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Steady state insulin-like growth factor-1 (IGF-1) levels vary significantly during continuous intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) in the first weeks of life in extremely preterm infants. We evaluated interleukin-6 (IL-6) and insulin-like growth factor binding protein-1 (IGFBP-1) levels as predictors of low IGF-1 levels. Nineteen extremely preterm infants were enrolled in a trial, 9 received rhIGF-1/rhIGFBP-3 and 10 received standard neonatal care. Blood samples were analyzed daily for IGF-1, IL-6 and IGFBP-1 during intervention with rhIGF-1/rhIGFBP-3. Thirty seven percent of IGF-1 values during active treatment were <20 μg/L. Among treated infants, higher levels of IL-6, one and two days before sampled IGF-1, were associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.30 (95% CI 1.03–1.63), p =.026, and 1.57 (95% CI 1.26–1.97), p <.001 respectively. Higher levels of IGFBP-1 one day before sampled IGF-1 was also associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.74 (95% CI 1.19–2.53), p =.004. In preterm infants receiving continuous infusion of rhIGF-1/rhIGFBP-3, higher levels of IL-6 and IGFBP-1 preceded lower levels of circulating IGF-1. These findings demonstrate a need to further evaluate if inflammation and/or infection suppress serum IGF-1 levels. The trial is registered at ClinicalTrials.gov (NCT01096784). • IGF-1 levels vary during rhIGF-1/rhIGFBP-3 treatment in preterm infants. • High IL-6 and IGFBP-1 levels predicted low serum IGF-1 < 20 μg/L. • The results suggest that inflammation and/or infection may suppress serum IGF-1. • This finding increases the understanding of the feasibility of rhIGF-1/rhIGFBP-3 treatment. [ABSTRACT FROM AUTHOR]

Introduction: Growing evidence indicates that circulating concentrations of insulin-like growth factor 1 (IGF-I), along with IGF-I relative to IGF-binding proteins (IGFBP), are associated with an increased risk of cancer. In accord, regular exercise is linked with a lower risk of cancer. Purpose: To assess the effects of a 16-week home-based strength training (HBST) program on serum IGF-I, IGFBP-1 and IGFBP-3. Methods: A total of 32 obese Latino adolescent males (aged 14–18 years) were randomized into a twice-weekly HBST (n = 16) or a control group (C, n = 16) for 16 weeks. The following were measured at pre- and post-intervention: IGF-I, IGFBP-1 and IGFBP-3, glucose/insulin indices by oral and/or intravenous (IV) glucose tolerance tests, strength by one-repetition maximum (1RM), dietary intake by 3-d records, body composition by DEXA and physical activity using the Actigraph GT1X. The generalized linear model (GLM) was used to assess differences in changes among outcome measures between the HBST and C groups. Results: Exercise adherence in the HBST group was 89%. IGF-1 showed a trend for significant within-subject improvements (p = 0.078) but no significant within-subject or between-subject differences for IGFBP-1, IGFBP-3 two-glucose, fasting glucose or 2-h glucose (p > 0.05). There was a significant decrease (p > 0.05) in fasting glucose in the C group (p = 0.02) and also in the intervention group (p = 0.03) between baseline and follow-up testing. A significant difference was also found in the C group for 2-h glucose with an increase at follow-up testing (p = 0.04). Conclusions: Though not statistically significant (p < 0.05), the results indicated that a 16-week HBST program decreased IGF-I and increased IGFBP-1, along with IGFBP-3, concentrations among overweight/obese Latino boys. However, further studies should consider increasing either the dose or the duration of the intervention to elicit greater improvements in this at-risk pediatric population. [ABSTRACT FROM AUTHOR]

