Isolation and partial characterization of six somatomedin-like peptides from human plasma Cohn fraction IV

1986 ◽  
Vol 111 (2) ◽  
pp. 271-284 ◽  
Author(s):  
Werner F. Blum ◽  
Michael B. Ranke ◽  
Jürgen R. Bierich
Keyword(s):  
Growth Factor ◽  
Human Plasma ◽  
Cell Membranes ◽  
Reversed Phase ◽  
Insulin Like Growth Factor ◽  
C Peptide ◽  
Sds Page ◽  
Igf I ◽  
Basic Peptides ◽  
Acidic Peptides

Abstract. Six somatomedin-like peptides were purified from human plasma Cohn fraction IV by a six-step procedure which included ethanol precipitation, reversed-phase extraction, gel filtration, chromatofocusing and reversed-phase high pressure liquid chromatography (HPLC). Purification was monitored with a competitive protein binding assay using a crude preparations of somatomedin carrier protein. The peptides isolated were homogeneous by reversed-phase HPLC and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Their apparent isoelectric points determined by chromatofocusing were 9.2 (Sm I), (Sm II), 8.2 (Sm III), 6.7 (Sm IV), 6.3 (Sm V), and 6.15 (Sm VI). SDS-PAGE under reducing conditions revealed that they are composed of a single peptide chain with apparent molecular weights of 6800 for Sm I, II and IV and 6400 for Sm III, V, and VI. They were equally potent in the porcine costal cartilage in vitro bioassay. The basic peptides (Sm I–III) were significantly more active in radioimmunoassays for somatomedin C (SmC) and insulin-like growth factor I C-peptide (IGF-I (30–41)), while only the slightly acidic peptides were active in a radioimmunoassay for insulin-like growth factor II C-peptide (IGF-II (33–40)). When receptor binding was tested with human placental cell membranes and Sm III as tracer, the basic peptides were significantly more potent than Sm IV–VI. With rat liver cell membranes and Sm V as tracer the slightly acidic peptides were more potent. These findings suggest 1) that human plasma may contain other somatomedin-like peptides besides the major components IGF-I/SmC and IGF-II, and 2) that the basic peptides are structurally related to IGF-I/SmC and the slightly acidic peptides are related to IGF-II.

scholarly journals Trajectories of body fatness from age 5 to 60 y and plasma biomarker concentrations of the insulin–insulin-like growth factor system

2018 ◽  
Vol 108 (2) ◽  
pp. 388-397 ◽  
Author(s):  
Ane S Kværner ◽  
Dong Hang ◽  
Edward L Giovannucci ◽  
Walter C Willett ◽  
Andrew T Chan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Moderate Increase ◽  
Insulin Like Growth Factor ◽  
Stable Group ◽  
Plasma Biomarker ◽  
Body Fatness ◽  
C Peptide ◽  
Percentage Difference ◽  
Igf I ◽  
Igfbp 3

Abstract Background A major pathway through which obesity increases the risk of cardiometabolic diseases and cancer is by inducing hormonal and metabolic abnormalities, including hyperinsulinemia and altered insulin-like growth factor (IGF) signaling. However, little is known about the influence of lifetime adiposity on the relevant biomarkers. Objective The aim of this study was to examine associations of trajectories of body fatness with plasma biomarker concentrations of the insulin-IGF system in 2 large prospective cohorts of US men and women. Design Associations between trajectories of body fatness and concentrations of plasma C-peptide, IGF-I, IGF-binding protein (IGFBP) 1, IGFBP-3, and the IGF-I–to–IGFBP-3 molar ratio was examined in 9386 women of the Nurses’ Health Study and 3941 men of the Health Professionals Follow-Up Study. Group-based trajectory modeling was used to create trajectory groups on the basis of self-reported somatotype data at ages 5, 10, 20, 30, and 40 y and body mass index (BMI) at ages 45, 50, 55, and 60 y. We used multivariate linear regression models to examine the associations of trajectories with biomarker concentrations. Results Five trajectories of body fatness were identified: “lean-stable,” “lean–moderate increase,” “lean–marked increase,” “medium-stable/increase,” and “medium–marked increase.” Compared with the lean-stable group, the lean–marked increase and medium–marked increase groups had significantly higher concentrations of C-peptide (percentage difference—women: 44% and 73%; men: 27% and 51%) and lower concentrations of IGFBP-1 (women: –61% and –78%; men: –47% and –65%). Adjustment for current BMI attenuated the association to null for the medium–marked increase group, but the lean–marked increase group still had modestly higher concentrations of C-peptide (women: 10%; men: 6%) and lower concentrations of IGFBP-1 (women: –18%; men: –21%) than the lean-stable group. Conclusions Adiposity across the life span was associated with higher C-peptide and lower IGFBP-1 concentrations in adulthood. The associations were largely driven by attained adiposity and, to a lesser extent, weight gain in early-middle adulthood. This trial was registered at www.clinicaltrials.gov as NCT03419455.

