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Sample records for circulating igf levels

  1. 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...

  2. IGF-I and IGFBP-3 polymorphisms in relation to circulating levels among African American and Caucasian women

    OpenAIRE

    D’Aloisio, Aimee A.; Schroeder, Jane C; North, Kari E; Poole, Charles; West, Suzanne L.; Travlos, Gregory S.; Baird, Donna D.

    2009-01-01

    Circulating insulin-like growth factor-one (IGF-I) and IGF binding protein-3 (IGFBP-3) levels have been associated with common diseases. Although family-based studies suggest that genetic variation contributes to circulating IGF-I and IGFBP-3 levels, analyses of associations with multiple IGF-I and IGFBP-3 single nucleotide polymorphisms (SNPs) have been limited, especially among African Americans. We evaluated 30 IGF-I and 15 IGFBP-3 SNPs and estimated diplotypes in association with plasma I...

  3. 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.

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    Alpa V Patel

    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.

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

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    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....

  5. Circulating levels of insulin-like growth factor-I (IGF-I correlate with disease status in leprosy

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    Rodrigues Luciana

    2011-12-01

    Full Text Available Abstract Background Caused by Mycobacterium leprae (ML, leprosy presents a strong immune-inflammatory component, whose status dictates both the clinical form of the disease and the occurrence of reactional episodes. Evidence has shown that, during the immune-inflammatory response to infection, the growth hormone/insulin-like growth factor-I (GH/IGF-I plays a prominent regulatory role. However, in leprosy, little, if anything, is known about the interaction between the immune and neuroendocrine systems. Methods In the present retrospective study, we measured the serum levels of IGF-I and IGBP-3, its major binding protein. These measurements were taken at diagnosis in nonreactional borderline tuberculoid (NR BT, borderline lepromatous (NR BL, and lepromatous (NR LL leprosy patients in addition to healthy controls (HC. LL and BL patients who developed reaction during the course of the disease were also included in the study. The serum levels of IGF-I, IGFBP-3 and tumor necrosis factor-alpha (TNF-α were evaluated at diagnosis and during development of reversal (RR or erythema nodosum leprosum (ENL reaction by the solid phase, enzyme-labeled, chemiluminescent-immunometric method. Results The circulating IGF-I/IGFBP-3 levels showed significant differences according to disease status and occurrence of reactional episodes. At the time of leprosy diagnosis, significantly lower levels of circulating IGF-I/IGFBP-3 were found in NR BL and NR LL patients in contrast to NR BT patients and HCs. However, after treatment, serum IGF-I levels in BL/LL patients returned to normal. Notably, the levels of circulating IGF-I at diagnosis were low in 75% of patients who did not undergo ENL during treatment (NR LL patients in opposition to the normal levels observed in those who suffered ENL during treatment (R LL patients. Nonetheless, during ENL episodes, the levels observed in RLL sera tended to decrease, attaining similar levels to those found in NR LL patients

  6. 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...

  7. IGF2R Genetic Variants, Circulating IGF2 Concentrations and Colon Cancer Risk in African Americans and Whites

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    Cathrine Hoyo

    2012-01-01

    Full Text Available The Mannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations between IGF2R non-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849, and c.901C>G, Leu252Val(rs8191754, circulating IGF2 levels, and colon cancer (CC risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS. Generalized linear models were used to compare circulating levels of IGF2 among 298 African American and 518 White controls. Logistic regression models were used to estimate odds ratios (ORs and 95% confidence intervals (CIs for the association of IGF2R genetic variants and CC risk. Women homozygous for the IGF2R c.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321 ng/ml compared to non-carriers, 595 (SD=217 ng/ml (p-value=0.01. This pattern was not apparent in individuals homozygous for the IGF2R c.901 C>G variant. Whites homozygous for the IGF2R c.901 C>G variant trended towards a higher risk of CC, OR=2.2 [95% CI(0.9–5.4], whereas carrying the IGF2R c.5002 G>A variant was not associated with CC risk. Our findings support the hypothesis that being homozygous for the IGF2R c.5002 G>A modulates IGF2 circulating levels in a sex-specific manner, and while carrying the IGF2R c.901 C>G may increase cancer risk, the mechanism may not involve modulation of circulating IGF2.

  8. Case report: low circulating IGF-I levels due to Acid-Labile Subunit deficiency in adulthood are not associated with early development of atherosclerosis and impaired heart function

    NARCIS (Netherlands)

    Rensing, K.L.; Duyvenvoorde, H.A. van; Cramer, M.J.; Teske, A.J.; Prokop, M.; Stroes, E.S.; Wit, J.M.; Hermus, A.R.M.M.; Twickler, T.B.

    2011-01-01

    OBJECTIVE: Decreased insulin-like growth factor-I (IGF-I) levels in adults have been associated with an increased risk of ischemic heart disease and heart failure. It is currently unknown whether patients with low circulating IGF-I levels due to a homozygous acid-labile subunit (IGFALS) gene mutatio

  9. Serum total IGF-I, free IGF-I, and IGFBP-1 levels in an elderly population - Relation to cardiovascular risk factors and disease

    NARCIS (Netherlands)

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

    1998-01-01

    Recently, a method to measure free insulin-like growth factor-I (IGF-I) levels has been developed. Free IGF-I levels may have greater physiological and clinical relevance than total (bound and free) IGF-I. The associations between the circulating IGF-I/IGF binding protein (IGFBP) system and cardiova

  10. IGF2R Genetic Variants, Circulating IGF2 Concentrations and Colon Cancer Risk in African Americans and Whites

    OpenAIRE

    Cathrine Hoyo; Susan K Murphy; Schildkraut, Joellen M; Vidal, Adriana C.; David Skaar; Millikan, Robert C.; Joseph Galanko; Sandler, Robert S.; Randy Jirtle; Temitope Keku

    2012-01-01

    The Mannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R) encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations between IGF2R non-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)), circulating IGF2 levels, and colon cancer (CC) risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS). Generalized linear models were u...

  11. 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...

  12. 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

    DEFF Research Database (Denmark)

    Thankamony, Ajay; Capalbo, Donatella; Marcovecchio, M Loredana;

    2014-01-01

    CONTEXT: 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. OBJECTIVE: Our objective was to explore glucose and lipid metabolism associated with variations in serum...

  13. 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

  14. Circulating IGF1 and IGF2 and SNP genotypes in men and pregnant and non-pregnant women

    OpenAIRE

    Gatford, K.L.; Heinemann, G K; Thompson, S D; Zhang, J V; Buckberry, S; Owens, J.A.; Dekker, G A; Roberts, C T; ,

    2014-01-01

    Circulating IGFs are important regulators of prenatal and postnatal growth, and of metabolism and pregnancy, and change with sex, age and pregnancy. Single-nucleotide polymorphisms (SNPs) in genes coding for these hormones associate with circulating abundance of IGF1 and IGF2 in non-pregnant adults and children, but whether this occurs in pregnancy is unknown. We therefore investigated associations of plasma IGF1 and IGF2 with age and genotype at candidate SNPs previously associated with circ...

