The association between IGF-1 polymorphisms, IGF-1 serum levels, and cognitive functions in healthy adults: the Amsterdam Growth and Health longitudinal study.

NARCIS (Netherlands)

Licht, C.M.M.; Turenhout, L.C. van; Deijen, J.B.; Koppes, L.L.J.; Mechelen, W. van; Twisk, J.W.R.; Drent, M.L.

2014-01-01

Several studies have demonstrated an association between polymorphisms in the insulin-like growth factor-1 (IGF-1) gene and IGF-1 serum levels. IGF-1 levels have been associated with cognitive functioning in older persons and growth hormone deficient patients. The present study investigates whether

Circulating levels of IGF-1 directly regulate bone growth and density

Science.gov (United States)

Yakar, Shoshana; Rosen, Clifford J.; Beamer, Wesley G.; Ackert-Bicknell, Cheryl L.; Wu, Yiping; Liu, Jun-Li; Ooi, Guck T.; Setser, Jennifer; Frystyk, Jan; Boisclair, Yves R.; LeRoith, Derek

2002-01-01

IGF-1 is a growth-promoting polypeptide that is essential for normal growth and development. In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS). This complex prolongs the half-life of serum IGFs and facilitates their endocrine actions. Liver IGF-1–deficient (LID) mice and ALS knockout (ALSKO) mice exhibited relatively normal growth and development, despite having 75% and 65% reductions in serum IGF-1 levels, respectively. Double gene disrupted mice were generated by crossing LID+ALSKO mice. These mice exhibited further reductions in serum IGF-1 levels and a significant reduction in linear growth. The proximal growth plates of the tibiae of LID+ALSKO mice were smaller in total height as well as in the height of the proliferative and hypertrophic zones of chondrocytes. There was also a 10% decrease in bone mineral density and a greater than 35% decrease in periosteal circumference and cortical thickness in these mice. IGF-1 treatment for 4 weeks restored the total height of the proximal growth plate of the tibia. Thus, the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis. PMID:12235108

R1507, an Anti-Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antibody, and EWS/FLI-1 siRNA in Ewing's Sarcoma: Convergence at the IGF/IGFR/Akt Axis

Science.gov (United States)

Rodon, Jordi; Sun, Michael; Kuenkele, Klaus-Peter; Parsons, Henrique A.; Trent, Jonathan C.; Kurzrock, Razelle

2011-01-01

A subset of patients with Ewing's sarcoma responds to anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies. Mechanisms of sensitivity and resistance are unknown. We investigated whether an anti-IGF-1R antibody acts via a pathway that could also be suppressed by small interfering (si) RNA against the EWS/FLI-1 fusion protein, the hallmark of Ewing's sarcoma. The growth of two Ewing's sarcoma cell lines (TC-32 and TC-71) was inhibited by the fully human anti-IGF-1R antibody, R1507 (clonogenic and MTT assays). TC-32 and TC-71 cells express high levels of IGF-2, while RD-ES and A4573 Ewing's cell lines, which were less responsive to R1507 in our assays, express low or undetectable IGF-2, respectively. TC-71 cells also expressed high levels of IGF-1R, and R1507 decreased steady-state levels of this receptor by internalization/degradation, an effect which was associated with a decrease in p-IGF-1R, p-IRS-1, and p-Akt. EWS/FLI-1 siRNA also decreased p-Akt, due to its ability to increase IGF-BP3 levels and subsequently decrease IGF-1 and IGF-2 levels, thus inhibiting signaling through p-IGF-1R. This inhibition correlated with growth suppression and apoptosis. The attenuation of Akt activation was confirmed in TC-71 and HEK-293 (human embryonic kidney) cells by transfecting them with IGF-1R siRNA. We conclude that antibodies and siRNA to IGF-1R, as well as siRNA to EWS/FLI-1, act via intersecting IGF/IGF-1R signals that suppress a common point in this pathway, namely the phosphorylation of Akt. PMID:22022506

R1507, an anti-insulin-like growth factor-1 receptor (IGF-1R antibody, and EWS/FLI-1 siRNA in Ewing's sarcoma: convergence at the IGF/IGFR/Akt axis.

Directory of Open Access Journals (Sweden)

Helen J Huang

Full Text Available A subset of patients with Ewing's sarcoma responds to anti-insulin-like growth factor-1 receptor (IGF-1R antibodies. Mechanisms of sensitivity and resistance are unknown. We investigated whether an anti-IGF-1R antibody acts via a pathway that could also be suppressed by small interfering (si RNA against the EWS/FLI-1 fusion protein, the hallmark of Ewing's sarcoma. The growth of two Ewing's sarcoma cell lines (TC-32 and TC-71 was inhibited by the fully human anti-IGF-1R antibody, R1507 (clonogenic and MTT assays. TC-32 and TC-71 cells express high levels of IGF-2, while RD-ES and A4573 Ewing's cell lines, which were less responsive to R1507 in our assays, express low or undetectable IGF-2, respectively. TC-71 cells also expressed high levels of IGF-1R, and R1507 decreased steady-state levels of this receptor by internalization/degradation, an effect which was associated with a decrease in p-IGF-1R, p-IRS-1, and p-Akt. EWS/FLI-1 siRNA also decreased p-Akt, due to its ability to increase IGF-BP3 levels and subsequently decrease IGF-1 and IGF-2 levels, thus inhibiting signaling through p-IGF-1R. This inhibition correlated with growth suppression and apoptosis. The attenuation of Akt activation was confirmed in TC-71 and HEK-293 (human embryonic kidney cells by transfecting them with IGF-1R siRNA. We conclude that antibodies and siRNA to IGF-1R, as well as siRNA to EWS/FLI-1, act via intersecting IGF/IGF-1R signals that suppress a common point in this pathway, namely the phosphorylation of Akt.

IGF-1 levels, complex formation, and IGF bioactivity in growth hormone-treated children with Prader-Willi syndrome

NARCIS (Netherlands)

Bakker, N. E.; Van Doorn, J.; Renes, J. S.; Donker, G. H.; Hokken-Koelega, A. C S

2015-01-01

Context: Children with Prader-Willi syndrome (PWS) attain high-serum immunoreactive IGF-1 levels during a standard-dose GH treatment, which leads to concern, but lowering the dose deteriorates their body composition. Objective: The objective of the study was to evaluate serum IGF-1, IGF binding

Effect of i.p. insulin administration onIGF1 and IGFBP1 in type1 diabetes

NARCIS (Netherlands)

van Dijk, P R; Logtenberg, S J J; Groenier, K H; Kleefstra, N; Bilo, H J G; Arnqvist, H J

2014-01-01

In type 1 diabetes mellitus (T1DM), low concentrations of IGF1 and high concentrations of IGF-binding protein 1 (IGFBP1) have been reported. It has been suggested that these abnormalities in the GH-IGF1 axis are due to low insulin concentrations in the portal vein. We hypothesized that the i.p.

Suckling induced insulin-like growth factor-1 (IGF-1) release in mother rats.

Science.gov (United States)

Lékó, András H; Cservenák, Melinda; Dobolyi, Árpád

2017-12-01

Lactation involves significant neuroendocrine changes. The elevated prolactin (PRL) release from the pituitary, induced markedly by suckling, is the most relevant example. Suckling also causes a significant and rapid elevation in growth hormone (GH) levels. GH is necessary for milk synthesis as milk yield is stopped completely in the absence of PRL and GH, while the absence of PRL alone causes only a 50% reduction. Insulin-like growth factor-1 (IGF-1) plays an important role in the GH axis. GH exerts its effects through IGF-1 in the periphery, for example in the mammary gland. In addition, IGF-1 is responsible for the long-loop feedback control of GH secretion. IGF-1 secretion has not been established yet in mothers. Therefore, in the present study, we investigated the effect of suckling on serum IGF-1 level in rat mothers and correlated it with serum PRL levels. We examined a potential mechanism of the regulation of IGF-1 level during suckling by administering IGF-1 into the lateral ventricle of rat mothers continuously for 12days, or acutely, right before the start of suckling. We described that suckling affected IGF-1 release based on one-way repeated measures ANOVA (F=10.8 and pIGF-1 level 30min after the start of suckling (pIGF-1 release. The prolonged central IGF-1 administration diminished the suckling-induced IGF-1 surge (F=9.19 and pIGF-1 release either by elevating PRL or GH. Long-loop feedback via IGF-1 in the GH axis can diminish this action. Copyright © 2017 Elsevier Ltd. All rights reserved.

Circulating levels of IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio and colorectal adenomas: A meta-analysis.

Science.gov (United States)

Yoon, Yeong Sook; Keum, NaNa; Zhang, Xuehong; Cho, Eunyoung; Giovannucci, Edward L

2015-12-01

Insulin-like growth factor-1(IGF-1) promotes cell proliferation and inhibits apoptosis, and is thereby implicated in carcinogenesis. Insulin-like growth factor binding protein-3 (IGFBP-3) may antagonize IGF-1 action, leading to inhibition of the potential tumorigenicity of IGF-1. We conducted this meta-analysis to estimate the association between IGF-1, IGFBP-3 and IGF-1/IGFBP-3 ratio and the risk of colorectal adenomas (CRAs). Further, we investigated whether this association was different between occurrent and recurrent CRA, by adjustment for obesity, and by advanced CRA. Pubmed and Embase were searched up to April, 2015 to identify relevant observational studies and summary odds ratio (OR) and the corresponding 95% confidence interval (95% CI) was estimated using a random-effects model. A total of 12 studies (11 studies including 3038 cases for IGF-1, 12 studies including 3208 cases for IGFBP-3, and 7 studies including 1867 cases for IGF-1/IGFBP-3 ratio) were included in this meta-analysis. The summary ORs of occurrent CRA for the highest versus lowest category of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 ratio were 1.13 (95% CI: 0.95-1.34), 0.99 (0.84-1.16), and 1.05 (0.86-1.29), respectively. Higher IGF-1 and IGF-1/IGFBP-3 ratio were significantly associated with decreased risk of recurrent CRA (OR for IGF-1=0.60 [95% CI: 0.42-0.85]; IGF-1/IGFBP-3 ratio=0.65 [0.44-0.96]). A stratified analysis by advancement of occurrent CRA produced a significant summary OR of IGF-1 for advanced CRA (OR=2.21 [1.08-4.52]) but not for non-advanced CRA (OR=0.89 [0.55-1.45]). We did not find significant publication bias or heterogeneity. Circulating levels of IGF-1, IGFBP-3 and their molar ratio were not associated with the risk of occurrence of CRA, but IGF-1 was associated with the increased risk for occurrence of advanced CRA. Copyright © 2015. Published by Elsevier Ltd.

Serum Levels Of Free And Total Insulin-Like Growth Factor (IGF)-1 And IGF Binding Protein-3 In Normal And Growth Hormone Deficient Children

International Nuclear Information System (INIS)

Shousha, M.A.; Soliman, S.E.T.; Hafez, M.H.

2006-01-01

Serum levels of total insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) reflect the endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening growth hormone deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-1 circulates in its free form, which is believed to be the biologically active form. Serum levels of free IGF-1, total IGF-I and IGFBP-3 were measured in 144 healthy children (72 boys and 72 girls, aged from 0 to 16 years) and in 12 pre-pubertal GH deficient (GHD) children to study the correlation between the age and free IGF-1, total IGF-1 and IGFBP-3 levels. In healthy subjects (both sexes), serum free IGF-1, total IGF-1 and IGFBP-3 levels were low in infancy, increasing during puberty and declining thereafter. Free IGF-1 in serum occupied about 0.97-1.45 % of the total IGF-1 values, and the ratios of free IGF-1 to total IGF-1 were significantly increased in the pubertal age groups than in the pre-pubertal age groups. Serum levels of free IGF-1 showed significant positive correlation with those of total IGF-I and IGFBP-3. Serum free IGF-1, total IGF-1 and IGFBP-3 levels in patients with GHD were decreased significantly with increasing the degree of hypopituitarism. These observations suggest that the increase in serum free IGF-1 level during puberty was caused by a dramatic increase in total IGF-1 rather than IGFBP-3. Also, high levels of these hormones may play an important role in pubertal growth spurt and may become a useful tool for diagnosing GHD and predicting growth response to long term GH therapy

Serum levels of free and total insulin-link growth factor (IGF)-1 and (IGF) binding protein-3 in normal and growth hormone deficient children

International Nuclear Information System (INIS)

Shousha, M.A.; Soliman, S.E.T.; Hafez, H.M.

2008-01-01

Serum levels of total insulin-like growth factor- 1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) reflect endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening GH deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-1 circulates in its free form, which is believed to be the biologically active form. Serum levels of free IGF-1, total IGF-I and IGFBP-3 were measured in 144 healthy children (72 boys and 72 girls, aged from 0 to 16 years) and in 12 prepubertal GH. deficient (GHD) children to study correlation between the age and free IGF-1, total IGF-1 and IGFBP-3 levels. In healthy subjects (both sexes), serum free IGF-1, total IGF-1 and IGFBP-3 levels were low in infancy, increasing during puberty and declining thereafter. Free IGF-1 in serum occupied about 0.97. 1.45 % of the total IGF-1 values, and the ratios of free IGF-1 to total IGF-1 were significantly increased in the pubertal age groups than in the prepubertal age groups. Serum levels of free IGF-1 showed significant positive correlation with those of total IGF-I and IGFBP-3. Serum free IGF-1, total IGF-1 and IGFBP-3 levels in patients with GHD decreased significantly with increasing degree of hypopituitarism. These observations suggest that the increase in serum free IGF-1 level during puberty was caused by a dramatic increase in total IGF-1 rather than IGFBP-3. Also, high levels of these hormones may play an important role in pubertal growth spurt and may become a useful tool for diagnosing GHD and predicting growth response to long term GH therapy

Serum IGF-1, IGFBP-3 and their ratio: Potential biochemical growth maturity indicators.

Science.gov (United States)

Jain, Nimisha; Tripathi, Tulika; Gupta, S K; Rai, Priyank; Kanase, Anup; Kalra, Shilpa

2017-12-01

Determination of skeletal maturation and remaining growth potential is an essential part of treatment planning in orthodontics. The aim of our study was to determine the relationship between IGF-1 levels, IGFBP-3 levels with CVM staging to track the pre pubertal and pubertal growth spurts in female patients in North Indian population. This cross-sectional study was conducted on ninety female subjects in the age group of 8-20 years. Blood samples were collected and centrifuged and serum samples were then analysed by Human IGF-1 and IGFBP-3 enzyme-linked immunosorbent assay kits, specific for IGF-1 and IGFBP-3, respectively. CVM staging on lateral cephalometric radiograph was determined for all patients. Analysis of variance test followed by a post hoc test was used to compare mean IGF-1 and IGFBP-3 corresponding to six stages of cervical vertebrae maturation stages. Linear Pearson's correlations were performed to determine the trends of IGF-1, IGFBP-3, and its ratio relating to CVM stage. The kappa statistic was used to measure inter and intra examiner reliability. P value IGF-1 levels were found to be highest (403.3 ± 12.3 ng/ml) at CVMI3 stage of CVMI. The post-hoc test revealed a significant difference in IGF-1 levels between all stages of CVMI, thereby indicating a specific range of IGF-1 levels for a specific skeletal stage. Mean serum IGFBP-3 levels were found to be highest (5186.8 ± 1384.2 ng/ml) at CVMI4 stage of CVMI. The mean serum IGFBP-3 levels at CVMI4 were found to be significantly higher than the levels at all other CVMI stages except CVMI3 stage. IGF-1 and IGFBP-3 can serve as a potential biochemical indicator for assessment of skeletal maturity.

Clinical significance of the dynamic changes of serum IGF-1 levels in patients with acute cerebro-vascular accident

International Nuclear Information System (INIS)

Chen Yujuan; Liu Xueyuan; Bian Weihong; Du Xinlu; Yang Hongyan

2006-01-01

Objective: To investigate the dynamic changes of serum insulin-like growth factor-1 (IGF-1) levels in patients with acute cerebrovascular accident. Methods: Serum IGF-1 levels were determined with RIA in 40 patients with cerebral infarction, 20 patients with lacunar infarcts and 40 patients with cerebral haemorrhage within 3days after onset and on d14 as well as in 30 controls. Results: The serum IGF-1 levels in patients with cerebral vascular accidents were significantly lower than those in controls (P 0.05). Conclusion: Serum levels of IGF-1 dropped markedly during the acute stage after cerebrovascular accident and the magnitude might reflect the severity of the event, IGF-1 might be capable of crossing the blood-brain barrier after cerebrovascular accident and providing some protection against nerve injury, this fact might be of potential clinical applicability. (authors)

Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth

OpenAIRE

Kl?ting, Nora; Koch, Linda; Wunderlich, Thomas; Kern, Matthias; Ruschke, Karen; Krone, Wilhelm; Br?ning, Jens C.; Bl?her, Matthias

2008-01-01

OBJECTIVE?IGF-1 and the IGF-1 receptor (IGF-1R) have been implicated in the regulation of adipocyte differentiation and lipid accumulation in vitro. RESEARCH DESIGN AND METHODS?To investigate the role of IGF-1 receptor in vivo, we have inactivated the Igf-1r gene in adipose tissue (IGF-1RaP2Cre mice) using conditional gene targeting strategies. RESULTS?Conditional IGF-1R inactivation resulted in increased adipose tissue mass with a predominantly increased lipid accumulation in epigonadal fat ...

Serum Levels of IGF-1 and IGFBP-3 in Relation to Clinical and Pathobiological Aspects of Head and Neck Squamous Cell Carcinomas.

Science.gov (United States)

Kalfert, David; Ludvikova, Marie; Topolcan, Ondrej; Celakovsky, Petr; Kucera, Radek; Windrichova, Jindra; Ludvik, Jaroslav; Skalova, Katerina; Kulda, Vlastimil; Pesta, Martin; Plzak, Jan

2017-06-01

Head and neck squamous cell carcinoma (HNSCC) includes tumors of various anatomical sites sharing multifactorial etiopathogenesis and generally dismal response to conventional treatment. The objective of this study was to determine the clinical significance of serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) in HNSCC. A total of 46 patients, with histologically-confirmed diagnosis of HNSCC (21 oropharyngeal, 21 laryngeal, and 4 hypopharyngeal cancers) were enrolled in this study. IGF-1 and IGFBP-3 serum levels were measured by an immunoradiometric assay using commercial kits. The adjustment of serum levels at 60 years of age was performed. Significant differences were found in IGF-1 serum concentrations between patients with p16 positive and p16 negative HNSCC (p=0.0062), with higher IGF-1 levels in p16 positive tumors, between low-grade and high-grade cancers (p=0.0323) only in larynx, with elevated IGF-1 concentrations associated with high-grade and between recurrent and non-recurrent HNSCC (p=0.0354), with lower IGF-1 levels in recurrent tumors. The conflicting results of this study may reflect some abnormality of IGF axis regulation in HNSCC, as well as the influence of other etiological factors (e.g. smoking, HPV infection). Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

[Effects of pulsed magnetic field on insulin-like growth factor-1 (IGF-1) in cerebrospinal fluid and effects of IGF-1 on functional recovery].

Science.gov (United States)

Song, Cheng-xian; Fan, Jian-zhong; Wu, Hong-ying; Wei, Yi; Zhen, Jian-rong

2010-10-01

To study the effects of pulsed magnetic field on insulin-like growth factor-1 (IGF-1) level in the cerebrospinal fluid (CSF) and the association of IGF-1 alterations with the activities of daily living (ADL) of patients with brain injury. Sixty-five patients with brain injury were divided randomly into the control group (n=30) and magnetic therapy group (n=35), both receiving conventional therapy and in the latter group, daily pulsed magnetic field treatment (20-40 mT, 50 Hz, 20 min per time, 1 time per day) for 14 consecutive days were administered. On the first and 14th days of the treatment, 2 ml CSF was collected from the cases patients for IGF-1 measurement by radioimmunoassay, and Barthel index (BI) was used to assess the ADL of the patients. After a 14-day treatment, IGF-1 level in the CSF were significantly increased in the magnetic group in comparison with the level before the treatment and with those in the control group (P0.05). The scores of BI increased significantly in both groups after the treatment (Pmagnetic therapy group (P<0.05). A significant positive correlation was found between IGF-1 level in the CSF and BI in these patients (r=0.283, P=0.022). Pulsed magnetic field might increase IGF-1 level in the CSF of patients with brain injury to promote the recovery of the patients ADL, suggesting its potential clinical value in the treatment of brain injury.

Comparison of IGF-1 (insulin like growth factor-1) levels in bovine serum sampled three times during the day using validated equine IGF-1 elisa

OpenAIRE

Mrkun J.; Kosec M.; Zrimšek Petra

2009-01-01

Cows in negative energy balance exhibit reduced fertility, mediated by metabolic signals that influence the reproductive system. Measurement of IGF-1 contributes to the diagnosis of negative energy balance. The aim of this study was to investigate possible variations in IGF-1 levels in samples taken at different times of the day. Equine IGF-1 ELISA was used for measuring IGF-1 in bovine samples. Statistical analysis was applied to the results. Using scatter diagrams fitted with Deming regress...

Elevated IGFBP3 levels in diabetic tears: a negative regulator of IGF-1 signaling in the corneal epithelium.

Science.gov (United States)

Wu, Yu-Chieh; Buckner, Benjamin R; Zhu, Meifang; Cavanagh, H Dwight; Robertson, Danielle M

2012-04-01

To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under elevated glucose conditions and to correlate these changes with total and phosphorylated levels of IGF-1R. Tear samples were collected noninvasively from diabetic subjects and non-diabetic controls; corneal sensitivity was assessed using a Cochet-Bonnet Aesthesiometer. Conditioned media were collected following culture of hTCEpi cells in normal (5 mM) and elevated (25 mM) glucose conditions; mannitol was used as an osmotic control. IGFBP3, IGF-1, and phosphorylated IGF-1R levels were assessed by ELISA. IGFBP3 and IGF-1R mRNA were assessed by real-time polymerase chain reaction (PCR). Total and phosphorylated IGF-1R expression in whole cell lysates was assessed by western blot. There was a 2.8-fold increase in IGFBP3 in diabetic tears compared to non-diabetic controls (P=0.006); IGF-1 levels were not significantly altered. No difference in corneal sensitivity was detected between groups. The concentration of IGFBP3 in tears was independent of IGF-1. Consistent with human tear measurements in vivo, IGFBP3 secretion was increased 2.2 fold (Ptears compared to normal controls blocked phosphorylation of the IGF-1R by IGF-1 (Ptears may attenuate IGF-1R signaling in the diabetic cornea. A long-term increase in IGFBP3 may contribute to epithelial compromise and the pathogenesis of ocular surface complications reported in diabetes. Copyright © 2012 Elsevier Inc. All rights reserved.

IGF-1R mRNA expression is increased in obese children.

Science.gov (United States)

Ricco, Rafaela Cristina; Ricco, Rubens Garcia; Queluz, Mariangela Carletti; de Paula, Mariana Teresa Sarti; Atique, Patricia Volpon; Custódio, Rodrigo José; Tourinho Filho, Hugo; Del Roio Liberatori, Raphael; Martinelli, Carlos Eduardo

2018-04-01

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. 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. Relative IGF-IR gene expression (2 -ΔΔCT ) 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 -ΔΔCT 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 (237ng/ml and 144ng/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. 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. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical significance of measurement of changes of serum IGF-II, EGF and CYFRA21-1 levels after chemotherapy in patients with lung cancer

International Nuclear Information System (INIS)

Chen Jianlin

2010-01-01

Objective: To study the clinical significance of changes of serum IGF-II, EGF and CYFRA21-1 levels after chemotherapy in patients with lung cancer. Methods: Serum IGF-II, EGF (with RIA), and CYFRA21-1 (with ECLIA) levels were determined both before and after chemotherapy in 39 patients with lung cancer as well as once in 35 controls. Results: Before chemotherapy, serum IGF-II, EGF and CYFRA21-1 levels were significantly higher in the patients than those in controls(P<0.01). Six months after chemotherapy, serum IGF-II, EGF and CYFRA21-1 levels dropped markedly, but remained significantly higher than those in controls(P<0.05). Conclusion: The development of lung cancer in patients was closely related to the serum IGF-II, EGF and CYFRA21-1 levels. (authors)

Low Levels of IGF-1 Contribute to Alveolar Macrophage Dysfunction in Cystic Fibrosis1

OpenAIRE

Bessich, Jamie L.; Nymon, Amanda B.; Moulton, Lisa A; Dorman, Dana; Ashare, Alix

2013-01-01

Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from CFTR−/− mice have impaired function, no study has investigated primary alveolar macrophages in adults with cystic fibrosis (CF). CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infectio...

The trajectory of IGF-1 across age and duration of type 1 diabetes.

Science.gov (United States)

Palta, Mari; LeCaire, Tamara J; Sadek-Badawi, Mona; Herrera, Victor M; Danielson, Kirstie K

2014-11-01

Individuals with type 1 diabetes may have low IGF-1, related to insulinopenia and insulin resistance. There are few longitudinal studies of IGF-1 levels to establish its pattern in type 1 diabetes with duration and age, and to examine whether IGF-1 tracks within individuals over time. We examine age and duration trends, and the relationship of IGF-1 to gender, glycaemic control, insulin level and other factors. Participants in the Wisconsin Diabetes Registry Study, an incident cohort study of type 1 diabetes diagnosed May 1987-April 1992, were followed for up to 18 years with IGF-1 samples up to age 45 for women and age 37 for men. IGF-1 is lower with type 1 diabetes than in normative samples. Although, the pattern across age resembles that in normative samples with a peak in adolescence and slow decline after age 20, the adolescent peak is delayed for women with type 1 diabetes. There was low to moderate tracking of IGF-1 within an individual. Higher insulin dose was associated with higher IGF-1 as was puberty, and female gender. Adjusted for these factors, IGF-1 declined rapidly across early diabetes duration. Lower HbA1c was most strongly related to higher IGF-1 at Tanner stages 1 and 2. IGF-1 is low in type 1 diabetes, with a delayed adolescent peak in women and is especially influenced by glycaemic control in early and pre-adolescence. High variability within an individual is likely a challenge in investigating associations between IGF-1 and long-term outcomes, and may explain contradictory findings. Copyright © 2014 John Wiley & Sons, Ltd.

Differential effects of casein versus whey on fasting plasma levels of insulin, IGF-1 and IGF-1/IGFBP-3

DEFF Research Database (Denmark)

Hoppe, Camilla; Mølgaard, Christian; Dalum, Cathrine

2009-01-01

to the identification of which components in milk that stimulate growth, we have performed an intervention study with 57 eight-year-old boys in which we examined the effects of the two major milk protein fractions, whey and casein, and milk minerals (Ca and P) in a 2x2 factorial design on IGFs and glucose......–insulin metabolism. The amounts of whey and casein were identical to the content in 1.5 l skim milk. The amounts of Ca and P were similar to 1.5 l skim milk in the high-mineral drinks, whereas the amounts of Ca and P were reduced in the low-mineral drinks. Results: There were no interactions between milk mineral...... groups (high, low) and milk protein groups (whey, casein). Serum IGF-1 increased by 15% (P...

Insulin-like growth factor-I (IGF-1), IGF-binding protein-3 (IGFBP-3) and mammographic features.

Science.gov (United States)

Izzo, L; Meggiorini, M L; Nofroni, I; Pala, A; De Felice, C; Meloni, P; Simari, T; Izzo, S; Pugliese, F; Impara, L; Merlini, G; Di Cello, P; Cipolla, V; Forcione, A R; Paliotta, A; Domenici, L; Bolognese, A

2012-05-01

The IGF system has recently been shown to play an important role in the regulation of breast tumor cell proliferation. However, also breast density is currently considered as the strongest breast cancer risk factor. It is not yet clear whether these factors are interrelated and if and how they are influenced by menopausal status. The purpose of this study was to examine the possible effects of IGF-1 and IGFBP-3 and IGF-1/IGFBP-3 molar ratio on mammographic density stratified by menopausal status. A group of 341 Italian women were interviewed to collect the following data: family history of breast cancer, reproductive and menstrual factors, breast biopsies, previous administration of hormonal contraceptive therapy, hormone replacement therapy (HRT) in menopause and lifestyle information. A blood sample was drawn for determination of IGF-1, IGFBP-3 levels. IGF-1/ IGFBP-3 molar ratio was then calculated. On the basis of recent mammograms the women were divided into two groups: dense breast (DB) and non-dense breast (NDB). Student's t-test was employed to assess the association between breast density and plasma level of IGF-1, IGFBP-3 and molar ratio. To assess if this relationship was similar in subgroups of pre- and postmenopausal women, the study population was stratified by menopausal status and Student's t-test was performed. Finally, multivariate analysis was employed to evaluate if there were confounding factors that might influence the relationship between growth factors and breast density. The analysis of the relationship between mammographic density and plasma level of IGF-1, IGFBP-3 and IGF-1/ IGFBP-3 molar ratio showed that IGF-1 levels and molar ratio varied in the two groups resulting in higher mean values in the DB group (IGF-1: 109.6 versus 96.6 ng/ml; p= 0.001 and molar ratio 29.4 versus 25.5 ng/ml; p= 0.001) whereas IGFBP-3 showed similar values in both groups (DB and NDB). Analysis of plasma level of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio

Effect Of IGF-1 On Expression Of Gh Receptor, IGF-1, IGF-1 ...

African Journals Online (AJOL)

... and the skin expression of growth hormone receptor (GHR), insulin-like growth factor1 (IGF-1), insulin-like growth factor receptor (IGF- R), KAP3.2 and KAP6-1 mRNA were measured by RT-PCR. The results indicated that IGF-1 could degrade GHR gene expression, have no effect of IGF-1 and IGF-1R gene expression, ...

The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery.

LENUS (Irish Health Repository)

Cooley, Sharon M

2012-02-01

AIMS: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a London University teaching hospital. Maternal IGF-1, IGF-2 and IGFBP-3 were measured in maternal blood at booking and analyzed with respect to gestational age at delivery. RESULTS: There was no significant association between maternal IGF-1 or IGF-2 and preterm birth (PTB). A significant reduction in mean IGFBP-3 levels was noted with delivery <32 completed weeks (P=0.02). CONCLUSION: Maternal mean IGFBP-3 levels are significantly reduced in cases complicated by delivery <32 completed weeks.

Elevated serum IGF-1 level enhances retinal and choroidal thickness in untreated acromegaly patients.

Science.gov (United States)

Zhang, Xia; Ma, Jin; Wang, Yuhan; Li, Lüe; Gao, Lu; Guo, Xiaopeng; Xing, Bing; Zhong, Yong

2018-03-01

1) To compare the retinal, choroidal, Haller's layer, and Sattler's/choriocapillaris thicknesses of untreated acromegaly patients without chiasm compression or diabetes mellitus and healthy controls. 2) To evaluate the correlations of retinal and choroidal thicknesses with serum growth hormone (GH) and insulin-like growth factor 1 (IGF) burden. This prospective, case-control study included 27 untreated acromegaly patients and 27 sex-matched and age-matched controls. Subfoveal choroidal, Haller's layer and Sattler's/choriocapillaris thicknesses were determined by enhanced-depth imaging optical coherence tomography (EDI-OCT). Foveal and macular retinal thicknesses were determined with SD-OCT. GH and IGF-1 burdens were defined as the product of disease duration and treatment-naïve serum GH and IGF-1 levels. Compared with healthy controls, patients with acromegaly exhibited significantly increased foveal retinal (p = 0.003), subfoveal choroidal (p IGF-1 level (p = 0.03) and IGF-1 burden (p = 0.009). No significant correlations were detected between choroidal thickness and GH burden (p = 0.44). Retinal thickness was not significantly correlated with any factor. The choroidal thickness of acromegaly patients was greater than that of healthy controls and was significantly correlated with disease duration, IGF-1 level and IGF-1 burden, indicating that excessive serum IGF-1 and its exposure time have a combined effect on choroidal thickness.

Expression of IGF-I, IGF-I receptor and IGF binding proteins-1, -2, -3, -4 and -5 in human atherectomy specimens.

Science.gov (United States)

Grant, M B; Wargovich, T J; Ellis, E A; Tarnuzzer, R; Caballero, S; Estes, K; Rossing, M; Spoerri, P E; Pepine, C

1996-12-17

The molecular and cellular processes that induce rapid atherosclerotic plaque progression in patients with unstable angina and initiate restenosis following coronary interventional procedures are uncertain. We examined primary (de novo) and restenotic lesions retrieved at the time of directional coronary atherectomy for expression of insulin-like-growth factor-I (IGF-I). IGF-I receptor, and five IGF binding proteins (IGFBPs), IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-5 in smooth muscle cells (SMCs) using colloidal gold immunocytochemistry. IGF-1, its receptor and binding proteins were not detected in SMCs of normal coronary arteries. IGF-I localized primarily in synthetic smooth muscle cells (sSMCs) in both de novo and restenotic plaques. IGF-I receptor localized on sSMCs and their processes and colocalized with IGF-I. Although morphometric analysis of IGF-I and IGF-I receptor immunoreactivity in sSMCs of de novo and restenotic lesions showed comparable levels of IGF-I (3.2 +/- 1.0 and 2.9 +/- 0.9, respectively). IGF-I receptor was significantly higher in de novo lesions as compared to restenotic lesions (10.7 +/- 2.5 and 4.2 +/- 1.3, P system.