Objectives Obese children are often taller than age-matched subjects. Reports on GH and IGF-I levels in obese individuals are controversial, with normal and reduced GH-IGF-I levels having been reported in this group of patients. Thus, the aim of this study was to analyse insulin-like growth factor type 1 receptor (IGF-IR) mRNA expression in obese children. Methods Forty-seven pre-pubertal children were included in this study: 29 were obese and taller than their target height, and 18 were normal eutrophic controls. Fasting blood samples were collected for IGF-IR mRNA expression in isolated lymphocytes and serum IGF-I, ALS, IGFBP-3, and IGFBP-1 concentration analysis. Results Relative IGF-IR gene expression (2 − ΔΔ C T ) was significantly ( P = 0.025) higher in obese children (median 1.87) than in controls (1.15). Fourteen of the 29 obese subjects showed 2 − ΔΔ C T values greater than or equal to 2, while only 2 individuals in the control group showed values above 2 ( P = 0.01). Obese children showed significantly ( P = 0.01) higher IGF-I concentrations than the control group (237 ng/ml and 144 ng/ml, respectively). Among obese patients, 65.5% had IGF-I values above the 75 percentile of the control group ( P = 0.02). ALS concentration was significantly ( P = 0.04) higher in the obese group, while IGFBP-3 levels were similar in obese and control children. IGFBP-1 concentration was lower in obese children, while insulin levels and HOMA-IR index were higher than in controls. Conclusions The higher IGF-IR mRNA expression observed in obese children, associated with the higher IGF-I and ALS and the lower IGFBP-1 levels, suggest that the higher stature observed in these children may be due to increased IGF-I bioactivity. [ABSTRACT FROM AUTHOR]

Introduction Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 (IGFBP-1) play an important role in vascular health. Many patients with type 1 diabetes are medicated with HMG-CoA reductase inhibitors, statins, in order to prevent vascular complications. Yet little is known about the effect of statins on the IGF-1/IGFBP-1 axis in these patients. Objectives The aim of this study was to evaluate the effect of atorvastatin treatment on IGF-1 and IGFBP-1 with regards to microvascular function. Design Twenty patients with type 1 diabetes received either placebo or 80 mg atorvastatin for two months in a double-blinded cross-over study. IGF-1 and IGFBP-1 levels were assessed before and after each treatment period. Skin microcirculation was studied using Doppler perfusion imaging during iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and endothelium-independent microvascular reactivity, respectively. Results Treatment with high-dose atorvastatin was associated with a significant decrease in IGF-1 levels compared to placebo ( p < 0.05, ANOVA repeated measures), whereas no effect was seen on IGFBP-1 or the IGF-1/IGFBP-1 ratio. These variables did not correlate with measurements of skin microvascular reactivity. Conclusions The study found that treatment with high-dose atorvastatin was associated with reduced IGF-1 levels, which may indicate a potential negative effect on microvascular function and long-term risk of microangiopathy development. [ABSTRACT FROM AUTHOR]

Importance Elevated cortisol levels and dysregulated insulin-like growth factor binding protein-1 (IGFBP-1; a marker of hepatic insulin sensitivity) are both related to insulin resistance and glucose abnormalities. It is unknown whether improvement in these parameters is related to improved glucose metabolism during treatment with sitagliptin. Objective To determine whether improved insulin sensitivity and beta-cell function during treatment with sitagliptin is related to lower cortisol levels and/or improved regulation of IGFBP-1 in patients with recent acute coronary syndrome (ACS) and newly discovered glucose abnormalities. Design Samples were taken from The BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction (BEGAMI) trial, a double-blinded, placebo-controlled randomized clinical trial on the efficacy and safety of sitagliptin for patients with ACS and newly discovered glucose abnormalities. Setting Cardiology departments (cardiac ICU and outpatient clinic) in two hospitals in Stockholm, Sweden. Participants Subjects hospitalized (or recently hospitalized) for ACS, in whom an oral glucose tolerance test revealed previously unknown glucose abnormalities. Interventions Subjects were randomized to sitagliptin 100 mg once daily (n = 34) or placebo (n = 37) for twelve weeks. Oral glucose tolerance test (OGTT) and randomization occurred after stabilization median 7 days after ACS. Main outcomes and measures Fasting serum cortisol and IGFBP-1 were analyzed before OGTT, around 8 a.m., and after at 10 a.m. The latter time point was chosen as the spread in cortisol levels around is small then, allowing improved chances to detect differences between groups. Results Glucose tolerance and insulin sensitivity improved in both groups, while HbA 1c and indices of β-cell function improved only in the sitagliptin group as reported previously. Both groups displayed decreased cortisol levels around 10 a.m. (from 338 ± 21 to 278 ± 14 nmol/L, p = 0.038, in the sitagliptin group; from 343 ± 17 to 302 ± 15 nmol/L, p = 0.017, in the placebo group), and improved correlation between fasting log-IGFBP-1 and insulin. Conclusions and relevance These findings suggest that a stress-related elevation in cortisol may have negative impact on glucose tolerance in patients with recent ACS. However, improved glycemic control with sitagliptin does not appear to be related to changes in cortisol levels or hepatic insulin sensitivity as assessed by IGFBP-1. [ABSTRACT FROM AUTHOR]