  15. Circulating IGF1 and IGF2 and SNP genotypes in men and pregnant and non-pregnant women.

    Science.gov (United States)

    Gatford, K L; Heinemann, G K; Thompson, S D; Zhang, J V; Buckberry, S; Owens, J A; Dekker, G A; Roberts, C T

    2014-09-01

    Circulating IGFs are important regulators of prenatal and postnatal growth, and of metabolism and pregnancy, and change with sex, age and pregnancy. Single-nucleotide polymorphisms (SNPs) in genes coding for these hormones associate with circulating abundance of IGF1 and IGF2 in non-pregnant adults and children, but whether this occurs in pregnancy is unknown. We therefore investigated associations of plasma IGF1 and IGF2 with age and genotype at candidate SNPs previously associated with circulating IGF1, IGF2 or methylation of the INS-IGF2-H19 locus in men (n=134), non-pregnant women (n=74) and women at 15 weeks of gestation (n=98). Plasma IGF1 concentrations decreased with age (PIGF1 and IGF2 concentrations were lower in pregnant women than in non-pregnant women or men (each PIGF1 (IGF2 rs680, IGF2 rs1004446 and IGF2 rs3741204) and IGF2 (IGF2 rs1004446, IGF2 rs3741204 and H19 rs217727). In single SNP models, effects of IGF2 rs680 were similar between groups, with higher plasma IGF1 concentrations in individuals with the GG genotype when compared with GA (P=0.016), or combined GA and AA genotypes (P=0.003). SNPs in the IGF2 gene associated with IGF1 or IGF2 were in linkage disequilibrium, hence these associations could reflect other genotype variations within this region or be due to changes in INS-IGF2-H19 methylation previously associated with some of these variants. As IGF1 in early pregnancy promotes placental differentiation and function, lower IGF1 concentrations in pregnant women carrying IGF2 rs680 A alleles may affect placental development and/or risk of pregnancy complications. PMID:25117571

  16. Circulating IGF-binding protein 7 (IGFBP7) levels are elevated in patients with endometriosis or undergoing diabetic hemodialysis

    OpenAIRE

    Sasajima Koji; Matsuda Akihisa; Matsutani Takeshi; Higuma Chinatsu; Itokazu Osamu; Isaka Keiichi; Momose Katsutoshi; Ishihara Ryosuke; Kutsukake Masahiko; Hara Takahiko; Tamura Kazuhiro

    2008-01-01

    Abstract Background Insulin-like growth factor-binding protein-7 (IGFBP7) is a secretory protein with a molecular mass of approximately 30 kDa. It is abundantly expressed in the uterine endometrium during the secretory phase of the menstrual cycle. Decreased IGFBP7 expression has been observed in some cancers and leiomyomata. Methods To determine whether serum IGFBP7 levels reflect changes in uterine IGFBP7 expression in humans during the menstrual cycle, and to examine whether serum IGFBP7 l...

  17. 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)

    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

  18. Short stature associated with high circulating insulin-like growth factor (IGF)-binding protein-1 and low circulating IGF-II: effect of growth hormone therapy.

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    Barreca, A; Bozzola, M; Cesarone, A; Steenbergh, P H; Holthuizen, P E; Severi, F; Giordano, G; Minuto, F

    1998-10-01

    We report a case of short stature associated with high circulating levels of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-10 and low levels of IGF-II responsive to pharmacological treatment with GH. Our patient suffered severe growth failure from birth (2.06 SD below the mean for normal full-term boys, and 5.2 and 7.3 SD below the mean at 5 and 10 months). Studies carried out before referral to our pediatric unit included normal 46,XY karyotype and normal encephalic imaging. Other endocrine and metabolic alterations and other systemic diseases were excluded. At 1.7 yr of age (length, 6.1 SD; weight, 4.6 SD; head circumference, 1.4 SD below the mean, respectively) the patient was referred to our pediatric unit. The baseline GH concentration was 31 microg/L, and the peak after an arginine load was 59.6 microg/L. In the same samples GH bioactivity was nearly superimposable (RIA/Nb2 bioactivity ratio = 0.9). Fasting insulin and glucose concentrations were 7.4 microU/mL and 65 mg/dL, respectively, both normally responsive to an oral glucose load. GH insensitivity was excluded by a basal IGF-I concentration (64 ng/mL) in the normal range for 0- to 5-yr-old boys and its increase after 2 IU/day hGH administration for 4 days. IGFBP-3 (0.5 microg/mL) was slightly reduced, whereas IGFBP-1 (2218 and 1515 ng/mL in two different basal samples) was well above the normal values for age and was suppressible by GH (maximum suppression, -77% at 84 h) and glucose load (maximum suppression, -46% at 150 min). The basal IGF-II concentration was below the normal range (86 ng/mL), whereas IGFBP-2 was normal (258 ng/mL). Analysis of the promoter region of IGFBP-1 and IGF-II failed to find major alterations. Neutral gel filtration of serum showed that almost all IGF-I activity was in the 35- to 45-kDa complex, coincident with IGFBP-1 peak, while the 150-kDa complex was absent, although the acid-labile subunit was normally represented. At 2.86 yr (height, 65.8 cm; height SD score

  19. Insulin-Like Growth Factor-1 (IGF-1 Reduces ischemic changes and increases circulating angiogenic factors in experimentally - induced myocardial infarction in rats

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    Lisa Mathews

    2011-06-01

    Full Text Available Abstract Background Coronary artery disease is a global health concern in the present day with limited therapies. Extensive efforts have been devoted to find molecular therapies to enhance perfusion and function of the ischemic myocardium. Aim of the present study was to look into the effects of insulin like growth factor -1 (IGF-1 on circulating angiogenic factors after myocardial ischemia in rats. Methods Adult male Sprague-Dawley rats were randomly divided into 10-days control, myocardial infarction, IGF-1 alone (2 μg/rat/day and ISO+IGF-1 groups. Isoproterenol (ISO, a synthetic catecholamine was used to induce myocardial infarction. Serum transforming growth factor-β (TGF-β and vascular endothelial growth factor (VEGF levels were checked after 10-days of IGF-1 administration. Results There was a significant increase in heart weight after IGF-1 treatment. A significant increase in cardiac enzyme level (CK-MB and LDH was seen in isoproterenol treated rats when compared to control group. IGF-1treatment induced a significant increase in serum angiogenic factors, IGF-1, VEGF and TGF beta levels. IGF-1 also reduced the ischemic changes in the myocardium when compared to the isoproterenol alone treated group. Conclusions In conclusion, treatment with insulin-like growth factor-1 (IGF-1 in myocardial infarction significantly increased circulating angiogenic growth factors like IGF-1, VEGF and TGF beta thus, protecting against myocardial ischemia.

  20. 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.

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

    Science.gov (United States)

    Vidal, Adriana C; Murtha, Amy P; Murphy, Susan K; Fortner, Kimberly; Overcash, Francine; Henry, Nikki; Schildkraut, Joellen M; Forman, Michele R; Demark-Wahnefried, Wendy; Kurtzberg, Joanne; Jirtle, Randy; Hoyo, Cathrine

    2013-01-01

    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/m(2); 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. PMID:23861689

  2. Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents

    DEFF Research Database (Denmark)

    Juul, A; Dalgaard, P; Blum, W F;

    1995-01-01

    Circulating IGF-I and -II are bound to specific insulin-like growth factor (IGF)-binding proteins (IGFBPs), of which IGFBP-3 binds the majority of the IGFs. IGFBP-3 levels are regulated by GH and have been suggested to provide additional information on GH secretory capacity compared to IGF...... in puberty. We found that IGFBP-3 levels increase with age in children, with maximal levels in puberty; girls experience peak values approximately 1 yr earlier than boys. Age, sex, height, BMI, and pubertal maturation were all important factors in determining the circulating levels of IGFBP-3, whereas IGF...

  3. 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

  4. Reduction of elevated IGF-1 levels in coincident amyotrophic lateral sclerosis and acromegaly.

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    Pereira, Erlick A C; Turner, Martin R; Wass, John A H; Talbot, Kevin

    2010-01-01

    We report a patient presenting with ALS in whom acromegaly was later confirmed. Insulin-like growth factor-1 (IGF-1) has been tried in the treatment of ALS and despite equivocal results from clinical trials, efforts have continued to try to harness the significant positive effects on motor neuron growth observed in vitro and in survival of mouse models of the disease. One subsequent study has reported an association between higher circulating serum IGF-1 levels and longer disease duration in ALS patients. Concern therefore arose in our case that treatment of the acromegaly with a somatostatin analogue might adversely affect the natural course of his ALS through lowering of potentially beneficial IGF-1 levels. Through clinical observation and prognostic modelling we suggest that this concern was unfounded. The potential interaction of these two rarely coincident disorders in our patient is discussed.