Placental IGF-1 and IGFBP-3 expression correlate with umbilical cord blood PAH and PBDE levels from prenatal exposure to electronic waste

International Nuclear Information System (INIS)

Xu, Xijin; Yekeen, Taofeek Akangbe; Xiao, Qiongna; Wang, Yuangping; Lu, Fangfang; Huo, Xia

2013-01-01

Electronic waste recycling produces Polycyclic Aromatic Hydrocarbons (PAHs) and Polybrominated Diphenyl Ethers (PBDEs) which may affect fetal growth and development by altering the insulin-like-growth factor (IGF) system. Questionnaires were administered to pregnant women (Guiyu, an e-waste site, n = 101; control, n = 53), and umbilical cord blood (UCB) and placentas were collected upon delivery. PBDEs and PAHs in UCB and placental IGF-1 and IGFBP-3 mRNA levels were analyzed using GC–MS and real-time PCR, respectively. Infant birth length and Apgar scores were lower in Guiyu. All PAHs (except Fl, Chr, IP, BbF and BP), total 16-PAHs, total/individual PBDEs, placental IGF-1 (median 0.23 vs 0.19; P < 0.05) and IGFBP-3 (median 1.91 vs 0.68; P < 0.001) levels were significantly higher in Guiyu. Spearman correlation showed that BDE-154, BDE-209 and ∑5ring-PAHs positively correlate with IGF-1 while PBDEs, 4 rings and total PAHs correlate with IGFBP-3 expression. Increased placental IGF-1 level might indirectly affect fetal growth and development. -- Highlights: •PAHs and PBDEs from e-waste may affect fetal growth via alteration of IGF system. •Infant birth length and Apgar scores were lower in Guiyu compared to Chaoan. •Most PAHs, all PBDEs, IGF-1 and IGFBP-3 levels were significantly higher in Guiyu. •IGF-1 positively correlates with BDE-154, BDE-209 and ∑5ring-PAHs. •The observed increase in IGF-1 might indirectly affect fetal growth and development. -- The correlation between POPs and placental IGF-1 and IGFBP-3 assessed provides more information on the human health risk associated with electronic waste

Clinical significance of combined determination of serum levels of free prostate specific antigen (fPSA) and insulin-like growth factor-1 (IGF-1) in patients with prostatic cancer

International Nuclear Information System (INIS)

Wang Xiaolong; Chen Baixun; Chen Yue

2004-01-01

Objective: To explore the clinical significance of combined determination of serum levels of fPSA and IGF-1 in patients with prostatic cancer. Methods: Serum levels of fPSA (with chemiluminescence) and IGF-1 (with IRMA) were measured in 48 patients with prostatic cancer, 63 patients with benign prostate hyperplasia and 38 controls. Results: Serum levels of fPSA and IGF-1 in the 111 patients were significantly higher than those in controls (P<0.05). The positive rate for prostatic cancer detection with fPSA, IGF-1 and fPSA combined with IGF-1 was 83.3%, 79.2% and 95.8% respectively. Conclusion: Combined measurement of fPSA and IGF-1 was most preferable for screening prostatic cancer

IGF-1, IGFBP-1, and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk: findings from the Breast and Prostate Cancer Cohort Consortium (BPC3.

Directory of Open Access Journals (Sweden)

Alpa V Patel

2008-07-01

Full Text Available IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-I and IGFBP-3 levels and breast cancer risk within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3. This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-I and 6,275 for circulating IGFBP-3 analyses comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the genes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP were selected to provide high coverage of common haplotypes; the haplotype structure was defined across four haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-I levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF levels does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women.

Interactive effects of eight weeks massage therapy along with Apium graveolens seed consumption on serum levels of IGF-1 and P53 in overweight women

Directory of Open Access Journals (Sweden)

Mahdieh Asadi

2014-04-01

Conclusion: The results show that massage therapy along with celery seed supplements, especially the combination of these two non-pharmaceutical approaches have beneficial effects on body weight and IGF-1 and P53 levels in overweight women.

Association between GH receptor polymorphism (exon 3 deletion), serum IGF1, semen quality, and reproductive hormone levels in 838 healthy young men

DEFF Research Database (Denmark)

Andreassen, M; Jensen, Rikke Bodin; Jørgensen, Niels

2014-01-01

=467) GHRd3/d3 homozygous individuals (n=69) tended to have larger semen volume (3.2 (2.4-4.3) vs 3.6 (2.6-4.7) ml, P=0.053) and higher serum inhibin-B levels (208 pg/ml (158-257) vs 227 pg/ml (185-264), P=0.050). Semen quality, levels of gonadotropins, testosterone, estradiol, sex hormone......-binding globulin, and IGF1 were not associated with GHRd3 genotype. A twofold increase in serum IGF1 was associated with a 13% (4-23) increase in calculated free testosterone (P=0.004). By contrast IGF1 was inversely associated with serum inhibin-B (P=0.027), but showed no associations to semen quality. GHR...

Metabolic Fingerprints of Circulating IGF-1 and the IGF-1/IGFBP-3 Ratio

DEFF Research Database (Denmark)

Knacke, Henrike; Pietzner, Maik; Do, Kieu Trinh

2016-01-01

OBJECTIVE: IGF-1 is known for its various physiological and severe pathophysiological effects on human metabolism; however, underlying molecular mechanisms still remain unsolved. To reveal possible molecular mechanisms mediating these effects, for the first time, we associated serum IGF-1 levels...... with multifluid untargeted metabolomics data. METHODS: Plasma/urine samples of 995 nondiabetic participants of the Study of Health in Pomerania were characterized by mass spectrometry. Sex-specific linear regression analyses were performed to assess the association of IGF-1 and IGF-1/IGF binding protein 3 ratio...... with metabolites. Additionally, the predictive ability of the plasma and urine metabolome for IGF-1 was assessed by orthogonal partial least squares analyses. RESULTS AND CONCLUSIONS: We revealed a multifaceted image of associated metabolites with large sex differences. Confirming previous reports, we detected...

IGF-1R Regulates the Extracellular Level of Active MMP-2, Pathological Neovascularization, and Functionality in Retinas of OIR Mouse Model.

Science.gov (United States)

Lorenc, Valeria E; Subirada Caldarone, Paula V; Paz, María C; Ferrer, Darío G; Luna, José D; Chiabrando, Gustavo A; Sánchez, María C

2018-02-01

In ischemic proliferative diseases such as retinopathies, persistent hypoxia leads to the release of numerous neovascular factors that participate in the formation of abnormal vessels and eventually cause blindness. The upregulation and activation of metalloproteinases (MMP-2 and MMP-9) represent a final common pathway in this process. Although many regulators of the neovascular process have been identified, the complete role of the insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) appears to be significantly more complex. In this study, we used an oxygen-induced retinopathy (OIR) mouse model as well as an in vitro model of hypoxia to study the role of MMP-2 derived from Müller glial cells (MGCs) and its relation with the IGF-1/IGF-1R system. We demonstrated that MMP-2 protein expression increased in P17 OIR mice, which coincided with the active phase of the neovascular process. Also, glutamine synthetase (GS)-positive cells were also positive for MMP-2, whereas IGF-1R was expressed by GFAP-positive cells, indicating that both proteins were expressed in MGCs. In addition, in the OIR model a single intravitreal injection of the IGF-1R blocking antibody (αIR3) administered at P12 effectively prevented pathologic neovascularization, accelerated physiological revascularization, and improved retinal functionality at P17. Finally, in MGC supernatants, the blocking antibody abolished the IGF-1 effect on active MMP-2 under normoxic and hypoxic conditions without affecting the extracellular levels of pro-MMP-2. These results demonstrate, for the first time, that the IGF-1/IGF-1R system regulates active MMP-2 levels in MGCs, thus contributing to MEC remodeling during the retinal neovascular process.

Effect of GenF20 Plus on serum IGF-1 levels in healthy adults: a randomized controlled study

Directory of Open Access Journals (Sweden)

Sonawane N

2015-03-01

Full Text Available Navneet Sonawane,1 Vinayak Kale,2 Suhas Erande,3 Jayesh Chaudhary1 1Vedic Lifesciences Pvt Ltd, Mumbai, India; 2Lokmanya Hospital, Pune, India; 3Akshay Hospital, Pune, India Background: Aging is related to a reduction of growth hormones, resulting in physiological derailment and affects overall wellbeing. GenF20 Plus is a dietary supplement postulated to naturally stimulate the secretion of human growth hormone (HGH through the anterior pituitary. This study sought to evaluate the effect of GenF20 Plus in enhancing the levels of insulin-like growth factor-1 (IGF-1, which is a marker of HGH levels. Methods: Seventy subjects aged 35–65 years visiting outpatient departments at five study centers across India, presenting with at least two of the following age-related complaints: decreased memory, decreased libido, low energy levels, or poor quality of sleep were randomly assigned to either GenF20 Plus (n=35 or placebo (n=35 for a period of 12 weeks (84 days. Randomization was carried out using computerized software. The primary outcome measure was serum IGF-1 levels. Changes in waist circumference, body mass index, body fat percentage, lean muscle mass, and scores for memory, libido, energy levels, and quality of sleep were also assessed. Trial registration: CTRI/2011/06/001784. Results: Sixty-one subjects completed the study as per protocol and were analyzed. The mean increase (mean ± standard deviation in IGF-1 levels at day 84 in the GenF20 Plus group was 13.46±36.12 ng/mL and in the placebo group was 6.35±36.56 ng/mL, which was not statistically significantly different (P>0.05 when compared across the groups. In the ≥40 years subgroup, the mean increase in IGF-1 in the GenF20 Plus group (14.59±40.08 ng/mL was not statistically significantly different when compared to the placebo group (3.17±16.09 ng/mL using analysis of variance (ANOVA; P>0.05. However, when this change was analyzed using analysis of covariance (ANCOVA considering

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors

Science.gov (United States)

Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Introduction Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). Materials and Methods IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. Results PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Discussion Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders. PMID:26967642

miR-342-3p suppresses hepatocellular carcinoma proliferation through inhibition of IGF-1R-mediated Warburg effect.

Science.gov (United States)

Liu, Wenpeng; Kang, Lei; Han, Juqiang; Wang, Yadong; Shen, Chuan; Yan, Zhifeng; Tai, Yanhong; Zhao, Caiyan

2018-01-01

Insulin-like growth factor-1 receptor (IGF-1R) is a well-studied oncogenic factor that promotes cell proliferation and energy metabolism and is overexpressed in numerous cancers including hepatocellular carcinoma (HCC). Aerobic glycolysis is a hallmark of cancer, and drugs targeting its regulators, including IGF-1R, are being developed. However, the mechanisms of IGF-1R inhibition and the physiological significance of the IGF-1R inhibitors in cancer cells are unclear. Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and real-time PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-342-3p and IGF-1R. The effect of miR-342-3p on glycolysis was determined by glucose uptake, ATP concentration, lactate generation, extracellular acidification rate and oxygen consumption rate assays. In vivo, subcutaneous tumor formation assay and PET were performed in nude mice. In this study, we demonstrate that by directly targeting the 3'-UTR (3'-untranslated regions) of IGF-1R, microRNA-342-3p (miR-342-3p) suppresses IGF-1R-mediated PI3K/AKT/GLUT1 signaling pathway both in vitro and in vivo. Through suppression of IGF-1R, miR-342-3p dampens glycolysis by decreasing glucose uptake, lactate generation, ATP production, and extracellular acidification rate (ECAR), and increasing oxygen consumption rate (OCR) in hepatoma cells. Importantly, glycolysis regulated by miR-342-3p is critical for its regulating HCC growth both in vitro and in vivo. Our findings provide clues regarding the role of miR-342-3p as a tumor suppressor in liver cancer mainly through the inhibition of IGF-1R. Targeting IGF-1R by miR-342-3p could be a potential therapeutic strategy in liver cancer.

Salivary and serum insulin-like growth factor (IGF-1) assays in anorexic patients.

Science.gov (United States)

Paszynska, Elzbieta; Dmitrzak-Weglarz, Monika; Slopien, Agnieszka; Tyszkiewicz-Nwafor, Marta; Rajewski, Andrzej

2016-12-01

The purpose of this study was to measure the salivary and serum free IGF-1 concentration of patients with anorexia nervosa (AN) in comparison to an average population. A controlled clinical trial was designed for an age- and gender-matched group of 121 AN patients and 77 healthy individuals. A clinical examination was made and blood and salivary samples were taken during the acute stage of AN (BMI measuring free IGF-1 was used. Anorexic patients had significant reductions in salivary unstimulated flow rate (UFR), pH and free IGF-1 levels in their saliva and serum. Significant correlations between serum IGF-1 and BMI; salivary IGF-1 and UFR and pH were detected. Salivary and serum IGF-1 analyses appear to be a reliable biochemical indicator of malnutrition in AN patients. Measurement of salivary IGF-1 levels would allow new perspectives in monitoring AN in its early stages.

Circulating IGF1 regulates hippocampal IGF1 levels and brain gene expression during adolescence

OpenAIRE

Yan, Han; Mitschelen, Matthew; Bixler, Georgina V; Brucklacher, Robert M; Farley, Julie A; Han, Song; Freeman, Willard M; Sonntag, William E

2011-01-01

GH and its anabolic mediator, IGF1, are important not only in somatic growth but also in the regulation of brain function. Even though GH treatment has been used clinically to improve body composition and exercise capacity in adults, its influence on central nervous system function has only recently been recognized. This is also the case for children with childhood-onset GH deficiency (GHD) where GH has been used to stimulate bone growth and enhance final adult height. Circulating IGF1 is tra...

High serum IGF-1 levels are associated with pregnancy loss following frozen-thawed euploid embryo transfer cycles.

Science.gov (United States)

Irani, Mohamad; Nasioudis, Dimitrios; Witkin, Steven S; Gunnala, Vinay; Spandorfer, Steven D

2018-06-01

An elevated level of insulin growth factor (IGF-1) in rat uterine fluid has been shown to exert detrimental effects of embryo development possibly leading to an increase in pregnancy loss. Interestingly, the administration of somatostatin to rats undergoing superovulation reduced IGF-1 levels in uterine luminal fluid and thus reversed its deleterious effects on embryo development and increased the number of normal embryos. Therefore, we investigated whether serum levels of IGF-1 correlate with the incidence of pregnancy loss following IVF. To account for aneuploidy and the effect of hormonal supplementation on serum IGF levels, we only included natural frozen-thawed euploid embryo transfer (N-FET) cycles. Sera collected in the follicular phase (cycle day 10) were tested for levels of IGF-1, IGF-2, and IGF-binding protein 1 (IGFBP-1) using quantitative ELISA. A total of 156 N-FET cycles were included: 120 resulted in a live birth whereas 36 led to a first trimester pregnancy loss. Women with a pregnancy loss had significantly higher serum IGF-1 levels compared to those who achieved a live birth (18.0 ± 1.1 vs. 14.6 ± 0.7 ng/mL, respectively). The two groups had comparable serum IGF-2 and IGFBP-1 levels. There was no significant difference in maternal age, body mass index, gravidity, parity, number of prior miscarriages, peak endometrial thickness, or infertility diagnosis between the two groups. In conclusion, women undergoing euploid blastocyst transfer with elevated serum IGF-1 concentrations may be at increased risk of pregnancy loss. This may constitute a novel molecular explanation of pregnancy loss of euploid conceptus. Copyright © 2018. Published by Elsevier B.V.

Serum IGF1 and insulin levels in girls with normal and precocious puberty

DEFF Research Database (Denmark)

Sørensen, Kaspar; Aksglaede, Lise; Petersen, Jørgen Holm

2012-01-01

IGF1 plays an important role in growth and metabolism during puberty. IGF1 levels are increased in girls with central precocious puberty (CPP). However, the relationship with insulin before and during gonadal suppression is unknown. In addition, the influence of the exon 3-deleted GH receptor gene...

The study of breast milk IGF-1, leptin, ghrelin and adiponectin levels as possible reasons of high weight gain in breast-fed infants.

Science.gov (United States)

Kon, Igor Ya; Shilina, Natalia M; Gmoshinskaya, Maria V; Ivanushkina, Tatiana A

2014-01-01

Excessive consumption of protein that leads to increased blood levels of insulin-like growth factor-1 (IGF-1) is an important risk factor for high growth velocity and obesity in formula-fed infants. However, it is not clear whether these factors can explain the high growth velocity in breast-fed infants. To study the possible links between the growth velocity in breast-fed infants and the levels of protein, IGF-1 and other hormones, which regulate energy homeostasis, in mothers' breast milk. We studied 103 mother-infant pairs. Their daily breast milk intake and level of IGF-1, leptin, ghrelin, adiponectin, protein and fat in breast milk were measured at 1, 2 and 3 months of lactation. The infant group was divided into three subgroups of low, normal and high weight gain tertiles. The breast milk consumed by the infants with high weight gain contained higher levels of IGF-1 than that consumed by those with low weight gain at all periods studied (p = 0.032 at 3 months of lactation), and ghrelin levels were higher at 1 and 2 months and leptin levels at 2 and 3 months of lactation (p milk IGF-1 level and infant weight gain (r = 0.294, p = 0.043). Total daily breast milk, fat and hormone intake was also higher in the high weight gain group compared to the low weight gain group. One of the reasons for the high growth velocity in breast-fed infants may be the enhanced levels of the studied hormones in breast milk.

IGF-1 receptor and IGF binding protein-3 might predict prognosis of patients with resectable pancreatic cancer

International Nuclear Information System (INIS)

Hirakawa, Toshiki; Yashiro, Masakazu; Murata, Akihiro; Hirata, Keiichiro; Kimura, Kenjiro; Amano, Ryosuke; Yamada, Nobuya; Nakata, Bunzo; Hirakawa, Kosei

2013-01-01

The present study aimed to elucidate the clinicopathologic role of insulin-like growth factor-1 receptor (IGF1R) and IGF binding protein-3 (IGFBP3) in patients with pancreatic cancer. The function of IGFBP3 is controversial, because both inhibition and facilitation of the action of IGF as well as IGF-independent effects have been reported. In this study, IGF1R and IGFBP3 expression was examined, and their potential roles as prognostic markers in patients with pancreatic cancer were evaluated. Clinicopathological features of 122 patients with curatively resected pancreatic cancer were retrospectively reviewed, and expression of IGF1R and IGFBP3 was immunohistochemically analyzed. Expression of IGF1R and IGFBP3 was observed in 50 (41.0%) and 37 (30.3%) patients, respectively. IGF1R expression was significantly associated with histological grade (p = 0.037). IGFBP3 expression had a significant association with tumor location (p = 0.023), and a significant inverse association with venous invasion (p = 0.037). Tumors with IGF1R-positive and IGFBP3-negative expression (n = 32) were significantly frequently Stage II and III (p = 0.011). The prognosis for IGF1R positive patients was significantly poorer than that for IGF1R negative patients (p = 0.0181). IGFBP3 protein expression did not correlate significantly with patient survival. The subset of patients with both positive IGF1R and negative IGFBP3 had worse overall survival (8.8 months versus 12.6 months, respectively, p < 0.001). IGF1R signaling might be associated with tumor aggressiveness, and IGFBP3 might show antiproliferative effects in pancreatic cancer. Both high IGF1R expression and low IGFBP3 expression represent useful prognostic markers for patients with curatively resected pancreatic cancer

miR-342-3p suppresses hepatocellular carcinoma proliferation through inhibition of IGF-1R-mediated Warburg effect

Directory of Open Access Journals (Sweden)

Liu W

2018-03-01

Full Text Available Wenpeng Liu,1,* Lei Kang,2,* Juqiang Han,3 Yadong Wang,1 Chuan Shen,1 Zhifeng Yan,4 Yanhong Tai,5 Caiyan Zhao1 1Department of Infectious Diseases, Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China; 2Department of Nuclear Medicine, Peking University First Hospital, Beijing, China; 3Institute of Liver Disease, Beijing Military General Hospital, Beijing, China; 4Department of Gynecology and Obstetrics, PLA General Hospital, Beijing, China; 5Department of Pathology, Hospital of PLA, Beijing, China *These authors contributed equally to this work Background: Insulin-like growth factor-1 receptor (IGF-1R is a well-studied oncogenic factor that promotes cell proliferation and energy metabolism and is overexpressed in numerous cancers including hepatocellular carcinoma (HCC. Aerobic glycolysis is a hallmark of cancer, and drugs targeting its regulators, including IGF-1R, are being developed. However, the mechanisms of IGF-1R inhibition and the physiological significance of the IGF-1R inhibitors in cancer cells are unclear. Materials and methods: Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and real-time PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-342-3p and IGF-1R. The effect of miR-342-3p on glycolysis was determined by glucose uptake, ATP concentration, lactate generation, extracellular acidification rate and oxygen consumption rate assays. In vivo, subcutaneous tumor formation assay and PET were performed in nude mice. Results: In this study, we demonstrate that by directly targeting the 3’-UTR (3’-untranslated regions of IGF-1R, microRNA-342-3p (miR-342-3p suppresses IGF-1R-mediated PI3K/AKT/GLUT1 signaling pathway both in vitro and in vivo. Through suppression of IGF-1R, miR-342-3p dampens glycolysis by decreasing glucose uptake, lactate generation

Correlation between GH and IGF-1 during treatment for acromegaly.

Science.gov (United States)

Oldfield, Edward H; Jane, John A; Thorner, Michael O; Pledger, Carrie L; Sheehan, Jason P; Vance, Mary Lee

2017-06-01

OBJECTIVE The relationship between growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in patients with acromegaly as serial levels drop over time after treatment has not been examined previously. Knowledge of this relationship is important to correlate pretreatment levels that best predict response to treatment. To examine the correlation between GH and IGF-1 and IGF-1 z-scores over a wide range of GH levels, the authors examined serial GH and IGF-1 levels at intervals before and after surgery and radiosurgery for acromegaly. METHODS This retrospective analysis correlates 414 pairs of GH and IGF-1 values in 93 patients with acromegaly. RESULTS Absolute IGF-1 levels increase linearly with GH levels only up to a GH of 4 ng/ml, and with IGF-1 z-scores only to a GH level of 1 ng/ml. Between GH levels of 1 and 10 ng/ml, increases in IGF-1 z-scores relative to changes in GH diminish and then plateau at GH concentrations of about 10 ng/ml. From patient to patient there is a wide range of threshold GH levels beyond which IGF-1 increases are no longer linear, GH levels at which the IGF-1 response plateaus, IGF-1 levels at similar GH values after the IGF-1 response plateaus, and of IGF-1 levels at similar GH levels. CONCLUSIONS In acromegaly, although IGF-1 levels represent a combination of the integrated effects of GH secretion and GH action, the tumor produces GH, not IGF-1. Nonlinearity between GH and IGF-1 occurs at GH levels far below those previously recognized. To monitor tumor activity and tumor viability requires measurement of GH levels.

Novel functional polymorphism in IGF-1 gene associated with multiple sclerosis: A new insight to MS.

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Shahbazi, Majid; Abdolmohammadi, Reza; Ebadi, Hamid; Farazmandfar, Touraj

2017-04-01

Interactions between several genes and environment may play a role in susceptibility to multiple sclerosis (MS). The IGF-1 plays a key role in proliferation, maintenance and survival of nerve cells. Therefore, we hypothesized that IGF-1 may be a target for prediction and control MS. We aimed to analysis IGF-1 gene promoter sequence, to investigate the effect of the single nucleotide variants on IGF-1 expression and its association with MS. We enrolled 339 MS patients and 431 healthy controls. A specific region in IGF-1 gene promoter was investigated by SSCP analysis. All samples were genotyped by SSP-PCR. In-vitro and in-vivo IGF-1 production was measured by ELISA assay. IGF-1 expression in PBMCs was measured using real-time PCR. We identified a T to C single nucleotide substitution at position -1089 and a C to T at position -383 from transcription start site in the IGF-1 gene promoter. There was a significant association between MS and genotypes IGF-1(-383) C/T (p=0.001) and IGF-1(-383) C/C (pMS (p=0.001). In-vitro and in-vivo IGF-1 level showed that IGF-1 production in samples with genotype IGF-1(-383) C/C significantly was less than T/T (p=0.004) but not T/C (p=0.220). According to IGF-1 roles in CNS and our results, this study suggests that low IGF-1 level may be associated with susceptibility to MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased cardiogenesis in P19-GFP teratocarcinoma cells expressing the propeptide IGF-1Ea

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Poudel, Bhawana [Heart Science Centre, National Heart and Lung Institute, Imperial College, London (United Kingdom); Bilbao, Daniel [EMBL, Mouse Biology Unit, Monterotondo (Italy); Sarathchandra, Padmini; Germack, Renee [Heart Science Centre, National Heart and Lung Institute, Imperial College, London (United Kingdom); Rosenthal, Nadia [Heart Science Centre, National Heart and Lung Institute, Imperial College, London (United Kingdom); Australian Regenerative Medicine Institute, Monash University, Melbourne (Australia); Santini, Maria Paola, E-mail: m.santini@imperial.ac.uk [Heart Science Centre, National Heart and Lung Institute, Imperial College, London (United Kingdom)

2011-12-16

Highlights: Black-Right-Pointing-Pointer In this study, we explored the function of IGF-1Ea propeptide in inducing cardiogenesis of stem cells. Black-Right-Pointing-Pointer IGF-1Ea promoted cardiac mesodermal induction in uncommitted cells. Black-Right-Pointing-Pointer Under differentiation condition, IGF-1Ea increased expression of cardiac differentiation markers. Black-Right-Pointing-Pointer Furthermore, it promoted formation of finely organized sarcomeric structure. Black-Right-Pointing-Pointer IGF-1Ea propeptide may be a good candidate to improve production of cardiomyocytes from pluripotent cells. -- Abstract: The mechanism implicated in differentiation of endogenous cardiac stem cells into cardiomyocytes to regenerate the heart tissue upon an insult remains elusive, limiting the therapeutical goals to exogenous cell injection and/or gene therapy. We have shown previously that cardiac specific overexpression of the insulin-like growth factor 1 propeptide IGF-1Ea induces beneficial myocardial repair after infarct. Although the mechanism is still under investigation, the possibility that this propeptide may be involved in promoting stem cell differentiation into the cardiac lineage has yet to be explored. To investigate whether IGF-1Ea promote cardiogenesis, we initially modified P19 embryonal carcinoma cells to express IGF-1Ea. Taking advantage of their cardiomyogenic nature, we analyzed whether overexpression of this propeptide affected cardiac differentiation program. The data herein presented showed for the first time that constitutively overexpressed IGF-1Ea increased cardiogenic differentiation program in both undifferentiated and DMSO-differentiated cells. In details, IGF-1Ea overexpression promoted localization of alpha-actinin in finely organized sarcomeric structure compared to control cells and upregulated the cardiac mesodermal marker NKX-2.5 and the ventricular structural protein MLC2v. Furthermore, activated IGF-1 signaling promoted cardiac

Increased cardiogenesis in P19-GFP teratocarcinoma cells expressing the propeptide IGF-1Ea

International Nuclear Information System (INIS)

Poudel, Bhawana; Bilbao, Daniel; Sarathchandra, Padmini; Germack, Renee; Rosenthal, Nadia; Santini, Maria Paola

2011-01-01

Highlights: ► In this study, we explored the function of IGF-1Ea propeptide in inducing cardiogenesis of stem cells. ► IGF-1Ea promoted cardiac mesodermal induction in uncommitted cells. ► Under differentiation condition, IGF-1Ea increased expression of cardiac differentiation markers. ► Furthermore, it promoted formation of finely organized sarcomeric structure. ► IGF-1Ea propeptide may be a good candidate to improve production of cardiomyocytes from pluripotent cells. -- Abstract: The mechanism implicated in differentiation of endogenous cardiac stem cells into cardiomyocytes to regenerate the heart tissue upon an insult remains elusive, limiting the therapeutical goals to exogenous cell injection and/or gene therapy. We have shown previously that cardiac specific overexpression of the insulin-like growth factor 1 propeptide IGF-1Ea induces beneficial myocardial repair after infarct. Although the mechanism is still under investigation, the possibility that this propeptide may be involved in promoting stem cell differentiation into the cardiac lineage has yet to be explored. To investigate whether IGF-1Ea promote cardiogenesis, we initially modified P19 embryonal carcinoma cells to express IGF-1Ea. Taking advantage of their cardiomyogenic nature, we analyzed whether overexpression of this propeptide affected cardiac differentiation program. The data herein presented showed for the first time that constitutively overexpressed IGF-1Ea increased cardiogenic differentiation program in both undifferentiated and DMSO-differentiated cells. In details, IGF-1Ea overexpression promoted localization of alpha-actinin in finely organized sarcomeric structure compared to control cells and upregulated the cardiac mesodermal marker NKX-2.5 and the ventricular structural protein MLC2v. Furthermore, activated IGF-1 signaling promoted cardiac mesodermal induction in undifferentiated cells independently of cell proliferation. This analysis suggests that IGF-1Ea may be a

Significance of measurement of serum somatostatin (SS), growth hormone (GH), insulin-like growth factor-1 (IGF-1) and some related cytokines levels in patients with graves' disease

International Nuclear Information System (INIS)

Zhu Bao; Ma Yunbao; Zhang Xiaoyi

2005-01-01

Objective: To study the possible roles of the related hormones and cytokines in the pathogenesis of Graves' disease. Methods: Serum levels of SS, GH, IGF-1, IL-2, IL-4 and IL-6 were measured with RIA in 1) 36 patients with Graves' disease before any treatment 2) another 30 patients with Graves' disease after successful anti-thyroid drug therapy and 3) 35 controls. Results: In the untreated group, the serum levels of SS, GH, IGF-1, IL-4 and IL-6 were significantly higher but serum IL-2 levels were significantly lower than those in the controls (P<0.01). In the successfully treated group, the serum levels of SS, GH, IGF-1, IL-4 and IL-6 were significantly lower (P<0.05 or P<0.01), but serum IL-2 levels were significantly higher (P<0.01) than those in the untreated group. Conclusion: These parameters played significant roles in the pathogenesis of Graves' disease; however, the precise mechanism remained to be speculative and further studies required. (authors)

Growth hormone as concomitant treatment in severe fibromyalgia associated with low IGF-1 serum levels. A pilot study

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Güell Maria

2007-11-01

Full Text Available Abstract Background There is evidence of functional growth hormone (GH deficiency, expressed by means of low insulin-like growth factor 1 (IGF-1 serum levels, in a subset of fibromyalgia patients. The efficacy of GH versus placebo has been previously suggested in this population. We investigated the efficacy and safety of low dose GH as an adjunct to standard therapy in the treatment of severe, prolonged and well-treated fibromyalgia patients with low IGF-1 levels. Methods Twenty-four patients were enrolled in a randomized, open-label, best available care-controlled study. Patients were randomly assigned to receive either 0.0125 mg/kg/d of GH subcutaneously (titrated depending on IGF-1 added to standard therapy or standard therapy alone during one year. The number of tender points, the Fibromyalgia Impact Questionnaire (FIQ and the EuroQol 5D (EQ-5D, including a Quality of Life visual analogic scale (EQ-VAS were assessed at different time-points. Results At the end of the study, the GH group showed a 60% reduction in the mean number of tender points (pairs compared to the control group (p vs. 8.25 ± 0.9. Similar improvements were observed in FIQ score (p Conclusion The present findings indicate the advantage of adding a daily GH dose to the standard therapy in a subset of severe fibromyalgia patients with low IGF-1 serum levels. Trial Registration NCT00497562 (ClinicalTrials.gov.

Aging, Atherosclerosis, and IGF-1

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Higashi, Yusuke; Sukhanov, Sergiy; Anwar, Asif; Shai, Shaw-Yung

2012-01-01

Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that circulates at high levels in the plasma and is expressed in most cell types. IGF-1 has major effects on development, cell growth and differentiation, and tissue repair. Recent evidence indicates that IGF-1 reduces atherosclerosis burden and improves features of atherosclerotic plaque stability in animal models. Potential mechanisms for this atheroprotective effect include IGF-1–induced reduction in oxidative stress, cell apoptosis, proinflammatory signaling, and endothelial dysfunction. Aging is associated with increased vascular oxidative stress and vascular disease, suggesting that IGF-1 may exert salutary effects on vascular aging processes. In this review, we will provide a comprehensive update on IGF-1's ability to modulate vascular oxidative stress and to limit atherogenesis and the vascular complications of aging. PMID:22491965

E-Peptides Control Bioavailability of IGF-1

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Piszczek, Agnieszka; Perlas, Emarald; Winn, Nadine; Nastasi, Tommaso; Rosenthal, Nadia

2012-01-01

Insulin-like growth factor 1 (IGF-1) is a potent cytoprotective growth factor that has attracted considerable attention as a promising therapeutic agent. Transgenic over-expression of IGF-1 propeptides facilitates protection and repair in a broad range of tissues, although transgenic mice over-expressing IGF-1 propeptides display little or no increase in IGF-1 serum levels, even with high levels of transgene expression. IGF-1 propeptides are encoded by multiple alternatively spliced transcripts including C-terminal extension (E) peptides, which are highly positively charged. In the present study, we use decellularized mouse tissue to show that the E-peptides facilitate in vitro binding of murine IGF-1 to the extracellular matrix (ECM) with varying affinities. This property is independent of IGF-1, since proteins consisting of the E-peptides fused to relaxin, a related member of the insulin superfamily, bound equally avidly to decellularized ECM. Thus, the E-peptides control IGF-1 bioavailability by preventing systemic circulation, offering a potentially powerful way to tether IGF-1 and other therapeutic proteins to the site of synthesis and/or administration. PMID:23251442

The evaluation of central corneal thickness and intraocular pressure in conjunction with tear IGF-1 levels in patients with acromegaly.

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Kan, Emrah; Kan, Elif K; Okuyucu, Ali

2017-08-30

To compare the central corneal thickness (CCT), intraocular pressure (IOP), and tear insulin-like growth factor 1 (IGF-1) levels between patients with acromegaly and a control group and to evaluate the possible effect of tear IGF-1 and duration of the disease on CCT and IOP. We included 31 patients with acromegaly (study group) and 40 age- and sex-matched controls in the study. Patients with acromegaly were divided into 2 subgroups based on disease status (active/inactive). All participants underwent complete ophthalmologic evaluation including CCT and IOP values. Basal tear samples were collected from both groups and tear IGF-1 levels were measured. The CCT, IOP, and tear IGF-1 levels were compared between groups and subgroups and the association between tear IGF-I levels and ocular parameters (CCT, IOP) and disease duration were also evaluated. Central corneal thickness, IOP, and tear IGF-1 levels did not show a significant difference between study and control groups. We also did not find a significant difference in terms of CCT, IOP, or tear IGF-1 levels between subgroups of patients. Correlation analysis did not show an association between the duration of disease and tear IGF-1 levels with CCT or IOP. There was no significant difference in tear IGF-1 levels between patients with acromegaly and controls. Additionally, there was no correlation between disease duration and tear IGF-1 levels with CCT or IOP levels. This lack of association may suggest that tear IGF-1 levels might not have an effect on CCT or IOP findings in patients with acromegaly.