Evaluation of a radioimmunoassay for somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) in human plasma

1990 ◽  
Vol 188 (3) ◽  
pp. 253-260 ◽  
Author(s):  
Daniel Giannella-Neto ◽  
Ana Mercedes Cavaleiro ◽  
Rosa Sadoyama ◽  
Bernardo Leo Wajchenberg ◽  
E.Martin Spencer
Keyword(s):  
Growth Factor ◽  
Human Plasma ◽  
Insulin Like Growth Factor ◽  
Somatomedin C ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

scholarly journals Differential effect of growth hormone and insulin-like growth factor-I, insulin-like growth factor-II, and insulin on Ig production and growth in human plasma cells

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1569-1574 ◽  
Author(s):  
H Kimata ◽  
A Yoshida
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Human Plasma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Thymidine Uptake ◽  
Insulin Like Growth Factor ◽  
Cell Responses ◽  
Factor I ◽  
Igf I

The effect of human growth hormone (GH) and insulin-like growth factor- I (IGF-I), IGF-II, and insulin on human plasma cell responses was studied. GH enhanced Ig production and thymidine uptake in the human plasma cell lines, IM-9 and AF-10. IGF-I, but not IGF-II or insulin, also enhanced Ig production and proliferation in them. However, enhancement by GH was not mediated by IGF-I, because enhancement was blocked by anti-GH antibody (Ab), but not by Ab to IGF-I or IGF-I receptor. Conversely, the enhancement by IGF-I was blocked by either Ab to IGF-I or IGF-I receptor, but not by anti-GH Ab. GH and IGF-I also enhanced production of IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, and IgM and thymidine uptake in PCA-1+ plasma cells generated in vitro. Again, enhancement by GH was specifically blocked by anti-GH Ab, whereas enhancement by IGF-I was specifically blocked by either Ab to IGF-I or IGF-I receptor. These results indicate that GH and IGF-I may play important roles in plasma cell responses.

Plasma half-lives of native and modified insulin-like growth factor-I in lambs

1988 ◽  
Vol 117 (2) ◽  
pp. 183-189 ◽  
Author(s):  
G. L. Francis ◽  
P. J. McNamara ◽  
O. H. Filsell ◽  
F. J. Ballard
Keyword(s):  
Growth Factor ◽  
Half Life ◽  
Binding Protein ◽  
Gel Permeation Chromatography ◽  
Reversed Phase ◽  
Insulin Like Growth Factor ◽  
Plasma Samples ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

ABSTRACT The clearance of labelled insulin-like growth factor-I (IGF-I) has been measured in lambs following acid gel-permeation chromatography and immunoprecipitation of plasma samples. The half-lives obtained in three experiments were between 5 and 7 h. Chromatography at neutral pH on a Fractogel HW55(S) column demonstrated that all the radioactivity associated with undegraded peptide in plasma was bound to a carrier protein. Similar studies with IGF-I that had been reduced by prior dithiothreitol treatment showed that two-thirds of the initial radioactivity in plasma decayed with a much shorter half-life and represented material that did not bind to carrier proteins in plasma. The remaining radioactivity was both associated with a binding protein and exhibited the characteristically long half-life of the native growth factor. Analysis of plasma samples using reversed-phase chromatography demonstrated that the radioactive component with a long half-life was IGF-I while that with a short half-life had been reoxidized to an incorrect form of the growth factor. When reoxidation of reduced IGF-I was blocked by S-carboxymethylation before injection of the radioactive peptide into lambs, it remained unbound in plasma and had a 0·8–0·9 h half-life. We suggest that reduced IGF-I only associates with the binding protein upon oxidation and correct folding and that this association is necessary in order for IGF-I to have a relatively long half-life. J. Endocr. (1988) 117, 183–189

Purification of a basic somatomedin, from human plasma Cohn fraction IV-1, with physicochemical and radioimmunoassay similarity to somatomedin-C and insulin-like growth factor

1979 ◽  
Vol 57 (11) ◽  
pp. 1289-1298 ◽  
Author(s):  
R. Marvin Bala ◽  
B. Bhaumick
Keyword(s):  
Growth Factor ◽  
Human Plasma ◽  
Protein Separation ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Extraction Procedure ◽  
Molecular Size ◽  
Protein Band ◽  
Insulin Like Growth Factor ◽  
Igf I