  5. Elevated circulating somatostatin levels in acromegaly.

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    Arosio, M; Porretti, S; Epaminonda, P; Giavoli, C; Gebbia, C; Penati, C; Beck-Peccoz, P; Peracchi, M

    2003-06-01

    GH increases hypothalamic somatostatin (SS) synthesis and secretion but it is unknown if chronic GH excess, as found in acromegaly, may influence circulating SS levels, that are mainly of enteropancreatic source and affect several gastrointestinal functions, including motility. Circulating SS occurs in several post-translational forms including somatostatin-14 (SS-14), somatostatin-28 (SS-28) and other small peptides. The aim of the present study was to characterize the fasting and postprandial pattern of plasma circulating somatostatin in normal subjects and patients with acromegaly. Fasting total SS and SS-28 levels were measured in 32 subjects, 16 acromegalic patients with a new diagnosis (A) (8 F, 8 M, median age 48) and 16 matched healthy volunteers (C) (8 F, 8 M, median age 45). SS was also determined after a standard solid-liquid meal (550 kCal) in 24 of the subjects (12 C and 12 A). Fasting SS and SS-28 were significantly higher in acromegalic patients as compared to healthy subjects. In the former, a positive correlation was found between IGF-I and SS levels (r = 0.525 p acromegaly. Excess GH/IGF-I could be a causal factor in somatostatin hypersecretion. Conceivably this abnormality might play a role in some alterations of gastrointestinal function of acromegalic patients such as prolonged bowel transit.

  6. The Association between IGF-1 Polymorphisms, IGF-1 Serum Levels, and Cognitive Functions in Healthy Adults: The Amsterdam Growth and Health Longitudinal Study

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    Carmilla M. M. Licht

    2014-01-01

    Full Text Available 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 IGF-1 polymorphisms, IGF-1 levels, and cognition are interconnected in healthy adults. Data of 277 participants (mean age: 42.4 years of the Amsterdam Growth and Health Longitudinal Study on IGF-1 promoter polymorphisms, IGF-1 serum level, spatial working memory (SWM, paired associate learning (PAL, and IQ tests were analyzed. (MANOVAs were applied to confirm the associations between IGF-1 polymorphisms and IGF-1 levels and between IGF-1 levels and cognition. Three groups were distinguished based on specific IGF-1 polymorphism alleles: a homozygote 192 bp/192 bp genotype, a heterozygote 192 bp/x genotype, and a noncarrier x/x genotype. Although different IGF-1 levels were found for the three genotypes, performance on all cognitive tasks and IQ measures was similar. Despite the associations between IGF-1 polymorphisms and IGF-1 levels, no association was found between cognition and IGF-1 levels. It seems that IGF-1 does not play a role in the cognitive performance of healthy middle-aged adults. Possible, IGF-1 fulfills a more developmental and protective role in cognition which becomes apparent during childhood, old-age, or disease.

  7. Insulin-like growth factors (IGF-I, free IGF-I and IGF-II) and insulin-like growth factor binding proteins (IGFBP-2, IGFBP-3, IGFBP-6, and ALS) in blood circulation

    DEFF Research Database (Denmark)

    Yu, Hao; Mistry, J; Nicar, M J;

    1999-01-01

    Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) play an important role in cell growth and differentiation. Clinical and epidemiological studies have indicated that measuring IGFs and IGFBPs in blood has potential implications in assessing growth-related abnormalities and risks...... of certain types of cancer. To facilitate the application, we reported a large collection of reference ranges of IGFs and IGFBPs in normal population and evaluations of these molecules in serum and plasma as well as the impact of freeze-thaw cycles on the measurement. IGF-I, IGFBP-3 andALS showed a...... similar pattern of change associated with age. Levels of these molecules were low at birth and increased with age through puberty. After puberty the levels declined slowly with age. Overall, IGF-I, IGFBP-3 and ALS were slightly higher in females than in males. Free IGF-I accounted for about 1% of the...

  8. 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

    1998-01-01

    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 cros

  9. 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

  10. 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

  11. Gender differences in serum GH and IGF-I levels and the GH response to dynamic tests in patients with acromegaly.

    Science.gov (United States)

    Tanaka, Satoshi; Fukuda, Izumi; Hizuka, Naomi; Takano, Kazue

    2010-01-01

    Gender affects the GH secretory pattern both in normal subjects and in patients with acromegaly by an uncertain mechanism. Here, we report the influence of gender on the relationship between serum GH and IGF-I levels and the GH response to dynamic tests in patients with acromegaly. Seventy-four patients with untreated acromegaly (M/F 27/47, age range 22-86 yr.) were studied. The serum GH levels did not differ between male and female (6.1 vs. 8.7 ng/ml; p=0.26), while serum IGF-I levels, IGF-I SDS and the IGF-I/GH ratio were lower in female than those in male (679 vs. 769 ng/ml; p50 yr, serum IGF-I levels and IGF-I/GH ratios were lower in female than those in male in patients 50 yrs (684 vs. 680 ng/ml; p=0.39 and 98.7 vs. 118.4; p=0.40). The GH responses to OGTT, TRH, octreotide, and bromocriptine tests were similar in male and female. In conclusion, IGF-I/GH ratio was significantly lower in female than that in male particularly in younger patients with acromegaly. These data suggest that gender, presumably sex steroids in female, may partially modulate the relationship between circulating IGF-I and GH levels in patients with acromegaly.

  12. Neuroprotective levels of IGF-1 exacerbate epileptogenesis after brain injury.

    Science.gov (United States)

    Song, Yu; Pimentel, Corrin; Walters, Katherine; Boller, Lauren; Ghiasvand, Shabnam; Liu, Jing; Staley, Kevin J; Berdichevsky, Yevgeny

    2016-01-01

    Exogenous Insulin-Like Growth Factor-1 (IGF-1) is neuroprotective in animal models of brain injury, and has been considered as a potential therapeutic. Akt-mTOR and MAPK are downstream targets of IGF-1 signaling that are activated after brain injury. However, both brain injury and mTOR are linked to epilepsy, raising the possibility that IGF-1 may be epileptogenic. Here, we considered the role of IGF-1 in development of epilepsy after brain injury, using the organotypic hippocampal culture model of post-traumatic epileptogenesis. We found that IGF-1 was neuroprotective within a few days of injury but that long-term IGF-1 treatment was pro-epileptic. Pro-epileptic effects of IGF-1 were mediated by Akt-mTOR signaling. We also found that IGF-1 - mediated increase in epileptic activity led to neurotoxicity. The dualistic nature of effects of IGF-1 treatment demonstrates that anabolic enhancement through IGF-1 activation of mTOR cascade can be beneficial or harmful depending on the stage of the disease. Our findings suggest that epilepsy risk may need to be considered in the design of neuroprotective treatments for brain injury. PMID:27561791

  13. 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...

  14. 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...

  15. 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...

  16. Prenatal stress affects insulin-like growth factor-1 (IGF-1) level and IGF-1 receptor phosphorylation in the brain of adult rats.

    Science.gov (United States)

    Basta-Kaim, Agnieszka; Szczesny, Ewa; Glombik, Katarzyna; Stachowicz, Katarzyna; Slusarczyk, Joanna; Nalepa, Irena; Zelek-Molik, Agnieszka; Rafa-Zablocka, Katarzyna; Budziszewska, Boguslawa; Kubera, Marta; Leskiewicz, Monika; Lason, Wladyslaw

    2014-09-01

    It has been shown that stressful events occurring in early life have a powerful influence on the development of the central nervous system. Insulin-like growth factor-1 (IGF-1) promotes the growth, differentiation and survival of both neurons and glial cells and is thought to exert antidepressant-like activity. Thus, it is possible that disturbances in the function of the IGF-1 system may be responsible for disturbances observed over the course of depression. Prenatal stress was used as a valid model of depression. Adult male offspring of control and stressed rat dams were subjected to behavioural testing (forced swim test). The level of IGF-1 in the blood and the expression of IGF-1, IGF-1R, and IRS-1/2 in the hippocampus and frontal cortex using RT-PCR, ELISA and western blotting were measured. In addition the effect of intracerebroventricularly administered IGF-1 and/or the IGF-1R receptor antagonist JB1 in the forced swim test was studied. Prenatally stressed rats showed depressive like behaviour, including increased immobility time as well as decreased mobility and climbing. Intracerebroventricular administration of IGF-1 reversed these effects in stressed animals, whereas concomitant administration of the IGF-1R antagonist JB1 completely blocked the effects. Biochemical analysis of homogenates from the hippocampus and frontal cortex revealed decreases in IGF-1 level and IGF-1R phosphorylation along with disturbances in IRS-1 phosphorylation. These findings reveal that prenatal stress alters IGF-1 signalling, which may contribute to the behavioural changes observed in depression.

