The phosphorylation pattern of insulin-like growth factor-binding protein-1 in normal plasma is different from that in amniotic fluid and changes during pregnancy.

Westwood, Melissa; Gibson, J. M.; Davies, Alison; Young, Robert J.; White, Anne

doi:10.1210/jcem.79.6.7527409

Cited by 94 publications

(113 citation statements)

References 11 publications

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…Cross-reactivity with intact proinsulin was Ͻ0.2% and interassay coefficients of variation were Ͻ7%. Levels of IGF-I and total IGFBP-I (using monoclonal antibody 6303, which detects all IGFBP-1 phosphoforms) were determined by previously reported antibody-based assays (27)(28)(29). The assays have respective detection limits of 28 ng/ml and 3 g/l and withinand between-assay coefficients of variation Ͻ10%.…”

Section: Methodsmentioning

confidence: 99%

Association between Insulin-Like Growth Factor-I

Sandhu

Gibson

Heald

et al. 2004

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Several prospective observational studies have suggested that elevated circulating IGF-I levels are associated with an increased risk of cancer. These observations may provide a potential mechanism through which previously identified metabolic and anthropometric factors, such as obesity and elevated insulin and glucose levels, may operate. We therefore examined metabolic and anthropometric influences on circulating levels of insulinlike growth factor-I (IGF-I), insulin-like growth factorbinding protein-1 (IGFBP-1), and the IGF-I:IGFBP-1 ratio in a middle-aged population of 349 men and 492 women. IGF-I showed only modest inverse associations with indices of adiposity. However, we found that low IGFBP-I levels and an increased IGF-I:IGFBP-1 ratio were strongly associated with increased levels of insulin and glucose in men and women. Body mass index was also positively related to the IGF-I:IGFBP-1 ratio in men (P < 0.001) and women (P < 0.001), independent of metabolic correlates of IGFBP-1 and IGF-I. Similarly, waist:hip ratio and waist circumference were also associated with an increased IGF-I:IGFBP-1 ratio and low circulating IGFBP-1 levels. These findings suggest that individuals with greater fat mass and upper body obesity may have elevated levels of bioavailable or free IGF-I, which could, in part, mediate the reported associations among metabolic and anthropometric factors and cancer risk.

show abstract

Section: Methodsmentioning

confidence: 99%

Association between Insulin-Like Growth Factor-I

Sandhu

Gibson

Heald

et al. 2004

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

show abstract

“…Comparison is by linear regression by site for each sex a Adjusted medians (SE) were predicted from quantile regression models, adjusted for covariates (age) Homeostasis model; HOMA B refers to beta-cell function and HOMA S to insulin sensitivity Assays IGFBP-1 levels were determined with a previously reported antibody based assay [23] with a detection limit 3 μg/l and within-and between-assay CVs of <8%. IGF-I was measured using the DPC Immulite Autoanalyser (DPC, Los Angeles, CA, USA).…”

Section: Values Are Arithmetic Means (Se)mentioning

confidence: 99%

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India

et al. 2005

View full text Add to dashboard Cite

Aims/hypotheses: We previously reported independent links between the IGF system and the development of impaired glucose tolerance and cardiovascular risk. This study tests the hypothesis that the lifestyle change which accompanies population migration, with attendant increases in cardiovascular risk, is reflected by changes in the IGF system. Materials and methods: We compared a specific Gujarati community in Sandwell, UK (n=205), with people still resident in the same villages of origin near Navsari, India (n=246). We performed anthropometry and measured fasting plasma insulin, IGF-I, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-3. Results: Daily calorie intake, BMI and WHR were significantly higher in UK Gujaratis than in Indian Gujaratis. IGFBP-1 was significantly lower in UK migrants (mean 29.5 [95% CI 25.9-33.0] vs 56.5 [50.6-62.5]μg/l; F=48.4, p<0.001). Conversely, fasting insulin, IGFBP-3 and IGF-I were all higher in UK Gujaratis (mean IGF-I 145.9 [138.1-153.6]ng/ml in UK Gujaratis and 100.9 [94.6-107.3] ng/ml in Navsari Gujaratis; F=76.6, p<0.001). These differences were still apparent when adjustment was made for BMI by location for IGF-I (F=57.4, p<0.001) and IGFBP-3 (F=5.7, p=0.02), but were no longer apparent for IGFBP-1 and insulin. At the population level, the decrease in IGFBP-1 for a given increase in insulin was significantly smaller in UK Gujaratis, suggesting greater hepatic insulin resistance in this group. Conclusions/interpretation: Environmental factors have profound effects on circulating IGF system components and on the relationship between IGFBP-1, IGF-I and related metabolic variables. This may have long-term implications for the development of worsening glucose tolerance and cardiovascular disease.