Unbound (bioavailable IGF1 enhances somatic growth

Directory of Open Access Journals (Sweden)

Sebastien Elis

2011-09-01

Understanding insulin-like growth factor-1 (IGF1 biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging. IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs and the acid labile subunit (ALS, which are present in serum and tissues. To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice or R3-Igf1 (KIR mice. The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or ‘free IGF1’. We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels. Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type. Both mutant mice showed increased body weight, body and bone lengths, and relative lean mass. We found selective organomegaly of the spleen, kidneys and uterus, enhanced mammary gland complexity, and increased skeletal acquisition. The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions.

IGF-1R signaling in chondrocytes modulates growth plate development by interacting with the PTHrP/Ihh pathway.

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Wang, Yongmei; Cheng, Zhiqiang; Elalieh, Hashem Z; Nakamura, Eiichiro; Nguyen, Minh-Thanh; Mackem, Susan; Clemens, Thomas L; Bikle, Daniel D; Chang, Wenhan

2011-07-01

Systemic derangements and perinatal death of generalized insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) knockout mice preclude definitive assessment of IGF-1R actions in growth-plate (GP) chondrocytes. We generated cartilage-specific Igf1r knockout ((Cart) Igf1r(-/-)) mice to investigate local control of chondrocyte differentiation in the GP by this receptor. These mice died shortly after birth and showed disorganized chondrocyte columns, delayed ossification and vascular invasion, decreased cell proliferation, increased apoptosis, and increased expression of parathyroid hormone-related protein (Pthrp) RNA and protein in their GPs. The increased Pthrp expression in the knockout GPs likely was due to an increase in gene transcription, as determined by the increased activity of a LacZ reporter that was inserted downstream of the endogenous PTHrP promoter and bred into the knockout mice. To circumvent the early death of (Cart) Igf1r(-/-) mice and investigate the role of IGF-1R during postnatal growth, we made tamoxifen (Tam)-inducible, cartilage-specific Igf1r knockout ((TamCart) Igf1r(-/-)) mice. At 2 weeks of age and 7 to 8 days after Tam injection, the (TamCart) Igf1r(-/-) mice showed growth retardation with a disorganized GP, reduced chondrocyte proliferation, decreased type 2 collagen and Indian Hedgehog (Ihh) expression, but increased expression of PTHrP. Consistent with in vivo observations, in vitro knockout of the Igf1r gene by adenoviral expression of Cre recombinase suppressed cell proliferation, promoted apoptosis, and increased Pthrp expression. Our data indicate that the IGF-1R in chondrocytes controls cell growth, survival, and differentiation in embryonic and postnatal GPs in part by suppression of Pthrp expression. Copyright © 2011 American Society for Bone and Mineral Research.

Low circulating levels of IGF-1 in healthy adults are associated with reduced β-cell function, increased intramyocellular lipid, and enhanced fat utilization during fasting.

Science.gov (United States)

Thankamony, Ajay; Capalbo, Donatella; Marcovecchio, M Loredana; Sleigh, Alison; Jørgensen, Sine Wanda; Hill, Nathan R; Mooslehner, Katrin; Yeo, Giles S H; Bluck, Les; Juul, Anders; Vaag, Allan; Dunger, David B

2014-06-01

Low serum IGF-1 levels have been linked to increased risk for development of type 2 diabetes. However, the physiological role of IGF-1 in glucose metabolism is not well characterized. Our objective was to explore glucose and lipid metabolism associated with variations in serum IGF-1 levels. IGF-1 levels were measured in healthy, nonobese male volunteers aged 18 to 50 years from a biobank (n = 275) to select 24 subjects (age 34.8 ± 8.9 years), 12 each in the lowest (low-IGF) and highest (high-IGF) quartiles of age-specific IGF-1 SD scores. Evaluations were undertaken after a 24-hour fast and included glucose and glycerol turnover rates using tracers, iv glucose tolerance test to estimate peripheral insulin sensitivity (IS) and acute insulin and C-peptide responses (indices of insulin secretion), magnetic resonance spectroscopy to measure intramyocellular lipids (IMCLs), calorimetry, and gene expression studies in a muscle biopsy. Acute insulin and C-peptide responses, IS, and glucose and glycerol rate of appearance (Ra) were evaluated. Fasting insulin and C-peptide levels and glucose Ra were reduced (all P IGF-1 levels could be an important marker of β-cell function and glucose as well as lipid metabolic responses during fasting.

Circulating IGF-1, IGFB-3, GH and TSH levels in multiple sclerosis and their relationship with treatment.

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Akcali, Aylin; Bal, Berrin; Erbagci, Binnur

2017-07-01

Improving the proficiency of oligodendrocytes in their ability to repair myelin damage is one of the major goals of multiple sclerosis treatment. Insulin-like growth factor-1 (IGF-1) is one of several polypeptides that are considered to have potential benefits in that sense. In the present study, we aimed to determine serum levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3), thyroid stimulating hormone (TSH) and growth hormone (GH) among treated and non-treated patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and a healthy control group. The study enrolled 100 RRMS patients and 100 age- and sex-matched control subjects diagnosed with definite multiple sclerosis (MS). Serum GH, IGF-1, IGFBP-3, and TSH levels were studied. The number of relapses and Expanded Disability Status Scale were negatively correlated and IGFBP-3 and GH were positively correlated with IGF-1. A statistically significant difference was not observed when patients were divided into two subgroups as patients treated with a MS-specific therapy (n = 54) and non-treated patients (n = 46). TSH and IGFBP-3 values were significantly lower in patient group vs. While no difference was determined with in IGF-1 levels, low levels of IGF-1 was in correlation with the least levels of IGFBP-3. To understand the relation between IGF-1 and IGFBP-3, the role of low levels of IGFBP-3 and TSH may be studied with clinic isolated syndrome patients and the evolution of these patients to definite MS.

IGF-I stimulates ERβ and aromatase expression via IGF1R/PI3K/AKT-mediated transcriptional activation in endometriosis.

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Zhou, Yan; Zeng, Cheng; Li, Xin; Wu, Pei-Li; Yin, Ling; Yu, Xiao-Lan; Zhou, Ying-Fang; Xue, Qing

2016-08-01

Estrogen receptor beta (ERβ, encoded by ESR2 gene) and cytochrome P450 aromatase (encoded by CYP19A1 gene) play critical roles in endometriosis, and the levels of insulin-like growth factor-I (IGF-I) in the peritoneal fluid are significantly higher in patients with endometriosis compared with those in normal women. However, the effects and mechanisms of IGF-I on ERβ and aromatase expression remain to be fully elucidated. In this study, human endometriotic stromal cells (ESCs) and endometrial cells (EMs) derived from ovarian endometriomas and eutopic endometrial tissues. ESCs were cultured with IGF-I, signal pathway inhibitors, and siRNAs. ERβ and aromatase expression were measured by real-time PCR and Western, respectively. The binding of c-Jun and CREB to the ESR2 and CYP19A1 promoters was assessed by chromatin immunoprecipitation assay. Animal experiments were performed in a xenograft mouse model. Levels of IGF-I mRNA in ESCs were markedly higher than those in EMs. IGF-I upregulated ERβ and aromatase expression in ESCs after stimulation of the IGF1R/PI3K/AKT pathway. Following IGF-I treatment, a marked increase in c-Jun and CREB phosphorylation occurred, enhancing binding to the ESR2 and CYP19A1 promoters. An IGF1R inhibitor in vivo reduced IGF-I-induced endometriosis graft growth and ERβ and aromatase expression. In conclusion, this is the first report to describe a mechanistic analysis of ERβ and aromatase expression regulated by IGF-I in ESCs. Moreover, an IGF1R inhibitor impeded ectopic lesion growth in nude mice. These findings suggest that an inhibitor of IGF1R might have therapeutic potential as an antiendometriotic drug. Level of IGF-I mRNA in ESCs is markedly higher than that in EMs. IGF-I up-regulates ERβ and aromatase expression via IGF1R/PI3K/AKT pathway. C-Jun and CREB are recruited to ESR2 or CYP19A1 promoter by IGF-I stimulation. IGF-1R inhibitors in vivo impede the growth of ectopic lesions in nude mice.

Evidence That Graves' Ophthalmopathy Immunoglobulins Do Not Directly Activate IGF-1 Receptors.

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Marcus-Samuels, Bernice; Krieger, Christine C; Boutin, Alisa; Kahaly, George J; Neumann, Susanne; Gershengorn, Marvin C

2018-05-01

Graves' ophthalmopathy (GO) pathogenesis involves thyrotropin (TSH) receptor (TSHR)-stimulating autoantibodies. Whether there are autoantibodies that directly stimulate insulin-like growth factor 1 receptors (IGF-1Rs), stimulating insulin-like growth factor receptor antibodies (IGFRAbs), remains controversial. This study attempted to determine whether there are stimulating IGFRAbs in patients with GO. Immunoglobulins (Igs) were purified from normal volunteers (NV-Igs) and patients with GO (GO-Igs). The effects of TSH, IGF-1, NV-Igs, and GO-Igs on pAKT and pERK1/2, members of pathways used by IGF-1R and TSHR, were compared in orbital fibroblasts from GO patients (GOFs) and U2OS-TSHR cells overexpressing TSHRs, and U2OS cells that express TSHRs at very low endogenous levels. U2OS-TSHR and U2OS cells were used because GOFs are not easily manipulated using molecular techniques such as transfection, and U2OS cells because they express TSHRs at levels that do not measurably stimulate signaling. Thus, comparing U2OS-TSHR and U2OS cells permits specifically distinguishing signaling mediated by the TSHR and IGF-1R. In GOFs, all GO-Igs stimulated pERK1/2 formation and 69% stimulated pAKT. In U2OS-TSHR cells, 15% of NV-IGs and 83% of GO-Igs stimulated increases in pERK1/2, whereas all NV-Igs and GO-Igs stimulated increases in pAKT. In U2OS cells, 70% of GO-Igs stimulated small increases in pAKT. Knockdown of IGF-1R caused a 65 ± 6.3% decrease in IGF-1-stimulated pAKT but had no effect on GO-Igs stimulation of pAKT. Thus, GO-Igs contain factor(s) that stimulate pAKT formation. However, this factor(s) does not directly activate IGF-1R. Based on the findings analyzing these two signaling pathways, it is concluded there is no evidence of stimulating IGFRAbs in GO patients.

Serum tree IGF-I, total IGF-I, IGFBP-1 and IGFBP-3 levels in an elderly population : relation to age and sex steroid levels

NARCIS (Netherlands)

Janssen, JAMJL; Stolk, RP; Pols, HAP; Grobbee, DE; de Jong, FH; Lamberts, SWJ

BACKGROUND Most previous studies concerning the relationship between IGF-I and age used assays measuring total IGF-I, Although free IGF-I is considered of greater biological relevance, little is known about its relationship with sex steroids levels in elderly healthy subjects, MEASUREMENTS In a

IGF-1 and Survival in ESRD

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Jia, Ting; Gama Axelsson, Thiane; Heimbürger, Olof; Bárány, Peter; Stenvinkel, Peter; Qureshi, Abdul Rashid

2014-01-01

Summary Background and objectives IGF-1 deficiency links to malnutrition in CKD patients; however, it is not clear to what extent it associates with survival among these patients. Design, setting, participants, & measurements Serum IGF-1 and other biochemical, clinical (subjective global assessment), and densitometric (dual energy x-ray absorptiometry) markers of nutritional status and mineral and bone metabolism were measured in a cohort of 365 Swedish clinically stable CKD stage 5 patients (median age of 53 years) initiating dialysis between 1994 and 2009; in 207 patients, measurements were also taken after 1 year of dialysis. Deaths were registered during a median follow-up of 5 years. Associations of mortality with baseline IGF-1 and changes of IGF-1 after 1 year of dialysis were evaluated by Cox models. Results At baseline, IGF-1 concentrations associated negatively with age, diabetes mellitus, cardiovascular disease, poor nutritional status, IL-6, and osteoprotegerin and positively with body fat mass, bone mineral density, serum phosphate, calcium, and fibroblast growth factor-23. At 1 year, IGF-1 had increased by 33%. In multivariate regression, low age, diabetes mellitus, and high serum phosphate and calcium associated with IGF-1 at baseline, and in a mixed model, these factors, together with high fat body mass, associated with changes of IGF-1 during the first 1 year of dialysis. Adjusting for calendar year of inclusion, age, sex, diabetes mellitus, cardiovascular disease, IL-6, and poor nutritional status, a 1 SD higher level of IGF-1 at baseline associated with lower mortality risk (hazard ratio, 0.57; 95% confidence interval, 0.32 to 0.98). Persistently low or decreasing IGF-1 levels during the first 1 year on dialysis predicted worse survival (adjusted hazard ratio, 2.19; 95% confidence interval, 1.06 to 4.50). Conclusion In incident dialysis patients, low serum IGF-1 associates with body composition and markers of mineral and bone metabolism, and it

Does adenotonsillectomy alter IGF-1 and ghrelin serum levels in children with adenotonsillar hypertrophy and failure to thrive? A prospective study.

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Jabbari Moghaddam, Yalda; Golzari, Samad E J; Saboktakin, Lida; Seyedashrafi, Mir Hojjat; Sabermarouf, Babak; Gavgani, Heidar Ali Esmaeili; Haghjo, Amir Ghorbani; Lotfi, Alireza; Ghabili, Kamyar

2013-09-01

Adenotonsillar hypertrophy (ATH) contributes to upper airway obstruction and recurrent tonsillitis in children. The aim of this study was to evaluate the effect of adenotonsillectomy on serum IGF-1 and ghrelin levels in children with ATH failure to thrive. Forty pre-pubertal children with more than 5 years of age (6.57 ± 1.284 years) suffering from ATH, sleep disorder breathing, snoring, open mouth breathing and growth retardation were studied. Blood samples were taken eight hours after fasting and weight and height were measured by SECA instrument. Blood samples were centrifuged immediately and the extracted sera were stored at -70 °C in Eppendorf vials. IGF-1 and ghrelin were measured by ELISA kit. Patients with adenotonsillectomy indication underwent adenotonsillectomy and serum levels of IGF-1 and ghrelin were measured 12 months after operation. Weight, height and BMI were increased significantly after operation (P failure to thrive increases IGF-1 and Ghrelin serum levels which might contribute to the improvement in the growth pattern of the children. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Differential Regulation of Hippocampal IGF-1-Associated Signaling Proteins by Dietary Restriction in Aging Mouse.

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Hadem, Ibanylla Kynjai Hynniewta; Sharma, Ramesh

2017-08-01

Time-dependent alterations in several biological processes of an organism may be characterized as aging. One of the effects of aging is the decline in cognitive functions. Dietary restriction (DR), an intervention where the consumption of food is lessened but without malnutrition, is a well-established mechanism that has a wide range of important outcomes including improved health span, delayed aging, and extension of lifespan of various species. It also plays a beneficial role in protecting against age-dependent deterioration of cognitive functions, and has neuroprotective properties against neurodegenerative diseases. Insulin-like growth factor (IGF)-1 plays an important role in the regulation of cellular and tissue functions, and relating to the aging process the most important pathway of IGF-1 is the phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt/PKB) signaling cascade. Although many have studied the changes in the level of IGF-1 and its effect on neural proliferation, the downstream signaling proteins have not been fully elucidated. Hence in the present investigation, the IGF-1 gene expression and the normal endogenous levels of IGF1R (IGF-1 receptor), PI3K, Akt, pAkt, and pFoxO in the hippocampus of young, adult, and old mice were determined using real-time PCR and Western blot analyses. The effects of DR on these protein levels were also studied. Results showed a decrease in the levels of IGF-1, IGF1R, PI3K, and pAkt, while pFoxO level increased with respect to age. Under DR, these protein levels are maintained in adult mice, but old mice displayed diminished expression levels of these proteins as compared to ad libitum-fed mice. Maintenance of PI3K/Akt pathway results in the phosphorylation of FoxOs, necessary for the enhancement of neural proliferation and survival in adult mice. The down-regulation of IGF-I signaling, as observed in old mice, leads to increasing the activity of FoxO factors that may be important for the neuroprotective

Relationship between cord blood IGF-I, IGFBP-3 levels and intrauterine growth retardation (IUGR)

International Nuclear Information System (INIS)

Yu Suqing; Chu Kaiqiu; Chen Shengjie

2008-01-01

Objective: To study the cord blood insulin-like growth factor-I (IGF-I) and its binding protein-3 (IGFBP-3) levels in neonates with intrauterine growth retardation (IUGR). Methods: Cord serum IGF-I (with RIA) and IGFBP-3 (with IRMA) levels were measured in 22 neonates with IUGR and 64 neonates with appropriate gestational age (AGA). Results: Cord blood IGF-I and IGFBP-3 levels in IUGR neonates were significantly lower than those in AGA neonates (P<0.001). Among the 86 neonates studied in this article, 44 were born pre-term and 42 were born full term. From the data, we could see that the cord blood IGF-I and IGFBP-3 levels in pre-term neonates were significantly lower than those in full-term neonates (P also <0.001). IGF-I and IGFBP-3 levels were mutually positively correlated (P<0.01). Conclusion: Cord blood IGF-I and IGFBP-3 levels were useful indicator of neonates growth. (authors)

Maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3 and the hypertensive disorders of pregnancy.

LENUS (Irish Health Repository)

Cooley, Sharon M

2010-07-01

To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational hypertension and pre-eclampsia (PET).

Children with severe Osteogenesis imperfecta and short stature present on average with normal IGF-I and IGFBP-3 levels.

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Hoyer-Kuhn, Heike; Höbing, Laura; Cassens, Julia; Schoenau, Eckhard; Semler, Oliver

2016-07-01

Osteogenesis imperfecta (OI) is characterized by bone fragility and short stature. Data about IGF-I/IGFBP-3 levels are rare in OI. Therefore IGF-I/IGFBP-3 levels in children with different types of OI were investigated. IGF-I and IGFBP-3 levels of 60 children (male n=38) were assessed in a retrospective cross-sectional setting. Height/weight was significant different [height z-score type 3 versus type 4: p=0.0011 and weight (p≤0.0001)] between OI type 3 and 4. Mean IGF-I levels were in the lower normal range (mean±SD level 137.4±109.1 μg/L). Mean IGFBP-3 measurements were in the normal range (mean±SD 3.105±1.175 mg/L). No significant differences between OI type 3 and 4 children have been observed (IGF-I: p=0.0906; IGFBP-3: p=0.2042). Patients with different severities of OI have IGF-I and IGFBP-3 levels in the lower normal range. The type of OI does not significantly influence these growth factors.

IGF-IR promotes prostate cancer growth by stabilizing α5β1 integrin protein levels.

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Aejaz Sayeed

Full Text Available Dynamic crosstalk between growth factor receptors, cell adhesion molecules and extracellular matrix is essential for cancer cell migration and invasion. Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization. They also mediate signal transduction to regulate cell proliferation and survival. The type 1 insulin-like growth factor receptor (IGF-IR mediates tumor cell growth, adhesion and inhibition of apoptosis in several types of cancer. We have previously demonstrated that β1 integrins regulate anchorage-independent growth of prostate cancer (PrCa cells by regulating IGF-IR expression and androgen receptor-mediated transcriptional functions. Furthermore, we have recently reported that IGF-IR regulates the expression of β1 integrins in PrCa cells. We have dissected the mechanism through which IGF-IR regulates β1 integrin expression in PrCa. Here we report that IGF-IR is crucial for PrCa cell growth and that β1 integrins contribute to the regulation of proliferation by IGF-IR. We demonstrate that β1 integrin regulation by IGF-IR does not occur at the mRNA level. Exogenous expression of a CD4 - β1 integrin cytoplasmic domain chimera does not interfere with such regulation and fails to stabilize β1 integrin expression in the absence of IGF-IR. This appears to be due to the lack of interaction between the β1 cytoplasmic domain and IGF-IR. We demonstrate that IGF-IR stabilizes the β1 subunit by protecting it from proteasomal degradation. The α5 subunit, one of the binding partners of β1, is also downregulated along with β1 upon IGF-IR knockdown while no change is observed in the expression of the α2, α3, α4, α6 and α7 subunits. Our results reveal a crucial mechanistic role for the α5β1 integrin, downstream of IGF-IR, in regulating cancer growth.

Clinical significance of measurement of changes of serum IGF-II, SCC and CYFRA21-1 levels after operation in patients with carcinoma of uterine cervix

International Nuclear Information System (INIS)

Kuang Lei

2010-01-01

Objective: To explore the clinical significance of changes of serum IGF-II, SCC and CYFRA21-1 levels after operation in patients with carcinoma uterine cervix. Methods: Serum levels of IGF-II, SCC and CYFRA21-1 were determined with RIA repeatedly in 31 patients with carcinoma of uterine cervix (before operation 1 month after operation and 6 month after operation) and once in 35 controls. Results: Before operation,serum levels of IGF-II, SCC and CYFRA21-1 in the patients were significantly higher than those in the controls (P<0.01). One month after operation all the serum levels were approaching normal. Six month later,the levels in the patients without recurrence remained normal. However, the levels in the 6 patients with recurrence returned to those before operation again. Conclusion: Changes of serum IGF-II, SCC and CYFRA21-1 levels are closely related to the tumor burden and may be of prognostic importance. (authors)

Influence of insulin therapy on circulating ghrelin and insulin-like ghrelinowth factor-1(IGF-1) levels in children with type-1 diabetes mellitus

International Nuclear Information System (INIS)

Moawad, A.T.; Nassar, E.M.; Mostafa, A.M.; Mohammed, S.K.

2009-01-01

Diabetes mellitus type 1 (IDDM)is a chronic disease associated with alterations in the growth hormone/insulin -like growth factor (GH-IGF) system and ghrelin level which may lead to changes in metabolic control. This study aimed to evaluate the circulating levels of the gut-derived peptides (ghrelin and insulin-like growth factors (IGF s ) in children with IDDM and to link these two peptides with the glucose level in diabetic children at diagnoses and after insulin therapy. Design and methods: the studied group consisted of 30 newly diagnosed diabetic children (17 females and 13 males) diagnosed in paediatric diabetes unit, children's hospital, Ain shams university. Their age ranged from (6.2-11.8) years with mean of 10.10± 1.74 years. Twenty non diabetic healthy children matching in age and sex served as controls. Serum ghrelin was determined by enzyme linked immuno absorbanet assay (ELISA), while IGF-1 and insulin-like growth factors binding proteins -1 and 3 (IGFBP s ) were assessed by radioimmunoassay(RIA). Results: body mass index (BMI) in patients was significantly decreased in the diabetic group as compared to the healthy group at diagnosis. After insulin therapy BMI was significantly increase as compared to its value at diagnosis (p< 0.05) such increase was not significant on comparing to controls. Regarding blood glucose level there was very highly significant decrease in the level of HBAI (glycolated HB) in diabetic patients after insulin therapy (p<0.0001) than at diagnosis . The mean ghrelin level was highly significantly decreased in diabetic children at diagnosis and after insulin therapy as compared to controls (p<0.0001). No differences were found in the mean ghrelin levels in diabetic children at diagnosis or after insulin therapy.conclusions : the decrease in mean gherlin levels in this study at diagnosis and after therapy could reflect an attempt by the body to decrease the glucose level and thus may prevent hyperglycemia in diabetic patients

Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through IGF1/IGF1R Signaling under Hypoxia.

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Toshiki Hirakawa

Full Text Available Pancreatic ductal adenocarcinoma (PDAC is characterized by its hypovascularity, with an extremely poor prognosis because of its highly invasive nature. PDAC proliferates with abundant stromal cells, suggesting that its invasive activity might be controlled by intercellular interactions between cancer cells and fibroblasts. Using four PDAC cell lines and two pancreas cancer-associated fibroblasts (CAFs, the expression of insulin-like growth factor-1 (IGF1 and IGF1 receptor (IGF1R was evaluated by RT-PCR, FACScan, western blot, or ELISA. Correlation between IGF1R and the hypoxia marker carbonic anhydrase 9 (CA9 was examined by immunohistochemical staining of 120 pancreatic specimens. The effects of CAFs, IGF1, and IGF1R inhibitors on the motility of cancer cells were examined by wound-healing assay or invasion assay under normoxia (20% O2 and hypoxia (1% O2. IGF1R expression was significantly higher in RWP-1, MiaPaCa-2, and OCUP-AT cells than in Panc-1 cells. Hypoxia increased the expression level of IGF1R in RWP-1, MiaPaCa-2, and OCUP-AT cells. CA9 expression was correlated with IGF1R expression in pancreatic specimens. CAFs produced IGF1 under hypoxia, but PDAC cells did not. A conditioned medium from CAFs, which expressed αSMA, stimulated the migration and invasion ability of MiaPaCa-2, RWP-1, and OCUP-AT cells. The motility of all PDAC cells was greater under hypoxia than under normoxia. The motility-stimulating ability of CAFs was decreased by IGF1R inhibitors. These findings might suggest that pancreas CAFs stimulate the invasion activity of PDAC cells through paracrine IGF1/IGF1R signaling, especially under hypoxia. Therefore the targeting of IGF1R signaling might represent a promising therapeutic approach in IGF1R-dependent PDAC.

IGF-1 Protects Dopamine Neurons Against Oxidative Stress: Association with Changes in Phosphokinases

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El Ayadi, Amina; Zigmond, Michael J.; Smith, Amanda D.

2016-01-01

Insulin-like growth factor-1 (IGF-1) is an endogenous peptide transported across the blood brain barrier that is protective in several brain injury models, including an acute animal model of Parkinson’s disease (PD). Motor deficits in PD are due largely to the progressive loss of nigrostriatal dopaminergic neurons. Thus, we examined the neuroprotective potential of IGF-1 in a progressive model of dopamine deficiency in which 6-hydroxydopamine (6-OHDA) is infused into the striatum. Rats received intrastriatal IGF-1 (5 or 50 μg) 6 hrs prior to infusion of 4 μg 6-OHDA into the same site and were sacrificed 1 or 4 wks later. Both concentrations of IGF-1 protected tyrosine hydroxylase (TH) immunoreactive terminals in striatum at 4 wks but not at 1 wk, indicating that IGF-induced restoration of the dopaminergic phenotype occurred over several weeks. TH-immunoreactive cell loss was only attenuated with 50 μg IGF-1. We then examined the effect of striatal IGF-1 on the Ras/ERK1/2 and PI3K/Akt pathways to ascertain if their activation correlated with IGF-1-induced protection. Striatal and nigral levels of phospho-ERK1/2 (pERK1/2) were maximal 6 hrs after IGF-1 infusion and, with the exception of an increase in nigral pERK2 at 48 hrs, returned to basal levels by 7 days. Phospho-Akt (Ser473) was elevated 6–24 hrs post-IGF-1 infusion in both striatum and substantia nigra concomitant with inhibition of pro-death GSK-3β, a downstream target of Akt. These results suggest that IGF-1 can protect the nigrostriatal pathway in a progressive PD model and that this protection is preceded by activation of key pro-survival signaling cascades PMID:26894890

Exercise Activates p53 and Negatively Regulates IGF-1 Pathway in Epidermis within a Skin Cancer Model.

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Yu, Miao; King, Brenee; Ewert, Emily; Su, Xiaoyu; Mardiyati, Nur; Zhao, Zhihui; Wang, Weiqun

2016-01-01

Exercise has been previously reported to lower cancer risk through reducing circulating IGF-1 and IGF-1-dependent signaling in a mouse skin cancer model. This study aims to investigate the underlying mechanisms by which exercise may down-regulate the IGF-1 pathway via p53 and p53-related regulators in the skin epidermis. Female SENCAR mice were pair-fed an AIN-93 diet with or without 10-week treadmill exercise at 20 m/min, 60 min/day and 5 days/week. Animals were topically treated with TPA 2 hours before sacrifice and the target proteins in the epidermis were analyzed by both immunohistochemistry and Western blot. Under TPA or vehicle treatment, MDM2 expression was significantly reduced in exercised mice when compared with sedentary control. Meanwhile, p53 was significantly elevated. In addition, p53-transcriptioned proteins, i.e., p21, IGFBP-3, and PTEN, increased in response to exercise. There was a synergy effect between exercise and TPA on the decreased MDM2 and increased p53, but not p53-transcripted proteins. Taken together, exercise appeared to activate p53, resulting in enhanced expression of p21, IGFBP-3, and PTEN that might induce a negative regulation of IGF-1 pathway and thus contribute to the observed cancer prevention by exercise in this skin cancer model.

DYNAMICS OF INSULIN-LIKE GROWTH FACTOR-1 (IGF-1 IN CHILDREN AFTER AB0-INCOMPATIBLE LIVER TRANSPLANTATION

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O.P. Shevchenko

2014-01-01

Full Text Available It is shown that liver transplantation (LT from donor with incompatible blood type (AB0i may be effective and safe, but the impact of such operation upon the various systems of the body has not been investigated yet. Insulinlike growth factor-1 (IGF-1 is synthesized in the liver and mediates the action of growth hormone. The level of IGF-1 is a marker of the processes of cell proliferation and tissue regeneration. Aim. To evaluate levels of IGF-1 in children-recipients with liver transplant from AB0i (incompatible and AB0c (compatible donors.Materials and methods. 140 children aged 3 to 36 (19,5 ± 16,5 months with congenital diseases of the hepatobiliar system, 58 of them boys, were surveyed. All patients underwent transplantation of left lateral liver sector from living related donors: 111 children were transplanted with fragment of the liver from AB0c donors, 29 – from AB0i donors; in 10 children with AB0i liver before and/or after LT operation anti-group antibodies (anti-A/B were revealed. The concentration of IGF-1 was determined by ELISA using specifi c kits (Immunodiagnostic System, USA in samples of blood plasma, which were received up to a month and a year after a liver transplant.Results. Average level of IGF-1 21,0 ± 29,5 μg/l in patients before LT was signifi cantly lower than in healthy children (52,2 ± 26,3 μg/l, p < 0,001 and did not vary in children, having received later a piece of liver from a compatible (AB0c donor and from donor AB0i (23,5 ± 30,9 and 21,2 ± 23,2 μg/l respectively, p = 0,70. In patients with anti-A/B prior to surgery average level of IGF-1 was not different from that of the patients without antibodies (32,6 ± 27,6 and 22,3 ± 29,6 μg/l respectively, p = 0,4. One month after LT level of IGF-1 has increased both in the general group, and in patients with AB0c and AV0i liver (92,1 ± 77,8 and 131,2 ± 106,7 μg/l respectively, p = 0,09. The level of IGF-1 was not varied in the group with antibodies

Possible roles of insulin, IGF-1 and IGFBPs in initiation and progression of colorectal cancer

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Jiang, Bo; Zhang, Xin; Du, Li-Li; Wang, Yan; Liu, Dong-Bo; Han, Cun-Zhi; Jing, Jie-Xian; Zhao, Xian-Wen; Xu, Xiao-Qin

2014-01-01

AIM: To investigate the roles of serum insulin, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding proteins (IGFBPs) in the initiation and progression of colorectal cancer. METHODS: We determined serum insulin, IGF-1 and IGFBPs levels in 615 colorectal cancer patients and 650 control healthy donors by enzyme-linked immunosorbent assay (ELISA). In the meantime, their body mass index (BMI) and waist-to-hip ratio (WHR) were measured. RESULTS: Serum levels of insulin and IGF-1 as well as IGF-1/IGFBP-3 ratio in pre-operation patients were significantly elevated, but the level of IGFBP-3 was significantly decreased compared with normal controls and post-operation patients (P 0.05) in the levels of insulin, IGF-1, IGFBP-1, IGFBP-3 and IGF-1/IGFBP-3 between the patients with and without hepatic as well as distal abdominal metastases. WHR and BMI of colon cancer patients were positively and significantly correlated with the levels of insulin and IGF-1/IGFBP-3. In contrast, WHR and BMI were negatively correlated with IGFBP-3 level. CONCLUSION: The elevation of insulin, IGF-1 as well as IGF-1/IGFBP-3 ratio and the reduction of IGFBP-3 may be related to the initiation of colorectal cancer, but they are not related to the progression and outcome of the disease. PMID:24587638

IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla

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Ma, Shu; Liu, Genxia; Jin, Lin; Pang, Xiyao; Wang, Yanqiu; Wang, Zilu; Yu, Yan; Yu, Jinhua

2016-01-01

Insulin-like growth factor-1 (IGF-1) and its receptor IGF-1R play a paramount role in tooth/bone formation while hsa-let-7c actively participates in the osteogenic differentiation of mesenchymal stem cells. However, the interaction between IGF-1/IGF-1R and hsa-let-7c on the committed differentiation of stem cells from apical papilla (SCAPs) remains unclear. In this study, human SCAPs were isolated and treated with IGF-1 and hsa-let-7c over/low-expression viruses. The odonto/osteogenic differentiation of these stem cells and the involvement of mitogen-activated protein kinase (MAPK) pathway were subsequently investigated. Alizarin red staining showed that hsa-let-7c low-expression can significantly promote the mineralization of IGF-1 treated SCAPs, while hsa-let-7c over-expression can decrease the calcium deposition of IGF-1 treated SCAPs. Western blot assay and real-time reverse transcription polymerase chain reaction further demonstrated that the expression of odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, COL-I/COL-I, DSPP/DSP, and DMP-1/DMP-1) in IGF-1 treated SCAPs were significantly upregulated in Let-7c-low group. On the contrary, hsa-let-7c over-expression could downregulate the expression of these odonto/osteogenic markers. Moreover, western blot assay showed that the JNK and p38 MAPK signaling pathways were activated in Let-7c-low SCAPs but inhibited in Let-7c-over SCAPs. Together, the IGF-1/IGF-1R/hsa-let-7c axis can control the odonto/osteogenic differentiation of IGF-1-treated SCAPs via the regulation of JNK and p38 MAPK signaling pathways. PMID:27833148

Gene Expression of IGF1, IGF1R, and IGFBP3 in Epiretinal Membranes of Patients with Proliferative Diabetic Retinopathy: Preliminary Study

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Dorota Romaniuk

2013-01-01

Full Text Available The molecular mechanism formation of secondary epiretinal membranes (ERMs after proliferative diabetic retinopathy (PDR or primary idiopathic ERMs is still poorly understood. Therefore, the present study focused on the assessment of IGF1, IGF1R, and IGFBP3 mRNA levels in ERMs and PBMCs from patients with PDR. The examined group comprised 6 patients with secondary ERMs after PDR and the control group consisted of 11 patients with idiopathic ERMs. Quantification of IGF1, IGF1R, and IGFBP3 mRNAs was performed by real-time QRT-PCR technique. In ERMs, IGF1 and IGF1R mRNA levels were significantly higher in patients with diabetes compared to control subjects. In PBMCs, there were no statistically significant differences of IGF1, IGF1R, and IGFBP3 expression between diabetic and nondiabetic patients. In conclusion, our study indicated IGF1 and IGF1R differential expression in ERMs, but not in PBMCs, of diabetic and nondiabetic patients, suggesting that these factors can be involved in the pathogenesis or progression of proliferative vitreoretinal disorders. This trial is registered with NCT00841334.