Objective Previous studies on the insulin-like growth factor (IGF) system and mortality have shown ambiguous results. We investigated the association between IGF-I and insulin- like growth factor binding protein-1 (IGFBP-1) with all-cause mortality in an elderly female Swedish population. Design and methods A prospective cohort study of elderly women (n = 338) aged between 68 and 79 years (mean age 72 years) with a mean follow-up time of 9.9 years. Baseline data in the PRIMOS (Primary Health Care and Osteoporosis) study were collected between 1999 and 2001. Data of risk factors for cardiovascular disease were collected. Death rates were registered from the Swedish Cause of Death register for the period 1999–2009. Cox regression models were used to calculate hazard ratios. IGF-I and IGFBP-1 levels were separately divided into 3 groups (high, medium and low), with cut offs at the 30th and the 70th percentiles. Results In a fully adjusted Cox proportional hazard model, increased risk of mortality was shown for women with high serum levels of IGFBP-1, HR 3.03 (95% CI 1.64–5.63) and also with low serum levels of IGFBP-1, HR 1.98 (95% CI 1.03–3.81), compared to women with moderate levels. No significant association between IGF-I and mortality was observed. Conclusions High and low serum insulin-like IGFBP-1 levels were associated with an increased risk of all-cause mortality in elderly women, compared to moderate levels. [ABSTRACT FROM AUTHOR]

IGFBP-1 and IGFBP-2 are suppressed by growth hormone and therefore represent less prominent members of the IGFBP family when compared to IGFBP-3 that carries most of the IGFs during circulation under normal conditions in humans in vivo. As soon as the GH signal is decreased expression of IGF-I and IGFBP-3 is reduced. Under conditions of lowered suppression by GH the time seems come for IGFBP-1 and IGFBP-2. Both IGFBPs are potent effectors of growth and metabolism. Secretion of IGFBP-1 and IGFBP-2 is further suppressed by insulin and diminished with increasing obesity. Both IGFBP family members share the RGD sequence motif that mediates binding to integrins and is linked to PTEN/PI3K signalling. In mice, IGFBP-2 prevents age- and diet-dependent glucose insensitivity and blocks differentiation of preadipocytes. The latter function is modulated by two distinct heparin-binding domains of IGFBP-2 which are lacking in IGFBP-1. IGFBP-2 is further regulated by leptin and has been demonstrated to affect insulin sensitivity and glucose tolerance, further supporting a particular role of IGFBP-2 in glucose and fat metabolism. Since IGFBP-2 is controlled by sex steroids as well, we devised a scheme to compare IGFBP effects in breast, ovarian and prostate cancer. While a positive association does not seem to exist with IGFBP-1 and risk of cancers within these reproductive tissues, a relationship between IGFBP-2 and breast cancer, ovarian cancer and prostate cancer does indeed appear to be present. To date, the specific roles of IGFBP-2 in estrogen signalling are unclear, though there is accumulating evidence for an effect of IGFBP-2 on PI3K signalling via PTEN, particularly in breast cancer. [ABSTRACT FROM AUTHOR]