A basic somatomedin (SM) was purified from human plasma Cohn fraction IV-1 using an initial acid–ethanol–acetone extraction procedure followed by alternating molecular size or charge protein separation techniques. The final recovery of SM bioactivity was approximately 2% of that present in the starting Cohn fraction. The purified SM has an approximate molecular weight of 7500, pI 8.6, 4000 SM bioactivity units per milligram (as measured by a hypophysectomized rat bioassay) and a parallel approximately equipotent radioimmunoassay dose–response curve to SM-C and insulin-like growth factor-I (IGF-I). Sodium dodecyl sulfate – polyacrylamide gel electrophoresis of this purified SM revealed a single protein band. The preliminary determination of the amino acid sequence of the N terminus suggested that this SM preparation was over 75% pure and the first five N-terminal amino acids were identical with those of IGF-I.

scholarly journals Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity of IGFs in cystic fibrosis

2006 ◽  
Vol 154 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Maria E Street ◽  
Maria A Ziveri ◽  
Cinzia Spaggiari ◽  
Isabella Viani ◽  
Cecilia Volta ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Growth Factor ◽  
Binding Protein ◽  
Serum Insulin ◽  
Molecular Forms ◽  
Insulin Like Growth Factor ◽  
Serum Concentrations ◽  
C Peptide ◽  
Igf I ◽  
Igfbp 3

Objective: In inflammatory bowel diseases, increased serum interleukin (IL)-6 levels are associated with high serum insulin-like growth factor-binding protein 2 (IGFBP-2) levels, and cytokines modify the insulin-like growth factor (IGF)/IGFBP system in models in vitro. In cystic fibrosis (CF) the IGF/IGFBP system has not been extensively studied, and relationships with proinflammatory cytokines have not been explored. The aim of this study was to investigate the IGF/IGFBP system and verify changes dependent on IL-1β, IL-6, tumour necrosis factor α (TNFα), and insulin. Methods: Eighteen subjects with CF (mean age 26.6 ± 1.1 years) and 18 controls, comparable for age, sex, and body mass index, were enrolled. Serum IGF-I, IGF-II, IGFBP-2, IGFBP-3, IL-1β, IL-6, TNFα, insulin and C-peptide were measured. Different molecular forms of IGFBP-2 and IGFBP-3 were investigated by Western immunoblotting. The patients were analysed as a whole and as two subgroups depending on established clinical criteria (Swachman–Kulczycki score). Results: Patients had higher serum concentrations of IL-1β, IL-6, TNFα and IGFBP-2 than controls. Serum concentrations of IGF-I and IGF-II were significantly lower and insulin and C-peptide levels significantly increased in CF compared with healthy controls whereas IGFBP-3 serum concentrations were similar, with comparable IGF-I/IGFBP-3 and decreased IGF-I/IGFBP-2 and IGF-II/IGFBP-2 molar ratios. From correlation analysis we detected a significant positive correlation between IGFBP-2 and IL-6 and a negative correlation between IGFBP-2 and IGFBP-3. Conclusions: Our findings suggest that inflammation is an important modulator of the IGF/IGFBP system with an overall reduction in IGF bioactivity in CF.

scholarly journals Regulation of insulin-like growth factor-binding protein-3 ternary complex in feline diabetes mellitus

2000 ◽  
Vol 166 (1) ◽  
pp. 21-27 ◽  
Author(s):  
MS Lewitt ◽  
SJ Hazel ◽  
DB Church ◽  
AD Watson ◽  
SE Powell ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factor ◽  
Complex Formation ◽  
Ternary Complex ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Ternary Complex Formation ◽  
Sds Page ◽  
Igf I ◽  
Igfbp 3

The 140 kDa ternary complex of insulin-like growth factor-binding protein-3 (IGFBP-3), IGFs and an acid-labile subunit (ALS) has previously been shown to be decreased in diabetes mellitus in humans and rats. We have studied IGF-I levels and ternary complex formation in normal and diabetic cats. Total IGF-I concentrations, measured by RIA using des(1-3)-IGF-I as tracer were (+/-s.e.m.) 54+/-13 nmol/l in eight normal and 227+/-57 nmol/l in eight diabetic cats (P<0.01). The size-distribution of IGFBPs in the cat circulation was determined by incubation with (125)I-IGF-II and Superose 12 chromatography. In normal animals 26+/-2% of the (125)I-IGF-II were in a 140 kDa form compared with 48+/-5% in diabetic cats (P<0.01). When samples from normal and diabetic animals were co-incubated 52+/-3% were at 140 kDa. A similar shift was seen when normal cat and normal human serum were co-incubated. A 2-fold increase in the 140 kDa form in diabetic cats was confirmed first by size-fractionating samples and then performing a ligand-binding assay with (125)I-IGF-I or -II and charcoal separation. SDS-PAGE and Western ligand blotting demonstrated a 45 kDa doublet (presumably IGFBP-3) and 30-35 kDa forms. There were no apparent differences between normal and diabetic profiles on SDS-PAGE, suggesting that a proportion of IGFBP-3 which circulates 'free' in normal cats forms a ternary complex in the diabetic circulation. We conclude that (i) in contrast to humans and rats, ALS is the limiting factor for ternary complex formation in normal cats, (ii) ALS concentrations increase in feline diabetes mellitus and, by promoting ternary complex formation, this leads to an increase in total IGF-I concentrations, and (iii) total IGF-I concentrations may not be reliable in the diagnosis of acromegaly in diabetic cats.