show abstract

“…IGF binding capacity of the IGFBPs is further modulated by phosphorylation lowering the total binding capacity. IGFBP-1 is regulated by low and high phosphorylation and the low and non-phosphorylated forms have significantly reduced affinity for IGFs [46,47]. Studies from our group fail, however, to verify any association between phosphorylation and fetal growth [17].…”

Section: Maternal Compartmentmentioning

confidence: 87%

Macrosomia and the IGF System: A Short Review

Al-Far¹,

Tjessem²,

Lauszus³

2017

Foc Sci

View full text Add to dashboard Cite

Introduction: Macrosomia in diabetic pregnancy is an ubiquitous finding and implies both maternal and fetal issues. Its incidence surpasses other critical obstetrical morbidity in diabetic pregnancy with increased placental size and polyhydramnios as comorbidity. The studies on the underlying factors contributing to macrosomia have focused on growth stimuli like IGF, glycemia, and insulin and their effects on regional organ function. IGF-I and -II in maternal serum are associated with birth weight and the bioavailabiliy is modulated by IGF-binding-proteins (IGFBP) and phosporylated isoforms of IGFBP and the presence of proteases and IGF split products. Human placental growth hormone regulates the effect of IGF-I in pregnancy. Methods: The literature on the IGF system′s possible effect on fetal growth in diabetic pregnancy is reviewed before our current studies and updated with respect to later findings. Regulation on bioavailability by proteolysis and phosporylation is described. The review discusses briefly the studies on pregnant women with type 1 diabetes with respect to vasculopathy. Results: The data show good correlation of IGF-1/2 levels with birth weight. No such correlation with IGFBP-1 and -3 is found. Fetal growth deviation in diabetic pregnancy is not uniform. In first trimester, growth delay is documented in fetal growth curves compared to non-diabetic controls. Accordingly, a shift in IGF-IGFBP regulation in second trimester is found with less proteolysis of IGFBPs and relative increase in total binding capacity. In third trimester, free IGF further increases as IGFBP binding decreases by proteolysis and modulation. The first trimester values may be used as predictor of fetal weight at term. Diabetic women show a two-to threefold increase in the in vitro IGFBP-3 proteolytic activity during pregnancy as compared to post-partum values. Conclusions: Prominent proteolysis of binding proteins and the modulation by insulin account for the mechanism leading to macrosomia. The two factors combined guarantee the stimulation by more bioavailable IGF and the glycemic levels reveal whether insulin dose are optimal. Structural factors of diabetes i.e. microangiopathy further modulate the sum of effects on fetal growth. In contrast to macrosomia, fetal growth restriction is associated with prominent maternal vascular endothelial complications, such as overt nephropathy, proliferative retinopathy, preeclampsia, and hypertension. In parallel to the growth inhibition, stimulatory effects are exerted by the GH axis including the placental growth hormones and occur probably as compensatory mechanism, similar to the increased IGFBP-3 proteolysis in late pregnancy found in growth retardation. This influence may in part explain the disproportionate growth in different tissue components occurring in the various stages of diabetic pregnancy.

show abstract

The phosphorylation pattern of insulin-like growth factor-binding protein-1 in normal plasma is different from that in amniotic fluid and changes during pregnancy.

Cited by 94 publications

References 11 publications

Association between Insulin-Like Growth Factor-I

Association between Insulin-Like Growth Factor-I

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India

Macrosomia and the IGF System: A Short Review

Contact Info

Product

Resources

About