Ultra-endurance competitions are becoming increasingly popular but there is limited research on female participants. The purpose of this study was to examine changes in estrogen and the IGF-I system in women after an ultra-marathon. Six pairs of pre- and post- menopausal women were matched for race finish times;mean finish time was 20 hours. Blood samples were drawn 24 hours before the race, at the finish, and 24 hours into recovery. Samples were analysed for estradiol, total IGF-I, IGFBP-1, and intact IGFBP-3. There was a significant increase in estradiol following the race in both groups (P<0.05). Total IGF-I decreased after the race (P<0.01) and remained lower in recovery. IGFBP-1 increased after the race (P<0.001) but returned to pre-race levels after 24 hours, while intact IGFBP-3 was significantly lower post-race and in recovery (P<0.001). Postmenopausal women had significantly lower estradiol at baseline, but there were no other group differences. These results demonstrate that among recreational female runners, an ultra-marathon is associated with IGF system changes that are consistent with an energy-deficient, catabolic state. Further research is needed to confirm the effect of these endocrine changes on health and performance. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Serum free insulin like growth factors-1 (IGF-1) and insulin like growth factor binding protein-1 (IGFBP-1) may have an association with insulin resistance and B-cell secretory dysfunction. Present study is undertaken to explore the independent association of IGF-1 and IGFBP-1with two basic defects in type 2 diabetic patients in a Bangladeshi population. Methods: Sixty eight type 2 diabetes mellitus (DM) subjects are studied along with age-, sex- and BMI-matched 61 healthy controls without family history of diabetes or prediabetes. Insulin, free IGF-1 and IGFBP-1 are measured by the standard ELISA method. Insulin secretory capacity (HOMA B) and insulin sensitivity (HOMA S) are calculated using fasting glucose and fasting insulin by HOMA-CIGMA software. Results: Fasting free IGF-1 and IGFBP-1 levels are not significantly different between the study groups. But the level of free IGF-1 is significantly higher (p =0.03) in type 2 DM subjects compared to controls in the low BMI group (BMI?23). In stepwise multiple regression analysis, positive association of HOMA B with free IGF-1 is evident. Similarly positive association of HOMA B and HOMA S with IGFBP-1 is shown in different models. In the same analysis, both free IGF-1 and IGFBP-1 are inversely associated with fasting insulin in different models of stepwise multiple regression analysis. Conclusion: Both IGF-1 and IGFBP-1 are negatively associated with fasting insulin levels. Moreover B-cell secretory dysfunction is positively associated with IGF-1 and both B-cell secretory dysfunction and insulin sensitivity are also positively associated with IGFBP-1 in type 2 diabetic patients. [Copyright &y& Elsevier]

Abstract: Hypoxia is one of many factors involved in the regulation of the IGF system. However, no information is available regarding the regulation of the IGF system by acute hypoxia in humans. Objective: The aim of this study was to evaluate the effect of acute hypoxia on the IGF system of children. Design: Twenty-seven previously health children (14 boys and 13 girls) aged 15days to 9.5years were studied in two different situations: during a hypoxemic state (HS) due to acute respiratory distress and after full recovery to a normoxemic state (NS). In these two situations oxygen saturation was assessed with a pulse-oximeter and blood samples were collected for serum IGF-I, IGF-II, IGFBP-1, IGFBP-3, ALS and insulin determination by ELISA; fluoroimmunometric assay determination for GH and also for IGF1R gene expression analysis in peripheral lymphocytes by quantitative real-time PCR. Data were paired and analyzed by the Wilcoxon non-parametric test. Results: Oxygen saturation was significantly lower during HS than in NS (P<0.0001). IGF-I and IGF-II levels were lower during HS than in NS (P<0.0001 and P=0.0004, respectively). IGFBP-3 levels were also lower in HS than in NS (P=0.0002) while ALS and basal GH levels were higher during HS (P=0.0015 and P=0.014, respectively). Moreover, IGFBP-1 levels were higher during HS than in NS (P=0.004). No difference was found regarding insulin levels. The expression of IGF1R mRNA as 2−ΔΔCT was higher during HS than in NS (P=0.03). Conclusion: The above results confirm a role of hypoxia in the regulation of the IGF system also in humans. This effect could be direct on the liver and/or mediated by GH and it is not restricted to the hepatocytes but involves other cell lines. During acute hypoxia a combination of alterations usually associated with reduced IGF action was observed. The higher expression of IGF1R mRNA may reflect an up-regulation of the transcriptional process. [Copyright &y& Elsevier]

