scholarly journals IGF-I and IGFBP-3 Polymorphisms in Relation to Circulating Levels among African American and Caucasian Women

2009 ◽  
Vol 18 (3) ◽  
pp. 954-966 ◽  
Author(s):  
Aimee A. D'Aloisio ◽  
Jane C. Schroeder ◽  
Kari E. North ◽  
Charles Poole ◽  
Suzanne L. West ◽  
...  
Keyword(s):  
African American ◽  
Igf I ◽  
Caucasian Women ◽  
Circulating Levels ◽  
Igfbp 3

The induction of a specific protease for insulin-like growth factor binding protein-3 in the circulation during severe illness

1991 ◽  
Vol 130 (3) ◽  
pp. 469-NP ◽  
Author(s):  
S. C. Davies ◽  
J. A. H. Wass ◽  
R. J. M. Ross ◽  
A. M. Cotterill ◽  
C. R. Buchanan ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Specific Binding ◽  
Nitrogen Retention ◽  
Late Pregnancy ◽  
Severe Illness ◽  
Igf I ◽  
Catabolic State ◽  
Specific Protease ◽  
Circulating Levels ◽  
Igfbp 3

ABSTRACT The insulin-like growth factors (IGF-I and IGF-II) are almost completely bound in the circulation to specific binding proteins (IGFBPs). These IGFBPs appear to play a pivotal role in maintaining circulating levels and modulating the delivery of the IGFs to the tissues. A large proportion of the circulating IGFs are bound with high affinity to one of the binding proteins, IGFBP-3. The mechanism by which these IGFs are transferred from the circulatory pool to the tissue receptors is at present unclear. Recent studies in late pregnancy have demonstrated the presence of specific proteases which may modify the IGFBPs such that their affinities for the IGFs are reduced. In this paper, we have demonstrated the presence of a heat-sensitive cation-dependent proteolytic enzyme specific for IGFBP-3 in the serum of five severely ill patients. The activity of this protease was found to vary in these patients, becoming more apparent during fasting than when studied after commencement of parenteral nutrition, indicating that one of the influencing factors in the activity of this protease is the nutritional intake of the patient. Age- and sex-matched healthy adults were also studied in a similar protocol, but no proteolytic modification of any of the IGFBPs was found in any of the samples examined. As the levels of both IGF-I and IGF-II were found to be low in the patients, the presence of a circulatory protease suggests that this may be an adaptive response to increase the bioavailability of the IGFs and possibly to improve the nitrogen retention and counter the catabolic state in severe illness. Journal of Endocrinology (1991) 130,469–473

scholarly journals Genetic variation and circulating levels of IGF-I and IGFBP-3 in relation to risk of proliferative benign breast disease

2010 ◽  
Vol 126 (1) ◽  
pp. 180-190 ◽  
Author(s):  
Xuefen Su ◽  
Graham A. Colditz ◽  
Walter C. Willett ◽  
Laura C. Collins ◽  
Stuart J. Schnitt ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Benign Breast Disease ◽  
Breast Disease ◽  
Igf I ◽  
Circulating Levels ◽  
Igfbp 3

scholarly journals Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC)

2007 ◽  
Vol 14 (1) ◽  
pp. 81-90 ◽  
Author(s):  
Petra H M Peeters ◽  
Annekatrin Lukanova ◽  
Naomi Allen ◽  
Franco Berrino ◽  
Tim Key ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Relative Risk ◽  
Cancer Risk ◽  
Binding Protein ◽  
Ovarian Cancer Risk ◽  
Relative Risks ◽  
Igf I ◽  
Circulating Levels ◽  
Igfbp 3 ◽  
Prospective Investigation

We set out to study the relationship between circulating levels of IGF-I and its major binding protein (IGFBP-3) in relation to ovarian cancer risk. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of IGF-I and IGFBP-3 were measured in prediagnostic serum samples of 214 women who subsequently developed ovarian cancer, and 388 matched control subjects. Conditional logistic regression models were used to estimate relative risks of ovarian cancer by tertiles of IGF-I and IGFBP-3 levels. For all women, there was no association between the circulating IGF-I or IGFBP-3 levels and the risk of ovarian cancer. However, among women diagnosed with ovarian cancer aged 55 or younger, the relative risk was higher in the middle or top tertiles of serum IGF-I, when compared with women in the lowest tertile (odds ratios (OR) = 1.8 (95%CI 0.7–4.3) and OR = 2.4 (95%CI 0.9–6.4); Ptrend = 0.08) respectively. These results were adjusted for body mass index, previous hormone use, fertility problems, and parity. Restricting the analysis to women who were premenopausal at blood donation, relative risks for ovarian cancer diagnosed before age 55 were higher (OR = 5.1 (95%CI 1.5–18.2) and OR = 5.6 (95%CI 1.5–20.8) respectively, for second and third tertiles; Ptrend = 0.02). Adjustment for serum IGFBP-3 levels only slightly attenuated relative risk estimates. Relations between IGFBP-3 and ovarian cancer before age 55 were in the same direction as for IGF-I, but less strong and statistically not significant. In women aged over 55, there was no association between serum IGF-I or IGFBP-3 and ovarian cancer risk. Our results suggest that the circulating levels of IGF-I may play a potentially important role in the development of ovarian cancer in women of a pre- or perimenopausal age.