  17. High expression levels of total IGF-1R and sensitivity of NSCLC cells in vitro to an anti-IGF-1R antibody (R1507.

    Directory of Open Access Journals (Sweden)

    Yixuan Gong

    Full Text Available BACKGROUND: The IGF receptor type 1 (IGF-1R pathway is frequently deregulated in human tumors and has become a target of interest for anti-cancer therapy. METHODOLOGY/PRINCIPAL FINDINGS: We used a panel of 22 non-small cell lung cancer (NSCLC cell lines to investigate predictive biomarkers of response to R1507, a fully-humanized anti-IGF-1R monoclonal antibody (Ab; Roche. 5 lines were moderately sensitive (25-50% growth inhibition to R1507 alone. While levels of phospho-IGF-1R did not correlate with drug sensitivity, 4 out of 5 sensitive lines displayed high levels of total IGF-1R versus 1 out of 17 resistant lines (p = 0.003, Fisher's Exact. Sensitive lines also harbored higher copy numbers of IGF-1R as assessed by independent SNP array analysis. Addition of erlotinib or paclitaxel to R1507 led to further growth inhibition in sensitive but not resistant lines. In one EGFR mutant lung adenocarcinoma cell line (11-18, R1507 and erlotinib co-treatment induced apoptosis, whereas treatment with either drug alone induced only cell cycle arrest. Apoptosis was mediated, in part, by the survival-related AKT pathway. Additionally, immunohistochemical (IHC staining of total IGF-1R with an anti-total IGF-1R Ab (G11;Ventana was performed on tissue microarrays (TMAs containing 270 independent NSCLC tumor samples. Staining intensity was scored on a scale of 0 to 3+. 39.3% of tumors showed medium to high IGF-1R IHC staining (scores of 2+ or 3+, respectively, while 16.7% had scores of 3+. CONCLUSIONS/SIGNIFICANCE: In NSCLC cell lines, high levels of total IGF-1R are associated with moderate sensitivity to R1507. These results suggest a possible enrichment strategy for clinical trials with anti-IGF-1R therapy.

  18. The relationship between dioxin-like polychlorobiphenyls and IGF-I serum levels in healthy adults: evidence from a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Octavio P Luzardo

    Full Text Available OBJECTIVE: Insulin-like growth factor I (IGF-I and dioxin-like polychlorobiphenyls (DL-PCBs have been associated with the pathogenesis of several diseases like cancer, diabetes and growth disorders. Because it has been suggested that organohalogenated contaminants could influence IGF-I levels in adults, the potential relationship between DL-PCBs and IGF-I serum levels was studied in 456 healthy adults from a representative sample of the general population of the Canary Islands (Spain. DESIGN: Free circulating serum levels of IGF-I and IGFBP-3 were measured through an ELISA methodology, while the serum levels of the 12 DL-PCBs congeners (IUPAC numbers # 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189 were measured by gas chromatography/mass spectrometry (GC-MS. RESULTS: DL-PCBs 156 and 167, Total DL-PCBs body burden (∑PCBs: sum over the 12 measured DL-PCBs, and Total toxic burden (in terms of toxic equivalence to dioxins: ∑TEQs showed a trend of inverse association with IGF-I serum levels in the whole studied population. After adjusting for potential confounders, including gender, body mass index (BMI, age, and IGF-binding protein-3 (IGFBP-3, younger (18-45 years women with lower BMI (<27 kg/m(2 and detectable levels of DL-PCB-156 showed significantly lower IGF-I levels than those in the same age and BMI subgroup with non-detectable levels of DL-PCB-156 (p<0.001. Similarly, ∑PCBs and ∑TEQs showed a tendency to an inverse association with IGF-I levels in the same group of women (p=0.017 and p=0.019 respectively. CONCLUSIONS: These findings suggest that DL-PCBs could be involved in the regulation of the IGF-system in a way possibly influenced by gender, age and BMI. Although these results should be interpreted with caution, such circumstances could contribute to explain the development of diseases associated to the IGF system.

  19. IGF-1 GENE EXPRESSION IN RAT COLONIC MUCOSA AFTER DIFFERENT EXERCISE VOLUMES

    Directory of Open Access Journals (Sweden)

    Katja Buehlmeyer

    2007-12-01

    Full Text Available The evidence is increasing for a close link between the insulin/insulin-like growth factor (IGF system and colon cancer prevention by physical exercise. To reveal exercise-induced alterations in colon mucosa, gene expression of IGF-1 and related genes and serum IGF-1 were investigated. Twenty male Wistar rats performed a 12 week voluntary exercise program. Nine rats served as the control group. Gene expression of IGF-1, IGF-1 receptor (IGF-1R and IGF-binding protein 3 (IGF-BP3 were quantified by real-time RT-PCR. Circulating IGF-1 was analyzed exercise volume-dependent. Based on 3 distinguished groups with low (L-EX, 8314 m·night-1, we observed lower serum IGF-1 levels (P < 0.05 in all exercise groups as compared to the control group and IGF-1 levels declined proportional to the increase in exercise volume. A significant (p < 0.05 positive correlation was found between IGF-1 concentration and body mass (r = 0.50 and a significant negative correlation exists between body mass and exercise volume (r = -0.50. Significant differences in colonic mRNA levels of IGF-1, IGF-1R and IGF-BP3 could not be observed. Based on our data we propose that the exercise as well as the body mass reduction leads to a decrease in circulating IGF-1 and this might represent a prime link to colon cancer prevention

  20. Quantitative analysis of the concentrations of IGFs and several IGF-binding proteins in a large fibrous abdominal tumor and the circulation of a patient with hypoglycemia

    NARCIS (Netherlands)

    van Doorn, Jaap; van de Hoef, Wouter; Dullaart, Robin P. F.

    2015-01-01

    The syndrome of nonislet cell tumor induced hypoglycemia (NICTH) represent extreme cases of excessive expression and production of incompletely processed high-molecular-mass pro-IGF-II forms (big IGF-II) by an often large tumor. Tumor-derived big IGF-II is responsible for enhanced insulin-like effec

  1. Acromegalia: comparación de los niveles séricos de IGF-I por dos inmunoensayos y su correlación con la prueba de tolerancia oral a la glucosa Acromegaly: Comparison of serum IGF-1 levels measured by two immunoassays and their correlation with the Oral Glucose Tolerance Test

    Directory of Open Access Journals (Sweden)

    L. Boero

    2010-12-01

    Full Text Available Introducción: La determinación de IGF-I en suero o plasma es una herramienta esencial en el diagnóstico y seguimiento de la acromegalia. Sin embargo, se deben tener presentes algunos inconvenientes en su medición por diferentes inmunoensayos. Objetivos: Evaluar dos inmunoensayos para la determinación de IGF-I y su correlación con el nadir de GH en el TTOG en pacientes acromegalicos. Materiales y métodos: Se analizaron 37 pacientes acromegálicos, 20 mujeres y 17 hombres. IGF-I fue determinada por Immulite 1000, (IMM y por IRMA (DSL. Se realizó el TTOG y se determinó glucosa y GH en todos los tiempos (basal, 30, 60, 90 y 120min. Se consideró respuesta normal un nadir de GH 1ng/ml se encontró en el 70%, con nadir de GH normal en el 13,5%. IGF-I normal con nadir >1ng/ml en el 2,7% y con nadir de GH normal en el 13,5%. El área bajo las curvas ROC no mostró diferencias significativas. Conclusiones: Los niveles de IGF-I determinados por IMM y DSL fueron significativamente diferentes mostrando un bias negativo para IMM. La mayoría de los valores del nadir de GH fueron consistentes con los niveles de IGF-I observándose una discrepancia en el 30% de los pacientes, estuvieran o no bajo tratamiento.Introduction: IGF-I determination in serum or plasma is an essential tool in the diagnosis and follow-up of acromegaly. Hepatic production of IGF-I is regulated by GH and circulates bound to several IGF-I binding proteins which extends its half life. IGF-I is not released in a pulsatile pattern and has no significant variability in 24 h. Objective: To evaluate two different methodologies in IGF-I levels determination and their correlation with GH nadir in OGTT in acromegalic patients. Material and methods: We analyzed 37 acromegalic patients, 20 women and 17 men, mean age was 45±12 years. IGF-I levels were assayed by Immulite 1000, DPC (IMM and DSL-5600 ACTIVE® IGF-I Coated-Tube IRMA (DSL and OGTTs (at baseline and at 30, 60, 90 and 120 minutes

  2. 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)....