Abstract: Aim and Background: Free IGF-1 and IGFBP-1 are associated with obesity which is one of the major features of insulin resistance. But very few studies exist on free IGF-1 and IGFBP-1 in IGT subjects. The present study was undertaken to investigate the association of free IGF-1 and IGFBP-1 with insulin sensitivity in IGT subjects. Subjects and Methods: Ninety-one subjects with impaired glucose tolerance (IGT) were studied along with age- sex- and BMI-matched sixty-one healthy Controls without family history of diabetes or prediabetes. Insulin, free IGF-1 and IGFBP-1 were measured by standard ELISA method. Insulin secretory capacity (HOMA B) and insulin sensitivity (HOMA S) were calculated using fasting glucose and fasting insulin by HOMA-CIGMA software. Results: Fasting free IGF-1 and IGFBP-1 levels were not significantly different among the study groups. In stepwise multiple regression analysis, when free IGF-1 was considered as a dependent variable with other independent variables, model 1 (β =−0.352, p =0.03), model 2 (β =−0.355, p =0.033) and model 5 (β =−0.378, p =0.026) have shown significant association of fasting glucose with free IGF-1. Similarly when IGFBP-1 was considered as a dependent variable, model 4 (β =−0.865, p =0.03) and model 5 (β =−0.1.07, p =0.004) have shown negative association of fasting glucose with IGFBP-1. In this analysis model 5 have also shown negative association of HOMA S with IGFBP-1 (β =−1.015, p =0.017). Conclusion: IGF1 and IGFBP-1 seems to be negatively associated with fasting glucose in IGT subjects and insulin sensitivity (HOMA S) may also be negatively associated with IGFBP-1 in IGT subjects. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Hemodialysis is associated with catabolism and one contributing factor could be decreased bioavailable IGF-I. The aim of this investigation was to study the response of IGF-I and IGFBP-1 to a euglycemic hyperinsulinemic clamp before hemodialysis in type 2 diabetes (T2D) with chronic kidney disease on hemodialysis (CKD5D). Stage 5 (Stages 0–5 according to renal function) indicates a GFR less than 15mL/min/1.73m2, D indicates hemodialysis. The response was compared with that in type 1 diabetes (T1D) with normal renal function. Design: Five overnight fasted patients with T2D with CKD5D were subjected to an insulin infusion (1.6mU/kg/h) for 4 h after which they had lunch followed by a four hour hemodialysis session. The results were compared with results from a previous study in seven T1D patients with normal renal function who had received a similar clamp the same insulin dose with the addition of an initial bolus dose. Blood samples were drawn at 15 to 30min intervals for analysis of IGFBP-1, IGF-I and insulin and at 5min intervals to determine blood glucose. Results: There was no significant change between pre- and postdialysis values of IGF-I but there was a significant 29% increase (p <0.05) at the end of hemodialysis compared with the basal levels before insulin infusion in the T2D patients with CKD5D. The fasting mean levels of IGFBP-1 were increased in both T1D with normal renal function (geometric mean: 216 μg/l, range 169–275 μg/l) and in T2D with CKD5D (geometric mean: 112 μg/l , range 78–162 μg/l, p =0.15 compared with T1D patients) in spite of a high mean insulin level (32±5mU/l). Insulin caused a similar decrease (p <0.05 all groups) in IGFBP-1 mean levels for the first 90min in the T2D patients with CKD5D (73±7% of basal IGFBP-1 values) and the T1D patients (69±6%) with normal renal function. After 90min there was a blunted response in the T2D patients with CKD5D whereas IGFBP-1 in the T1D patients with normal renal function continued to decline. After hemodialysis the IGFBP-1 serum levels increased compared with the levels at the end of insulin infusion but the predialysis values remained significantly lower than before the insulin infusion. Conclusion: Type 2 diabetes patients with chronic kidney disease requiring hemodialysis (CKD5D) have a high mean basal level of IGFBP-1 in spite of increased insulin levels. The first 90min response of IGFBP-1 to insulin infusion is similar in T2D patients with CKD5D and T1D patients with normal renal function. After 90min of insulin infusion a blunted decrease in IGFBP-1 was seen in T2D patients with CKD5D compared with type \1 diabetes with normal renal function. Insulin infusion before hemodialysis reduced the earlier reported increase in IGFBP-1 and increased IGF-I levels. Insulin infusion before dialysis in patients with CKD5D should be further studied since it could contribute to an anabolic effect with more bioavaialable IGF-I thus reducing the catabolic effect of hemodialysis. [Copyright &y& Elsevier]

