf I ◽  
Near Term ◽  
Insulin Like Growth Factors

Intermittent umbilical cord compression with resultant fetal hypoxia can have a negative impact on fetal growth and development. Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are the most important regulators of fetal growth. In preterm (107-108 days of gestation) and near-term (128-131 days of gestation) ovine fetuses, we have determined the effect of intermittent umbilical cord occlusion (UCO) over a period of 4 days on the profile and expression of IGFs and IGFBPs. In experimental group animals (preterm n=7; near term n=7) UCOs were carried out by complete inflation of an occluder cuff (duration 90 s) every 30 min for 3-5 h each day, while control fetuses (preterm n=7; near term n=7) received no UCOs. Ewes were euthanized at the end of day 4, and fetal heart, lung, kidney, liver, skeletal muscle and placenta were collected. During UCOs, PO(2! ) fell (by approximately 13 mmHg), pH fell (by approximately 0.05) and PCO(2) increased (by approximately 7 mmHg), and changed to a similar extent in both preterm and near-term groups. In both preterm and near-term groups, there was no difference in fetal body or organ weight between UCO and control fetuses. No significant changes were observed in plasma IGF-I and -II concentrations or IGFBP-1, -2, -3 or -4 levels throughout the 4-day study at either gestational age. In the preterm group UCO fetuses, IGF-II mRNA (1.2-6.0 kb) levels were lower in fetal lung (33%, P<0.05), heart (54%, P<0.01) and skeletal muscle (29%, P<0.05), but there were no differences in IGF-I mRNA levels (7.3 kb); IGFBP-2 mRNA (1.5 kb) levels were lower in the right lobe of the liver (42%, P<0.05) and kidney (22%, P<0.01), but hig! her in the heart (72%, P<0.01), while IGFBP-4 (2.4 kb) levels were lower in skeletal muscle (21%, P<0.01). In the near-term group UCO fetuses, IGFBP-2 mRNA levels were greater in the placenta (39%, P<0.05). Thus, intermittent UCO as studied has a greater effect on the expression of genes encoding certain peptides of the fetal IGF system in selected tissues in preterm fetuses than that in near-term fetuses. Altered IGFBP-2 mRNA levels with reduced IGF-II mRNA levels in selected tissues may mediate changes in growth and/or differentiation that might become apparent if the length of the UCO study were extended.

Ontogeny of Insulin-like Growth Factors (IGF-I and IGF-II) and IGF-Binding Proteins in the Chicken Following Hatching

1997 ◽  
Vol 107 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Steven V. Radecki ◽  
Marie C. Capdevielle ◽  
Frances C. Buonomo ◽  
Colin G. Scanes
Keyword(s):  
Growth Factors ◽  
Binding Proteins ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Igf Binding ◽  
Insulin Like Growth Factors

scholarly journals The Role of the Insulin-Like Growth Factors and Their Binding Proteins in Glucose Homeostasis

2003 ◽  
Vol 4 (4) ◽  
pp. 213-224 ◽  
Author(s):  
Liam J. Murphy
Keyword(s):  
Growth Factors ◽  
Glucose Homeostasis ◽  
Binding Proteins ◽  
Biological Fluids ◽  
Short Term ◽  
High Affinity ◽  
Igf I ◽  
Igfbp 3 ◽  
Insulin Like Growth Factors

The insulin like growth factors (IGF-I and -II) are structurally and functionally related to insulin. While insulin is a key regulator of glucose homeostasis over the short term, emerging evidence suggests that the IGFs are involved in the longer term glucose homeostasis, possibly by modulating insulin sensitivity. Unlike insulin, the IGFs are present in most biological fluids as complexes with high affinity binding proteins, the insulin-like growth factor binding proteins (IGFBPs). The IGFBPs regulate the bioavailability of the IGFs. Of the six IGFBPs identified there is evidence from studies in transgenic mice that both IGFBP-1 and IGFBP-3 may have a role in glucose regulation.

scholarly journals Somatomedins/insulin-like growth factors, their receptors and binding proteins are present during mouse embryogenesis

Development ◽  
1987 ◽  
Vol 101 (1) ◽  
pp. 73-82
Author(s):  
E.P. Smith ◽  
T.W. Sadler ◽  
A.J. D'Ercole
Keyword(s):  
Growth Factors ◽  
Cell Line ◽  
Binding Proteins ◽  
Insulin Receptors ◽  
Embryonal Carcinoma Cell ◽  
Igf Binding Proteins ◽  
Embryonic Tissues ◽  
Embryonic Growth ◽  
Igf I ◽  
Insulin Like Growth Factors

Somatomedins/insulin-like growth factors (Sm/IGFs) are considered to have important roles in regulating fetal growth; however, because of limited quantities of tissue, few studies have been performed on their effects on embryonic growth. To assess a potential role for these factors, we evaluated mouse embryonic tissues for the presence of Sm/IGF and insulin receptors and Sm/IGF-binding proteins by chemical affinity labelling. In addition, we measured extractable Sm-C/IGF-I radioimmunoactivity in mouse embryonic tissues. Finally, we compared these data with those from the embryonal carcinoma cell line, PC13. All embryos from day 9 (3–4 somites) to day 12 (45 somites) possessed both Sm-C/IGF-I and IGF-II receptors in apparent greater abundance than insulin receptors. The visceral yolk sac appeared to have proportionally more insulin receptors than the corresponding embryonic tissue. Extracts from the embryos contained immunoreactive Sm-C/IGF-I and binding proteins of 30–45 X 10(3) Mr. PC13 cells possessed all three receptors and the apparent abundance of the insulin and IGF-II receptors was reduced after differentiation was induced with retinoic acid. PC13 cells released both immunoreactive Sm-C/IGF-I- and Sm-C/IGF-I-binding proteins into their medium. When differentiated, the binding proteins resembled the native ones extracted from the intact embryos. The presence of Sm/IGF activity, receptors and binding proteins in early embryogenesis suggests a role for these factors in embryonic growth. The PC13 cell line appears to only partially reflect normal development.

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