Autophagy resolves early retinal inflammation in Igf1-deficient mice

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Ana I. Arroba

2016-09-01

Full Text Available Insulin-like growth factor-1 (IGF-1 is a growth factor with differentiating, anti-apoptotic and metabolic functions in the periphery, and anti-inflammatory properties in the nervous system. Mice that have mutations in the Igf1 gene, rendering the gene product inactive (Igf1−/−, present with age-related visual loss accompanied by structural alterations in the first synapses of the retinal pathway. Recent advances have revealed a crucial role of autophagy in immunity and inflammation. Keeping in mind this close relationship, we aimed to decipher these processes in the context of the defects that occur during ageing in the retina of Igf1−/− mice. Tnfa and Il1b mRNAs, and phosphorylation of JNK and p38 MAPK were elevated in the retinas of 6- and 12-month old Igf1−/− mice compared to those in age-matched Igf1+/+ controls. In 6-month-old Igf1−/− retinas, increased mRNA levels of the autophagy mediators Becn1, Atg9, Atg5 and Atg4, decreased p62 (also known as SQSTM1 protein expression together with an increased LC3-II:LC3-I ratio reflected active autophagic flux. However, in retinas from 12-month-old Igf1−/− mice, Nlrp3 mRNA, processing of the IL1β pro-form and immunostaining of active caspase-1 were elevated compared to those in age-matched Igf1+/+ controls, suggesting activation of the inflammasome. This effect concurred with accumulation of autophagosomes and decreased autophagic flux in the retina. Microglia localization and status of activation in the retinas of 12-month-old Igf1+/+ and Igf1−/− mice, analyzed by immunostaining of Cd11b and Iba-1, showed a specific distribution pattern in the outer plexiform layer (OPL, inner plexiform layer (IPL and inner nuclear layer (INL, and revealed an increased number of activated microglia cells in the retina of 12-month-old blind Igf1−/− mice. Moreover, reactive gliosis was exclusively detected in the retinas from 12-month-old blind Igf1−/− mice. In conclusion, this study

Experimental approach to IGF-1 therapy in CCl4-induced acute liver damage in healthy controls and mice with partial IGF-1 deficiency.

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Morales-Garza, Luis A; Puche, Juan E; Aguirre, Gabriel A; Muñoz, Úrsula; García-Magariño, Mariano; De la Garza, Rocío G; Castilla-Cortazar, Inma

2017-05-04

Cell necrosis, oxidative damage, and fibrogenesis are involved in cirrhosis development, a condition in which insulin-like growth factor 1 (IGF-1) levels are diminished. This study evaluates whether the exogenous administration of low doses of IGF-1 can induce hepatoprotection in acute carbon tetrachloride (CCl 4 )-induced liver damage compared to healthy controls (Wt Igf +/+ ). Additionally, the impact of IGF-1 deficiency on a damaged liver was investigated in mice with a partial deficit of this hormone (Hz Igf1 +/- ). Three groups of 25 ± 5-week-old healthy male mice (Wt Igf +/+ ) were included in the protocol: untreated controls (Wt). Controls that received CCl 4 (Wt + CCl 4 ) and Wt + CCl 4 were treated subcutaneously with IGF-1 (2 µg/100 g body weight/day) for 10 days (Wt + CCl 4  + IGF1). In parallel, three IGF-1-deficient mice (Hz Igf1 +/- ) groups were studied: untreated Hz, Hz + CCl 4 , and Hz + CCl 4  + IGF-1. Microarray and real-time quantitative polymerase chain reaction (RT-qPCR) analyses, serum aminotransferases levels, liver histology, and malondialdehyde (MDA) levels were assessed at the end of the treatment in all groups. All data represent mean ± SEM. An altered gene coding expression pattern for proteins of the extracellular matrix, fibrosis, and cellular protection were found, as compared to healthy controls, in which IGF-1 therapy normalized in the series including healthy mice. Liver histology showed that Wt + CCl 4  + IGF1 mice had less oxidative damage, fibrosis, lymphocytic infiltrate, and cellular changes when compared to the Wt + CCl 4 . Moreover, there was a correlation between MDA levels and the histological damage score (Pearson's r = 0.858). In the IGF-1-deficient mice series, similar findings were identified, denoting a much more vulnerable hepatic parenchyma. IGF1 treatment improved the biochemistry, histology, and genetic expression of pro-regenerative and cytoprotective factors in both series

Higher circulating levels of IGF-1 are associated with longer leukocyte telomere length in healthy subjects

DEFF Research Database (Denmark)

Barbieri, Michelangela; Paolisso, Giuseppe; Kimura, Masayuki

2009-01-01

Mutations that inhibit the insulin-like growth factor-1 (IGF-1) extend the lifespan of worms, flies and mice. However, it appears that relatively low circulating levels of IGF-1 in humans are associated with aging-related diseases and diminished longevity. As leukocyte telomere length (LTL) is os...

Serum levels of IGF-1 are related to human skin characteristics including the conspicuousness of facial pores.

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Sugiyama-Nakagiri, Y; Naoe, A; Ohuchi, A; Kitahara, T

2011-04-01

Conspicuous facial pores are one type of serious aesthetic defects for many women. However, the mechanism(s) that underlie the conspicuousness of facial pores remains unclear. We previously characterized the epidermal architecture around facial pores that correlates with the appearance of those pores in various ethnic groups including Japanese. The goal of this study was to evaluate the possible relationships between facial pore size, the severity of impairment of epidermal architecture around facial pores and sebum output levels to investigate the possible role of IGF-1 in the pathogenesis of conspicuous facial pores. The subjects consisted of 38 healthy Japanese women (aged 22-41 years). IGF-1 was measured using immunoradiometric assay. Surface replicas were collected to compare pore sizes of cheek skin and horizontal cross-section images of cheek skin were obtained non-invasively from the same subjects using in vivo confocal laser scanning microscopy and the severity of impairment of epidermal architecture around facial pores was determined. The skin surface lipids of each subject were collected from their cheeks and lipid classes were determined using gas chromatography/flame ionization detection. The serum level of IGF-1 correlated significantly with total pore area (R = 0.36, P facial pores (R = 0.43, P pore area (R = 0.32, P facial skin characteristics including facial pore size and with the severity of impairment of epidermal architecture around facial pores. © 2010 The Authors. Journal compilation © 2010 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Insulin-like growth factor 1 (IGF1) and its active peptide (1-3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms.

LENUS (Irish Health Repository)

Corvin, Aiden P

2012-06-27

Insulin-like growth factor-1 (IGF1) and its active peptide (1-3)IGF1 modulate brain growth and plasticity and are candidate molecules for treatment of brain disorders. IGF1 N-terminal portion is naturally cleaved to generate the tri-peptide (1-3)IGF1 (glycine-praline-glutamate). IGF1 and (1-3)IGF have been proposed as treatment for neuropathologies, yet their effect on nerve cells has not been directly compared. In this study we examine the effects of IGF1 and (1-3)IGF1 in primary cortical cultures and measure the expression levels of markers for intracellular pathways and synaptic function. We find that both treatments activate the IGF1 receptor and enhance the expression of synaptic markers, however, they activate different intracellular pathways. Furthermore, (1-3)IGF1 administration increases the expression of endogenous IGF1, suggesting a direct interaction between the two molecules. The results show that the two molecules increase the expression of synaptic proteins through activating different cellular mechanisms.

Human GH Receptor-IGF-1 Receptor Interaction: Implications for GH Signaling

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Gan, Yujun; Buckels, Ashiya; Liu, Ying; Zhang, Yue; Paterson, Andrew J.; Jiang, Jing; Zinn, Kurt R.

2014-01-01

GH signaling yields multiple anabolic and metabolic effects. GH binds the transmembrane GH receptor (GHR) to activate the intracellular GHR-associated tyrosine kinase, Janus kinase 2 (JAK2), and downstream signals, including signal transducer and activator of transcription 5 (STAT5) activation and IGF-1 gene expression. Some GH effects are partly mediated by GH-induced IGF-1 via IGF-1 receptor (IGF-1R), a tyrosine kinase receptor. We previously demonstrated in non-human cells that GH causes formation of a GHR-JAK2-IGF-1R complex and that presence of IGF-1R (even without IGF-1 binding) augments proximal GH signaling. In this study, we use human LNCaP prostate cancer cells as a model system to further study the IGF-1R's role in GH signaling. GH promoted JAK2 and GHR tyrosine phosphorylation and STAT5 activation in LNCaP cells. By coimmunoprecipitation and a new split luciferase complementation assay, we find that GH augments GHR/IGF-1R complex formation, which is inhibited by a Fab of an antagonistic anti-GHR monoclonal antibody. Short hairpin RNA-mediated IGF-1R silencing in LNCaP cells reduced GH-induced GHR, JAK2, and STAT5 phosphorylation. Similarly, a soluble IGF-1R extracellular domain fragment (sol IGF-1R) interacts with GHR in response to GH and blunts GH signaling. Sol IGF-1R also markedly inhibits GH-induced IGF-1 gene expression in both LNCaP cells and mouse primary osteoblast cells. On the basis of these and other findings, we propose a model in which IGF-1R augments GH signaling by allowing a putative IGF-1R-associated molecule that regulates GH signaling to access the activated GHR/JAK2 complex and envision sol IGF-1R as a dominant-negative inhibitor of this IGF-1R-mediated augmentation. Physiological implications of this new model are discussed. PMID:25211187

Inhibition of p70S6K1 Activation by Pdcd4 Overcomes the Resistance to an IGF-1R/IR Inhibitor in Colon Carcinoma Cells.

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Zhang, Yan; Wang, Qing; Chen, Li; Yang, Hsin-Sheng

2015-03-01

Agents targeting insulin-like growth factor 1 receptor (IGF-1R) are being actively examined in clinical trials. Although there has been some initial success of single-agent targeting IGF-1R, attempts in later studies failed because of resistance. This study aimed to understand the effects of programmed cell death 4 (Pdcd4) on the chemosensitivity of the IGF-1R inhibitor OSI-906 in colorectal cancer cells and the mechanism underlying this impact. Using OSI-906-resistant and -sensitive colorectal cancer cells, we found that the Pdcd4 level directly correlates with cell chemosensitivity to OSI-906. In addition, tumors derived from Pdcd4 knockdown cells resist the growth inhibitory effect of OSI-906 in a colorectal cancer xenograft mouse model. Moreover, Pdcd4 enhances the antiproliferative effect of OSI-906 in resistant cells through suppression of p70S6K1 activation. Knockdown of p70S6K1, but not p70S6K2, significantly increases the chemosensitivity of OSI-906 in cultured colorectal cancer cells. Furthermore, the combination of OSI-906 and PF-4708671, a p70S6K1 inhibitor, efficiently suppresses the growth of OSI-906-resistant colon tumor cells in vitro and in vivo. Taken together, activation of p70S6K1 that is inhibited by Pdcd4 is essential for resistance to the IGF-1R inhibitor in colon tumor cells, and the combinational treatment of OSI-906 and PF-4708671 results in enhanced antiproliferation effects in colorectal cancer cells in vitro and in vivo, providing a novel venue to overcome the resistance to the IGF-1R inhibitor in treating colorectal cancer. ©2015 American Association for Cancer Research.

Elevated Serum Levels of IGF-1 Are Sufficient to Establish Normal Body Size and Skeletal Properties Even in the Absence of Tissue IGF-1

OpenAIRE

Elis, Sebastien; Courtland, Hayden-William; Wu, Yingjie; Rosen, Clifford J; Sun, Hui; Jepsen, Karl J; Majeska, Robert J; Yakar, Shoshana

2010-01-01

Use of recombinant insulin-like growth factor 1 (IGF-1) as a treatment for primary IGF-1 deficiency in children has become increasingly common. When untreated, primary IGF-1 deficiency may lead to a range of metabolic disorders, including lipid abnormalities, insulin resistance, and decreased bone density. To date, results of this therapy are considered encouraging; however, our understanding of the role played by IGF-1 during development remains limited. Studies on long-term treatment with r...

A dynamic ribosomal biogenesis response is not required for IGF-1-mediated hypertrophy of human primary myotubes.

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Crossland, Hannah; Timmons, James A; Atherton, Philip J

2017-12-01

Increased ribosomal DNA transcription has been proposed to limit muscle protein synthesis, making ribosome biogenesis central to skeletal muscle hypertrophy. We examined the relationship between ribosomal RNA (rRNA) production and IGF-1-mediated myotube hypertrophy in vitro Primary skeletal myotubes were treated with IGF-1 (50 ng/ml) with or without 0.5 µM CX-5461 (CX), an inhibitor of RNA polymerase I. Myotube diameter, total protein, and RNA and DNA levels were measured along with markers of RNA polymerase I regulatory factors and regulators of protein synthesis. CX treatment reduced 45S pre-rRNA expression (-64 ± 5% vs. IGF-1; P IGF-1; P IGF-1-treated myotubes. IGF-1-mediated increases in myotube diameter (1.27 ± 0.09-fold, P IGF-1 treatment did not prevent early increases in AKT (+203 ± 39% vs. CX; P IGF-1, myotube diameter and protein accretion were sustained. Thus, while ribosome biogenesis represents a potential site for the regulation of skeletal muscle protein synthesis and muscle mass, it does not appear to be a prerequisite for IGF-1-induced myotube hypertrophy in vitro. -Crossland, H., Timmons, J. A., Atherton, P. J. A dynamic ribosomal biogenesis response is not required for IGF-1-mediated hypertrophy of human primary myotubes. © The Author(s).

Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty

DEFF Research Database (Denmark)

Juul, A; Scheike, Thomas Harder; Nielsen, C T

1995-01-01

between IGF-I and IGFBP-3 (i.e. free biologically active IGF-I) declined concomitantly with a decrease in growth velocity. Serum levels of IGF-I and IGFBP-3 (expressed as the SD score for bone age), but not those of estradiol, correlated with height velocity before and during treatment (r = 0.34; P ...Central precocious puberty (CPP) is characterized by early activation of the pituitary-gonadal axis, which leads to increased growth velocity and development of secondary sexual characteristics. It is generally believed that gonadal sex steroids stimulate pulsatile GH secretion, which, in turn......, stimulates insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) production. However, little is known about GH, IGF-I, and IGFBP-3 serum levels in children with precocious puberty. Treatment of CPP by GnRH agonists has become the treatment of choice. However, the effect of long term...

IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway

Energy Technology Data Exchange (ETDEWEB)

Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Takahashi, Yutaka, E-mail: takahash@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)

2012-08-24

Highlights: Black-Right-Pointing-Pointer Cellular senescence plays an important role in tumorigenesis and aging process. Black-Right-Pointing-Pointer We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. Black-Right-Pointing-Pointer IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. Black-Right-Pointing-Pointer These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated {beta}-galactosidase (SA-{beta}-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, {gamma}H2AX, the increased levels of p53 and p21 proteins, and activated SA-{beta}-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-{beta}-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

IGF-I enhances cellular senescence via the reactive oxygen species–p53 pathway

International Nuclear Information System (INIS)

Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro; Takahashi, Yutaka

2012-01-01

Highlights: ► Cellular senescence plays an important role in tumorigenesis and aging process. ► We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. ► IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. ► These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated β-galactosidase (SA-β-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, γH2AX, the increased levels of p53 and p21 proteins, and activated SA-β-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-β-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

IGF-1 promotes the development and cytotoxic activity of human NK cells

Science.gov (United States)

Ni, Fang; Sun, Rui; Fu, Binqing; Wang, Fuyan; Guo, Chuang; Tian, Zhigang; Wei, Haiming

2013-01-01

Insulin-like growth factor 1 (IGF-1) is a critical regulator of many physiological functions, ranging from longevity to immunity. However, little is known about the role of IGF-1 in natural killer cell development and function. Here, we identify an essential role for IGF-1 in the positive regulation of human natural killer cell development and cytotoxicity. Specifically, we show that human natural killer cells have the ability to produce IGF-1 and that differential endogenous IGF-1 expression leads to disparate cytotoxicity in human primary natural killer cells. Moreover, miR-483-3p is identified as a critical regulator of IGF-1 expression in natural killer cells. Overexpression of miR-483-3p has an effect similar to IGF-1 blockade and decreased natural killer cell cytotoxicity, whereas inhibition of miR-483-3p has the opposite effect, which is reversible with IGF-1 neutralizing antibody. These findings indicate that IGF-1 and miR-483-3p belong to a new class of natural killer cell functional modulators and strengthen the prominent role of IGF-1 in innate immunity. PMID:23403580

Rufinamide, an antiepileptic drug, improves cognition and increases neurogenesis in the aged gerbil hippocampal dentate gyrus via increasing expressions of IGF-1, IGF-1R and p-CREB.

Science.gov (United States)

Chen, Bai Hui; Ahn, Ji Hyeon; Park, Joon Ha; Song, Minah; Kim, Hyunjung; Lee, Tae-Kyeong; Lee, Jae Chul; Kim, Young-Myeong; Hwang, In Koo; Kim, Dae Won; Lee, Choong-Hyun; Yan, Bing Chun; Kang, Il Jun; Won, Moo-Ho

2018-04-25

Rufinamide is a novel antiepileptic drug and commonly used in the treatment of Lennox-Gastaut syndrome. In the present study, we investigated effects of rufinamide on cognitive function using passive avoidance test and neurogenesis in the hippocampal dentate gyrus using Ki-67 (a marker for cell proliferation), doublecortin (DCX, a marker for neuroblast) and BrdU/NeuN (markers for newly generated mature neurons) immunohistochemistry in aged gerbils. Aged gerbils (24-month old) were treated with 1 mg/kg and 3 mg/kg rufinamide for 4 weeks. Treatment with 3 mg/kg rufinamide, not 1 mg/kg rufinamide, significantly improved cognitive function and increased neurogenesis, showing that proliferating cells (Ki-67-immunoreactive cells), differentiating neuroblasts (DCX-immunoreactive neuroblasts) and mature neurons (BrdU/NeuN-immunoreactive cells) in the aged dentate gyrus compared with those in the control group. When we examined its mechanisms, rufinamide significantly increased immunoreactivities of insulin-like growth factor-1 (IGF-1), its receptor (IGF-1R), and phosphorylated cAMP response element binding protein (p-CREB). However, rufinamide did not show any increase in immunoreactivities of brain-derived neurotrophic factor and its receptor. Therefore, our results indicate that rufinamide can improve cognitive function and increase neurogenesis in the hippocampus of the aged gerbil via increasing expressions of IGF-1, IGF-1R and p-CREB. Copyright © 2018 Elsevier B.V. All rights reserved.

Circulating levels of IGF1 are associated with muscle strength in middle-aged- and oldest-old women

NARCIS (Netherlands)

Taekema, Diana G.; Ling, Carolina H Y; Blauw, Gerard Jan; Meskers, Carel G.; Westendorp, Rudi G J; De Craen, Anton J M; Maier, Andrea B.

2011-01-01

Objective: In aging populations, poor handgrip strength has been associated with physical disability and mortality. IGF1 is an important mediator of muscle growth and regeneration affecting muscle function. We studied the relationship between circulating levels of IGF1, its binding protein 3

Investigation on the role of IGF-1 signal transduction in the biological radiation responses

Energy Technology Data Exchange (ETDEWEB)

Jung, U Hee; Jo, Sung Kee; Park, Hae Ran; Oh, Soo Jin; Cho, Eun Hee; Eom, Hyun Soo; Ju, Eun Jin

2009-05-15

Effects of {gamma}-irradiation on the IGF-1 related gene expressions and activations in various cell lines - Various expression patterns of IGF-1 and IGF-1R following {gamma}-irradiation were observed according to the cell lines - The increased expressions of IGF-1 and IGF-1R were observed in Balb/3T3 and NIH/3T3 cells - Among the IGF-1 downstream signaling molecules, the phosphorylated ERK5 were not changed by {gamma}-irradiation in all three examined cell lines, whereas the phosphorylated p65 were increased by {gamma} -irradiation in all cell lines. The role of IGF-1 and p38 signaling in {gamma}-irradiated mouse embryonic fibroblast (MEF) cells - In MEF cells, IGF-1 signaling molecules were decreased and p21/phosphorylated p38 were increased by {gamma}-irradiation - The experiments with IGF-1R inhibitor (AG1024) and p38 inhibitor (SB203580) revealed that IGF-1 signaling is involved but not essential in radiation-induced cell growth arrest and senescence and that p38 MAP kinase play a important role in this cellular radiation response. The role of IGF-1 and p38 signaling in {gamma}-irradiated mouse fibroblast (NIH/3T3) cell - In NIH/3T3 cells, IGF-1 signaling molecules and p21/phosphorylated p38 were increased by {gamma} -irradiation. - However, the experiments with IGF-1R inhibitor (AG1024) and p38 inhibitor (SB203580) revealed that IGF-1 and p38 signaling do not play a crucial role in radiation-induced cell growth arrest and senescence in NIH/3T3 cells. Effects of {gamma}-irradiation on the expressions and activations on the genes related to the IGF-1 signaling in mouse tissues - In {gamma}-irradiated mice, the increased expressions of IGF-1 and IGF-1R were observed in the lung and kidney at 2 months after irradiation, and in all the tissues examined (lung, liver and kidney) at 6 months after irradiation. - In the lung of {gamma}-irradiated mice at 6 months after irradiation, the increases of IGF-1R, phosphorylated FOXO3a, p65, p38, p21 were observed. - The

Investigation on the role of IGF-1 signal transduction in the biological radiation responses

International Nuclear Information System (INIS)

Jung, U Hee; Jo, Sung Kee; Park, Hae Ran; Oh, Soo Jin; Cho, Eun Hee; Eom, Hyun Soo; Ju, Eun Jin

2009-05-01

Effects of γ-irradiation on the IGF-1 related gene expressions and activations in various cell lines - Various expression patterns of IGF-1 and IGF-1R following γ-irradiation were observed according to the cell lines - The increased expressions of IGF-1 and IGF-1R were observed in Balb/3T3 and NIH/3T3 cells - Among the IGF-1 downstream signaling molecules, the phosphorylated ERK5 were not changed by γ-irradiation in all three examined cell lines, whereas the phosphorylated p65 were increased by γ -irradiation in all cell lines. The role of IGF-1 and p38 signaling in γ-irradiated mouse embryonic fibroblast (MEF) cells - In MEF cells, IGF-1 signaling molecules were decreased and p21/phosphorylated p38 were increased by γ-irradiation - The experiments with IGF-1R inhibitor (AG1024) and p38 inhibitor (SB203580) revealed that IGF-1 signaling is involved but not essential in radiation-induced cell growth arrest and senescence and that p38 MAP kinase play a important role in this cellular radiation response. The role of IGF-1 and p38 signaling in γ-irradiated mouse fibroblast (NIH/3T3) cell - In NIH/3T3 cells, IGF-1 signaling molecules and p21/phosphorylated p38 were increased by γ -irradiation. - However, the experiments with IGF-1R inhibitor (AG1024) and p38 inhibitor (SB203580) revealed that IGF-1 and p38 signaling do not play a crucial role in radiation-induced cell growth arrest and senescence in NIH/3T3 cells. Effects of γ-irradiation on the expressions and activations on the genes related to the IGF-1 signaling in mouse tissues - In γ-irradiated mice, the increased expressions of IGF-1 and IGF-1R were observed in the lung and kidney at 2 months after irradiation, and in all the tissues examined (lung, liver and kidney) at 6 months after irradiation. - In the lung of γ-irradiated mice at 6 months after irradiation, the increases of IGF-1R, phosphorylated FOXO3a, p65, p38, p21 were observed. - The patterns of altered expressions showed significant

Shifting the IGF-axis: An age-related decline in human tear IGF-1 correlates with clinical signs of dry eye.

Science.gov (United States)

Patel, Roshni; Zhu, Meifang; Robertson, Danielle M

2018-02-06

The human corneal epithelium expresses both the insulin-like growth factor type 1 receptor (IGF-1R) and the IGF-1R/insulin receptor (INSR) hybrid. Despite the previous identification of IGF-1 in human tear fluid, little is known regarding the regulation of IGF-1 in tear fluid and its role in corneal epithelial homeostasis. In the present study, we investigated the impact of biological parameters on the concentration of human tear levels of IGF-1. Tear levels of IGF-1 were measured in 41 healthy, human volunteers without any reported symptoms of dry eye. All volunteers underwent standard biomicroscopic examination of the cornea and tear film. In a subgroup of volunteers, corneal staining with sodium fluorescein, tear film break up time and tear production using a Schirmer's test strip were measured to assess clinical signs of dry eye. Tears were collected from the inferior tear meniscus using glass microcapillary tubes and IGF-1 levels were measured using a solid phase sandwich ELISA. Tear levels of IGF-1 were highest in young adults and significantly decreased in older adults (P = 0.003). There were no differences in tear IGF-1 between males and females (P = 0.628). Tear IGF-1 levels were correlated with tear film break up time (R = 0.738) and tear production (R = 0.826). These data indicate that there is a progressive decline in tear IGF-1 due to aging that is associated with clinical signs of dry eye. This effect is likely due to age-related changes in the lacrimal gland. Copyright © 2018 Elsevier Ltd. All rights reserved.

Decreased IGF-1 concentration during the first trimester of pregnancy in women with normal somatotroph function.

Science.gov (United States)

Persechini, Marie-Laure; Gennero, Isabelle; Grunenwald, Solange; Vezzosi, Delphine; Bennet, Antoine; Caron, Philippe

2015-08-01

A decrease of insulin-like growth factor-I levels (IGF-I) has been reported during the first trimester of pregnancy in women with acromegaly before the secretion of placental growth hormone (GH) progressively increases IGF-1 concentration. To evaluate variations of concentrations of IGF-1, insulin-like growth factor (IGF)-binding protein-3 (IGF-BP3) and GH during the first trimester of pregnancy in women with normal somatotroph function. Sixteen women (median age 31 years) with as who were followed for benign thyroid disorders (n = 15) or prolactin-secreting microadenoma (n = 1) were evaluated before and in the first trimester of pregnancy. Serum concentrations of GH, IGF-1, IGF-BP3, TSH and estradiol (E2) were measured before and in the first trimester (5.4 ± 2.2 weeks of gestation). Before pregnancy, somatotroph and thyroid functions (median TSH 1.2 mU/L) were normal in all women. At the first trimester IGF-1 levels decreased significantly (before = 210 ng/mL, first trimester = 145 ng/mL, p function, IGF-1 levels decrease in the first trimester of pregnancy without changes in GH or IGF-BP3 levels. These results confirm liver resistance to GH as a consequence of the physiological increase of estrogens during the first trimester.

Changes in circulating level of IGF-I and IGF-binding protein-1 from the first to second trimester as predictors of preeclampsia

DEFF Research Database (Denmark)

Vatten, Lars J; Nilsen, Tom I L; Juul, Anders

2008-01-01

To assess whether circulating IGF-I and IGF-binding protein-1 (IGFBP-1) in the first and second trimester are associated with subsequent risk of preterm and term preeclampsia.......To assess whether circulating IGF-I and IGF-binding protein-1 (IGFBP-1) in the first and second trimester are associated with subsequent risk of preterm and term preeclampsia....

Serum insulin-like growth factor-I (IGF-I) levels during long-term IGF-I treatment of children and adults with primary GH resistance (Laron syndrome).

Science.gov (United States)

Laron, Z; Klinger, B; Silbergeld, A

1999-01-01

Serum IGF-I levels were measured in 14 patients (9 children and 5 adults) with Laron syndrome (LS) during long-term treatment by IGF-I. Recombinant IGF-I (FK-780, Fujisawa Pharmaceutical Co. Ltd., Japan) was administered once daily subcutaneously before breakfast for 3-5 years to the children and for 9 months to the adults. The initial daily dose was 150 micrograms/kg for children and 120 micrograms/kg for adults. Before initiation of treatment the mean overnight fasting levels of serum IGF-I in the children was 3.2 +/- 0.8 nmol/l (mean +/- SEM), rising to 10 +/- 1.7 nmol/l during long-term treatment even on a dose of 120 micrograms/kg/day. The serum IGF-I levels 4 hours after injection rose from 31.2 +/- 3.5 to 48 +/- 2 nmol/l. In the adult patients, the initial basal IGF-I was 4.1 +/- 0.7 nmol/l, rising to 16.1 +/- 3.84 nmol/l after 8-9 months treatment. Serum IGF-I levels at 4 hours after injection rose in the adult patients from 24.1 +/- 5.8 up to 66.8 +/- 15.4 nmol/l. A progressively increasing half-life during long term exogenous administration of IGF-I to patients with Laron syndrome was demonstrated by following serum IGF-I dynamics after injection. Based on the fact that no antibodies to IGF-I were detected and on findings in previous studies, it is speculated that the increasing serum IGF-I levels during long-term IGF-I treatment are caused by an increase in serum IGFBP-3 induced by chronic IGF-I administration. It is concluded that treatment with IGF-I necessitates regular monitoring of serum IGF-I levels; in patients in whom the age adjusted maximal levels are exceeded, a reduction of the daily IGF-I dose is indicated to avoid undesirable effects.

Exercise and obesity in fibromyalgia: beneficial roles of IGF-1 and resistin?

Science.gov (United States)

Bjersing, Jan L; Erlandsson, Malin; Bokarewa, Maria I; Mannerkorpi, Kaisa

2013-02-27

Severe fatigue is a major health problem in fibromyalgia (FM). Obesity is common in FM, but the influence of adipokines and growth factors is not clear. The aim was to examine effects of exercise on fatigue, in lean, overweight and obese FM patients. In a longitudinal study, 48 FM patients (median 52 years) exercised for 15 weeks. Nine patients were lean (body mass index, BMI 18.5 to 24.9), 26 overweight (BMI 25 to 29.9) and 13 obese. Fatigue was rated on a 0 to 100 mm scale (fibromyalgia impact questionnaire [FIQ] fatigue) and multidimensional fatigue inventory (MFI-20) general fatigue (MFIGF). Higher levels in FIQ fatigue and MFIGF indicate greater degree of fatigue. Free and total IGF-1, neuropeptides, adipokines were determined in serum and cerebrospinal fluid (CSF). Baseline FIQ fatigue correlated negatively with serum leptin (r=-0.345; P=0.016) and nerve growth factor (NGF; r=-0.412; P=0.037). In lean patients, baseline MFIGF associated negatively with serum resistin (r=-0.694; P=0.038). FIQ Fatigue associated negatively with CSF resistin (r=-0.365; P=0.073). Similarly, FIQ fatigue (r=-0.444; P=0.026) and MFIGF correlated negatively with CSF adiponectin (r=-0.508; P=0.01). In lean patients, FIQ fatigue (P=0.046) decreased after 15 weeks. After 30 weeks, MFIGF decreased significantly in lean (MFIGF: P=0.017), overweight (MFIGF: P=0.001), and obese patients (MFIGF: P=0.016). After 15 weeks, total IGF-1 increased in lean (P=0.043) patients. ∆Total IGF-1 differed significantly between lean and obese patients (P=0.010). ∆Total IGF-1 related negatively with ∆MFIGF after 15 weeks (r=-0.329; P=0.050). After 30 weeks, ∆FIQ fatigue negatively correlated with ∆NGF (r=-0.463; P=0.034) and positively with ∆neuropeptide Y (NPY) (r=0.469; P=0.032). Resistin increased after 30 weeks (P=0.034). ∆MFIGF correlated negatively with ∆resistin (r=-0.346; P=0.031), being strongest in obese patients (r=-0.815; P=0.007). In obese patients, ∆FIQ fatigue after 30 weeks

Clinical significance of determination of serum IGF-I and SIL-2R levels in patients with prostatic cancer

International Nuclear Information System (INIS)

Zhang Zaigao; Lv Yuliang; Li Jiacheng

2006-01-01

Objective: To investigate the significance of changes of serum IGF-I and SIL-2R levels in patients with prostatic cancer. Methods: Serum IGF-I levels (with RIA) and SIL-2R levels (with ELISA) were measured in 31 patients with prostatic cancer and 30 controls. Results: Serum levels of IGF-I and SIL-2R in the 31 patients were significantly higher than those in controls (P<0.01), serum IGF-I and SIL-2R levels were mutually positively correlated (r=0.6182, P<0.01). Conclusion: Serum IGF-I and SIL-2R were useful markers for prostatic cancer. (authors)

Study on the correlationship between serum IGF-I and HA, PIIIP levels in patients with chronic hepatitis C

International Nuclear Information System (INIS)

Li Yong; Sun Yefu; Xia Aiping

2008-01-01

Objective: To study the inter-relationship between serum IGF-I and HA, PIIIP levels in patients with chronic hepatitis C. Methods: Serum IGF-I, HA and PIIIP levels were determined with RIA in 39 patients with chronic hepatitis C and 35 controls. Results: Serum IGF-I, HA and PIIIP levels in the patients were significantly higher than those in controls (P<0.01). The serum IGF-I levels and HA, PIIIP levels were mutually positively correlated (r=0.8018, 0.7126, P<0.01). Conclusion: Serum IGF-I, HA and PIIIP were useful diagnostic markers in patients with chronic hepatitis C. (authors)

Urinary growth hormone level and insulin-like growth factor-1 standard deviation score (IGF-SDS) can discriminate adult patients with severe growth hormone deficiency.