Abstract: Aim: Saudi and Caucasian subjects, matched for adiposity, and of differing glycaemic status were compared using several insulin sensitivity indices and to also to assess insulin, glucose and insulin-like growth factor binding protein-1 (IGFBP-1) responses to intravenous glucose. Methods: Subjects with normal glucose tolerance (NGT; n =24), impaired fasting glucose (IFG; n =12), impaired glucose tolerance (IGT; n =12), and type 2 diabetes (DM; n =13) were recruited from Saudi (n =33) and Caucasian (n =28) populations. All had specimens taken in the context of a standard oral glucose tolerance test at their first visit and had the insulin sensitivity parameter (Si) determined by frequently-sampled intravenous glucose tolerance test (FSIVGTT) at a second visit. Results: Saudis in the NGT and pooled glucose intolerance categories had significantly higher diastolic blood pressure (p <0.001, p <0.05 respectively) and HbA1c (p <0.01, p <0.05 respectively) compared to Caucasians. Caucasians in the NGT category had significantly higher Si, fasting and 2h IGFBP-1 (p <0.01, p <0.05 and p <0.01 respectively) compared to Saudis. Two hours following oral or intravenous glucose serum IGFBP-1 decreased to 44% (p <0.001) and 50% (p <0.05) of baseline levels respectively. Conclusions: Our data suggest that adult Saudis with normal glucose tolerance appear to be more insulin resistant than Caucasians matched for adiposity. In normal individuals at 2h the IGFBP-1 level will be about half the baseline level regardless of the route of glucose administration. [Copyright &y& Elsevier]

The article examines the impact of birth weight, gender and catch-up growth on metabolic parameters in extremely low birth weight (ELBW) infants. Metabolic parameters considered in the analysis include Insulin-like Growth Factor Binding Proteins (IGFBP)-1, leptin and fasting insulin. Information is presented on the height and weight of ELBW-small-for-gestational age (SGA) and ELBW-appropriate for gestational age (AGA). It relates the role of catch-up growth and sex-dependent weight development in modulating the metabolic parameters in ELBW children.

Abstract: Vascular endothelial dysfunction is an early event in the development of atherosclerosis and is also linked to insulin resistance and type 2 diabetes mellitus. Serum IGFBP-1 and IGF can be used as markers of insulin sensitivity and secretion. The aim was to investigate if microvascular reactivity in healthy males with and without heredity of type 2 diabetes mellitus is related to serum levels of IGF-1 and its binding protein IGFBP-1. Thirty-six middle-aged male subjects free of medication, non-smokers and with normal oral glucose tolerance test were investigated. Nineteen of the subjects had known heredity for type 2 diabetes. The groups were matched for age and body mass index. Skin microcirculation was studied with laser Doppler perfusion imaging before and after iontophoretic application of endothelial (acetylcholine (Ach)) and non-endothelial dependent (sodium nitroprusside (SNP)) substances. The microvascular responses to iontophoretic application of Ach and SNP, respectively, were weaker (p =0.01 and p =0.02, respectively) in subjects with diabetes heredity than in those without. In subjects without heredity a significant correlation was observed between the peak microvascular responses to Ach (r =0.57; p <0.02), SNP (r =0.51; p <0.05), and levels of IGFBP-1, while no significant correlation was found in subjects with diabetes heredity. In summary our study shows that healthy male subjects with no heredity for type 2 diabetes have low fasting IGFBP-1 which were associated with impaired microvascular responses to both endothelial and non-endothelial stimulation. [Copyright &y& Elsevier]