Circulating levels of IGF-I and IGFBP-3 in patients with COPD

2015 ◽  
Author(s):  
Ümran Toru ◽  
Ceylan Ayada ◽  
Osman Genç ◽  
Server Sahin ◽  
Özlem Arik ◽  
...  
Keyword(s):  
Igf I ◽  
Circulating Levels ◽  
Igfbp 3

Effect of training on the GH/IGF-I axis during exercise in middle-aged men: relationship to glucose homeostasis

2002 ◽  
Vol 283 (5) ◽  
pp. E929-E936 ◽  
Author(s):  
Jérôme Manetta ◽  
Jean Frederic Brun ◽  
Laurent Maimoun ◽  
Albert Callis ◽  
Christian Préfaut ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Endurance Exercise ◽  
Ventilatory Threshold ◽  
Middle Aged ◽  
Long Duration ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Circulating Levels ◽  
Igfbp 3

The aim of this study was to compare circulating levels of growth hormone (GH), IGF-I, and IGF-binding protein (IGFBP)-1 and IGFBP-3 in response to a long-duration endurance exercise in trained vs. sedentary middle-aged males and to determine whether a relationship with glucose homeostasis exists. Seven trained men (Tr) were compared with seven age-matched sedentary men (Sed) during two trials of 60 min of cycling exercise performed below (−VT) and above (+VT) the ventilatory threshold. Insulin sensitivity (SI) was higher in Tr than in Sed ( P < 0.001). Basal GH, IGF-I, and IGFBP-1 and -3 were higher in Tr ( P < 0.05). During +VT, Tr had a threefold higher GH response, whereas their blood glucose level was better maintained ( P < 0.05). Basal IGFBP-1 was correlated with SI ( P < 0.01). These data indicate that endurance training in middle-aged men increased the activity of the GH/IGF-I system and improved glucoregulation both at rest and during high-intensity endurance exercise.

scholarly journals D440N Mutation in the Acid-Labile Subunit of Insulin-Like Growth Factor Complexes Inhibits Secretion and Complex Formation

2011 ◽  
Vol 25 (2) ◽  
pp. 307-314 ◽  
Author(s):  
Sue M. Firth ◽  
Xiaolang Yan ◽  
Robert C. Baxter
Keyword(s):  
Complex Formation ◽  
Molecular Mass ◽  
Growth Retardation ◽  
Glycosylation Site ◽  
Wild Type ◽  
Igf I ◽  
Acid Labile Subunit ◽  
Circulating Levels ◽  
Acid Labile ◽  
Igfbp 3

Abstract The acid-labile subunit (ALS) regulates IGF bioavailability by forming heterotrimeric complexes with IGFs and IGF-binding protein-3 (IGFBP-3). A homozygous missense mutation (D440N) resulting in undetectable circulating levels of ALS with a concomitant reduction in IGF-I and IGFBP-3 has been reported to cause mild growth retardation. To understand how this particular mutation affects ALS circulating levels and IGF-transport function, we expressed recombinant ALS and its variants, D440N-ALS, T442A-ALS, and D440N/T442A-ALS, using adenovirus vectors. Compared with wild-type ALS, the secretion of D440N-ALS was 80% lower. The D440N mutation was proposed to generate an N-glycosylation site additional to the seven existing motifs in ALS. D440N-ALS appeared larger than ALS, attributable to N-linked glycans because deglycosylation with N-glycosidase F reduced both proteins to the same molecular mass. When ALS was incubated with IGF-I and IGFBP-3, 70–80% of IGF-I was detected by gel-filtration chromatography in forms corresponding to the 150-kDa ternary complex. In contrast, when D440N-ALS was tested, less than 30% of IGF-I was found in high molecular mass complexes. Two other ALS variants mutated in the same putative glycosylation site, D440N/T442A-ALS and T442A-ALS, showed similar chromatographic profiles to wild-type ALS. The D440N mutation in ALS generates a hyperglycosylated form with impaired secretion and complex formation, potentially leading to dysregulation of endocrine IGF, thus contributing to the growth retardation observed in the affected patient. This is the first study to explain how a natural mutation, D440N, in ALS impairs its function.

The effect of epidermal growth factor on circulating levels of IGF and IGF-binding proteins in adult Goettingen minipigs

1996 ◽  
Vol 151 (3) ◽  
pp. 401-407 ◽  
Author(s):  
L Vinter-Jensen ◽  
C Orloff Juhl ◽  
J Frystyk ◽  
E Z Dajani ◽  
N Oksbjerg ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Binding Proteins ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Before And After ◽  
Igf Binding ◽  
Epidermal Growth ◽  
Circulating Levels ◽  
Igfbp 3

Abstract It has recently been demonstrated that epidermal growth factor (EGF) administration to neonatal rodents causes growth retardation with concomitant reductions in circulation levels of IGF-I. We describe the effects of systemic EGF administration for 4 weeks on circulating levels of IGF-I and IGF-binding proteins (IGFBPs) and on thyroid hormones (tri-iodothyronine, T3; thyroxine, T4) in sexually mature pigs. Goettingen minipigs of either sex were treated with placebo (n=5) or EGF (30 μg/kg per day, n=6) s.c. for 4 weeks (in relation to an oesophageal sclerotherapy regimen). Blood samples were taken under anaesthesia before and after 1, 2, 3 and 4 weeks of treatment. Circulating levels of IGF-I, insulin, glucose, T3 and T4 were analysed every week and IGFBPs every second week. IGF-I was not reduced significantly after 1 week but significantly reduced after 2 and 3 weeks of EGF treatment. A similar decline was observed for the major IGFBP, IGFBP-3, which was reduced after 2 and 4 weeks. IGFBP-1, IGFBP-2 and IGFBP-4 increased throughout the treatment period (all significantly at week 4). EGF treatment induced increased circulating T3 after 2, 3 and 4 weeks of EGF treatment. In conclusion, we report that EGF treatment for 4 weeks in Goettingen minipigs reduces circulating IGF-I and IGFBP-3, increases circulating IGFBP-1, IGFBP-2 and IGFBP-4, and induces a slight hyperthyroidism as judged from increased circulating levels of T3. Journal of Endocrinology (1996) 151, 401–407

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