  3. 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.

  4. The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels.

    Science.gov (United States)

    Alsina-Sanchis, Elisenda; Figueras, Agnès; Lahiguera, Álvaro; Vidal, August; Casanovas, Oriol; Graupera, Mariona; Villanueva, Alberto; Viñals, Francesc

    2016-10-15

    In a search for new therapeutic targets for treating epithelial ovarian cancer, we analyzed the Transforming Growth Factor Beta (TGFβ) signaling pathway in these tumors. Using a TMA with patient samples we found high Smad2 phosphorylation in ovarian cancer tumoral cells, independently of tumor subtype (high-grade serous or endometrioid). To evaluate the impact of TGFβ receptor inhibition on tumoral growth, we used different models of human ovarian cancer orthotopically grown in nude mice (OVAs). Treatment with a TGFβRI&II dual inhibitor, LY2109761, caused a significant reduction in tumor size in all these models, affecting cell proliferation rate. We identified Insulin Growth Factor (IGF)1 receptor as the signal positively regulated by TGFβ implicated in ovarian tumor cell proliferation. Inhibition of IGF1R activity by treatment with a blocker antibody (IMC-A12) or with a tyrosine kinase inhibitor (linsitinib) inhibited ovarian tumoral growth in vivo. When IGF1R levels were decreased by shRNA treatment, LY2109761 lost its capacity to block tumoral ovarian cell proliferation. At the molecular level TGFβ induced mRNA IGF1R levels. Overall, our results suggest an important role for the TGFβ signaling pathway in ovarian tumor cell growth through the control of IGF1R signaling pathway. Moreover, it identifies anti-TGFβ inhibitors as being of potential use in new therapies for ovarian cancer patients as an alternative to IGF1R inhibition. PMID:27299695

  5. The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels.

    Science.gov (United States)

    Alsina-Sanchis, Elisenda; Figueras, Agnès; Lahiguera, Álvaro; Vidal, August; Casanovas, Oriol; Graupera, Mariona; Villanueva, Alberto; Viñals, Francesc

    2016-10-15

    In a search for new therapeutic targets for treating epithelial ovarian cancer, we analyzed the Transforming Growth Factor Beta (TGFβ) signaling pathway in these tumors. Using a TMA with patient samples we found high Smad2 phosphorylation in ovarian cancer tumoral cells, independently of tumor subtype (high-grade serous or endometrioid). To evaluate the impact of TGFβ receptor inhibition on tumoral growth, we used different models of human ovarian cancer orthotopically grown in nude mice (OVAs). Treatment with a TGFβRI&II dual inhibitor, LY2109761, caused a significant reduction in tumor size in all these models, affecting cell proliferation rate. We identified Insulin Growth Factor (IGF)1 receptor as the signal positively regulated by TGFβ implicated in ovarian tumor cell proliferation. Inhibition of IGF1R activity by treatment with a blocker antibody (IMC-A12) or with a tyrosine kinase inhibitor (linsitinib) inhibited ovarian tumoral growth in vivo. When IGF1R levels were decreased by shRNA treatment, LY2109761 lost its capacity to block tumoral ovarian cell proliferation. At the molecular level TGFβ induced mRNA IGF1R levels. Overall, our results suggest an important role for the TGFβ signaling pathway in ovarian tumor cell growth through the control of IGF1R signaling pathway. Moreover, it identifies anti-TGFβ inhibitors as being of potential use in new therapies for ovarian cancer patients as an alternative to IGF1R inhibition.

  6. The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients

    DEFF Research Database (Denmark)

    Juul, A; Main, K; Blum, W F;

    1994-01-01

    Several in-vitro studies have suggested that the biological actions of IGF-I can be modified by the presence of specific IGF binding proteins. In man, the 24-hour serum levels of IGF-I and IGFBP-3 remain constant, but short-term changes in the IGF-I/IGFBP-3 ratio have been described following GH...... administration. Serum levels of IGF-I and IGFBP-3 decrease with age in normal adults and are elevated in active acromegaly due to excessive GH secretion. However, the individual ratios between serum levels of IGF-I and IGFBP-3 in acromegalic and healthy adults have not been described previously....

  7. 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

    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...

  8. IGF-1 Restores Visual Cortex Plasticity in Adult Life by Reducing Local GABA Levels

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    José Fernando Maya-Vetencourt

    2012-01-01

    Full Text Available The central nervous system architecture is markedly modified by sensory experience during early life, but a decline of plasticity occurs with age. Recent studies have challenged this dogma providing evidence that both pharmacological treatments and paradigms based on the manipulation of environmental stimulation levels can be successfully employed as strategies for enhancing plasticity in the adult nervous system. Insulin-like growth factor 1 (IGF-1 is a peptide implicated in prenatal and postnatal phases of brain development such as neurogenesis, neuronal differentiation, synaptogenesis, and experience-dependent plasticity. Here, using the visual system as a paradigmatic model, we report that IGF-1 reactivates neural plasticity in the adult brain. Exogenous administration of IGF-1 in the adult visual cortex, indeed, restores the susceptibility of cortical neurons to monocular deprivation and promotes the recovery of normal visual functions in adult amblyopic animals. These effects were accompanied by a marked reduction of intracortical GABA levels. Moreover, we show that a transitory increase of IGF-1 expression is associated to the plasticity reinstatement induced by environmental enrichment (EE and that blocking IGF-1 action by means of the IGF-1 receptor antagonist JB1 prevents EE effects on plasticity processes.

  9. Analysis of circulating insulin-like growth factor-1 (IGF-1 and IGF binding protein-3 (IGFBP-3 in tobacco smokers and non-smokers

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    Palmer RM

    2002-06-01

    Full Text Available Abstract Background IGF-1 and the major serum IGF-1 binding protein, IGFBP-3, are under extensive investigation as potential prognostic markers of specific malignancies and vascular diseases. However, there is conflicting evidence that tobacco smoking may influence systemic concentrations of IGF-1 and IGFBP-3. Subjects and methods Serum concentrations of IGF-1 and IGFBP-3 were measured in 20 smokers and 20 non-smokers, matched for age and gender. Serum concentrations of cotinine, the major metabolite of nicotine, and ICAM-1, known to exhibit a dose-dependent relationship with cotinine, were also assayed. Results There was no difference between the systemic concentrations of IGF-1 or IGFBP-3 found in smokers and non-smokers (IGF-1: mean [s.d]; 104 29 vs 101 24 ng ml-1, respectively; and IGFBP-3: 2562 [522] vs 2447 [570] ng ml-1, respectively. Similarly, there was no correlation between serum cotinine and IGF-1 or IGFBP-3 concentrations in smokers. Soluble ICAM-1 concentrations were significantly increased in smokers, compared to non-smokers (mean [s.d]; 258 [60] vs 194 [50] ng ml-1, respectively; p = 0.002. Conclusion There was no relationship noted between tobacco smoking and either IGF-1 or IGFBP-3. These data suggest that smoking would not appear to be a major confounder of the reported clinical associations between IGF-1, IGFBP-3, or IGF-1/IGFBP-3 ratios and specific disease entities.

  10. Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins -1 and -3 and IGFBP-3 protease activity in boys with normal or precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Flyvbjerg, Allan; Frystyk, Jan;

    1996-01-01

    Circulating IGF-I and IGF binding protein-3 (IGFBP-3) levels both increase in puberty where growth velocity is high. The amount of free IGF-I is dependent on the IGF-I level and on the concentrations of the specific IGFBPs. Furthermore, IGFBP-3 proteolysis regulates the bioavailability of IGF......-I. However, the concentration of free IGF-I and possible IGFBP-3 proteolytic activity in puberty has not previously been studied....