Science.gov (United States)

Hirohata, Toshio; Saito, Nobuhito; Takano, Koji; Yamada, So; Son, Jae-Hyun; Yamada, Shoko M; Nakaguchi, Hiroshi; Hoya, Katsumi; Murakami, Mineko; Mizutani, Akiko; Okinaga, Hiroko; Matsuno, Akira

2013-01-01

Adult growth hormone (GH) deficiency (AGHD) in Japan is diagnosed based on peak GH concentrations during GH provocative tests such as GHRP-2 stimulation test. In this study, we aimed to evaluate the ability of serum insulin-like growth factor-1 (sIGF-1) and urinary GH (uGH) at the time of awakening to diagnose AGHD. Fifty-nine patients with pituitary disease (32 men and 27 women; age 20-85 y (57.5 ± 15.5, mean ± SD) underwent GHRP-2 stimulation and sIGF-1 testing. Thirty-six and 23 patients were diagnosed with and without severe AGHD, respectively based on a peak GH response of standard deviation score (IGF-1 SDS) based on age and sex. We determined whether uGH levels in urine samples from 42 of the 59 patients at awakening were above or below the sensitivity limit. We evaluated IGF-1 SDS and uGH levels in a control group of 15 healthy volunteers. Values for IGF-1 SDS were significantly lower in patients with, than without (-2.07 ± 1.77 vs.-0.03 ± 0.92, mean ± SD; p -1.4. IGF-1 SDS discriminated AGHD more effectively in patients aged ≤60 years. The χ2 test revealed a statistical relationship between uGH and AGHD (test statistic: 7.0104 ≥ χ2 (1; 0.01) = 6.6349). When IGF-1 SDS is < -1.4 or uGH is below the sensitivity limit, AGHD can be detected with high sensitivity.

Relative IGF-1 and IGF-2 gene expression in maternal and fetal tissues from diabetic swine

International Nuclear Information System (INIS)

Wolverton, C.K.; Leaman, D.W.; White, M.E.; Ramsay, T.G.

1990-01-01

Fourteen pregnant, crossbred gilts were utilized in this study. Seven gilts were injected with alloxan (50 mg/kg) at day 75 of gestation to induce diabetes. Gilts underwent caesarean section on day 105 of gestation. Samples were collected from maternal skeletal muscle, adipose tissue, uterus and endometrium; and from fetal skeletal muscle, adipose tissue, placenta, liver, lung, kidney, heart, brain and spleen. Tissues were frozen in liquid nitrogen for later analysis of IGF-1 and IGF-2 gene expression. Samples were pooled and total RNA was isolated using the guanidine isothiocynate method. Total mRNA was analyzed by dot blot hybridization. Blots were probed with 32 P-cDNA for porcine IGF-1 and rat IGF-2. IGF-1 gene expression in maternal tissues was unaffected by diabetes. Maternal diabetes increased IGF-2 mRNA in maternal adipose tissue but exhibited no effect in muscle or uterus. Expression of IGF-2 by maternal endometrium was decreased by diabetes. Maternal diabetes induced an increase in IGF-1 gene expression in muscle and placenta while causing an increase in IGF-2 expression in fetal liver and placenta. IGF-2 mRNA was lower in lung from fetuses of diabetic mothers than in controls. These results suggest that maternal diabetes alters IGF-1 and IGF-2 gene expression in specific tissues and differential regulation of these genes appears to exist in the mother and developing fetus

Study on changes of serum leptin, IGF-I and IL-2 levels in elderly subjects with osteoporosis

International Nuclear Information System (INIS)

Sun Zihan; Luo Nanping; Niu Aijun; Qi Falian

2006-01-01

Objective: To investigate the changes of serum leptin, IGF-I and IL-2 levels in elderly subjects with osteoporosis. Methods: Serum leptin, IGF-I, IL-2 levels (with RIA), total cholesterol contents (with biochemical method) and bone mineral density (BMD) were examined in 65 aged patients with osteoporosis. Results: The serum leptin levels in subjects with osteoporosis were significantly higher than controls (P<0.01). The serum IGF-I and IL-2 levels in subjects with osteoporosis were significantly lower than those in controls (P<0.05, P<0.01). The BMD was positively correlated with the IGF-I levels and negatively correlated with leptin level. Conclusion: Derangement of leptin and IGF-I, IL-2 metabolism is one of the major causes of decreased bone mass and bone formation elderly subjects with osteoporosis. Measurement of serum levels of these parameters is of diagnostic help. (authors)

The single IGF-1 partial deficiency is responsible for mitochondrial dysfunction and is restored by IGF-1 replacement therapy.

Science.gov (United States)

Olleros Santos-Ruiz, M; Sádaba, M C; Martín-Estal, I; Muñoz, U; Sebal Neira, C; Castilla-Cortázar, I

2017-08-01

We previously described in cirrhosis and aging, both conditions of IGF-1 deficiency, a clear hepatic mitochondrial dysfunction with increased oxidative damage. In both conditions, the hepatic mitochondrial function was improved with low doses of IGF-1. The aim of this work was to explore if the only mere IGF-1 partial deficiency, without any exogenous insult, is responsible for hepatic mitochondrial dysfunction. Heterozygous (igf1 +/- ) mice were divided into two groups: untreated and treated mice with low doses of IGF-1. WT group was used as controls. Parameters of hepatic mitochondrial function were determined by flow cytometry, antioxidant enzyme activities were determined by spectrophotometry, and electron chain transport enzyme levels were determined by immunohistochemistry and immunofluorescence analyses. Liver expression of genes coding for proteins involved in mitochondrial protection and apoptosis was studied by microarray analysis and RT-qPCR. Hz mice showed a significant reduction in hepatic mitochondrial membrane potential (MMP) and ATPase activity, and an increase in intramitochondrial free radical production and proton leak rates, compared to controls. These parameters were normalized by IGF-1 replacement therapy. No significant differences were found between groups in oxygen consumption and antioxidant enzyme activities, except for catalase, whose activity was increased in both Hz groups. Relevant genes coding for proteins involved in mitochondrial protection and survival were altered in Hz group and were reverted to normal in Hz+IGF-1 group. The mere IGF-1 partial deficiency is per se associated with hepatic mitochondrial dysfunction sensitive to IGF-1 replacement therapy. Results in this work prove that IGF-1 is involved in hepatic mitochondrial protection, because it is able to reduce free radical production, oxidative damage and apoptosis. All these IGF-1 actions are mediated by the modulation of the expression of genes encoding citoprotective

HFpEF and HFrEF Display Different Phenotypes as Assessed by IGF-1 and IGFBP-1.

Science.gov (United States)

Faxén, Ulrika Ljung; Hage, Camilla; Benson, Lina; Zabarovskaja, Stanislava; Andreasson, Anna; Donal, Erwan; Daubert, Jean-Claude; Linde, Cecilia; Brismar, Kerstin; Lund, Lars H

2017-04-01

Anabolic drive is impaired in heart failure with reduced ejection fraction (HFrEF) but insufficiently studied in heart failure with preserved ejection fraction (HFpEF). Insulin-like growth factor 1 (IGF-1) mediates growth hormone effects and IGF binding protein 1 (IGFBP-1) regulates IGF-1 activity. We tested the hypothesis that HFpEF and HFrEF are similar with regard to IGF-1 and IGFBP-1. In patients with HFpEF (n = 79), HFrEF (n = 85), and controls (n = 136), we analyzed serum IGF-1 and IGFBP-1 concentrations, correlations, and associations with outcome. Age-standardized scores of IGF-1 were higher in HFpEF, median arbitrary units (interquartile range); 1.21 (0.57-1.96) vs HFrEF, 0.09 (-1.40-1.62), and controls, 0.22 (-0.47-0.96), P overall IGF-1 was associated with outcomes in HFrEF, hazard ratio per natural logarithmic increase in IGF-1 SD score 0.51 (95% confidence interval 0.32-0.82, P = .005), but not significantly in HFpEF. IGFBP-1 was not associated with outcomes in either HFpEF nor HFrEF. HFpEF and HFrEF phenotypes were similar with regard to increased IGFBP-1 concentrations but differed regarding IGF-1 levels and prognostic role. HFrEF and HFpEF may display different impairment in anabolic drive. Copyright © 2016 Elsevier Inc. All rights reserved.

IGF-1 Prevents Diastolic and Systolic Dysfunction Associated with Cardiomyopathy and Preserves Adrenergic Sensitivity

Science.gov (United States)

Roof, Steve R.; Boslett, James; Russell, Duncan; del Rio, Carlos; Alecusan, Joe; Zweier, Jay L.; Ziolo, Mark T.; Hamlin, Robert; Mohler, Peter J.; Curran, Jerry

2015-01-01

Aims Insulin-like growth factor 1 (IGF-1)-dependent signaling promotes exercise-induced physiological cardiac hypertrophy. However, the in vivo therapeutic potential of IGF-1 for heart disease is not well established. Here we test the potential therapeutic benefits of IGF-1 on cardiac function using an in vivo model of chronic catecholamine-induced cardiomyopathy. Methods Rats were perfused with isoproterenol via osmotic pump (1 mg/kg/day) and treated with 2 mg/kg IGF-1 (2 mg/kg/day, 6 days a week) for 2 or 4 weeks. Echocardiography, ECG, and blood pressure were assessed. In vivo pressure-volume loop studies were conducted at 4 weeks. Heart sections were analyzed for fibrosis and apoptosis, and relevant biochemical signaling cascades were assessed. Results After 4 weeks, diastolic function (EDPVR, EDP, tau, E/A ratio), systolic function (PRSW, ESPVR, dP/dtmax), and structural remodeling (LV chamber diameter, wall thickness) were all adversely affected in isoproterenol-treated rats. All these detrimental effects were attenuated in rats treated with Iso+IGF-1. Isoproterenol-dependent effects on BP were attenuated by IGF-1 treatment. Adrenergic sensitivity was blunted in isoproterenol-treated rats but was preserved by IGF-1 treatment. Immunoblots indicate that cardioprotective p110α signaling and activated Akt are selectively upregulated in Iso+IGF-1 treated hearts. Expression of iNOS was significantly increased in both the Iso and Iso+IGF-1 groups, however tetrahydrobiopterin (BH4) levels were decreased in the Iso group and maintained by IGF-1 treatment. Conclusion IGF-1 treatment attenuates diastolic and systolic dysfunction associated with chronic catecholamine-induced cardiomyopathy while preserving adrenergic sensitivity and promoting BH4 production. These data support the potential use of IGF-1 therapy for clinical applications for cardiomyopathies. PMID:26399932

Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in non-obese men and women: a randomized clinical trial

Science.gov (United States)

Young-onset calorie restriction (CR) in rodents decreases serum IGF-1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anti-cancer and anti-aging effects. However, little is known on the effects of CR on the IGF-1 system and c...

Application of determination of PRA, Ang II and IGF-1 levels in the study of typing of essential hypertension

International Nuclear Information System (INIS)

Lu Yongyi; Chen Qun; Yang Yongqing

2010-01-01

Objective: To study the clinical application of determination of plasma renin activity (PRA), Angiotensin II (Ang II ) and insulin-like growth factor-1 (IGF-1) levels in typing of essential hypertension (EH). Methods: Determined the levels of PRA and Aug II in 256 patients with EH and 70 healthy volunteers (as control group) by radioimmunoassay, and measured IGF-1 level by enzyme immunoassay. Research on the typing of EH and the difference between the groups. Results: The PRA and Ang II in control group was (0.432±0.236) μg·L -1 ·h -1 and (31.7±7.4) μg/L respectively. In 256 patients with EH, PRA was increased, normal and decreased in 18.0%, 71.8% and 10.2% respectively, while the level of Ang II was increased, normal and decreased in 12.9%, 76.2% and 10.9% respectively. The IGF-1 levels in 256 patients with EH were increased following the increase of blood pressure. Conclusion: Typing of EH patients with PRA and Ang II as well as the determination of IGF-1 were useful in treating and following up the patients with EH. (authors)

The role of IGF-1 and the distribution of body fat in decreasing the number of prostate rebiopsies.

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Morán, E; Martínez, M; Budía, A; Broseta, E; Cámara, R; Boronat, F

2017-03-01

To assess the usefulness of IGF-1 and internal organ fat measured by bioelectrical impedance audiometry to avoid rebiopsies in patients with persistently high prostate-specific antigen (PSA) levels. A prospective study was conducted with 92 patients who underwent prostate rebiopsy due to high PSA levels with negative results in the rectal examination and a lack of preneoplastic lesions. The patients previously had their IGF-1 levels measured and had undergone an impedance audiometry test using the abdominal Fat Analyser AB-140 TANITA system. We calculated the receiver operating characteristic (ROC) curves for the PSA levels, %PSA, internal organ fat and IGF-1 and PSA density. Twenty-five patients were diagnosed with prostate cancer. These patients had significantly higher PSA, PSAd and IGF-1 values and a tendency towards higher internal organ fat levels and lower %PSA readings (p=.001, p=.003, p=.001, p=.24 and P=0.28, respectively). The ROC curve showed an area under the curve for IGF-1 and PSA of .82 and .81, respectively. Using the cutoff points for 95% sensitivity and using the 3 criteria as an indication of rebiopsy, 74% of the biopsies would have been spared, leaving undiagnosed only 1 patient with clinically significant cancer -Gleason score>7 (4+3)-. The positive and negative predictive values for the set of variables were higher than for each one separately (PPV: 66/NPV: 63). The cost of both determinations was 82 euros. Our results suggest that measuring IGF-1 could significantly decrease the number of unnecessary rebiopsies in an inexpensive and safe manner. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

miR-130b-3p Modulates Epithelial-Mesenchymal Crosstalk in Lung Fibrosis by Targeting IGF-1.

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Li, Shuhong; Geng, Jing; Xu, Xuefeng; Huang, Xiaoxi; Leng, Dong; Jiang, Dingyuan; Liang, Jiurong; Wang, Chen; Jiang, Dianhua; Dai, Huaping

2016-01-01

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and usually lethal fibrotic lung disease with largely unknown etiology and pathogenesis. Evidence suggests microRNAs (miRNA) contribute to pathogenesis of IPF. In this study, we sought to identify miRNA expression signatures and determine the role of miR-130b-3p in lung fibrosis. The miRNA expression profile of the lungs from patients with IPF and normal donors was determined by Affymetrix microarray, and transcriptome with Affymetrix array. The functions and signal pathways as well as miRNA-mRNA networks were established by bioinformatics analysis. Luciferase assays and ELISA were used to confirm the miRNA target gene. The effect of miRNA-transfected epithelium on fibroblast activities was assessed using a co-culture system. The fibroblast activities were determined by qRT-PCR, western blotting, Transwell and BrdU assays. Seven miRNAs were significantly decreased in IPF lungs, with miR-130b-3p being the highest in the miRNA-mRNA network. Insulin-like growth factor (IGF-1) was a target gene of miR-130b-3p in the epithelium. miR-130b-3p inhibition in the epithelium induced collagen I expression and enhanced the proliferation and migration ability of fibroblast in co-culture systems, which mimicked the functions of exogenous IGF-1 on fibroblasts. Neutralizing IGF-1 with an antibody significantly reduced the modulatory effects of miR-130b-3p inhibitor-transfected epithelium on the activation of fibroblasts. Our results show that miR-130b-3p was downregulated in IPF lungs. miR-130b-3p downregulation contributed to the activation of fibroblasts and the dysregulated epithelial-mesenchymal crosstalk by promoting IGF-1 secretion from lung epithelium, suggesting a key regulatory role for this miRNA in preventing lung fibrosis.

Urinary growth hormone (U-GH) excretion and serum insulin-like growth factor 1 (IGF-1) in patients with alcoholic cirrhosis

DEFF Research Database (Denmark)

Møller, S; Grønbaek, M; Main, K

1993-01-01

was significantly higher in patients than in the healthy controls (p liver function assessed by modified Child-Turcotte score (p encephalopathy (p ...Basal serum growth hormone (GH) levels are elevated and insulin-like growth factor 1 (IGF-1) concentrations in serum are suppressed in patients with chronic liver disease. The aim of this study was to measure the urinary GH (U-GH) excretion and IGF-1 concentrations in patients with cirrhosis...... and correlated with liver function (p

Study on the relationship between serum TNF-α, IGF-I levels and lipid peroxidation in patients with fatty liver

International Nuclear Information System (INIS)

Li Yuqiang; Niu Guoping

2006-01-01

Objective: To assess the relationship between serum TNF-α, IGF-I levels and lipid peroxidation in patients with fatty liver. Methods: Serum TNF-α, IGF-I (with RIA) levels were examined in 44 patients with fatty liver and 30 controls. Ser- um levels of malondialdehyde (MDA), superoxidase (SOD) were measured with chemocolorimetry in these subjects. Results: Serum levels of TNF-α, IGF-I were significantly higher in patients with fatty liver than those in controls P<0.01 ), while the serum levels of MDA, SOD were significantly lower (P<0.01). Serum levels of IGF-I were negatively correlated with MDA levels ( r -0. 4132, P<0.05), TNF-α levels were positive correlated with MDA levels (r=0.4318, P<0.05). Conclusion: Lipid peroxidation was present in patients with fatty liver, with correlated changes of TNF-α and IGF-I levels. (authors)

The role of the IGF axis in IGFBP-1 and IGF-I induced renal enlargement in Snell dwarf mice

NARCIS (Netherlands)

M. van Kleffens (Marjolein); D.J. Lindenbergh-Kortleve (Dicky); J.G. Koster; J.W. van Neck (Han); A. Flyvbjerg (Allan); R. Rasch; S.L.S. Drop (Stenvert); S.C. van Buul-Offers

2001-01-01

textabstractInsulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is generally believed to inhibit IGF action in the circulation. In contrast, IGFBP-1 has been reported to interact with cell surfaces and enhance IGF-I action locally in some tissues. Renal IGFBP-1 levels are

The fetal programming effect of prenatal smoking on Igf1r and Igf1 methylation is organ- and sex-specific.

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Meyer, Karolin F; Verkaik-Schakel, Rikst Nynke; Timens, Wim; Kobzik, Lester; Plösch, Torsten; Hylkema, Machteld N

2017-01-01

The impact of prenatal smoke exposure (PSE) on DNA methylation has been demonstrated in blood samples from children of smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. As the identified differentially methylated genes can be associated with developmental processes, and insulin-like growth factors (IGFs) play a critical role in prenatal tissue growth, we hypothesized that PSE induces fetal programming of Igf1r and Igf1. Using a mouse model of smoking during pregnancy, we show that PSE alters promoter methylation of Igf1r and Igf1 and deregulates their gene expression in lung and liver of fetal (E17.5) and neonatal (D3) mouse offspring. By further comparing female versus male, lung versus liver, or fetal versus neonatal time point, our results demonstrate that CpG site-specific aberrant methylation patterns sex-dependently vary per organ and time point. Moreover, PSE reduces gene expression of Igf1r and Igf1, dependent on organ, sex, and offspring's age. Our results indicate that PSE may be a source of organ-specific rather than general systemic fetal programming. This is exemplified here by gene promoter methylation and mRNA levels of Igf1r and Igf1, together with a sex- and organ-specific naturally established correlation of both parameters that is affected by prenatal smoke exposure. Moreover, the comparison of fetuses with neonates suggests a CpG site-dependent reversibility/persistence of PSE-induced differential methylation patterns.

Dietary protein-induced hepatic IGF-1 secretion mediated by PPARγ activation.

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Wan, Xiaojuan; Wang, Songbo; Xu, Jingren; Zhuang, Lu; Xing, Kongping; Zhang, Mengyuan; Zhu, Xiaotong; Wang, Lina; Gao, Ping; Xi, Qianyun; Sun, Jiajie; Zhang, Yongliang; Li, Tiejun; Shu, Gang; Jiang, Qingyan

2017-01-01

Dietary protein or amino acid (AA) is a crucial nutritional factor to regulate hepatic insulin-like growth factor-1 (IGF-1) expression and secretion. However, the underlying intracellular mechanism by which dietary protein or AA induces IGF-1 expression remains unknown. We compared the IGF-1 gene expression and plasma IGF-1 level of pigs fed with normal crude protein (CP, 20%) and low-protein levels (LP, 14%). RNA sequencing (RNA-seq) was performed to detect transcript expression in the liver in response to dietary protein. The results showed that serum concentrations and mRNA levels of IGF-1 in the liver were higher in the CP group than in the LP group. RNA-seq analysis identified a total of 1319 differentially expressed transcripts (667 upregulated and 652 downregulated), among which the terms "oxidative phosphorylation", "ribosome", "gap junction", "PPAR signaling pathway", and "focal adhesion" were enriched. In addition, the porcine primary hepatocyte and HepG2 cell models also demonstrated that the mRNA and protein levels of IGF-1 and PPARγ increased with the increasing AA concentration in the culture. The PPARγ activator troglitazone increased IGF-1 gene expression and secretion in a dose dependent manner. Furthermore, inhibition of PPARγ effectively reversed the effects of the high AA concentration on the mRNA expression of IGF-1 and IGFBP-1 in HepG2 cells. Moreover, the protein levels of IGF-1 and PPARγ, as well as the phosphorylation of mTOR, significantly increased in HepG2 cells under high AA concentrations. mTOR phosphorylation can be decreased by the mTOR antagonist, rapamycin. The immunoprecipitation results also showed that high AA concentrations significantly increased the interaction of mTOR and PPARγ. In summary, PPARγ plays an important role in the regulation of IGF-1 secretion and gene expression in response to dietary protein.

S-nitrosylation of the IGF-1 receptor disrupts the cell proliferative action of IGF-1.

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Okada, Kazushi; Zhu, Bao-Ting

2017-09-30

The insulin-like growth factor 1 receptor (IGF-1R) is a disulfide-linked heterotetramer containing two α-subunits and two β-subunits. Earlier studies demonstrate that nitric oxide (NO) can adversely affect IGF-1 action in the central nervous system. It is known that NO can induce S-nitrosylation of the cysteine residues in proteins, thereby partly contributing to the regulation of protein function. In the present study, we sought to determine whether S-nitrosylation of the cysteine residues in IGF-1R is an important post-translational modification that regulates its response to IGF-1. Using cultured SH-SY5Y human neuroblastoma cells as an in vitro model, we found that treatment of cells with S-nitroso-cysteine (SNOC), a NO donor that can nitrosylate the cysteine residues in proteins, induces S-nitrosylation of the β subunit of IGF-1R but not its α-subunit. IGF-1Rβ S-nitrosylation by SNOC is coupled with increased dissociation of the IGF-1R protein complex. In addition, disruption of the IGF-1R function resulting from S-nitrosylation of the IGF-1Rβ subunit is associated with disruption of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways. Further, we observed that SNOC-induced IGF-1Rβ S-nitrosylation results in a dose-dependent inhibition of cell proliferation and survival. Together, these results suggest that elevated nitrosative stress may result in dysfunction of cellular IGF-1R signaling through S-nitrosylation of the cysteine residues in the IGF-1Rβ subunit, thereby disrupting the downstream PI3K and MAPK signaling functions and ultimately resulting in inhibition of cell proliferation and survival. Copyright © 2017. Published by Elsevier Inc.

IGF-1-dependent subunit communication of the IGF-1 holoreceptor: Interactions between αβ heterodimeric receptor halves

International Nuclear Information System (INIS)

Wilden, P.A.; Treadway, J.L.; Morrison, B.D.; Pessin, J.E.

1989-01-01

Examination of 125 I-IGF-1 affinity cross-linking and β-subunit autophosphorylation has indicated that IGF-1 induces a covalent association of isolated αβ heterodimeric IGF-1 receptors into an α 2 β 2 heterotetrameric state, in a similar manner to that observed for the insulin receptor. The formation of the α 2 β 2 heterotetrameric IGF-1 receptor complex from the partially purified αβ heterodimers was time dependent with half-maximal formation in approximately 30 min at saturating IGF-1 concentrations. The IGF-1-dependent association of the partially purified αβ heterodimers into an α 2 β 2 heterotetrameric state was specific for the IGF-1 receptors since IGF-1 was unable to stimulate the protein kinase activity of the purified αβ heterodimeric insulin receptor complex. Incubation of the α 2 β 2 heterotetrameric IGF-1 holoreceptor with the specific sulfhydryl agent iodoacetamide (IAN) did not alter 125 I-IGF-1 binding or IGF-1 stimulation of protein kinase activity. However, IAN treatment of the αβ heterodimeric IGF-1 receptors inhibited the IGF-1 dependent covalent formation of the disulfide-linked α 2 β 2 heterotetrameric complex. These data indicate that IGF-1 induces the covalent association of isolated αβ heterodimeric IGF-1 receptor complexes into a disulfide-linked α 2 β 2 heterotetrameric state whereas Mn/MgATP induces a noncovalent association. Therefore, unlike the insulin receptor in which noncovalent association is sufficient for kinase activation, only the covalent assembly of the IGF-1 receptor αβ heterodimers into the α 2 β 2 heterotetrameric holoreceptor complex is associated with ligand-stimulated protein kinase activation

Cyclic glycine-proline regulates IGF-1 homeostasis by altering the binding of IGFBP-3 to IGF-1

Science.gov (United States)

Guan, Jian; Gluckman, Peter; Yang, Panzao; Krissansen, Geoff; Sun, Xueying; Zhou, Yongzhi; Wen, Jingyuan; Phillips, Gemma; Shorten, Paul R.; McMahon, Chris D.; Wake, Graeme C.; Chan, Wendy H. K.; Thomas, Mark F.; Ren, April; Moon, Steve; Liu, Dong-Xu

2014-03-01

The homeostasis of insulin-like growth factor-1 (IGF-1) is essential for metabolism, development and survival. Insufficient IGF-1 is associated with poor recovery from wounds whereas excessive IGF-1 contributes to growth of tumours. We have shown that cyclic glycine-proline (cGP), a metabolite of IGF-1, can normalise IGF-1 function by showing its efficacy in improving the recovery from ischemic brain injury in rats and inhibiting the growth of lymphomic tumours in mice. Further investigation in cell culture suggested that cGP promoted the activity of IGF-1 when it was insufficient, but inhibited the activity of IGF-1 when it was excessive. Mathematical modelling revealed that the efficacy of cGP was a modulated IGF-1 effect via changing the binding of IGF-1 to its binding proteins, which dynamically regulates the balance between bioavailable and non-bioavailable IGF-1. Our data reveal a novel mechanism of auto-regulation of IGF-1, which has physiological and pathophysiological consequences and potential pharmacological utility.

Diagnostic value of combined tet of cPSA, IGF-1 and TGFα for prostate cancer

International Nuclear Information System (INIS)

Dai Feng; Yang Qingling

2006-01-01

To assess the clinical value of serum complexed prostate specific antigen (cPSA), insulinlike growth factor(IGF-1),transforming growth factor a (TGFα) in the diagnosis of pros- tate cancer (PCα), serum samples were obtained from 46 men with PCa, 64 men with untreated benign prostatic hyperplasia(BPH) and 73 men of a healthy control group. The levels of cPSA, IGF-1 and TGFα were determined by autoimmunochemistry luminescence method, IRMA and RIA method. Postoperative observation was conducted for the change of cPSA, IGF-1 and TGFa in the serum from men with PCa obtained in one month, three months and six months after the operations. Results showed that the levels of cPSA, IGF-1 and TGFα in PCa serum were significantly higher than the BPH group and control group(P 0.05). The combined test of cPSA, IGF-1 and TGFα is meaningful for the prevision, diagnosis and therapy of PCa. (authors)

A preliminary study of pamidronic acid downregulation of angiogenic factors IGF-1/PECAM-1 expression in circulating level in bone metastatic breast cancer patients

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Wang Z

2016-05-01

Full Text Available Zeng Wang,1,2 Lei Lei,2,3 Xin-jun Cai,4 Ling Ya Chen,1,2 Meiqin Yuan,2,3 Guonong Yang,1,2 Ping Huang,1,2 Xiaojia Wang2,3 1Department of Pharmacy, 2Zhejiang Key Lab of Diagnosis & Treatment Technology on Thoracic Oncology, 3Department of Chemotherapy Center, Zhejiang Cancer Hospital, 4Department of Pharmacy, Integrated Chinese and Western Medicine Hospital of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China Objective: To evaluate the expressions of circulating angiogenic factors affected by pamidronic acid (PA intravenous infusion in bone metastatic breast cancer patients and the impact on their prognosis.Methods: Peripheral blood of ten bone metastatic breast cancer patients was collected for serum insulin-like growth factor-1 (IGF-1 and platelet endothelial cell adhesion molecule-1 expression detection just before and 2 days after PA infusion.Results: Both IGF-1 and platelet endothelial cell adhesion molecule-1 concentrations decreased after PA treatment for 48 hours (P<0.05. Modification was defined as >20% decrease recorded 2 days after PA administration. The decrease of IGF-1 was more significant in breast cancer patients who had received previous hormonotherapy. Moreover, the progression-free survival of first-line chemotherapy treatment of IGF-1 modified patients was longer than that of IGF-1 unmodified patients (P=0.009.Conclusion: PA treatment could suppress circulating serum IGF-1 and platelet endothelial cell adhesion molecule-1 concentrations; moreover, the prognosis of patients in IGF-1 unmodified group was relatively poor. Keywords: pamidronic acid, insulin-like growth factor-1, platelet endothelial cell adhesion molecule-1, bone metastatic breast cancer, prognosis

Impact of IGF-1, IGF-1R, and IGFBP-3 promoter methylation on the risk and prognosis of esophageal carcinoma.

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Ye, Peng; Qu, Chang-Fa; Hu, Xue-Lin

2016-05-01

The aim of this study is to investigate IGF-1, IGF-1R, and IGFBP-3 methylations in esophageal carcinoma (EC) patients and their relationship with the development and prognosis of EC. This study population consisted of 264 patients (case group) whom EC radical resection was performed and 283 healthy individuals (control group). Methylation-specific PCR (MSP) detected the methylation status of IGF-1, IGF-1R, and IGFBP-3 in the peripheral blood in both groups. The expressions of IGF-1, IGF-1R, and IGFBP-3 in EC and adjacent normal tissues were detected by immunohistochemistry (IHC). The methylation rates of IGF-1, IGF-1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 in the case group were higher than those in the control group (all P IGF-1, IGF-1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 IGF-1 among patients of different clinicopathological features (all P IGF-1 and IGF-1R in EC were significantly higher than those in adjacent normal tissues (both P IGF-1 and IGF1R gene promoter methylation was positively correlated with the positive expressions of IGF-1 (r = 0.139, P = 0.024) and IGF-1R (r = 0.135, P = 0.028), while the IGFBP3 methylation was negatively correlated with the positive expression of IGFBP3 (r = -0.133, P = 0.031). The positive expressions of IGF-1, IGF-1R, and IGFBP-3 were related to different clinicopathological features (all P IGF-1, IGF-1R, and IGF-1 + IGF1R + IGFBP3 ; expressions of IGF-1 and IGF-1R protein; infiltration depth; and lymph node metastasis (LNM) were independent factors of EC prognosis. Our study demonstrated that methylation of IGF-1, IGF1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 was closely linked with the occurrence of EC and patients' clinicopathological features. Besides, the methylation status of the target genes and the expressions of IGF-1 and IGF-1R protein were independent factors of EC prognosis, which could provide a direction for the prognosis and treatment of EC.

Stress-altered synaptic plasticity and DAMP signaling in the hippocampus-PFC axis; elucidating the significance of IGF-1/IGF-1R/CaMKIIα expression in neural changes associated with a prolonged exposure therapy.

Science.gov (United States)

Ogundele, Olalekan M; Ebenezer, Philip J; Lee, Charles C; Francis, Joseph

2017-06-14

Traumatic stress patients showed significant improvement in behavior after a prolonged exposure to an unrelated stimulus. This treatment method attempts to promote extinction of the fear memory associated with the initial traumatic experience. However, the subsequent prolonged exposure to such stimulus creates an additional layer of neural stress. Although the mechanism remains unclear, prolonged exposure therapy (PET) likely involves changes in synaptic plasticity, neurotransmitter function and inflammation; especially in parts of the brain concerned with the formation and retrieval of fear memory (Hippocampus and Prefrontal Cortex: PFC). Since certain synaptic proteins are also involved in danger-associated molecular pattern signaling (DAMP), we identified the significance of IGF-1/IGF-1R/CaMKIIα expression as a potential link between the concurrent progression of synaptic and inflammatory changes in stress. Thus, a comparison between IGF-1/IGF-1R/CaMKIIα, synaptic and DAMP proteins in stress and PET may highlight the significance of PET on synaptic morphology and neuronal inflammatory response. In behaviorally characterized Sprague-Dawley rats, there was a significant decline in neural IGF-1 (pIGF-1R expression. These animals showed a significant loss of presynaptic markers (synaptophysin; pIGF-1 (pIGF-1R was recorded in the Stress-PET group (pIGF-1/IGF-1R, an increase in activated hippocampal and cortical microglia was seen in stress (pIGF1/IGF-1R/CaMKIIα. Firstly, we showed a direct relationship between IGF-1/IGF-1R expression, presynaptic function (synaptophysin) and neurotransmitter activity in stress and PET. Secondly, we identified the possible role of CaMKIIα in post-synaptic function and regulation of small ion conductance channels. Lastly, we highlighted some of the possible links between IGF1/IGF-1R/CaMKIIα, the expression of DAMP proteins, Microglia activation, and its implication on synaptic plasticity during stress and PET. Copyright © 2017

The GH-IGF1 axis and longevity. The paradigm of IGF1 deficiency.

Science.gov (United States)

Laron, Zvi

2008-01-01

Primary or secondary IGF1 deficiency has been implicated in shortening of lifespan. This paper reviews available data on the influence of IGF1 deficiency on lifespan and longevity in animals and man. It has been shown that inactivation of the IGF1 gene or of the GH receptor in both invertebrates (C-elegans, flies-Drosphila) and rodents (mice and rats), leading to IGF1 deficiency, prolong life, particularly in females. In man, evaluation of the 2 largest cohorts of patients with Laron syndrome (inactive GH receptor resulting in IGF1 deficiency) in Israel and Ecuador revealed that despite their dwarfism and marked obesity, patients are alive at the ages of 75-78 years, with some having reached even more advanced ages. It is assumed that a major contributing factor is their protection from cancer, a major cause of death in the general population.

Adiponectin, Leptin, IGF-1, and Tumor Necrosis Factor Alpha As Potential Serum Biomarkers for Non-Invasive Diagnosis of Colorectal Adenoma in African Americans.