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Abstract: MMP-3 has been detected in human placenta and reduced expression of the enzyme was observed in invasive trophoblasts of patients with severe preeclampsia. However, detailed expression pattern, regulation and biological properties of the placental protease have not been elucidated so far. RT-PCR analyses, Western blotting and enzyme activity assays revealed that pro- and active form of MMP-3 were predominantly expressed in purified first trimester villous trophoblasts, in invasive cytotrophoblasts of differentiating explant cultures and in trophoblastic SGHPL-4 cells. Accordingly, immunofluorescene of first trimester placental tissues detected MMP-3 mainly in villous and extravillous cytotrophoblasts. IL-1β, an inducer of MMP-3 in decidual cells, increased secretion and activity of the protease in trophoblast supernatants in a dose- and time-dependent manner. IL-1β-stimulated production of the enzyme was suppressed in the presence of inhibitors of MAPK and AKT signalling. Similar to recombinant MMP-3, MMP-3 in supernatants of IL-1β-stimulated decidual stromal or SGHPL-4 cells degraded IGFBP-1 in vitro resulting in the appearance of cleavage products at approximately 25, 22, 17, 14 and 11kD. However, cleavage assays using recombinant MMP-2 suggested that the gelatinase may contribute to IGFBP-1 degradation in trophoblast supernatants. Despite its effects on MMP-3 expression IL-1β failed to significantly alter invasion of SGHPL-4 cells through Matrigel-coated transwells. In conclusion, the data suggest that invasive trophoblast cell models secrete bioactive MMP-3. Inducible expression of the protease involves MAPK and AKT signalling. In addition to the decidua, MMP-3 of trophoblasts may contribute to the regulation of the IGF system by degrading IGFBP-1. [Copyright &y& Elsevier]

The article discusses a study to determine interrelationships between insulin-like growth factor-I (IGF-I) IGF binding proteins (IGFBPs) and adiposity in overweight Hispanic American adolescents in the U.S. The study, which involved 178 adolescents with an average body mass index of 28.2, made use of immunoradiometric assays to obtain measurements of IGF-I, IGFBP-1 and IGFBP-3. Magnetic resonance imaging (MRI) was utilized to measure visceral and subcutaneous adipose tissue. The study found that the three IGFs are inversely related to adiposity in the adolescents.

Abstract: Introduction: Alcohol induces disturbances in insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) levels. The aim of the present study was to compare pure ethanol and alcopop effects on total and free IGF-I, IGFBP-1, IGF-I:IGFBP-1 complex, insulin and plasma glucose levels in healthy subjects. Methods: Five males and seven females (21–51 years) consumed pure ethanol and alcopops with identical alcohol content in a cross-over design after 6h fasting. Blood samples were obtained for determination of serum ethanol and plasma glucose at 0, 30, 60, 90, 120 and 180min. Serum total and free IGF-I, IGFBP-1, IGF-I:IGFBP-1 complex, and insulin were measured at 0, 60 and 180min. Results: Area under the curve for serum ethanol concentration was significantly less following alcopop compared to pure ethanol (1124±201 vs. 1691±359mmol/Lh, P <0.01). Serum insulin and glucose levels were unchanged by ethanol while alcopop intake was followed by a transient increase in glucose and insulin levels (P <0.05). Pure ethanol and alcopop reduced free IGF-I levels by the end of the study period (P =0.05). IGFBP-1 and the IGF-I:IGFBP-1 complex increased following ethanol intake (P <0.05) while only a small transient IGFBP-1 increase was observed following alcopop intake. No change in total IGF-I was observed. Conclusion: Both drinks resulted in reduced free IGF-I levels, however, only pure ethanol increased IGFBP-1 and the IGF-I:IGFBP-1 complex. Alcopop intake was associated with a transient increase in IGFBP-1 and unchanged IGF-I:IGFBP-1 complex levels probably due to marked changes in insulin and glucose levels. [Copyright &y& Elsevier]

Abstract: Background: Insulin-like growth factors (IGF) regulate fetal growth through their effects on placenta. Their actions are influenced by IGF binding protein-1. Phosphorylated IGFBP-1 (pIGFBP-1) has high affinity for IGF-I and usually inhibits IGF-I activity but during pregnancy, it is de-phosphorylated to generate lower affinity isoforms and consequently, increased IGF bioavailability. Here we investigate the role of placenta in this process. Results: Our data show that term human placental explants, but not their conditioned medium, can de-phosphorylate IGFBP-1 through the action of placental alkaline phosphatase (PLAP). Discussion: PLAP-mediated de-phosphorylation of IGFBP-1 may provide a mechanism for controlling IGF-I bioavailability and action at the maternal/fetal interface. [Copyright &y& Elsevier]