  11. The IGF1 P2 promoter is an epigenetic QTL for circulating IGF1 and human growth

    OpenAIRE

    Ouni, Meriem; Gunes, Yasemin; Belot, Marie-Pierre; Castell, Anne-Laure; Fradin, Delphine; Bougnères, Pierre

    2015-01-01

    Background Even if genetics play an important role, individual variation in stature remains unexplained at the molecular level. Indeed, genome-wide association study (GWAS) have revealed hundreds of variants that contribute to the variability of height but could explain only a limited part of it, and no single variant accounts for more than 0.3% of height variance. At the interface of genetics and environment, epigenetics contributes to phenotypic diversity. Quantifying the impact of epigenet...

  12. Avaliação plasmática de igf-1 no prolactinoma IGF-1 plasma levels evaluation in prolactinoma

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    Daniela Zylberberg

    2006-09-01

    Full Text Available Prolactinomas são os tumores hipofisários mais comuns, podendo co-secretar GH (hormônio do crescimento. IGF-1 (fator de crescimento insulina-símile-1 é o principal responsável pelas ações do GH e parâmetro diagnóstico de acromegalia. Objetivando determinar por uma dosagem de IGF-1, na avaliação inicial de pacientes com prolactinoma, ocorrência de tumores mistos [GH e prolactina (PRL], estudamos 7 homens e 27 mulheres, entre 19 e 72 anos, confrontando-os aos resultados de GH basal e durante teste oral de tolerância à glicose, quando GH basal >0,4 ng/mL ou níveis de IGF-1 alterados. A proporção de pacientes com GH >0,4 ng/mL e IGF-1 elevada foi alta; mas, após administração de 75g de glicose por via oral, nenhum paciente foi diagnosticado como acromegálico. Sugerimos, porém que a dosagem de IGF-1 seja realizada pelo risco de co-secreção de GH nos prolactinomas. Atenção especial para pacientes que apresentem significativa diminuição dos níveis de PRL, sem correspondente regressão do tamanho do adenoma.Prolactinomas are the most frequent pituitary tumors and may co-secrete GH (growth hormone. IGF-1 (insulin-like growth factor-1 is the main responsible for GH actions and a parameter for the diagnosis of acromegaly. With the objective of identifying through a IGF-1 levels analysis, in the initial evaluation of prolactinoma patients, the existence of mixed tumors [GH and prolactin (PRL], we studied 7 men and 27 women, aged between 19 and 72 years, confronting them with the results of basal and glucose stimulated (glucose tolerance test - GTT GH levels, indicated when GH >0.4 ng/mL or IGF-1 levels were elevated. The prevalence of patients with GH >0.4 ng/mL and elevated IGF-1 was higher than expected; however, after GTT, no patient fulfilled the diagnostic criteria for acromegaly. However, we suggest that, they should be submitted to IGF-1 evaluation, due to the risk of GH co-secretion in prolactinomas. Special attention

  13. Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels.

    Science.gov (United States)

    Bonilla, Carolina; Lewis, Sarah J; Rowlands, Mari-Anne; Gaunt, Tom R; Davey Smith, George; Gunnell, David; Palmer, Tom; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Grönberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Lathrop, Mark; Martin, Richard M; Holly, Jeff M P

    2016-10-01

    Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. PMID:27225428

  14. Low serum levels of free and total insulin-like growth factor I (IGF-I) in patients with anorexia nervosa are not associated with increased IGF-binding protein-3 proteolysis

    DEFF Research Database (Denmark)

    Støving, R K; Flyvbjerg, A; Frystyk, J;

    1999-01-01

    Patients with anorexia nervosa (AN) are GH resistant, with elevated GH levels and low serum levels of total insulin-like growth factor I (IGF-I). IGF-I action is modulated by IGF-binding proteins (IGFBPs), and a variety of catabolic states has been characterized by the presence of increased IGFBP-3...... for the adaption of the GH-IGF-IGFBP axis in AN may be different from other catabolic conditions, because the low levels of free and total IGF-I in AN are not associated with increased IGFBP-3 proteolysis....

  15. Higher TNF-α, IGF-1 and leptin levels are found in tasters than non-tasters

    Directory of Open Access Journals (Sweden)

    Rui eWang

    2014-07-01

    Full Text Available Taste perception is controlled by taste cells that are present in the tongue and produce and secrete various metabolic hormones. Recent studies have demonstrated that taste receptors in tongue, gut and the pancreas are associated with local hormone secretion. The aim of this study was to determine whether there is a link between taste sensitivity and levels of circulating metabolic hormones in human and whether taste sensitivity is potentially related to peripheral metabolic regulation. 31 subjects were recruited and separated into tasters and non-tasters based on their phenol thiocarbamide (PTC bitter taste test results. Fasting plasma and saliva were collected and levels of hormones and cytokines were assayed. We observed significant differences in both hormone levels and hormone-body mass index (BMI correlation between tasters and non-tasters. Tasters had higher plasma levels of leptin (p=0.05, tumor necrosis factor-α (TNF-α (p=0.04, and Insulin-like growth factor 1 (IGF-1 (p=0.03. There was also a trend towards increased IGF-1 levels in the saliva of tasters (p=0.06. We found a positive correlation between plasma levels of glucose and BMI (R=0.4999, p=0.04 exclusively in non-tasters, not in tasters. In contrast, plasma C-peptide levels were found to be positively correlated to BMI (R=0.5563, p=0.03 in tasters. Saliva TNF-α levels were negatively correlated with BMI in tasters (R= -0.5908, p=0.03. Our findings demonstrate that there are differences in circulating levels of leptin, TNF-α and IGF-1 between tasters and non-tasters. These findings indicate that in addition to regulate eating behaviours, taste perception could also affect energy metabolism by controlling hormone secretion. People with different taste sensitivity may respond differently to the nutrient stimulation. Further work investigating the link between taste perception and peripheral metabolic control could potentially lead to the development of novel therapies for obese

  16. Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis

    DEFF Research Database (Denmark)

    Pedersen, N; Larsen, S; Seidelin, J B;

    2004-01-01

    Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate the...... circulating levels of IL-6, MCP-1, TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic pancreatitis (CP)....

  17. Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis

    DEFF Research Database (Denmark)

    Pedersen, N; Larsen, S; Seidelin, J B;

    2004-01-01

    Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate...... the circulating levels of IL-6, MCP-1, TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic pancreatitis (CP)....

  18. Humanin: Functional Interfaces with IGF-I.

    Science.gov (United States)

    Xiao, J; Kim, S-J; Cohen, P; Yen, K

    2016-08-01

    Humanin is the first newly discovered peptide encoded in the mitochondrial genome in over three decades. It is the first member of a novel class of mitochondrial derived peptides. This small, 24 amino acid peptide was initially discovered to have neuroprotective effects and subsequent experiments have shown that it is beneficial in a diverse number of disease models including stroke, cardiovascular disease, and cancer. Over a decade ago, our lab found that humanin bound IGFBP-3 and more recent studies have found it to decrease circulating IGF-I levels. In turn, IGF-I also seems to regulate humanin levels and in this review, we cover the known interaction between humanin and IGF-I. Although the exact mechanism for how humanin and IGF-I regulate each other still needs to be elucidated, it is clear that humanin is a new player in IGF-I signaling. PMID:27082450

  19. Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients.

    Directory of Open Access Journals (Sweden)

    Liesbeth Bieghs

    Full Text Available Insulin-like growth factor (IGF signalling plays a key role in homing, progression, and treatment resistance in multiple myeloma (MM. In the extracellular environment, the majority of IGF molecules are bound to one of six IGF-binding proteins (IGFBP1-6, leaving a minor fraction of total IGF free and accessible for receptor activation. In MM, high IGF-receptor type 1 expression levels correlate with a poor prognosis, but the status and role of IGF and IGFBPs in the pathobiology of MM is unknown. Here we measured total IGF1, IGF2, and intact IGFBP levels in blood and bone marrow samples from MM (n = 17, monoclonal gammopathy of undetermined significance (MGUS (n = 37, and control individuals (n = 15, using ELISA (IGFs and 125I-IGF1 Western Ligand Blotting (IGFBPs. MGUS and MM patients displayed a significant increase in intact IGFBP-2 (2.5-3.8 fold and decrease in intact IGFBP-3 (0.6-0.5 fold in the circulation compared to control individuals. Further, IGFBP-2 as well as total IGFBP levels were significantly lower in bone marrow compared to circulation in MM and MGUS only, whereas IGF1, IGF2, and IGFBP-3 were equally distributed between the two compartments. In conclusion, the profound change in IGFBP profile strongly suggests an increased IGF bioavailability in the bone marrow microenvironment in MGUS and MM, despite no change in growth factor concentration.