Science.gov (United States)

Ashktorab, Hassan; Soleimani, Akbar; Nichols, Alexandra; Sodhi, Komal; Laiyemo, Adeyinka O; Nunlee-Bland, Gail; Nouraie, Seyed Mehdi; Brim, Hassan

2018-01-01

The potential role of adiponectin, leptin, IGF-1, and tumor necrosis factor alpha (TNF-α) as biomarkers in colorectal adenoma is not clear. Therefore, we aimed to investigate the blood serum levels of these biomarkers in colorectal adenoma. The case-control study consisted of serum from 180 African American patients with colon adenoma (cases) and 198 healthy African Americans (controls) at Howard University Hospital. We used ELISA for adiponectin, leptin, IGF-1, and TNF-α detection and quantification. Statistical analysis was performed by t -test and multivariate logistic regression. The respective differences in median leptin, adiponectin, IGF-1, and TNF-α levels between control and case groups (13.9 vs. 16.4), (11.3 vs. 46.0), (4.5 vs. 12.9), and (71.4 vs. 130.8) were statistically significant ( P  IGF-1 were 2.0 (95% CI = 1.6-2.5; P  IGF-1 concentrations with age ( r  = 0.17, P  IGF-1, and leptin concentration with body mass index (BMI) ( r  = 0.44, P  IGF-1, and TNF-α high levels correlate with higher risk of colon adenoma and can thus be used for colorectal adenomas risk assessment.

Effects of High Intensity Interval Training on Plasma Levels of GH and IGF-I

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Seyyed Mahmoud Hejazi

2017-04-01

Full Text Available Introduction: It is well-recognized that exercise has a significant impact on the GH/IGF system but less is known about the effects of HIIT on this axis. Aim of the present study was to evaluate the effect of ten weeks of HIIT on plasma levels of GH and IGF-I in healthy men. Methods: Twenty young men (age 23.34 ± 2.56 weight 72.47 ± 12.01 height 174.10 ± 5.75 recruited and randomly assigned into control (n=10 and HIIT (n=12 groups. HIIT protocol was started with 4 cycles. Then, every two weeks one cycle was added to the previous ones. Finally, it was to 8 cycles/ session in tenth weeks that lasted 16 minutes. Blood samples were collected prior to and after HIIT program for all subjects and IGF-I and GH levels were measured. Result: HIIT subjects showed a significant increase in IGF-I (P=0.002, F=12.38. However, no significant change was shown in GH levels (P=0.716, F=0.62. Discussion and conclusion: Our findings indicate that the HIIT caused increase in circulating levels of IGF-I independently from GH levels. Both hormones may contribute to positive effects of anabolic conditions.

Regulation of hypoxia-inducible factor-1α (HIF-1α expression by interleukin-1β (IL-1 β, insulin-like growth factors I (IGF-I and II (IGF-II in human osteoarthritic chondrocytes

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Angelica Rossi Sartori-Cintra

2012-01-01

Full Text Available OBJECTIVE: Hypoxia-inducible factor 1 alpha regulates genes related to cellular survival under hypoxia. This factor is present in osteroarthritic chondrocytes, and cytokines, such as interleukin-1 beta, participate in the pathogenesis of osteoarthritis, thereby increasing the activities of proteolytic enzymes, such as matrix metalloproteinases, and accelerating cartilage destruction. We hypothesize that Hypoxia Inducible Factor-1 alpha (HIF-1α can regulate cytokines (catabolic action and/or growth factors (anabolic action in osteoarthritis. The purpose of this study was to investigate the modulation of HIF-1α in human osteoarthritic chondrocytes by interleukin-1 beta (IL-1β and insulin-like growth factors I (IGF-I and II (IGF-II and to determine the involvement of the phosphatidylinositol-3kinase (PI-3K pathway in this process. METHODS: Human osteroarthritic chondrocytes were stimulated with IL-1β, IGF-I and IGF-II and LY294002, a specific inhibitor of PI-3K. Nuclear protein levels and gene expression were analyzed by western blot and quantitative reverse transcription-polymerase chain reaction analyses, respectively. RESULTS: HIF-1α expression was upregulated by IL-1β at the protein level but not at the gene level. IGF-I treatment resulted in increases in both the protein and mRNA levels of HIF-1α , whereas IGF-II had no effect on its expression. However, all of these stimuli exploited the PI-3K pathway. CONCLUSION: IL-1β upregulated the levels of HIF-1α protein post-transcriptionally, whereas IGF-I increased HIF-1α at the transcript level. In contrast, IGF-II did not affect the protein or gene expression levels of HIF-1α . Furthermore, all of the tested stimuli exploited the PI-3K pathway to some degree. Based on these findings, we are able to suggest that Hypoxia inducible Factor-1 exhibits protective activity in chondrocytes during osteoarthritis.

Changes of Cerebral and/or Peripheral Adenosine A1 Receptor and IGF-I Concentrations under Extended Sleep Duration in Rats

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Mounir Chennaoui

2017-11-01

Full Text Available Extended sleep improves sustained attention and reduces sleep pressure in humans. Downregulation of adenosine A1 receptor (A1R and modulation of the neurotrophic factor insulin growth factor-1 (IGF-I in brain structures controlling attentional capacities could be involved. In the frontal cortex and hippocampus of rats, we measured adenosine A1R and IGF-I protein concentrations after photoperiod-induced sleep extension. Two groups of twelve rats were adapted over 14 days to a habitual (CON 12:12 light–dark (LD schedule and an extended (EXT 16:8 LD schedule. IGF-I content was also measured in plasma, liver, and skeletal muscle. In EXT, compared to CON rats, A1R content in the frontal cortex was significantly lower (p < 0.05, while IGF-I content was higher (p < 0.001, and no significant change was observed in the hippocampus. IGF-I content in plasma and muscle was higher (p < 0.001 and p < 0.01, while it was lower in liver (p < 0.001. The absolute weight and weight gain were higher in EXT rats (p < 0.01. These data suggest that 14 days under a 16:8 LD photoperiod respectively down- and upregulated cortical A1R and IGF-I levels. This photoperiod induced an anabolic profile with increased weight gain and circulating and muscular IGF-I levels. An extension of sleep duration might favor cerebral and peripheral anabolism, which may help attentional and physical capacities.

Associations between depressive symptoms and memory deficits vary as a function of insulin-like growth factor (IGF-1) levels in healthy older adults.

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Lin, Feng; Suhr, Julie; Diebold, Stephanie; Heffner, Kathi L

2014-04-01

Accumulating evidence suggests an adverse association between depressive symptoms and cognition, but a positive association between insulin-like growth factor (IGF)-1 and cognition. The present study examined the influence of IGF-1 in the relationship between depressive symptoms and learning and memory. A cross-sectional study of 94 healthy fit older adults. Blood was collected and plasma IGF-1 was measured. Depressive symptoms were assessed with the Geriatric Depression Scale (GDS), and learning and memory were assessed using the Rey Auditory Verbal Learning Test (AVLT). Among older adults with lower IGF-1 levels, higher depressive symptoms scores were associated with lower AVLT delayed recall and recognition. Older adults with higher IF-1 levels showed no associations between depressive symptoms and memory. The association between depressive symptoms and cognition is stronger among older adults with lower levels of circulating IGF-1. Further validation studies on groups with depression or different stages of cognitive impairment are needed. IGF-1 may be a novel intervention target for slowing cognitive decline in older adults with depressive symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Polychlorinated dibenzo-p-dioxins, furans, and biphenyls (PCDDs/PCDFs and PCBs) in breast milk and early childhood growth and IGF1

DEFF Research Database (Denmark)

Wohlfahrt-Veje, Christine; Audouze, Karine Marie Laure; Brunak, Søren

2014-01-01

Experimental studies have shown that dioxin-like chemicals may interfere with aspects of the endocrine system including growth. However, human background population studies are, however, scarce. We aimed to investigate whether early exposure of healthy infants to dioxin-like chemicals...... was associated with changes in early childhood growth and serum IGF1. In 418 maternal breast milk samples of Danish children (born 1997-2001) from a longitudinal cohort, we measured polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and polychlorinated biphenyls (pg or ng/g lipid) and calculated...... to dioxin-like chemicals was associated with being skinny at birth and with higher infant levels of circulating IGF1 as well as accelerated early childhood growth (rapid catch-up growth)....

The association between peripheral total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 and functional and cognitive outcomes in the Mayo Clinic Study of Aging.

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Wennberg, Alexandra M V; Hagen, Clinton E; Machulda, Mary M; Hollman, John H; Roberts, Rosebud O; Knopman, David S; Petersen, Ronald C; Mielke, Michelle M

2018-06-01

Levels of insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, and their ratio in the blood may be useful for monitoring those at risk of cognitive and functional decline. However, the association between IGF measures and functional and cognitive outcomes has been mixed, and the associations may vary by sex. The present study investigated the cross-sectional, sex-specific associations between serum measures total IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 ratio, gait speed, and cognition in 1320 cognitively unimpaired participants aged 50-95 years enrolled in the Mayo Clinic Study of Aging. We used multivariable linear regression models to determine the association between IGF measures and gait speed or cognitive test performance by sex. IGF measures were not associated with cognitive or functional performance among men. Among women, higher levels of log total IGF-1 and IGFBP-3 were associated with better performance in attention, visuospatial, and global cognitive domains, independent of the gait speed. These findings suggest that among women, IGF measures are associated with cognition, and these associations are independent of function. Copyright © 2018 Elsevier Inc. All rights reserved.

Helicobacter pylori Infection in Children: Nutritional Status and Associations with Serum Leptin, Ghrelin, and IGF-1 Levels.

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Erdemir, Gulin; Ozkan, Tanju Basarir; Ozgur, Taner; Altay, Derya; Cavun, Sinan; Goral, Guher

2016-08-01

Helicobacter pylori is associated with gastrointestinal diseases such as gastritis, peptic ulcers, malignancy and lymphoma, and extra-gastrointestinal conditions. H. pylori infection is negatively associated with children's growth. Chronic inflammation of the stomach that results in the loss of appetite and, dysregulation of neuroendocrine hormones such as leptin, and ghrelin are the probable reasons of this negative association. The objective of this study is to determine the serum levels of leptin, ghrelin, and IGF-1 in H. pylori-infected children and their relations with growth. A hundred and sixty-one school children aged between 6 and 14 years were selected randomly from five primary schools representing a cross section of population. Demographic and sociocultural characteristics, and anthropometric measurements were recorded. Serum H. pylori IgG, insulin-like growth factor-1, leptin, and ghrelin levels were measured in all children. The children were grouped according to the nutritional status and Helicobacter pylori seropositivity. Nutritional indices were compared among groups in association with serum leptin, ghrelin, and insulin-like growth factor-1 levels. H. pylori IgG positivity was found in 34.2%, and 14.9% of children were malnourished. H. pylori seropositivity was significantly higher in older ages (10.32 ± 2.26 vs 9.53 ± 2.36 years, p = .036), and body weight and height Z scores were significantly lower in H. pylori-seropositive children (-0.33 ± 1.08 vs 0.04 ± 1.26, p = .044 and 0.13 ± 0.92 vs 0.23 ± 0.91, p = .018 respectively). H. pylori seropositivity was found to be an independent risk factor for shorter body height (p = .01). Serum leptin, ghrelin, and IGF-1 levels were not associated with H. pylori IgG seropositivity (0.35 vs 0.55 ng/mL, p = .3; 3267.4 ± 753.0 vs 2808.3 ± 911.4 pg/mL, p = .06; 470 ± 176 vs 521 ± 179 ng/mL, p = .32, respectively). Children infected with H. pylori are prone to short stature. This effect seems to be

IGF-1, IGFBP-3 and ALS in adult patients with chronic kidney disease.

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Lepenies, Julia; Wu, Zida; Stewart, Paul M; Strasburger, Christian J; Quinkler, Marcus

2010-04-01

Insulin-like growth factor I (IGF-1) is for the most part bound in a ternary complex with IGF-binding protein-3 (IGFBP-3) and acid-labile subunit (ALS). This ternary complex is a storage form of IGF-1 in blood and passes not through the renal glomerulus. Little information is available in regard to the components of the ternary complex in adult renal disease. To investigate levels of serum IGF-1, IGFBP-3 and ALS in relation to renal function and extent of proteinuria. We measured IGF-1, IGFBP-3 and ALS concentrations in 137 patients who were investigated due to proteinuria and/or haematuria and/or renal impairment. The patients received renal biopsies and the histological diagnosis was documented. Urinary albumin excretion and relevant clinical parameter were evaluated. IGF-1 showed a highly positive correlation to IGFBP-3 and ALS, and the latter to IGFBP-3. IGF-1, IGFBP-3 and ALS decreased with increasing age. IGF-1 and IGFBP-3 showed no significant change depending on the creatinine clearance. However, ALS decreased with decreasing renal function. In patients with heavy proteinuria ALS levels, but not IGF-1 and IGFBP-3 levels, decreased significantly. Patients with chronic ischaemic renal damage and diabetic glomerulopathy showed higher IGF-1 and IGFBP-3 levels compared to patients with thin glomerular basement membrane disease despite their older age. IGF-1 and IGFBP-3 levels seem to be independent of renal function and severity of proteinuria. However, ALS levels are altered in renal failure and nephrotic syndrome, which may be due to increased renal loss or diminished hepatic production or both. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Sex, Sport, IGF-1 and the Community Effect in Height Hypothesis

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Barry Bogin

2015-05-01

Full Text Available We test the hypothesis that differences in social status between groups of people within a population may induce variation in insulin-like growth factor-1(IGF-1 levels and, by extension, growth in height. This is called the community effect in height hypothesis. The relationship between IGF-1, assessed via finger-prick dried blood spot, and elite level sport competition outcomes were analysed for a sample of 116 undergraduate men and women. There was a statistically significant difference between winners and losers of a competition. Winners, as a group, had higher average pre-game and post-game IGF-1 levels than losers. We proposed this type of difference as a proxy for social dominance. We found no evidence that winners increased in IGF-1 levels over losers or that members of the same team were more similar in IGF-1 levels than they were to players from other teams. These findings provide limited support toward the community effect in height hypothesis. The findings are discussed in relation to the action of the growth hormone/IGF-1 axis as a transducer of multiple bio-social influences into a coherent signal which allows the growing human to adjust and adapt to local ecological conditions.

IGF-1 levels across the spectrum of normal to elevated in acromegaly: relationship to insulin sensitivity, markers of cardiovascular risk and body composition.

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Reid, Tirissa J; Jin, Zhezhen; Shen, Wei; Reyes-Vidal, Carlos M; Fernandez, Jean Carlos; Bruce, Jeffrey N; Kostadinov, Jane; Post, Kalmon D; Freda, Pamela U

2015-12-01

Activity of acromegaly is gauged by levels of GH and IGF-1 and epidemiological studies demonstrate that their normalization reduces acromegaly's excess mortality rate. However, few data are available linking IGF-1 levels to features of the disease that may relate to cardiovascular (CV) risk. Therefore, we tested the hypothesis that serum IGF-1 levels relative to the upper normal limit relate to insulin sensitivity, serum CV risk markers and body composition in acromegaly. In this prospective, cross-sectional study conducted at a pituitary tumor referral center we studied 138 adult acromegaly patients, newly diagnosed and previously treated surgically, with fasting and post-oral glucose levels of endocrine and CV risk markers and body composition assessed by DXA. Active acromegaly is associated with lower insulin sensitivity, body fat and CRP levels than acromegaly in remission. %ULN IGF-1 strongly predicts insulin sensitivity, better than GH and this persists after adjustment for body fat and lean tissue mass. %ULN IGF-1 also relates inversely to CRP levels and fat mass, positively to lean tissue and skeletal muscle estimated (SM(E)) by DXA, but not to blood pressure, lipids, BMI or waist circumference. Gender interacts with the IGF-1-lean tissue mass relationship. Active acromegaly presents a unique combination of features associated with CV risk, reduced insulin sensitivity yet lower body fat and lower levels of some serum CV risk markers, a pattern that is reversed in remission. %ULN IGF-1 levels strongly predict these features. Given the known increased CV risk of active acromegaly, these findings suggest that of these factors insulin resistance is most strongly related to disease activity and potentially to the increased CV risk of active acromegaly.

Growth inhibition of human pancreatic cancer cells by lipofection mediated IGF-1R antisense oligodeoxynucletides in combination with ionizing radiation

International Nuclear Information System (INIS)

Pan Yaozhen; Sun Chengyi; Wang Yuzhi

2004-01-01

Objective: To study the growth inhibition of human pancreatic cancer cells (PC-3) by lipofection-mediated and ionizing radiation improving transfection of IGF-1R antisense oligodeoxynucletides (ASON) in vitro. Methods: Colonigenicity of PC-3 cells in vitro after 60 Co γ-radiation was observed for ascertaining their radiosensitivity and optimal radiation dose was selected according to the radiation sensitivity. PC-3 cells were transfected by two ways: 1) by lipofection-mediated IGF-1R ASON combined with ionizing radiation. 2) by lipo-ASON alone without ionizing radiation. Cell growth was assessed by MTT method. The expression of IGF-1R at mRNA level was examined by RT-PCR. Flow cytometry was used to demonstrate apoptotic changes in lipo-ASON-treated cells. Results: The inhibitory efficiency of lipo-ASON combined with ionizing radiation was higher than that without ionizing radiation (P < 0.05). The apoptotic efficiency and the decreased level of IGF-1R at mRNA were significantly improved (P < 0.05). Conclusion: Lipofection-mediated and ionizing radiation-promoted transfection of IGF-1R antisense oligodeoxynucletides (ASON) significantly decreases IGF-1R at mRNA level and induces apoptosis of human pancreatic cancer cells in vitro

Recombinant human IGF-1 produced by transgenic plant cell suspension culture enhances new bone formation in calvarial defects.

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Poudel, Sher Bahadur; Bhattarai, Govinda; Kook, Sung-Ho; Shin, Yun-Ji; Kwon, Tae-Ho; Lee, Seung-Youp; Lee, Jeong-Chae

2017-10-01

Transgenic plant cell suspension culture systems have been utilized extensively as convenient and efficient expression systems for the production of recombinant human growth factors. We produced insulin-like growth factor-1 using a plant suspension culture system (p-IGF-1) and explored its effect on new bone formation in calvarial defects. We also compared the bone regenerating potential of p-IGF-1 with commercial IGF-1 derived from Escherichia coli (e-IGF-1). Male C57BL/6 mice underwent calvarial defect surgery, and the defects were loaded with absorbable collagen sponge (ACS) only (ACS group) or ACS impregnated with 13μg of p-IGF-1 (p-IGF-1 group) or e-IGF-1 (e-IGF-1 group). The sham group did not receive any treatment with ACS or IGFs after surgery. Live μCT and histological analyses showed critical-sized bone defects in the sham group, whereas greater bone formation was observed in the p-IGF-1 and e-IGF-1 groups than the ACS group both 5 and 10weeks after surgery. Bone mineral density, bone volume, and bone surface values were also higher in the IGF groups than in the ACS group. Local delivery of p-IGF-1 or e-IGF-1 more greatly enhanced the expression of osteoblast-specific markers, but inhibited osteoclast formation, in newly formed bone compared with ACS control group. Specifically, p-IGF-1 treatment induced higher expression of alkaline phosphatase, osteocalcin, and osteopontin in the defect site than did e-IGF-1. Furthermore, treatment with p-IGF-1, but not e-IGF-1, increased mineralization of MC3T3-E1 cells, with the attendant upregulation of osteogenic marker genes. Collectively, our findings suggest the potential of p-IGF-1 in promoting the processes required for bone regeneration. Copyright © 2017. Published by Elsevier Ltd.

Dwarfism in Mice Lacking Collagen-binding Integrins α2β1 and α11β1 Is Caused by Severely Diminished IGF-1 Levels*

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Blumbach, Katrin; Niehoff, Anja; Belgardt, Bengt F.; Ehlen, Harald W. A.; Schmitz, Markus; Hallinger, Ralf; Schulz, Jan-Niklas; Brüning, Jens C.; Krieg, Thomas; Schubert, Markus; Gullberg, Donald; Eckes, Beate

2012-01-01

Mice with a combined deficiency in the α2β1 and α11β1 integrins lack the major receptors for collagen I. These mutants are born with inconspicuous differences in size but develop dwarfism within the first 4 weeks of life. Dwarfism correlates with shorter, less mineralized and functionally weaker bones that do not result from growth plate abnormalities or osteoblast dysfunction. Besides skeletal dwarfism, internal organs are correspondingly smaller, indicating proportional dwarfism and suggesting a systemic cause for the overall size reduction. In accordance with a critical role of insulin-like growth factor (IGF)-1 in growth control and bone mineralization, circulating IGF-1 levels in the sera of mice lacking either α2β1 or α11β1 or both integrins were sharply reduced by 39%, 64%, or 81% of normal levels, respectively. Low hepatic IGF-1 production resulted from diminished growth hormone-releasing hormone expression in the hypothalamus and, subsequently, reduced growth hormone expression in the pituitary glands of these mice. These findings point out a novel role of collagen-binding integrin receptors in the control of growth hormone/IGF-1-dependent biological activities. Thus, coupling hormone secretion to extracellular matrix signaling via integrins represents a novel concept in the control of endocrine homeostasis. PMID:22210772

Dwarfism in mice lacking collagen-binding integrins α2β1 and α11β1 is caused by severely diminished IGF-1 levels.

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Blumbach, Katrin; Niehoff, Anja; Belgardt, Bengt F; Ehlen, Harald W A; Schmitz, Markus; Hallinger, Ralf; Schulz, Jan-Niklas; Brüning, Jens C; Krieg, Thomas; Schubert, Markus; Gullberg, Donald; Eckes, Beate

2012-02-24

Mice with a combined deficiency in the α2β1 and α11β1 integrins lack the major receptors for collagen I. These mutants are born with inconspicuous differences in size but develop dwarfism within the first 4 weeks of life. Dwarfism correlates with shorter, less mineralized and functionally weaker bones that do not result from growth plate abnormalities or osteoblast dysfunction. Besides skeletal dwarfism, internal organs are correspondingly smaller, indicating proportional dwarfism and suggesting a systemic cause for the overall size reduction. In accordance with a critical role of insulin-like growth factor (IGF)-1 in growth control and bone mineralization, circulating IGF-1 levels in the sera of mice lacking either α2β1 or α11β1 or both integrins were sharply reduced by 39%, 64%, or 81% of normal levels, respectively. Low hepatic IGF-1 production resulted from diminished growth hormone-releasing hormone expression in the hypothalamus and, subsequently, reduced growth hormone expression in the pituitary glands of these mice. These findings point out a novel role of collagen-binding integrin receptors in the control of growth hormone/IGF-1-dependent biological activities. Thus, coupling hormone secretion to extracellular matrix signaling via integrins represents a novel concept in the control of endocrine homeostasis.

Clinical significance of measurement of changes of plasma NPY, CGRP and serum IGF-I levels in patients with acute cerebral infarction

International Nuclear Information System (INIS)

Deng Weiqun; Zhao Yushan

2007-01-01

Objective: To investigate the clinical significance of changes of plasma NPY, CGRP and serum IGF-I levels in patients with acute cerebral infarction. Methods: Plasma NPY, CGRP and serum IGF-I levels were determined with RIA in 32 patients with acute cerebral infarction both before and after treatment and 30 controls. Results: Before treatment plasma NPY levels were significantly higher (P<0.01) than those in the controls, while plasma CGRP and serum IGF-I levels were lower than those in controls (P<0.01). After treatment, plasma NPY levels decreased significantly (vs before treatment P<0.05), and plasma CGRP and serum IGF-I levels increased (P<0.05). Conclusion: Changes of plasma NPY, CGRP and serum IGF-I levels were closely related to the disease process in patients with acute cerebral infarction, determination of which was of important clinical values. (authors)

Changes in circulating level of IGF-I and IGF-binding protein-1 from the first to second trimester as predictors of preeclampsia

DEFF Research Database (Denmark)

Vatten, Lars J; Nilsen, Tom I L; Juul, Anders

2008-01-01

OBJECTIVE: To assess whether circulating IGF-I and IGF-binding protein-1 (IGFBP-1) in the first and second trimester are associated with subsequent risk of preterm and term preeclampsia. METHODS: Nested case-control study within a cohort of 29 948 pregnant women. Cases were women, who later...... developed preeclampsia, and controls were randomly selected women, who did not develop preeclampsia. IGF-I and IGFBP-1 were measured with ELISA in maternal blood samples that were collected in the first and second trimesters. We assessed associations of IGF-I and IGFBP-1 concentrations with later...... development of preterm (before the 37th week of gestation) and term preeclampsia. RESULTS: An increase in IGF-I from the first to second trimester was associated with higher risk of preterm preeclampsia; the odds ratio (OR) for the highest compared with lowest quartile of increase was 4.9 (95% confidence...

study on the serum levels of E2, IL-6 and IGF-I in patients with post-menopausal osteoporosis (PMO)

International Nuclear Information System (INIS)

Lv Kuan; Liu Chunyu; Lu Yingju

2006-01-01

Objective: To study the changes of serum levels of E 2 , IL-6, IGF-I in patients with post-menopausal osteoporosis (PMO). Methods: Serum levels of E 2 (with CLIA), IL-6, IGF-I, BGP (with RIA) were measured in the following subjects: (1) 32 patients with PMO (2) 32 post-menopausal women without PMO and (3) 30 pre-menopausal controls. Serum P, Ca and AKP levels were also determined. Results: As a whole, serum levels of IL -6 in postmenopausal women were higher than those in controls. Levels in subjects with PMO were significantly higher than those without PMO (P 2 and BMD index (r=-0. 587, - 0. 438 respectively, P 2 and BMD index (r=0.569, 0.433 respectively, P 2 levels will in someway promote the expression of IL-6 ( osteoclastic) and reduce the expression of IGF-I (osteoclastic), resulting in lessening of bone mass. HRT, despite of the controversy over cardio-vascalar safety, is beneficial for osteoporosis. (authors)

Insulin-like growth factor 1 (IGF-1 enhances the protein expression of CFTR.

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Ha Won Lee

Full Text Available Low levels of insulin-like growth factor 1 (IGF-1 have been observed in the serum of cystic fibrosis (CF patients. However, the effects of low serum IGF-1 on the cystic fibrosis transmembrane conductance regulator (CFTR, whose defective function is the primary cause of cystic fibrosis, have not been studied. Here, we show in human cells that IGF-1 increases the steady-state levels of mature wildtype CFTR in a CFTR-associated ligand (CAL- and TC10-dependent manner; moreover, IGF-1 increases CFTR-mediated chloride transport. Using an acceptor photobleaching fluorescence resonance energy transfer (FRET assay, we have confirmed the binding of CAL and CFTR in the Golgi. We also show that CAL overexpression inhibits forskolin-induced increases in the cell-surface expression of CFTR. We found that IGF-1 activates TC10, and active TC10 alters the functional association between CAL and CFTR. Furthermore, IGF-1 and active TC10 can reverse the CAL-mediated reduction in the cell-surface expression of CFTR. IGF-1 does not increase the expression of ΔF508 CFTR, whose processing is arrested in the ER. This finding is consistent with our observation that IGF-1 alters the functional interaction of CAL and CFTR in the Golgi. However, when ΔF508 CFTR is rescued with low temperature or the corrector VRT-325 and proceeds to the Golgi, IGF-1 can increase the expression of the rescued ΔF508 CFTR. Our data support a model indicating that CAL-CFTR binding in the Golgi inhibits CFTR trafficking to the cell surface, leading CFTR to the degradation pathway instead. IGF-1-activated TC10 changes the interaction of CFTR and CAL, allowing CFTR to progress to the plasma membrane. These findings offer a potential strategy using a combinational treatment of IGF-1 and correctors to increase the post-Golgi expression of CFTR in cystic fibrosis patients bearing the ΔF508 mutation.

Cyclic glycine-proline regulates IGF-1 homeostasis by altering the binding of IGFBP-3 to IGF-1

OpenAIRE

Guan, Jian; Gluckman, Peter; Yang, Panzao; Krissansen, Geoff; Sun, Xueying; Zhou, Yongzhi; Wen, Jingyuan; Phillips, Gemma; Shorten, Paul R.; McMahon, Chris D.; Wake, Graeme C.; Chan, Wendy H. K.; Thomas, Mark F.; Ren, April; Moon, Steve

2014-01-01

The homeostasis of insulin-like growth factor-1 (IGF-1) is essential for metabolism, development and survival. Insufficient IGF-1 is associated with poor recovery from wounds whereas excessive IGF-1 contributes to growth of tumours. We have shown that cyclic glycine-proline (cGP), a metabolite of IGF-1, can normalise IGF-1 function by showing its efficacy in improving the recovery from ischemic brain injury in rats and inhibiting the growth of lymphomic tumours in mice. Further investigation ...

Maternal BMI, IGF-I Levels, and Birth Weight in African American and White Infants

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Adriana C. Vidal

2013-01-01

Full Text Available At birth, elevated IGF-I levels have been linked to birth weight extremes; high birth weight and low birth weight are risk factors for adult-onset chronic diseases including obesity, cardiovascular disease, and type 2 diabetes. We examined associations between plasma IGF-I levels and birth weight among infants born to African American and White obese and nonobese women. Prepregnancy weight and height were assessed among 251 pregnant women and anthropometric measurements of full term infants (≥37 weeks of gestation were taken at birth. Circulating IGF-I was measured by ELISA in umbilical cord blood plasma. Linear regression models were utilized to examine associations between birth weight and high IGF-I, using the bottom two tertiles as referents. Compared with infants with lower IGF-I levels (≤3rd tertile, those with higher IGF-I levels (>3rd tertile were 130 g heavier at birth, (β-coefficient=230, se=58.0, P=0.0001, after adjusting for gender, race/ethnicity, gestational age, delivery route, maternal BMI and smoking. Stratified analyses suggested that these associations are more pronounced in infants born to African American women and women with BMI ≥30 kg/m2; the cross product term for IGF-I and maternal BMI was statistically significant (P≤0.0004. Our findings suggest that the association between IGF-I levels and birth weight depends more on maternal obesity than African American race/ethnicity.

Role of insulin-like growth factor-1 (IGF-1) in regulating cell cycle progression

International Nuclear Information System (INIS)

Ma, Qi-lin; Yang, Tian-lun; Yin, Ji-ye; Peng, Zhen-yu; Yu, Min; Liu, Zhao-qian; Chen, Fang-ping

2009-01-01

Aims: Insulin-like growth factor-1 (IGF-1) is a polypeptide protein hormone, similar in molecular structure to insulin, which plays an important role in cell migration, cell cycle progression, cell survival and proliferation. In this study, we investigated the possible mechanisms of IGF-1 mediated cell cycle redistribution and apoptosis of vascular endothelial cells. Method: Human umbilical vein endothelial cells (HUVECs) were pretreated with 0.1, 0.5, or 2.5 μg/mL of IGF-1 for 30 min before the addition of Ang II. Cell cycle redistribution and apoptosis were examined by flow cytometry. Expression of Ang II type 1 (AT 1 ) mRNA and cyclin E protein were determined by RT-PCR and Western blot, respectively. Results: Ang II (1 μmol/L) induced HUVECs arrested at G 0 /G 1 , enhanced the expression level of AT 1 mRNA in a time-dependent manner, reduced the enzymatic activity of nitric oxide synthase (NOS) and nitric oxide (NO) content as well as the expression level of cyclin E protein. However, IGF-1 enhanced NOS activity, NO content, and the expression level of cyclin E protein, and reduced the expression level of AT 1 mRNA. L-NAME significantly counteracted these effects of IGF-1. Conclusions: Our data suggests that IGF-1 can reverse vascular endothelial cells arrested at G 0 /G 1 and apoptosis induced by Ang II, which might be mediated via a NOS-NO signaling pathway and is likely associated with the expression levels of AT1 mRNA and cyclin E proteins.

IGF-1 colocalizes with muscle satellite cells following acute exercise in humans.

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Grubb, Amanda; Joanisse, Sophie; Moore, Daniel R; Bellamy, Leeann M; Mitchell, Cameron J; Phillips, Stuart M; Parise, Gianni

2014-04-01

Insulin-like growth factor-1 (IGF-1) regulates stem cell proliferation and differentiation in vitro. The aim of this study was to quantify the change in satellite cell (SC) specific IGF-1 colocalization following exercise. We observed a significant increase (p IGF-1 colocalization from baseline to 72 h after a bout of resistance exercise. This strongly supports a role for IGF-1 in human SC function following exercise.

The association between insulin-like growth factor 1 (IGF-1), IGF-binding proteins (IGFBPs), and the carboxyterminal propeptide of type I procollagen (PICP) in pre- and postmenopausal women with rheumatoid arthritis.

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Szeremeta, A; Jura-Półtorak, A; Komosińska-Vassev, K; Zoń-Giebel, A; Kapołka, D; Olczyk, K

2017-05-01

To assess the association between plasma levels of the insulin-like growth factor (IGF) system including IGF-1, IGF-binding proteins (IGFBPs) including IGFBP-1, total (t-)IGFBP-3 and functional (f-)IGFBP-3, and the carboxyterminal propeptide of type I procollagen (PICP) in pre- and postmenopausal women with rheumatoid arthritis (RA). Plasma concentrations of IGF-1, IGFBP-1, t-IGFBP-3, f-IGFBP-3, and PICP were measured by immunoassay. No significant difference was observed in plasma IGF-1 levels between pre- and postmenopausal subjects. Plasma levels of IGFBP-1 were elevated in RA. PICP and f-IGFBP-3 were greatly affected by menopausal status. Of the three IGFBPs tested, only f-IGFBP-3 plasma levels in RA women correlated negatively with age and disease duration. A positive correlation was demonstrated between PICP and erythrocyte sedimentation rate (ESR) in RA. Moreover, there was no correlation between PICP and IGF-1 and any of the IGFBPs in RA women. Considerable disruption of the IGF system in RA was found to be related to disease activity and duration. Changes in the IGF-IGFBP axis and PICP levels were different in pre- and postmenopausal women with RA. Elevated plasma PICP concentrations may indicate an increased rate of bone formation in postmenopausal RA women. Additionally, the observed changes in the IGF/IGFBP system did not affect bone formation during RA.