scholarly journals Similarity of Serum and Plasma Insulin-like Growth Factor Concentrations

2015 ◽  
Vol 7 ◽  
pp. BIC.S23088
Author(s):  
Lauren C. Houghton ◽  
Michael N. Pollak ◽  
Yuzhen Tao ◽  
Ying Gang Tu ◽  
Amanda Black ◽  
...  
Keyword(s):  
Growth Factor ◽  
Correlation Coefficients ◽  
Systematic Bias ◽  
Insulin Like Growth Factor ◽  
Plasma Samples ◽  
Ovarian Cancer Screening ◽  
C Peptide ◽  
Igf I ◽  
Highly Correlated ◽  
Igfbp 3

Background Insulin-like growth factors (IGFs) are implicated in many normal physiological processes and pathological states, including cancer. For large consortia projects, it may be necessary to make comparisons among studies with different specimens that were not collected specifically to optimize the measurement of IGFs. Objective This study aimed to compare IGFs in matched serum and plasma samples. Methods We measured IGF-I, IGF-II, insulin-like growth factor-binding protein (IGFBP)-3, C-peptide, and leptin in serum and ethylenediaminetetraacetic–containing-plasma samples obtained concurrently from 30 healthy women aged 64–80 years in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial using chemiluminescent or colorimetric enzyme-linked immune assays. Coefficients of variation (CVs) and correlations were determined. Results Intraassay CVs ranged from 0.4% for IGFBP-3 to 10% for IGF-II. Mean concentrations of all analytes were higher in the serum, but the differences in mean concentrations of the analytes between serum and plasma were all <11%. Concordance correlation coefficients of matched serum/plasma specimens were 0.92, 0.91, 0.82, 0.96, and 0.99 for IGF-I, IGFBP-3, IGF-II, C-peptide, and leptin, respectively. Conclusion IGF concentrations measured in serum and plasma are highly correlated but are consistently slightly higher in serum, suggesting that IGF values should be corrected for systematic bias, particularly in consortial efforts when pooling data derived from different specimens.

scholarly journals Insulin, the Insulin-Like Growth Factor Axis, and Mortality in Patients With Nonmetastatic Colorectal Cancer

2009 ◽  
Vol 27 (2) ◽  
pp. 176-185 ◽  
Author(s):  
Brian M. Wolpin ◽  
Jeffrey A. Meyerhardt ◽  
Andrew T. Chan ◽  
Kimmie Ng ◽  
Jennifer A. Chan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Lifestyle Factors ◽  
Insulin Like Growth Factor ◽  
C Peptide ◽  
Colorectal Cancer Resection ◽  
Increased Risk ◽  
Igf I ◽  
Risk Of Cancer ◽  
Igfbp 3

Purpose Obesity, sedentary lifestyle, and Western dietary pattern have been linked to increased risk of cancer recurrence and mortality among patients with surgically resected colorectal cancer. Excess energy balance leads to increased circulating insulin and depressed levels of circulating insulin-like growth factor binding protein (IGFBP) -1, which promote cancer cell growth in preclinical models. Patients and Methods Among 373 patients diagnosed with nonmetastatic colorectal cancer between 1991 and 2004, we performed a prospective observational study nested within two large US cohorts to evaluate the association between mortality and prediagnosis circulating C-peptide (a marker of insulin secretion), IGFBP-1, insulin-like growth factor-I (IGF-I), and IGFBP-3. Results Compared with patients in the bottom quartile, patients in the top quartile of plasma C-peptide had an age-adjusted hazard ratio (HR) for death of 1.87 (95% CI, 1.04 to 3.36; P = .03 for trend), whereas those in the top quartile of circulating IGFBP-1 had a significant reduction in mortality (HR = 0.48; 95% CI, 0.28 to 0.84; P = .02 for trend). Little change in these estimates was noted after adjusting for other covariates known or suspected to influence survival. No associations were noted between mortality and IGF-I or IGFBP-3, which are two components of the IGF axis not closely correlated with lifestyle factors. Conclusion Among patients with surgically resected colorectal cancer, higher levels of prediagnosis plasma C-peptide and lower levels of prediagnosis plasma IGFBP-1 were associated with increased mortality. Circulating insulin and IGFBP-1 are potential mediators of the association between lifestyle factors and mortality after colorectal cancer resection.

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