  20. Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients.

    Science.gov (United States)

    Bieghs, Liesbeth; Brohus, Malene; Kristensen, Ida B; Abildgaard, Niels; Bøgsted, Martin; Johnsen, Hans E; Conover, Cheryl A; De Bruyne, Elke; Vanderkerken, Karin; Overgaard, Michael T; Nyegaard, Mette

    2016-01-01

    Insulin-like growth factor (IGF) signalling plays a key role in homing, progression, and treatment resistance in multiple myeloma (MM). In the extracellular environment, the majority of IGF molecules are bound to one of six IGF-binding proteins (IGFBP1-6), leaving a minor fraction of total IGF free and accessible for receptor activation. In MM, high IGF-receptor type 1 expression levels correlate with a poor prognosis, but the status and role of IGF and IGFBPs in the pathobiology of MM is unknown. Here we measured total IGF1, IGF2, and intact IGFBP levels in blood and bone marrow samples from MM (n = 17), monoclonal gammopathy of undetermined significance (MGUS) (n = 37), and control individuals (n = 15), using ELISA (IGFs) and 125I-IGF1 Western Ligand Blotting (IGFBPs). MGUS and MM patients displayed a significant increase in intact IGFBP-2 (2.5-3.8 fold) and decrease in intact IGFBP-3 (0.6-0.5 fold) in the circulation compared to control individuals. Further, IGFBP-2 as well as total IGFBP levels were significantly lower in bone marrow compared to circulation in MM and MGUS only, whereas IGF1, IGF2, and IGFBP-3 were equally distributed between the two compartments. In conclusion, the profound change in IGFBP profile strongly suggests an increased IGF bioavailability in the bone marrow microenvironment in MGUS and MM, despite no change in growth factor concentration. PMID:27111220

  1. Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients

    DEFF Research Database (Denmark)

    Bieghs, Liesbeth; Brohus, Malene; Kristensen, Ida B;

    2016-01-01

    and accessible for receptor activation. In MM, high IGF-receptor type 1 expression levels correlate with a poor prognosis, but the status and role of IGF and IGFBPs in the pathobiology of MM is unknown. Here we measured total IGF1, IGF2, and intact IGFBP levels in blood and bone marrow samples from MM.......6-0.5 fold) in the circulation compared to control individuals. Further, IGFBP-2 as well as total IGFBP levels were significantly lower in bone marrow compared to circulation in MM and MGUS only, whereas IGF1, IGF2, and IGFBP-3 were equally distributed between the two compartments. In conclusion, the...... profound change in IGFBP profile strongly suggests an increased IGF bioavailability in the bone marrow microenvironment in MGUS and MM, despite no change in growth factor concentration....

  2. Serum IGF1, IGF2 and IGFBP3 and risk of advanced colorectal adenoma.

    Science.gov (United States)

    Gao, Ying; Katki, Hormuzd; Graubard, Barry; Pollak, Michael; Martin, Michael; Tao, Yuzhen; Schoen, Robert E; Church, Timothy; Hayes, Richard B; Greene, Mark H; Berndt, Sonja I

    2012-07-15

    The insulin-like growth factor (IGF) signaling pathway is involved in cell proliferation and differentiation. Elevated serum IGF1 levels have been associated with increased colorectal cancer risk; however, studies of this association with colorectal adenoma are inconclusive. We examined serum IGF1, IGF2 and IGFBP3 levels in relation to risk of advanced colorectal adenoma in a case-control study within the prostate, lung, colorectal and ovarian cancer screening trial. A total of 764 advanced, left-sided colorectal adenoma cases and 775 controls frequency-matched on gender and ethnicity, without evidence of a left-sided polyp on sigmoidoscopy were included in the current study. Serum levels of IGF1, IGF2 and IGFBP3 were measured using an enzyme linked immunosorbent assay in serum samples collected at baseline. Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the associations adjusting for age, race, sex, year of blood draw, body mass index, smoking and education. Higher IGF1 levels were associated with increased adenoma risk: ORs = 1.58 (95% CI = 1.16-2.16), 1.42 (95% CI = 1.04-1.93), and 1.80 (95% CI = 1.30-2.47) for the second, third and fourth quartiles, respectively (p(trend) = 0.002). Elevated IGF2 levels were also associated with increased adenoma risk (OR = 1.43, 95% CI = 1.05-1.96 for the fourth vs. first quartile, p(trend) = 0.02), but the association was no longer significant after adjustment for IGF1 (p(trend) = 0.28). IGFBP3 levels were not associated with adenoma risk. Our analysis showed a significant positive association between circulating IGF1 levels and risk of advanced colorectal adenoma, suggesting that IGF1 is associated with the pivotal precursor to colorectal cancer. PMID:21932422

  3. Growth hormone (GH) secretory dynamics in a case of acromegalic gigantism associated with hyperprolactinemia: nonpulsatile secretion of GH may induce elevated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 levels.

    Science.gov (United States)

    Yoshida, T; Shimatsu, A; Sakane, N; Hizuka, N; Horikawa, R; Tanaka, T

    1996-01-01

    We describe a case of pituitary gigantism with low levels of growth hormone (GH), elevated insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 (IGF-BP-3). The patient had characteristic clinical features of gigantism and acromegaly. The basal serum GH levels ranged from 1.2-1.9 micrograms/L, which were considered to be within normal limits. Serum GH response to either insulin-induced hypoglycemia or GH-releasing hormone was blunted. Frequent blood samplings during daytime and at night showed nonpulsatile GH secretion. Serum prolactin, IGF-I and IGF-binding protein-3 levels were elevated. After unsuccessful surgery, bromocryptine treatment normalized serum prolactin without affecting serum GH and IGF-I levels. Combined administration of octreotide and bromocryptine reduced serum GH and IGF-I levels. GH bioactivity as measured by Nb2 cell proliferation assay was within reference range. In the present case, nonpulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-I and IGF-BP-3 and cause clinical acromegalic gigantism. PMID:8550769

  4. The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients

    DEFF Research Database (Denmark)

    Juul, A; Main, K; Blum, W F;

    1994-01-01

    administration. Serum levels of IGF-I and IGFBP-3 decrease with age in normal adults and are elevated in active acromegaly due to excessive GH secretion. However, the individual ratios between serum levels of IGF-I and IGFBP-3 in acromegalic and healthy adults have not been described previously....

  5. IGF-1 and ADMA Levels Are Inversely Correlated in Nondiabetic Ankylosing Spondylitis Patients Undergoing Anti-TNF-Alpha Therapy

    Directory of Open Access Journals (Sweden)

    Fernanda Genre

    2014-01-01

    Full Text Available Like rheumatoid arthritis, ankylosing spondylitis (AS is also an inflammatory disease associated with accelerated atherosclerosis and the presence of metabolic syndrome (MeS features. AS patients often display osteoporosis as well as new bone formation. Insulin-like growth factor 1 (IGF-1 is a protein involved in both inflammation and bone metabolism. In the present study we assessed whether disease activity, systemic inflammation, MeS features, adipokines, and biomarkers of endothelial activation were associated with IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3 levels in a series of 30 nondiabetic AS patients without CV disease undergoing TNF-α antagonist-infliximab therapy. All determinations were made in the fasting state, immediately before an infliximab infusion. Although no association of IGF-1 and IGFBP-3 levels with angiopoietin-2 or osteopontin was found, an inverse correlation between IGF-1 levels and asymmetric dimethylarginine (ADMA, an endogenous endothelial nitric oxide synthase inhibitor that impairs nitric oxide production and secretion promoting endothelial dysfunction, was found (r=-0.397; P=0.04. However, no significant association was found between IGF-1 and IGFBP-3 levels and disease activity, systemic inflammation, metabolic syndrome features, or adipokines. In conclusion, in nondiabetic patients with AS undergoing periodic anti-TNF-α therapy, IGF-1 and ADMA are inversely correlated.