Preclinical screening for retinopathy of prematurity risk using IGF1 levels at 3 weeks post-partum.

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Pérez-Muñuzuri, Alejandro; Couce-Pico, Maria Luz; Baña-Souto, Ana; López-Suárez, Olalla; Iglesias-Deus, Alicia; Blanco-Teijeiro, José; Fernández-Lorenzo, José Ramón; Fraga-Bermúdez, José María

2014-01-01

Following current recommendations for preventing retinopathy of prematurity (ROP) involves screening a large number of patients. We performed a prospective study to establish a useful screening system for ROP prediction and we have determined that measuring serum levels of IGF1 at week three and the presence of sepsis have a high predictive value for the subsequent development of ROP. A total of 145 premature newborn, with birthweight <1500 g and/or <32 weeks gestational age, were enrolled. 26.9% of them showed some form of retinopathy. A significant association was found between the development of retinopathy and each of the following variables: early gestational age, low birthweight, requiring mechanical ventilation, oxygen treatment, intracranial haemorrhage, sepsis during the first three weeks, bronchopulmonary dysplasia, the need for erythrocyte transfusion, erythropoietin treatment, and low levels of serum IGF1 in the third week. A multiple logistic regression analysis was used to obtain curves for the probability of developing ROP, based on the main factors linked with ROP, namely serum levels of IGF1 and presence of sepsis. Such preclinical screening has the ability to identify patients with high-risk of developing retinopathy and should lead to better prediction for ROP, while at the same time optimising the use of clinical resources, both human and material.

Relevance of fruits, vegetables and flavonoids from fruits and vegetables during early life, mid-childhood and adolescence for levels of insulin-like growth factor (IGF-1) and its binding proteins IGFBP-2 and IGFBP-3 in young adulthood.

Science.gov (United States)

Krupp, Danika; Remer, Thomas; Penczynski, Katharina J; Bolzenius, Katja; Wudy, Stefan A; Buyken, Anette E

2016-02-14

The growth hormone (GH) insulin-like growth factor (IGF) axis has been linked to insulin metabolism and cancer risk. Experimental evidence indicates that the GH-IGF axis itself can be influenced by dietary flavonoids. As fruit and vegetable (FV) intake is a major source of flavonoid consumption, FV's beneficial health effects may be explained via flavonoids' influence on the GH-IGF axis, but observational evidence is currently rare. We used data from Dortmund Nutritional and Anthropometric Longitudinally Designed Study participants to analyse prospective associations between FV, fruit intake and flavonoid intake from FV (FlavFV) with IGF-1 and its binding proteins IGFBP-2 and IGFBP-3. Subjects needed to provide a fasting blood sample in adulthood (18-39 years) and at least two 3-d weighed dietary records in early life (0·5-2 years, n 191), mid-childhood (3-7 years, n 265) or adolescence (girls: 9-15 years, boys: 10-16 years, n 261). Additional analyses were conducted among those providing at least three 24-h urine samples in adolescence (n 236) to address the predictor urinary hippuric acid (HA), a biomarker of polyphenol intake. Higher fruit intake in mid-childhood and adolescence was related to higher IGFBP-2 in adulthood (P=0·03 and P=0·045). Comparable trends (P=0·045-0·09) were discernable for FV intake (but not FlavFV) in all three time windows. Similarly, higher adolescent HA excretion tended to be related (P=0·06) to higher adult IGFBP-2 levels. Regarding IGFBP-3, a marginal (P=0·08) positive association was observed with FlavFV in mid-childhood only. None of the investigated dietary factors was related to IGF-1. In conclusion, higher fruit and FV intakes during growth may be relevant for adult IGFBP-2, but probably not for IGFBP-3 or IGF-1.

Insulin Resistance Negatively Influences the Muscle-Dependent IGF-1-Bone Mass Relationship in Premenarcheal Girls.

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Kindler, J M; Pollock, N K; Laing, E M; Jenkins, N T; Oshri, A; Isales, C; Hamrick, M; Lewis, R D

2016-01-01

IGF-1 promotes bone growth directly and indirectly through its effects on skeletal muscle. Insulin and IGF-1 share a common cellular signaling process; thus, insulin resistance may influence the IGF-1-muscle-bone relationship. We sought to determine the effect of insulin resistance on the muscle-dependent relationship between IGF-1 and bone mass in premenarcheal girls. This was a cross-sectional study conducted at a university research center involving 147 girls ages 9 to 11 years. Glucose, insulin, and IGF-1 were measured from fasting blood samples. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin. Fat-free soft tissue (FFST) mass and bone mineral content (BMC) were measured by dual-energy x-ray absorptiometry. Our primary outcome was BMC/height. In our path model, IGF-1 predicted FFST mass (b = 0.018; P = .001), which in turn predicted BMC/height (b = 0.960; P IGF-1 predicted BMC/height (b = 0.001; P = .002), but not after accounting for the mediator of this relationship, FFST mass. The HOMA-IR by IGF-1 interaction negatively predicted FFST mass (b = -0.044; P = .034). HOMA-IR had a significant and negative effect on the muscle-dependent relationship between IGF-1 and BMC/height (b = -0.151; P = .047). Lean body mass is an important intermediary factor in the IGF-1-bone relationship. For this reason, bone development may be compromised indirectly via suboptimal IGF-1-dependent muscle development in insulin-resistant children.

Central insulin-like growth factor-1 (IGF-1) restores whole-body insulin action in a model of age-related insulin resistance and IGF-1 decline.

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Huffman, Derek M; Farias Quipildor, Gabriela; Mao, Kai; Zhang, Xueying; Wan, Junxiang; Apontes, Pasha; Cohen, Pinchas; Barzilai, Nir

2016-02-01

Low insulin-like growth factor-1 (IGF-1) signaling is associated with improved longevity, but is paradoxically linked with several age-related diseases in humans. Insulin-like growth factor-1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF-1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole-body insulin action in aging. Utilizing hyperinsulinemic-euglycemic clamps, we show that old insulin-resistant rats with age-related declines in IGF-1 level demonstrate markedly improved whole-body insulin action, when treated with central IGF-1, as compared to central vehicle or insulin (P IGF-1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P IGF-1 action in the brain and periphery provides a 'balance' between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at 'tipping the balance' of IGF-1 action centrally are the optimal approach to achieve healthy aging and longevity in humans. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

A Longitudinal Study of Growth, Sex Steroids, and IGF-1 in Boys With Physiological Gynecomastia.

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Mieritz, Mikkel G; Rakêt, Lars L; Hagen, Casper P; Nielsen, John E; Talman, Maj-Lis M; Petersen, Jørgen H; Sommer, Stefan H; Main, Katharina M; Jørgensen, Niels; Juul, Anders

2015-10-01

Physiological gynecomastia is common and affects a large proportion of otherwise healthy adolescent boys. It is thought to be caused by an imbalance between estrogen and testosterone, although this is rarely evident in analyses of serum. This study aimed to describe the frequency of physiological gynecomastia and to determine possible etiological factors (eg, auxology and serum hormone levels) in a longitudinal setup. A prospective cohort study of 106 healthy Danish boys (5.8-16.4 years) participated in the longitudinal part of the COPENHAGEN Puberty Study. The boys were examined every 6 months during an 8-year follow-up. Median number of examinations was 10 (2-15). Blood samples were analyzed for FSH, LH, testosterone, estradiol, SHBG, inhibin B, anti-Müllerian hormone, IGF-1, and IGF binding protein-3 by immunoassays. Auxological parameters, pubertal development, and the presence of gynecomastia were evaluated at each visit. Fifty-two of 106 boys (49%) developed gynecomastia, of which 10 (19%) presented with intermittent gynecomastia. Boys with physiological gynecomastia reached peak height velocity at a significantly younger age than boys who did not develop gynecomastia (13.5 versus 13.9 years, P = .027), and they had significantly higher serum levels of IGF-1 (P = .000), estradiol (P = .013), free testosterone (P Gynecomastia is frequent in pubertal boys. Increased IGF-1 levels and pubertal growth appear to be associated, whereas changes in estrogen to testosterone ratio seem negligible.

IGF1 stimulates greater muscle hypertrophy in the absence of myostatin in male mice.

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Hennebry, Alexander; Oldham, Jenny; Shavlakadze, Tea; Grounds, Miranda D; Sheard, Philip; Fiorotto, Marta L; Falconer, Shelley; Smith, Heather K; Berry, Carole; Jeanplong, Ferenc; Bracegirdle, Jeremy; Matthews, Kenneth; Nicholas, Gina; Senna-Salerno, Mônica; Watson, Trevor; McMahon, Christopher D

2017-08-01

Insulin-like growth factors (IGFs) and myostatin have opposing roles in regulating the growth and size of skeletal muscle, with IGF1 stimulating, and myostatin inhibiting, growth. However, it remains unclear whether these proteins have mutually dependent, or independent, roles. To clarify this issue, we crossed myostatin null ( Mstn -/- ) mice with mice overexpressing Igf1 in skeletal muscle ( Igf1 + ) to generate six genotypes of male mice; wild type ( Mstn +/+ ), Mstn +/- , Mstn -/- , Mstn +/+ :Igf1 + , Mstn +/- :Igf1 + and Mstn -/- :Igf1 + Overexpression of Igf1 increased the mass of mixed fibre type muscles (e.g. Quadriceps femoris ) by 19% over Mstn +/+ , 33% over Mstn +/- and 49% over Mstn -/- ( P  Myostatin regulated the number, while IGF1 regulated the size of myofibres, and the deletion of Mstn and Igf1 + independently increased the proportion of fast type IIB myosin heavy chain isoforms in T. anterior (up to 10% each, P  myostatin is absent and IGF1 is in excess. Finally, we show that myostatin and IGF1 regulate skeletal muscle size, myofibre type and gonadal fat through distinct mechanisms that involve increasing the total abundance and phosphorylation status of AKT and rpS6. © 2017 Society for Endocrinology.

The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery.

LENUS (Irish Health Repository)

Cooley, Sharon M

2010-05-01

To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery.

Serum insulin-like growth factor-1 levels in females and males in different cervical vertebral maturation stages

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Gupta, Shreya; Deoskar, Anuradha; Gupta, Puneet; Jain, Sandhya

2015-01-01

OBJECTIVE: The aim of this cross sectional study was to assess serum insulin-like growth factor-1 (IGF-1) levels in female and male subjects at various cervical vertebral maturation (CVM) stages. MATERIAL AND METHODS: The study sample consisted of 60 subjects, 30 females and 30 males, in the age range of 8-23 years. For all subjects, serum IGF-1 level was estimated from blood samples by means of chemiluminescence immunoassay (CLIA). CVM was assessed on lateral cephalograms using the method described by Baccetti. Serum IGF-1 level and cervical staging data of 30 female subjects were included and taken from records of a previous study. Data were analyzed by Kruska-Wallis and Mann Whitney test. Bonferroni correction was carried out and alpha value was set at 0.003. RESULTS: Peak value of serum IGF-1 was observed in cervical stages CS3 in females and CS4 in males. Differences between males and females were observed in mean values of IGF-1 at stages CS3, 4 and 5. The highest mean IGF-1 levels in males was observed in CS4 followed by CS5 and third highest in CS3; whereas in females the highest mean IGF-1 levelswas observed in CS3 followed by CS4 and third highest in CS5. Trends of IGF-1 in relation to the cervical stages also differed between males and females. The greatest mean serum IGF-1 value for both sexes was comparable, for females (397 ng/ml) values were slightly higher than in males (394.8 ng/ml). CONCLUSIONS: Males and females showed differences in IGF-1 trends and levels at different cervical stages. PMID:25992990

Serum insulin-like growth factor-1 levels in females and males in different cervical vertebral maturation stages.

Science.gov (United States)

Gupta, Shreya; Deoskar, Anuradha; Gupta, Puneet; Jain, Sandhya

2015-01-01

The aim of this cross sectional study was to assess serum insulin-like growth factor-1 (IGF-1) levels in female and male subjects at various cervical vertebral maturation (CVM) stages. The study sample consisted of 60 subjects, 30 females and 30 males, in the age range of 8-23 years. For all subjects, serum IGF-1 level was estimated from blood samples by means of chemiluminescence immunoassay (CLIA). CVM was assessed on lateral cephalograms using the method described by Baccetti. Serum IGF-1 level and cervical staging data of 30 female subjects were included and taken from records of a previous study. Data were analyzed by Kruska-Wallis and Mann Whitney test. Bonferroni correction was carried out and alpha value was set at 0.003. Peak value of serum IGF-1 was observed in cervical stages CS3 in females and CS4 in males. Differences between males and females were observed in mean values of IGF-1 at stages CS3, 4 and 5. The highest mean IGF-1 levels in males was observed in CS4 followed by CS5 and third highest in CS3; whereas in females the highest mean IGF-1 levelswas observed in CS3 followed by CS4 and third highest in CS5. Trends of IGF-1 in relation to the cervical stages also differed between males and females. The greatest mean serum IGF-1 value for both sexes was comparable, for females (397 ng/ml) values were slightly higher than in males (394.8 ng/ml). Males and females showed differences in IGF-1 trends and levels at different cervical stages.

MiR-223 suppresses cell proliferation by targeting IGF-1R.

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Cheng You Jia

Full Text Available To study the roles of microRNA-223 (miR-223 in regulation of cell growth, we established a miR-223 over-expression model in HeLa cells infected with miR-223 by Lentivirus pLL3.7 system. We observed in this model that miR-223 significantly suppressed the proliferation, growth rate, colony formation of HeLa cells in vitro, and in vivo tumorigenicity or tumor formation in nude mice. To investigate the mechanisms involved, we scanned and examined the potential and putative target molecules of miR-223 by informatics, quantitative PCR and Western blot, and found that insulin-like growth factor-1 receptor (IGF-1R was the functional target of miR-223 inhibition of cell proliferation. Targeting IGF-1R by miR-223 was not only seen in HeLa cells, but also in leukemia and hepatoma cells. The downstream pathway, Akt/mTOR/p70S6K, to which the signal was mediated by IGF-1R, was inhibited as well. The relative luciferase activity of the reporter containing wild-type 3'UTR(3'untranslated region of IGF-1R was significantly suppressed, but the mutant not. Silence of IGF-1R expression by vector-based short hairpin RNA resulted in the similar inhibition with miR-223. Contrarily, rescued IGF-1R expression in the cells that over-expressed miR-223, reversed the inhibition caused by miR-223 via introducing IGF-1R cDNA that didn't contain the 3'UTR. Meanwhile, we also noted that miR-223 targeted Rasa1, but the downstream molecules mediated by Rasa1 was neither targeted nor regulated. Therefore we believed that IGF-1R was the functional target for miR-223 suppression of cell proliferation and its downstream PI3K/Akt/mTOR/p70S6K pathway suppressed by miR-223 was by targeting IGF-1R.

The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

Energy Technology Data Exchange (ETDEWEB)

Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Hidalgo, Cecilia [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Lavandero, Sergio, E-mail: slavander@uchile.cl [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile)

2009-10-09

Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal {alpha}-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

International Nuclear Information System (INIS)

Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo; Hidalgo, Cecilia; Lavandero, Sergio

2009-01-01

Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal α-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

INSULIN-LIKE GROWTH FACTOR-1 (IGF-1: DEMOGRAPHIC, CLINICAL AND LABORATORY DATA IN 120 CONSECUTIVE ADULT PATIENTS WITH THALASSAEMIA MAJOR

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V. De Sanctis

2014-11-01

Full Text Available Introduction:  Insulin-like growth factor 1 (IGF-1 is a key peptide involved in cell growth and protein turnover, acting as the primary mediator of many of the responses regulated by growth hormone (GH in tissues. Signs and symptoms of adult GH deficiency (AGHD in patients with β-thalassaemia major (TM  may be subtle and overlap with those of the disease itself; therefore, the diagnosis may be missed or delayed, with potentially serious consequences. The diagnosis of AGHD requires an appropriate clinical setting and is confirmed through biochemical testing. The  aim of this study  was  to measure IGF-1 values and other clinical data in a large number of adult  patients with TM and to  evaluate whether an  IGF-1 concentration 2 SDs below normative values  could be used as an effective index supporting  the probable presence of  AGHD. Patients and Methods: A cohort of 120 adult patients with TM was studied for plasma levels of IGF-1. Plasma total IGF-1 was determined by chemiluminescent immunometric assay (CLIA method. In eleven patients (4 males the GH response during glucagon stimulation test (GST was also evaluated.  Results:  Fifty percent of patients (33 males and 27 females had IGF-1 levels   -2SDs. In multivariate regression analyses,  height, weight, BMI, serum ferritin, ALT, HCV serology and left ventricular ejection fraction (LVEF were not significantly related to IGF-1,  but a significant correlation was found in females between HCV-RNA positivity and IGF-1, ALT and serum ferritin (p= 0.043. AGHD was diagnosed in 6 (4 males out of 11 patients (54.5% who had glucagon stimulation tests and in 5 out of 8 (62.5% with IGF-1 <-2SD. The mean age of patients with GHD was 39.3 years (range: 25-49 years versus 35.8 years (range: 27-45 years in non-GHD patients. A positive correlation between GH peak after GST and IGF-1 level was found (r: 0.6409; p: < 0.05. Conclusions: On the basis of the present results and data from the

Role of insulin-like growth factor-1 (IGF-1) in regulating cell cycle progression

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Ma, Qi-lin; Yang, Tian-lun [Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Yin, Ji-ye [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Peng, Zhen-yu [Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Yu, Min [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Liu, Zhao-qian, E-mail: liuzhaoqian63@126.com [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Chen, Fang-ping, E-mail: xychenfp@public.cs.hn.Cn [Department of Haematology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China)

2009-11-06

Aims: Insulin-like growth factor-1 (IGF-1) is a polypeptide protein hormone, similar in molecular structure to insulin, which plays an important role in cell migration, cell cycle progression, cell survival and proliferation. In this study, we investigated the possible mechanisms of IGF-1 mediated cell cycle redistribution and apoptosis of vascular endothelial cells. Method: Human umbilical vein endothelial cells (HUVECs) were pretreated with 0.1, 0.5, or 2.5 {mu}g/mL of IGF-1 for 30 min before the addition of Ang II. Cell cycle redistribution and apoptosis were examined by flow cytometry. Expression of Ang II type 1 (AT{sub 1}) mRNA and cyclin E protein were determined by RT-PCR and Western blot, respectively. Results: Ang II (1 {mu}mol/L) induced HUVECs arrested at G{sub 0}/G{sub 1}, enhanced the expression level of AT{sub 1} mRNA in a time-dependent manner, reduced the enzymatic activity of nitric oxide synthase (NOS) and nitric oxide (NO) content as well as the expression level of cyclin E protein. However, IGF-1 enhanced NOS activity, NO content, and the expression level of cyclin E protein, and reduced the expression level of AT{sub 1} mRNA. L-NAME significantly counteracted these effects of IGF-1. Conclusions: Our data suggests that IGF-1 can reverse vascular endothelial cells arrested at G{sub 0}/G{sub 1} and apoptosis induced by Ang II, which might be mediated via a NOS-NO signaling pathway and is likely associated with the expression levels of AT1 mRNA and cyclin E proteins.

Changes in Insulin-like Growth Factor-1 Level in Patients with Sepsis and Septic Shock

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Sang Hoon Lee

2016-11-01

Full Text Available Background Despite many ongoing, prospective studies on the topic, sepsis still remains one of the main causes of death in hospital. The hormone insulin-like growth factor 1 (IGF-1 has a similar molecular structure to that of insulin. IGF-1 exerts anabolic effects and plays important roles in both normal physiology and pathologic processes. Previous studies have observed low serum IGF-1 level in patients with critical illnesses. Here, we evaluated changes in IGF-1 level based on survival of septic patients. Methods We evaluated 140 patients with sepsis and septic shock (21 with sepsis and 119 with septic shock admitted to the intensive care unit of a university-affiliated hospital in Korea. Serum IGF-1 level was measured on days 0, 1, 3, and 7. Patients with liver disease were excluded from this study. All data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA. Results Patients with septic shock had significantly lower serum IGF-1 level on days 1 and 3 than patients without septic shock (p = 0.002 and p = 0.007, respectively. Generally, there was a negative relationship between IGF-1 and serum cortisol levels; however, this relationship was only significant on day 3 (p = 0.029. Furthermore, renin showed significantly negative correlation with IGF-1 on day 3 (p = 0.038. IGF-1 level did not show significant difference between survivors and non-survivors. Conclusions Our results showed that IGF-1 was associated with septic shock, and that the IGF-1 axis is severely disrupted in septic patients. Additionally, serum cortisol and renin levels were associated with IGF-1 level.

IGF-1 protects cardiac myocytes from hyperosmotic stress-induced apoptosis via CREB

International Nuclear Information System (INIS)

Maldonado, Carola; Cea, Paola; Adasme, Tatiana; Collao, Andres; Diaz-Araya, Guillermo; Chiong, Mario; Lavandero, Sergio

2005-01-01

Hyperosmotic stress stimulates a rapid and pronounced apoptosis in cardiac myocytes which is attenuated by insulin-like growth factor-1 (IGF-1). Because in these cells IGF-1 induces intracellular Ca 2+ increase, we assessed whether the cyclic AMP response element-binding protein (CREB) is activated by IGF-1 through Ca 2+ -dependent signalling pathways. In cultured cardiac myocytes, IGF-1 induced phosphorylation (6.5 ± 1.0-fold at 5 min), nuclear translocation (30 min post-stimulus) and DNA binding activity of CREB. IGF-1-induced CREB phosphorylation was mediated by MEK1/ERK, PI3-K, p38-MAPK, as well as Ca 2+ /calmodulin kinase and calcineurin. Exposure of cardiac myocytes to hyperosmotic stress (sorbitol 600 mOsm) decreased IGF-1-induced CREB activation Moreover, overexpression of a dominant negative CREB abolished the anti-apoptotic effects of IGF-1. Our results suggest that IGF-1 activates CREB through a complex signalling pathway, and this transcription factor plays an important role in the anti-apoptotic action of IGF-1 in cultured cardiac myocytes

IGF-1 and insulin as growth hormones.

Science.gov (United States)

Laron, Zvi

2004-01-01

IGF-1 generated in the liver is the anabolic effector and linear growth promoting hormone of the pituitary growth hormone (GH). This is evidenced by dwarfism in states of congenital IGF-1 deficiency, Igf1 gene mutation/deletions or knockouts, and in Laron syndrome (LS), due to GH receptor gene mutations/deletions or IGF-1 receptor blocking. In a positive way, daily IGF-1 administration to stunted patients with LS or hGH gene deletion accelerates linear growth velocity. IGF-1 acts on the proliferative cells of the epiphyseal cartilage. IGF-1 also induces organ and tissue growth; its absence causing organomicria. Insulin shares a common ancestry with IGF-1 and with 45% amino acid homology, as well as very close relationships in the structure of its receptors and post-receptor cascade, also acts as a growth hormone. It has protein anabolic activity and stimulates IGF-1 synthesis. Pancreas agenesis causes short babies, and obese children with hyperinsulinism, with or without pituitary GH, have an accelerated growth rate and skeletal maturation; so do babies with macrosomia. Whether the insulin growth effect is direct, or mediated by IGF-1 or leptin is controversial.

Effects of short-term caloric restriction on circulating free IGF-I, acid-labile subunit, IGF-binding proteins (IGFBPs)-1-4, and IGFBPs-1-3 protease activity in obese subjects

DEFF Research Database (Denmark)

Rasmussen, Michael Højby; Juul, Anders; Kjems, Lise Lund

2006-01-01

, no published data exist on free IGF-I levels, acid labile subunit (ALS), or IGFBP protease activity in relation to GH release during a hypocaloric diet. The main purpose of this study was to determine free IGF-I, ALS, IGFBPs-1-4, and IGFBPs-1-3 protease activity in relation to 24-h GH release before and after......Decreased levels of GH and total IGF-I have been reported in obesity. It has been hypothesized that increased free (biologically active) IGF-I levels generated from IGF-binding protein (IGFBP) protease activity could be the mechanism for the low GH release in dieting obese subjects. However...... a short-term very low-calorie diet (VLCD)....

Effects of short-term caloric restriction on circulating free IGF-I, acid-labile subunit, IGF-binding proteins (IGFBPs)-1-4, and IGFBPs-1-3 protease activity in obese subjects

DEFF Research Database (Denmark)

Rasmussen, Michael Højby; Juul, Anders; Kjems, Lise Lund

2006-01-01

Decreased levels of GH and total IGF-I have been reported in obesity. It has been hypothesized that increased free (biologically active) IGF-I levels generated from IGF-binding protein (IGFBP) protease activity could be the mechanism for the low GH release in dieting obese subjects. However......, no published data exist on free IGF-I levels, acid labile subunit (ALS), or IGFBP protease activity in relation to GH release during a hypocaloric diet. The main purpose of this study was to determine free IGF-I, ALS, IGFBPs-1-4, and IGFBPs-1-3 protease activity in relation to 24-h GH release before and after...... a short-term very low-calorie diet (VLCD)....

IGF-1 deficiency impairs cerebral myogenic autoregulation in hypertensive mice.

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Toth, Peter; Tucsek, Zsuzsanna; Tarantini, Stefano; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Koller, Akos; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2014-12-01

Aging impairs autoregulatory protection in the brain, exacerbating hypertension-induced cerebromicrovascular injury, neuroinflammation, and development of vascular cognitive impairment. Despite the importance of the age-related decline in circulating insulin-like growth factor-1 (IGF-1) levels in cerebrovascular aging, the effects of IGF-1 deficiency on functional adaptation of cerebral arteries to high blood pressure remain elusive. To determine whether IGF-1 deficiency impairs autoregulatory protection, hypertension was induced in control and IGF-1-deficient mice (Igf1(f/f)+TBG-iCre-AAV8) by chronic infusion of angiotensin-II. In hypertensive control mice, cerebral blood flow (CBF) autoregulation was extended to higher pressure values and the pressure-induced tone of middle cerebral arteries (MCAs) was increased. In hypertensive IGF-1-deficient mice, autoregulation was markedly disrupted, and MCAs did not show adaptive increases in myogenic tone. In control mice, the mechanism of adaptation to hypertension involved upregulation of TRPC channels in MCAs and this mechanism was impaired in hypertensive IGF-1-deficient mice. Likely downstream consequences of cerebrovascular autoregulatory dysfunction in hypertensive IGF-1-deficient mice included exacerbated disruption of the blood-brain barrier and neuroinflammation (microglia activation and upregulation of proinflammatory cytokines and chemokines), which were associated with impaired hippocampal cognitive function. Collectively, IGF-1 deficiency impairs autoregulatory protection in the brain of hypertensive mice, potentially exacerbating cerebromicrovascular injury and neuroinflammation mimicking the aging phenotype.

Early changes of serum insulin-like growth factor-II (IGF-II) levels in patients with acute brain injury

International Nuclear Information System (INIS)

Liu Cegang; Zhang Xinlu; Tao Jin; Xu Anding; Xu Shanshui; Huang Zhenpeng

2003-01-01

Objective: To investigate the early changes and clinical significance of serum Insulin-like growth factor-II (IGF-II) levels in patients with acute brain injury. Methods: Radioimmunoassay was used for measurement of the serum IGF-II concentration in 30 controls and 29 acute brain injury patients before and after treatment (within 1 day, at 3 and 7 days). Results: The serum IGF-II levels in brain injury patients at 1 day, 3 day 7 days after injury were 0.131 ± 0.047 ng/ml, 0.117 ± 0.046 ng/ml and 0.123 ±0.050 ng/ml respectively and were significantly lower than those in controls 0.44 ± 0.014 ng/ml, p<0.01. Differences among the values of the three days were not significant. Conclusion: IGF-II might play important role in the pathophysiological process of early acute brain injury

Cross-talk between Integrin α6β4 and Insulin-like Growth Factor-1 Receptor (IGF1R) through Direct α6β4 Binding to IGF1 and Subsequent α6β4-IGF1-IGF1R Ternary Complex Formation in Anchorage-independent Conditions*

OpenAIRE

Fujita, Masaaki; Ieguchi, Katsuaki; Davari, Parastoo; Yamaji, Satoshi; Taniguchi, Yukimasa; Sekiguchi, Kiyotoshi; Takada, Yoko K.; Takada, Yoshikazu

2012-01-01

Background: Integrin αvβ3-extracellular matrix interaction and/or αvβ3 binding to insulin-like growth factor-1 (IGF1; and integrin-IGF1-IGF1 receptor ternary complex formation) is critical for IGF signaling.

Preclinical screening for retinopathy of prematurity risk using IGF1 levels at 3 weeks post-partum.

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Alejandro Pérez-Muñuzuri

Full Text Available Following current recommendations for preventing retinopathy of prematurity (ROP involves screening a large number of patients. We performed a prospective study to establish a useful screening system for ROP prediction and we have determined that measuring serum levels of IGF1 at week three and the presence of sepsis have a high predictive value for the subsequent development of ROP. A total of 145 premature newborn, with birthweight <1500 g and/or <32 weeks gestational age, were enrolled. 26.9% of them showed some form of retinopathy. A significant association was found between the development of retinopathy and each of the following variables: early gestational age, low birthweight, requiring mechanical ventilation, oxygen treatment, intracranial haemorrhage, sepsis during the first three weeks, bronchopulmonary dysplasia, the need for erythrocyte transfusion, erythropoietin treatment, and low levels of serum IGF1 in the third week. A multiple logistic regression analysis was used to obtain curves for the probability of developing ROP, based on the main factors linked with ROP, namely serum levels of IGF1 and presence of sepsis. Such preclinical screening has the ability to identify patients with high-risk of developing retinopathy and should lead to better prediction for ROP, while at the same time optimising the use of clinical resources, both human and material.

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan.

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Ashpole, Nicole M; Logan, Sreemathi; Yabluchanskiy, Andriy; Mitschelen, Matthew C; Yan, Han; Farley, Julie A; Hodges, Erik L; Ungvari, Zoltan; Csiszar, Anna; Chen, Sixia; Georgescu, Constantin; Hubbard, Gene B; Ikeno, Yuji; Sonntag, William E

2017-04-01

Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igf f/f C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.

Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production.

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Courtland, Hayden-William; Sun, Hui; Beth-On, Mordechay; Wu, Yingjie; Elis, Sebastien; Rosen, Clifford J; Yakar, Shoshana

2011-04-01

Deficiencies in either growth hormone (GH) or insulin-like growth factor 1 (IGF-1) are associated with reductions in bone size during growth in humans and animal models. Liver-specific IGF-1-deficient (LID) mice, which have 75% reductions in serum IGF-1, were created previously to separate the effects of endocrine (serum) IGF-1 from autocrine/paracrine IGF-1. However, LID mice also have two- to threefold increases in GH, and this may contribute to the observed pubertal skeletal phenotype. To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age. Treatment of LID mice with pegvisomant resulted in significant reductions in body weight, femur length (Le), and femur total area (Tt.Ar), as well as further reductions in serum IGF-1 levels by 8 weeks of age, compared with the mean values of vehicle-treated LID mice. Reductions in both Tt.Ar and Le were proportional after treatment with pegvisomant. On the other hand, the relative amount of cortical tissue formed (RCA) in LID mice treated with pegvisomant was significantly less than that in both vehicle-treated LID and control mice, indicating that antagonizing GH action, either directly (through GH receptor signaling inhibition) or indirectly (through further reductions in serum/tissue IGF-1 levels), results in disproportionate reductions in the amount of cortical bone formed. This resulted in bones with significantly reduced mechanical properties (femoral whole-bone stiffness and work to failure were markedly decreased), suggesting that compensatory increases of GH in states of IGF-1 deficiency (LID mice) act to protect against a severe inhibition of bone modeling during growth, which otherwise would result in bones that are too weak for normal and/or extreme loading conditions. Copyright © 2011 American Society for

Early programming of the IGF-I axis

DEFF Research Database (Denmark)

Larnkjær, Anni; Ingstrup, Helga Kristensen; Schack-Nielsen, Lene

2009-01-01

-I production. Conversely, studies suggest that later in childhood, those breastfed are taller and have higher IGF-I levels. Therefore, it has been suggested that the IGF-I axis may be programmed by diet during infancy. The association between IGF-I in infancy and later life is not known. OBJECTIVE: To examine...... for gender, breastfeeding, and other covariates. Likelihood ratio test based on residual log likelihood was applied for analysis including all measurements during infancy. RESULTS: There was an inverse association between IGF-I at 9 months and 17 years (r=-0.39, P=0.014, and n=40). A 1 ng/ml higher IGF...... covariates except IGF-I at 2 months which was significantly negatively associated with IGF-I at 17 years (P=0.030) corresponding to a 0.96 ng/ml lower IGF-I concentration at 17 years per ng/ml IGF-I at 2 months. Inclusion of all measurements during infancy showed a negative association with 17-year values (r...

Serum insulin-like growth factor-1 levels in females and males in different cervical vertebral maturation stages

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Shreya Gupta

2015-04-01

Full Text Available OBJECTIVE: The aim of this cross sectional study was to assess serum insulin-like growth factor-1 (IGF-1 levels in female and male subjects at various cervical vertebral maturation (CVM stages. MATERIAL AND METHODS: The study sample consisted of 60 subjects, 30 females and 30 males, in the age range of 8-23 years. For all subjects, serum IGF-1 level was estimated from blood samples by means of chemiluminescence immunoassay (CLIA. CVM was assessed on lateral cephalograms using the method described by Baccetti. Serum IGF-1 level and cervical staging data of 30 female subjects were included and taken from records of a previous study. Data were analyzed by Kruska-Wallis and Mann Whitney test. Bonferroni correction was carried out and alpha value was set at 0.003. RESULTS: Peak value of serum IGF-1 was observed in cervical stages CS3 in females and CS4 in males. Differences between males and females were observed in mean values of IGF-1 at stages CS3, 4 and 5. The highest mean IGF-1 levels in males was observed in CS4 followed by CS5 and third highest in CS3; whereas in females the highest mean IGF-1 levelswas observed in CS3 followed by CS4 and third highest in CS5. Trends of IGF-1 in relation to the cervical stages also differed between males and females. The greatest mean serum IGF-1 value for both sexes was comparable, for females (397 ng/ml values were slightly higher than in males (394.8 ng/ml. CONCLUSIONS: Males and females showed differences in IGF-1 trends and levels at different cervical stages.

Clinical significance of measurement of changes of serum IGF-II and NO levels after treatment in elderly patients with chronic bronchitis

International Nuclear Information System (INIS)

Gu Tao

2006-01-01

Objective: To study the clinical significance of changes of serum IGF-II and NO levels after treatment in elderly patients with chronic bronchitis. Methods: Serum IGF-II (with RIA) and NO (with Biochemical method) levels were measured in 42 elderly patients with chronic bronchitis both before and after treatment as well as in 30 controls. Results: Before treatment in the patients the serum IGF-II levels were significantly higher than those in controls (P<0.01), while the NO levels were significantly lower (P<0.01). After two weeks of treatment, the levels though dropped markedly, lemained higher than those in controls (P<0. 05). Conclusion: Serum IGF-II and NO levels changes could reflect the disease status as well as the progress of diseases. (authors)

Changes of serum insulin-like growth factor-1 and growth hormone levels in patients with Graves' disease

International Nuclear Information System (INIS)

Jin Yueling; Xie Kejian; Xia Yuxiang; Pan Furong

2003-01-01

Objective: To investigate the changes of serum insulin-like growth factor-1(IGF-1) and growth hormone (GH) levels in patients with Graves' disease (GD). Methods: The serum IGF-1 and GH levels were determined with RIA in 42 cases of GD, 20 cases of GD patients after therapy (in euthyroid state) and 30 normal controls. Results: The level of serum IGF-1 (170.8±44.4 ng/ml) and GH (2.80±1.18 ng/ml) were significantly higher in GD patients than those in controls [IGF-1 (90.5±30.5 ng/ml), GH(1.58±1.20 ng/ml)] (p<0.01, p<0.05). IGF-1 levels were positively correlated to FT4 levels (r=0.58, p<0.01). The levels of serum IGF-1 (110.4±33.2 ng/ml) and GH (1.71±1.36 ng/ml) after treatment were significantly lower than those before treatment (p<0.01, p<0.05). Conclusion: The levels of serum IGF-1 and GH were markedly increase in GD patients and might be influenced by changes of thyroid hormone levels

A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

International Nuclear Information System (INIS)

Dearth, Robert K; Kuiatse, Isere; Wang, Yu-Fen; Liao, Lan; Hilsenbeck, Susan G; Brown, Powel H; Xu, Jianming; Lee, Adrian V

2011-01-01

Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm 3 . For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Using the first transgenic animal model to

Mechanisms Underlying Testicular Damage and Dysfunction in Mice With Partial IGF-1 Deficiency and the Effectiveness of IGF-1 Replacement Therapy.

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Castilla-Cortázar, Inma; Gago, Alberto; Muñoz, Úrsula; Ávila-Gallego, Elena; Guerra-Menéndez, Lucía; Sádaba, María Cruz; García-Magariño, Mariano; Olleros Santos-Ruiz, María; Aguirre, G A; Puche, Juan Enrique

2015-12-01

To determine whether insulin-like growth factor (IGF-1) deficiency can cause testicular damage and to examine changes of the testicular morphology and testicular function-related gene expression caused by IGF-1 deficiency. Therefore, this study aims to determine the benefits of low doses of IGF-1 and to explore the mechanisms underlying the IGF-1 replacement therapy. A murine model of IGF-1 deficiency was used to avoid any factor that could contribute to testicular damage. Testicular weight, score of histopathological damage, and gene expressions were studied in 3 experimental groups of mice: controls (wild-type Igf1(+/+)), heterozygous Igf1(+/-) with partial IGF-1 deficiency, and heterozygous Igf1(+/-) treated with IGF-1. Results show that the partial IGF-1 deficiency induced testicular damage and altered expression of genes involved in IGF-1 and growth hormone signaling and regulation, testicular hormonal function, extracellular matrix establishment and its regulation, angiogenesis, fibrogenesis, inflammation, and cytoprotection. In addition, proteins involved in tight junction expression were found to be reduced. However, low doses of IGF-1 restored the testicular damage and most of these parameters. IGF-1 deficiency caused the damage of the blood-testis barrier and testicular structure and induced the abnormal testicular function-related gene expressions. However, low doses of IGF-1 constitute an effective replacement therapy that restores the described testicular damage. Data herein show that (1) cytoprotective activities of IGF-1 seem to be mediated by heat shock proteins and that (2) connective tissue growth factor could play a relevant role together with IGF-1 in the extracellular matrix establishment. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of phosphorylatable short peptide-conjugated chitosan-mediated IL-1Ra and igf-1 gene transfer on articular cartilage defects in rabbits.

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Ronglan Zhao

Full Text Available Previously, we reported an improvement in the transfection efficiency of the plasmid DNA-chitosan (pDNA/CS complex by the utilization of phosphorylatable short peptide-conjugated chitosan (pSP-CS. In this study, we investigated the effects of pSP-CS-mediated gene transfection of interleukin-1 receptor antagonist protein (IL-1Ra combined with insulin-like growth factor-1 (IGF-1 in rabbit chondrocytes and in a rabbit model of cartilage defects. pBudCE4.1-IL-1Ra+igf-1, pBudCE4.1-IL-1Ra and pBudCE4.1-igf-1 were constructed and combined with pSP-CS to form pDNA/pSP-CS complexes. These complexes were transfected into rabbit primary chondrocytes or injected into the joint cavity. Seven weeks after treatment, all rabbits were sacrificed and analyzed. High levels of IL-1Ra and igf-1 expression were detected both in the cell culture supernatant and in the synovial fluid. In vitro, the transgenic complexes caused significant proliferation of chondrocytes, promotion of glycosaminoglycan (GAG and collagen II synthesis, and inhibition of chondrocyte apoptosis and nitric oxide (NO synthesis. In vivo, the exogenous genes resulted in increased collagen II synthesis and reduced NO and GAG concentrations in the synovial fluid; histological studies revealed that pDNA/pSP-CS treatment resulted in varying degrees of hyaline-like cartilage repair and Mankin score decrease. The co-expression of both genes produced greater effects than each single gene alone both in vitro and in vivo. The results suggest that pSP-CS is a good candidate for use in gene therapy for the treatment of cartilage defects and that igf-1 and IL-1Ra co-expression produces promising biologic effects on cartilage defects.

Development and clinical evaluation of a novel immunoassay for the binary complex of IGF-I and IGF-binding protein-1 in human serum

DEFF Research Database (Denmark)

Frystyk, Jan; Højlund, Kurt; Rasmussen, Kirsten Nyborg

2002-01-01

Correlation studies have suggested that IGF-binding protein (IGFBP)-1 is a dynamic regulator of free IGF-I. To further study this, we developed a monoclonal immunofluorometric assay specific for the binary complex of IGF-I and IGFBP-1 in human serum. An IGFBP-1 antibody, which recognizes all...... phospho-forms of IGFBP-1, was used for coating. An europium-labeled IGF-I antibody served as tracer. Assay incubation was performed at conditions approaching those in vivo (i.e. pH 7.4, 37 C). The assay was highly specific: no signal was obtained unless both IGF-I and IGFBP-1 were present and neither...

Possible effects of insulin-like growth factor-I, IGF-binding protein-3 and IGF-1/IGFBP-3 molar ratio on mammographic density: a cross-sectional study.

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Meggiorini, M L; Cipolla, V; Borgoni, G; Nofroni, I; Pala, A; de Felice, C

2012-01-01

The purpose of this study was to examine the possible effects of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio on mammographic density and assess whether this relationship was similar in subgroups of pre- and postmenopausal women. A group of 341 Italian women of childbearing age or naturally postmenopausal who had performed mammographic examination at the section of radiology of our department a maximum three months prior to recruitment were enrolled. A blood sample was drawn for determination of IGF-1, IGFBP-3 levels and IGF-1/IGFBP-3 molar ratio was calculated. On the basis of recent mammograms the women were divided into two groups: dense breast (DB) and non-dense breast (NDB). To assess the association between mammographic density and IGF-1, IGFBP-3 and Molar ratio Student's t-test was employed before and after stratified by menopausal status. The analysis of the relationship between mammographic density and plasma levels of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio showed that IGF-1 levels and molar ratio varied in the two groups resulting in higher mean values in the DB group whereas IGFBP-3 showed similar values in both groups (DB and NDB). After stratification of the study population by menopausal status, no association was found. Our study provides strong evidence of a crude association between breast density, and plasma levels of IGF-1 and molar ratio. IGF-1 and molar ratio might increase mammographic density and thus the risk of developing breast cancer.

IGF-1 and Insulin Resistance Are Major Determinants of Common Carotid Artery Thickness in Morbidly Obese Young Patients.

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Sirbu, Anca; Nicolae, Horia; Martin, Sorina; Barbu, Carmen; Copaescu, Catalin; Florea, Suzana; Panea, Cristina; Fica, Simona

2016-03-01

We assessed the relationship between insulin resistance, serum insulin-like growth factor 1 (IGF-1) levels, and common carotid intima-media thickness (CC-IMT) in morbidly obese young patients. A total of 249 patients (aged 37.9 ± 9.8 years, body mass index [BMI] 45.6 ± 8.3 kg/m(2)) were evaluated (metabolic tests, serum IGF-1 measurements, homeostasis model assessment-insulin resistance [HOMA-IR], and ultrasonographically assessed CC-IMT) in a research program for bariatric surgery candidates. After adjusting for age, gender, BMI, systolic blood pressure, uric acid, antihypertensive and lipid-lowering treatment, metabolic syndrome, and metabolic class, both HOMA-IR and IGF-1 z-score were significantly associated with CC-IMT. These results were confirmed in logistic regression analysis, in which age (β = 1.11, P = .001), gender (β = 3.19, P = .001), HOMA-IR (β = 1.221, P = .005), and IGF-1 z-score (β = 1.734, P = .009) were the only independent determinants of abnormal CC-IMT, presumably modulating the effect of the other risk factors included in the regression. Area under the receiver-operating characteristic curve for the model was 0.841 (confidence interval: 0.776-0.907; P IGF-1 z-score are significantly associated with CC-IMT, independent of other major cardiovascular risk factors. © The Author(s) 2015.

Impaired IGF1R signaling in cells expressing longevity-associated human IGF1R alleles

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Tazearslan, Cagdas; Huang, Jing; Barzilai, Nir; Suh, Yousin

2011-01-01

Dampening of insulin/insulin like growth factor-1 (IGF1) signaling results in extension of lifespan in invertebrate as well as murine models. The impact of this evolutionarily conserved pathway on modulation of human lifespan remains unclear. We previously identified two IGF1R mutations (Ala-37-Thr and Arg-407-His) that are enriched in Ashkenazi Jewish centenarians as compared to younger controls and are associated with reduced activity of the IGF1 receptor as measured in immortalized lymphoc...

Levels and clinical significance of serum IGF-II in patients with five kinds of malignant tumors

International Nuclear Information System (INIS)

Qi Falian; Xu Jun; Du Xiumin; Ke Bingkun; Yang Daoli

2002-01-01

Objective: To study the levels and clinical significance of serum IGF-II in patients with malignant tumor. Methods: Levels of serum IGF-II were detected in patients with gastric cancer, lung cancer, liver cancer, ovarian carcinoma and endometrial carcinoma by radioimmunoassay, levels in patients with hepatic cirrhosis, uterine myoma and normal controls were also determined for comparison. Results: The levels of serum IGF-II in patients with gastric cancer, lung cancer and liver cancer were significantly higher than those in normal controls (p 0.05). Conclusion: The determination of serum IGF-II has no clinical significance in patients with endometrial carcinoma, ovarian carcinoma and uterine myoma but it could be useful to judge the severity and evaluate the prognosis in patients with gastric cancer, lung cancer, liver cancer and cirrhosis

Branchial expression and localization of the insulin-like growth factor 1 (IGF-1) receptor and changes in plasma IGF-1 and IGF-1 binding protein in striped bass during salinity acclimation

DEFF Research Database (Denmark)

Tipsmark, Christian Kølbæk; Madsen, Steffen; Borski, Russell

2006-01-01

In euryhaline teleosts the insulin-like growth factor 1 (IGF-1)/growth hormone axis is known to affect salinity tolerance and gill Na,K-ATPase activity. However, virtually nothing is known on expression and cellular localization of the IGF-1 receptor (IGF-1R) in the teleost gill during salinity a...

IRS-1 acts as an endocytic regulator of IGF-I receptor to facilitate sustained IGF signaling.

Science.gov (United States)

Yoneyama, Yosuke; Lanzerstorfer, Peter; Niwa, Hideaki; Umehara, Takashi; Shibano, Takashi; Yokoyama, Shigeyuki; Chida, Kazuhiro; Weghuber, Julian; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

2018-04-11

Insulin-like growth factor-I receptor (IGF-IR) preferentially regulates the long-term IGF activities including growth and metabolism. Kinetics of ligand-dependent IGF-IR endocytosis determines how IGF induces such downstream signaling outputs. Here, we find that the insulin receptor substrate (IRS)-1 modulates how long ligand-activated IGF-IR remains at the cell surface before undergoing endocytosis in mammalian cells. IRS-1 interacts with the clathrin adaptor complex AP2. IRS-1, but not an AP2-binding-deficient mutant, delays AP2-mediated IGF-IR endocytosis after the ligand stimulation. Mechanistically, IRS-1 inhibits the recruitment of IGF-IR into clathrin-coated structures; for this reason, IGF-IR avoids rapid endocytosis and prolongs its activity on the cell surface. Accelerating IGF-IR endocytosis via IRS-1 depletion induces the shift from sustained to transient Akt activation and augments FoxO-mediated transcription. Our study establishes a new role for IRS-1 as an endocytic regulator of IGF-IR that ensures sustained IGF bioactivity, independent of its classic role as an adaptor in IGF-IR signaling. © 2018, Yoneyama et al.

MiRNA-199a-3p Regulates C2C12 Myoblast Differentiation through IGF-1/AKT/mTOR Signal Pathway

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Long Jia

2013-12-01

Full Text Available MicroRNAs constitute a class of ~22-nucleotide non-coding RNAs. They modulate gene expression by associating with the 3' untranslated regions (3' UTRs of messenger RNAs (mRNAs. Although multiple miRNAs are known to be regulated during myoblast differentiation, their individual roles in muscle development are still not fully understood. In this study, we showed that miR-199a-3p was highly expressed in skeletal muscle and was induced during C2C12 myoblasts differentiation. We also identified and confirmed several genes of the IGF-1/AKT/mTOR signal pathway, including IGF-1, mTOR, and RPS6KA6, as important cellular targets of miR-199a-3p in myoblasts. Overexpression of miR-199a-3p partially blocked C2C12 myoblast differentiation and the activation of AKT/mTOR signal pathway, while interference of miR-199a-3p by antisense oligonucleotides promoted C2C12 differentiation and myotube hypertrophy. Thus, our studies have established miR-199a-3p as a potential regulator of myogenesis through the suppression of IGF-1/AKT/mTOR signal pathway.

The relationship between serum IGF-1, handgrip strength, physical performance and falls in elderly men and women.

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Van Nieuwpoort, Caroline; Vlot, Mariska; Schaap, Laura; Lips, Paul; Drent, Madeleine

2018-05-22

Human aging is accompanied by a decrease in growth hormone secretion and serum IGF-1 levels. Also, loss of muscle mass, strength and impairment of physical performance, ending in a state of frailty, are seen in elderly. We aimed to investigate whether handgrip strength, physical performance and recurrent falls are related to serum IGF-1 levels in community dwelling elderly. Observational cohort study (cross-sectional and prospective). We studied the association between IGF-1 and handgrip strength, physical performance and falls in participants of the Longitudinal Aging Study Amsterdam. 1292 participants were included (633 men, 659 women). Serum IGF-1 levels were divided into quartiles (IGF-1-Q1 to IGF-1-Q4). Data on falls were collected prospectively for a period of three years. All analyses were stratified for age and physical activity and adjusted for relevant confounders. Men with a low physical activity score in IGF-1-Q1 and IGF-1-Q2 of the younger age group had a lower handgrip strength compared to IGF-1-Q4. In younger more active males in IGF-1-Q2 physical performance was worse. Recurrent fallers were less prevalent in older, low active males with low IGF-1 levels. In females, recurrent fallers were more prevalent in older, more active females in IGF-1-Q2. IGF-1 quartile may predict changes in handgrip strength and physical performance in men and women. Our results indicate that lower IGF-1 levels are associated with lower handgrip strength and worse physical performance, but less recurrent fallers especially in men. Associations were often more robust in IGF-1-Q2. Future studies on this topic are desirable.

IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms.

Science.gov (United States)

Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

2016-02-01

Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, whereas others report that loss of IGF-1 is beneficial because it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igf(f/f) mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan: early in postnatal development (crossing albumin-cyclic recombinase [Cre] mice with Igf(f/f) mice); and in early adulthood and in late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using micro-computed tomography (μCT) and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NF-κB-ligand (RANKL) levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2-fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data

Matrix metalloproteinase-1 facilitates MSC migration via cleavage of IGF-2/IGFBP2 complex.

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Guan, Shou P; Lam, Alan T L; Newman, Jennifer P; Chua, Kevin L M; Kok, Catherine Y L; Chong, Siao T; Chua, Melvin L K; Lam, Paula Y P

2018-01-01

The specific mechanism underlying the tumor tropism of human mesenchymal stem cells (MSCs) for cancer is not well defined. We previously showed that the migration potential of MSCs correlated with the expression and protease activity of matrix metalloproteinase (MMP)-1. Furthermore, highly tumor-tropic MSCs expressed higher levels of MMP-1 and insulin-like growth factor (IGF)-2 than poorly migrating MSCs. In this study, we examined the functional roles of IGF-2 and MMP-1 in mediating the tumor tropism of MSCs. Exogenous addition of either recombinant IGF-2 or MMP-1 could stimulate MSC migration. The correlation between IGF-2, MMP-1 expression, and MSC migration suggests that MMP-1 may play a role in regulating MSC migration via the IGF-2 signaling cascade. High concentrations of IGF binding proteins (IGFBPs) can inhibit IGF-stimulated functions by blocking its binding to its receptors and proteolysis of IGFBP is an important mechanism for the regulation of IGF signaling. We thus hypothesized that MMP-1 acts as an IGFBP2 proteinase, resulting in the cleavage of IGF-2/IGFBP2 complex and extracellular release of free IGF-2. Indeed, our results showed that conditioned media from highly migrating MSCs, which expressed high levels of MMP-1, cleaved the IGF-2/IGFBP2 complex. Taken together, these results showed that the MMP-1 secreted by highly tumor-tropic MSCs cleaved IGF-2/IGFBP2 complex. Free IGF-2 released from the complex may facilitate MSC migration toward tumor.

Serial analysis of resected prostate cancer suggests up-regulation of type 1 IGF receptor with disease progression.

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Turney, Benjamin W; Turner, Gareth D H; Brewster, Simon F; Macaulay, Valentine M

2011-05-01

• To compare immunostaining protocols using different antibodies for the type 1 insulin-like growth factor receptor (IGF-1R) in channel transurethal resection of the prostate (chTURP) chips, and to investigate how IGF-1R expression varies with time in serial prostate cancer specimens from individual patients. • We studied IGF-1R expression in 44 prostate cancer specimens from 18 patients who had undergone serial chTURP at least 3 months apart. • Retrospective analysis of the hospital notes was undertaken to obtain clinical information, including age, Gleason score, prostate-specific antigen (PSA) level, hormone treatment and metastatic disease status at the time of each operation. • After an optimization process using three commercially-available IGF-1R antibodies, we used two antibodies for semiquantititve immunostaining of serial chTURP chips. • Santa Cruz antibody sc713 gave positive staining in IGF-1R null R- cells, and was not used further. Antibodies from Cell Signaling Technology (Beverly, MA, USA) (CS) and NeoMarkers Inc. (Fremont, CA, USA) (NM) did not stain R- cells and, in prostate tissue, showed staining of the glandular epithelium, with negligible stromal staining. All 44 chTURP samples contained identifiable malignant tissue and, of these, 73% and 64% scored moderately or strongly (score 3 or 4) with the CS and NM antibodies respectively. • There was significant correlation of IGF-1R scores of malignant tissue between the two antibodies (P < 0.001). By contrast, staining of benign glands showed poor correlation between antibodies: CS gave significantly weaker staining than malignant epithelium in the same sections (P < 0.001), whereas NM showed poor discrimination between malignant and benign glands. IGF-1R staining scores generated by the CS antibody were used to analyze the clinical data. • Most patients (six of seven) with falling IGF-1R staining scores were responding to androgen deprivation therapy (confirmed by PSA response

Clinical significance of serum circulating insulin-like growth factor-1 (IGF-1) mRNA in hepatocellular carcinoma.

Science.gov (United States)

Karabulut, S; Duranyıldız, D; Tas, F; Gezer, U; Akyüz, F; Serilmez, M; Ozgür, E; Yasasever, C T; Vatansever, S; Aykan, N F

2014-03-01

The principal aim of our study was to investigate the usefulness of serum protein and circulating mRNA of insulin-like growth factor-1 (IGF-1) as a diagnostic and prognostic tool in hepatocellular carcinoma (HCC). Fifty-four HCC patients and age- and sex-matched 20 healthy controls were enrolled into this study. Pretreatment serum IGF-1 and IGF-1 mRNA were determined by the solid-phase sandwich ELISA and quantitative RT-PCR method, respectively. The median age at diagnosis was 60 years, range 36-77 years; where majority of group were male (n = 48, 88.8%). All patients had cirrhotic history. Forty-six percent (n = 25) of patients had Child-Pugh score A, 30% (n = 16) had score B or C. All of the patients were treated with local therapies and none of them received sorafenib. The baseline serum IGF-1 mRNA levels were significantly higher in HCC patients than in the control group (p = 0.04), whereas no significant difference was observed for IGF-1 protein levels between the two group (p = 0.18). Patients with history of HBV infection, who were not treated, and who received multiple palliative treatment for HCC had higher serum IGF-1 mRNA levels (p = 0.03, 0.03, and 0.05, respectively). Poor performance status (p IGF-1 nor serum IGF-1 mRNA had significantly adverse effect on survival (p = 0.53 and 0.42, respectively).

A polymorphism in the IGF-I gene influences the age-related decline in circulating total IGF-I levels

NARCIS (Netherlands)

I. Rietveld (Ingrid); J.A.M.J.L. Janssen (Joseph); A. Hofman (Albert); C.M. van Duijn (Cornelia); S.W.J. Lamberts (Steven); H.A.P. Pols (Huib)

2003-01-01

markdownabstractOBJECTIVE: Recent studies have demonstrated an association between a 192 bp polymorphism of the IGF-I gene and total IGF-I serum levels, birth weight, body height and the risk of developing diabetes and cardiovascular diseases later on in life. This IGF-I gene polymorphism in the

Serum insulin-like growth factor 1(IGF-I) and prostatic cancer risk a retrospective study

International Nuclear Information System (INIS)

Li Liren; Liu Jiumin; Lu Bailing

2001-01-01

Objective: To investigate the relationship between serum IGF-I levels and prostatic cancer. Methods: Serum IGF-I levels were determined by immunoradiometric assay (IRMA) in 30 cases of prostatic cancer, 30 cases of benign prostatic hyperplasia (BPH) and 30 healthy subjects as controls. Results: The mean levels of serum IGF-I in prostatic cancer (148 +- 49.6 μg/L) were significantly higher than those in BPH (91.0 +- 32.8 μg/L) and healthy subjects (105 +- 25.6 μg/L) (P 0.05). The IGF-I levels were not relates to BHP, but increased values of IGF-I were associated with increased risk of prostatic cancer. The odds ratio was 11.23 for patients of prostatic cancer compared with healthy subjects, (95 percent confidence interval 3.09 - 40.7). Conclusion: This finding suggests that high IGF-I may be associated with increase risk of prostate cancer in human

INFLUENCE OF INTRAMUSCULAR APPLICATION OF AUTOLOGOUS CONDITIONED PLASMA ON SYSTEMIC CIRCULATING IGF-1

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Gert Schippinger

2011-09-01

Full Text Available Platelet-rich plasma (PRP to increase levels of platelets and growth factors has been used for the treatment of sports injuries suggesting to improve healing and regeneration. This method offers some potential especially for elite athletes. However, the insulin like growth factor-1 (IGF-1 is prohibited by the World Anti Doping Agency and, in addition, there may be a possible link between increased levels of IGF-1 and cancer risk. Aim of the study was to evaluate a systemic increase of IGF-1 after local intramuscular administration of PRP in young healthy moderately trained male subjects. Blood samples were drawn and PRP preparation was performed by means of centrifugation. Enriched plasma was injected into the gluteus muscle. Venous blood was collected and serum prepared before as well as after 0.5, 3 and 24 hours after PRP administration. IGF-1 analysis was performed applying an ELISA test kit. No significant systemic increase of mean IGF-1 was found after the PRP injection. Only one subject showed an increase after 24 h, but all IGF-1 values were found within reference limits. We conclude that a single intramuscular application of PRP does not significantly increase systemic IGF-1 levels. Therefore, a single application of PRP is safe with respect to systemic IGF-1 response and cancer risk and this should be allowed for treatment of muscle injuries in elite athletes

Role of IGF-1/IGF-1R in regulation of invasion in DU145 prostate cancer cells

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Setya Hemani

2008-07-01

Full Text Available Abstract Background Prostate cancer progression to androgen independence is the primary cause of mortality by this tumor type. The IGF-1/IGF-1R axis is well known to contribute to prostate cancer initiation, but its contribution to invasiveness and the downstream signalling mechanisms that are involved are unclear at present. Results We examined the invasive response of androgen independent DU145 prostate carcinoma cells to IGF-1 stimulation using Matrigel assays. We then examined the signaling mechanisms and protease activities that are associated with this response. IGF-1 significantly increased the invasive capacity of DU145 cells in vitro, and this increase was inhibited by blocking IGF-1R. We further demonstrated that specific inhibitors of the MAPK and PI3-K pathways decrease IGF-1-mediated invasion. To determine potential molecular mechanisms for this change in invasive capacity, we examined changes in expression and activity of matrix metalloproteinases. We observed that IGF-1 increases the enzymatic activity of MMP-2 and MMP-9 in DU145 cells. These changes in activity are due to differences in expression in the case of MMP-9 but not in the case of MMP-2. This observation is corroborated by the fact that correlated changes of expression in a regulator of MMP-2, TIMP-2, were also seen. Conclusion This work identifies a specific effect of IGF-1 on the invasive capacity of DU145 prostate cancer cells, and furthermore delineates mechanisms that contribute to this effect.

Clinical significance of determination of changes of serum IGF-Ⅱ, L-6 levels after treatment in patients with child bronchopneumonia

International Nuclear Information System (INIS)

Yin Hongxia

2007-01-01

Objective: To study the clinical significance of changes of serum IGF-Ⅱ, L-6 levels after treatment in patients with child bronchopneumonia. Methods: Serum IGF-Ⅱ, L-6 levels were determined with RIA in 40 patients with child bronchopneumonia both before and after treatment as well as in 30 controls. Results: Before treatment, serum IGF-Ⅱ, L-6 levels in the patients were significantly higher than those in the controls (P 0.05). Conclusion: Determination serum IGF-Ⅱ, L-6 levels in patients with child bronchopneumonia was important for diagnosis and outcome prediction. (authors)

Development and clinical evaluation of a novel immunoassay for the binary complex of IGF-I and IGF-binding protein-1 in human serum

DEFF Research Database (Denmark)

Frystyk, Jan; Højlund, Kurt; Rasmussen, Kirsten Nyborg

2002-01-01

Correlation studies have suggested that IGF-binding protein (IGFBP)-1 is a dynamic regulator of free IGF-I. To further study this, we developed a monoclonal immunofluorometric assay specific for the binary complex of IGF-I and IGFBP-1 in human serum. An IGFBP-1 antibody, which recognizes all...... phospho-forms of IGFBP-1, was used for coating. An europium-labeled IGF-I antibody served as tracer. Assay incubation was performed at conditions approaching those in vivo (i.e. pH 7.4, 37 C). The assay was highly specific: no signal was obtained unless both IGF-I and IGFBP-1 were present and neither...... IGFBP-2, -3, -4, nor IGF-II caused any cross-reaction. The linear standard curve covered 3 orders of magnitude, and within and in-between assay coefficients of variation were less than 5 and 15%, respectively. To study the dynamic relationship between free IGF-I and binary complex formation, seven...

Targeted Morphoproteomic Profiling of Ewing's Sarcoma Treated with Insulin-Like Growth Factor 1 Receptor (IGF1R) Inhibitors: Response/Resistance Signatures

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Subbiah, Vivek; Naing, Aung; Brown, Robert E.; Chen, Helen; Doyle, Laurence; LoRusso, Patricia; Benjamin, Robert; Anderson, Pete; Kurzrock, Razelle

2011-01-01

Background Insulin-like growth factor 1 receptor (IGF1R) targeted therapies have resulted in responses in a small number of patients with advanced metastatic Ewing's sarcoma. We performed morphoproteomic profiling to better understand response/resistance mechanisms of Ewing's sarcoma to IGF1R inhibitor-based therapy. Methodology/Principal Findings This pilot study assessed two patients with advanced Ewing's sarcoma treated with IGF1R antibody alone followed by combined IGF1R inhibitor plus mammalian target of rapamycin (mTOR) inhibitor treatment once resistance to single-agent IGF1R inhibitor developed. Immunohistochemical probes were applied to detect p-mTOR (Ser2448), p-Akt (Ser473), p-ERK1/2 (Thr202/Tyr204), nestin, and p-STAT3 (Tyr 705) in the original and recurrent tumor. The initial remarkable radiographic responses to IGF1R-antibody therapy was followed by resistance and then response to combined IGF1R plus mTOR inhibitor therapy in both patients, and then resistance to the combination regimen in one patient. In patient 1, upregulation of p-Akt and p-mTOR in the tumor that relapsed after initial response to IGF1R antibody might explain the resistance that developed, and the subsequent response to combined IGF1R plus mTOR inhibitor therapy. In patient 2, upregulation of mTOR was seen in the primary tumor, perhaps explaining the initial response to the IGF1R and mTOR inhibitor combination, while the resistant tumor that emerged showed activation of the ERK pathway as well. Conclusion/Significance Morphoproteomic analysis revealed that the mTOR pathway was activated in these two patients with advanced Ewing's sarcoma who showed response to combined IGF1R and mTOR inhibition, and the ERK pathway in the patient in whom resistance to this combination emerged. Our pilot results suggests that morphoproteomic assessment of signaling pathway activation in Ewing's sarcoma merits further investigation as a guide to understanding response and resistance signatures. PMID

Insulin-like growth factor (IGF-I and IGF binding proteins axis in diabetes mellitus

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Min Sun Kim

2015-06-01

Full Text Available Increasing evidence suggests an important role of the insulin-like growth factor (IGF-IGF binding protein (IGFBP axis in the maintenance of normal glucose and lipid metabolism. Significant changes occur in the local IGF-I-IGFBPs environment in response to the diabetic milieu. A significant reduction of serum IGF-I levels was observed in patients with type 1 diabetes mellitus (T1DM. Inversely, considerably increased serum levels of IGF-I and IGFBP-3 levels were detected in individuals with glucose intolerance including T2DM. Recently, several prospective studies indicated that baseline levels of IGF-I and IGFBPs are associated with the development of diabetes. These findings suggest that disturbances in insulin and IGF-I-IGFBP axis can affect the development of glucose intolerance including diabetes.

Efficient and sustained IGF-1 expression in the adipose tissue-derived stem cells mediated via a lentiviral vector.

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Chen, Ting; Huang, Dangsheng; Chen, Guanghui; Yang, Tingshu; Yi, Jun; Tian, Miao

2015-02-01

The adipose tissue-derived stem cells (ADSCs) represent a significant area of the cell therapy. Genetic modification of ADSCs may further improve their therapeutic potential. Here, we aimed to generate a lentiviral vector expressing insulin-like growth factor-I (IGF-1) and investigate the impact of IGF-1 transduction on the properties of cultured ADSCs. Isolated rat ADSCs were assessed by flow cytometric analysis. IGF-1 was cloned and inserted into the pLenO-DCE plasmid to acquire pLenO-DCE-IGF-1 plasmid. Lentivirus was enveloped with pRsv-REV, pMDlg-pRRE and pMD2G plasmids in 293T cells. The ADSCs were transfected with the vectors. And then IGF-1-induced anti-apoptosis was evaluated by annexin V-FITC. Besides, proliferation of cells was detected by MTT assay and EdU. Moreover, Akt phosphorylation was evaluated by Western blotting analysis. Stable expression of IGF-1 in ADSCs was confirmed. ADSCs were positive for CD90 and CD29, but negative for CD31, CD34 and CD45. The transduction of IGF-1 to the ADSCs caused a dramatic increase in P-Akt expression. Over-expression of IGF-1 in ADSCs could improve the paracine of IGF-1 in a time-dependent manner, but could not promote the proliferation of ADSCs. This study indicated that lentiviral vectors offered a promising mean of delivering IGF-1 to the ADSCs. Lentiviral-mediated over-expression of therapeutic IGF-1 gene in ADSCs could prolong the anti-apoptosis effect of IGF-1, which might be induced by the activation of the PI3K/Akt pathway. And our data would improve the efficacy of ADSC-based therapies.

Clinical significance of determination of changes of serum IGF-II, CRP levels after treatment in pediatric patients with broncho-pneumonia

International Nuclear Information System (INIS)

Chen Chuanbin

2006-01-01

Objective: To investigate the changes of serum insulin-like growth factor-II (IGF-II), CRP levels after treatment in pediatric patients with bronchopneumonia. Methods: Serum IGF-II levels were measured with RIA and serum CRP levels with immune method both before and after treatment in 33 pediatric patients with bronchopneumonia and 35 controls. Results: Before treatment the serum levels of IGF-II, CRP were significantly higher in the patients than those in controls (P 0.05). Conclusion: Determination of serum IGF-II, CRP levels is clinically useful in the management of pediatric patients with bronchopneumonia. (authors)

Lower levels of circulating IGF-I in Type 1 diabetic women with frequent severe hypoglycaemia during pregnancy