  6. Reciprocal Association of Plasma IGF-1 and Interleukin-6 Levels With Cardiometabolic Risk Factors in Nondiabetic Subjects

    OpenAIRE

    Succurro, Elena; Andreozzi, Francesco; Sciaqua, Angela; Hribal, Marta Letizia; Perticone, Francesco; Sesti, Giorgio

    2008-01-01

    OBJECTIVE—To examine the relationship between plasma IGF-1 and interleukin-6 (IL-6) levels in Caucasian nondiabetic subjects and evaluate the association of IGF-1 and IL-6 with the cardiometabolic risk factors characterizing metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS—The study group consisted of 186 Caucasian nondiabetic subjects who underwent an oral glucose tolerance test and an euglycemic-hyperinsulinemic clamp. A logistic regression analysis, adjusted for age and sex, was used...

  7. 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

    Background/Objectives: Milk increases both fasting insulin and insulin-like growth factor 1 (IGF-1), and thereby growth, in healthy prepubertal boys. It is, however, unknown which components in milk are responsible for milk’s growth-stimulating effect. Subjects/Methods: To get closer to the ident......Background/Objectives: Milk increases both fasting insulin and insulin-like growth factor 1 (IGF-1), and thereby growth, in healthy prepubertal boys. It is, however, unknown which components in milk are responsible for milk’s growth-stimulating effect. Subjects/Methods: To get closer......–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...

  8. The Effect of Glycemic Control on Plasma Ghrelin and Serum IGF-1 Levels in Type 1 Diabetic Girls

    Directory of Open Access Journals (Sweden)

    Tolga Altuğ Şen

    2009-12-01

    Full Text Available Introduction: The aim of this study was to investigate the effect of glycemic control on plasma ghrelin levels and serum IGF-1 levels in girls with type 1 diabetes. Materials and Method: The study group composed of 32 diabetic girls between the ages of 14.0-20.0 years with Tanner pubertal stage 5; and 15 healthy girls in similar ages with Tanner pubertal stage 5 formed the control group. Diabetic girls were classified as well glycemic controlled (n=18 and poor glycemic controlled (n=14 according to last year’s mean glycosylated hemoglobin levels. All subjects were tested for fasting plasma ghrelin and serum IGF-1 levels. Results: The mean fasting plasma ghrelin levels in girls with well controlled diabetes, in girls wtih poor controlled diabetes and in control group were 483.4±221.9 pg/ml, 310.7±110.2 pg/ml, 471.9±175.0 pg/ml respectively. The mean serum IGF-1 levels in girls with well controlled diabetes was 233.9±59.2 ng/ml, in girls with poor controlled diabetes 183.9±36.7 ng/ml, and in healthy controls 247.3±48.5 ng/ml. Plasma ghrelin levels and serum IGF-1 levels were similar in girls with well controlled diabetes and in the control group, however it was significantly supressed in those with poorly controlled diabetes. Conclusion: The metabolic control may be a determinative factor on plasma ghrelin and serum IGF-1 levels of type 1 diabetics. Plasma ghrelin and serum IGF-1 levels were similar in well glycemic controlled diabetics and control group, while they were suppressed in only poor glycemic controlled diabetics. (Journal of Current Pediatrics 2009; 7: 104-10

  9. IGFBP1 and IGFBP3 polymorphisms predict circulating IGFBP-3 levels among women from high-risk breast cancer families

    OpenAIRE

    Rosendahl, Ann; Hietala, Maria; Henningson, Maria; Olsson, Håkan; Jernström, Helena

    2010-01-01

    Abstract The insulin-like growth factor (IGF) pathway has been implicated as risk modifier in premenopausal breast cancer. In this study, associations between single nucleotide polymorphisms (SNPs) and diplotypes in the IGFBP1 and IGFBP3 genes and circulating IGFBP-3 levels, BRCA family status and breast cancer among women from high-risk breast cancer families were investigated. Nine IGFBP1 and IGFBP3 SNPs were genotyped with PCR-based methods in 323 women. Nine IGFBP1 and ten IGFB...

  10. Genetic architecture of circulating lipid levels

    DEFF Research Database (Denmark)

    Demirkan, Ayşe; Amin, Najaf; Isaacs, Aaron;

    2011-01-01

    Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid...... suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture...... levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from...

  11. Common polymorphism in H19 associated with birthweight and cord blood IGF-II levels in humans

    Directory of Open Access Journals (Sweden)

    Petry Clive J

    2005-05-01

    Full Text Available Abstract Background Common genetic variation at genes that are imprinted and exclusively maternally expressed could explain the apparent maternal-specific inheritance of low birthweight reported in large family pedigrees. We identified ten single nucleotide polymorphisms (SNPs in H19, and we genotyped three of these SNPs in families from the contemporary ALSPAC UK birth cohort (1,696 children, 822 mothers and 661 fathers in order to explore associations with size at birth and cord blood IGF-II levels. Results Both offspring's and mother's H19 2992C>T SNP genotypes showed associations with offspring birthweight (P = 0.03 to P = 0.003 and mother's genotype was also associated with cord blood IGF-II levels (P = 0.0003 to P = 0.0001. The offspring genotype association with birthweight was independent of mother's genotype (P = 0.01 to P = 0.007. However, mother's untransmitted H19 2992T allele was also associated with larger birthweight (P = 0.04 and higher cord blood IGF-II levels (P = 0.002, suggesting a direct effect of mother's genotype on placental IGF-II expression and fetal growth. The association between mother's untransmitted allele and cord blood IGF-II levels was more apparent in offspring of first pregnancies than subsequent pregnancies (P-interaction = 0.03. Study of the independent Cambridge birth cohort with available DNA in mothers (N = 646 provided additional support for mother's H19 2992 genotype associations with birthweight (P = 0.04 and with mother's glucose levels (P = 0.01 in first pregnancies. Conclusion The common H19 2992T allele, in the mother or offspring or both, may confer reduced fetal growth restraint, as indicated by associations with larger offspring birth size, higher cord blood IGF-II levels, and lower compensatory early postnatal catch-up weight gain, that are more evident among mother's smaller first-born infants.

  12. Body composition and circulating high-molecular-weight adiponectin and IGF-I in infants born small for gestational age: breast- versus formula-feeding.

    Science.gov (United States)

    de Zegher, Francis; Sebastiani, Giorgia; Diaz, Marta; Sánchez-Infantes, David; Lopez-Bermejo, Abel; Ibáñez, Lourdes

    2012-08-01

    Prenatal growth restraint, if followed by postnatal overweight, confers risk for adult disease including diabetes. The mechanisms whereby neonatal nutrition may modulate such risk are poorly understood. We studied the effects of nutrition (breast-feeding [BRF] vs. formula-feeding [FOF]) on weight partitioning and endocrine state (as judged by high-molecular-weight [HMW] adiponectin and IGF-I) of infants born small for gestational age (SGA). Body composition (by absorptiometry), HMW adiponectin, and IGF-I were assessed at birth and 4 months in BRF infants born appropriate for gestational age (AGA; n = 72) and SGA infants receiving BRF (n = 46) or FOF (n = 56), the latter being randomized to receive a standard (FOF1) or protein-rich formula (FOF2). Compared with AGA-BRF infants, the catchup growth of SGA infants was confined to lean mass, independently of nutrition. Compared with AGA-BRF infants, SGA-BRF infants had normal HMW adiponectin and IGF-I levels at 4 months, whereas SGA-FOF infants had elevated levels of HMW adiponectin (particularly SGA-FOF1) and IGF-I (particularly SGA-FOF2). In conclusion, neonatal nutrition seems to influence endocrinology more readily than body composition of SGA infants. Follow-up will disclose whether the endocrine abnormalities in SGA-FOF infants can serve as early markers of an unfavorable metabolic course and whether they may contribute to design early interventions that prevent subsequent disease, including diabetes. PMID:22648385

  13. Expression profile of IGF paralog genes in liver and muscle of a GH-transgenic zebrafish.

    Science.gov (United States)

    Nornberg, Bruna Felix; Figueiredo, Marcio Azevedo; Marins, Luis Fernando

    2016-01-15

    The objective of this study was to investigate the relationship between IGFs produced in the liver and skeletal muscle with muscle hypertrophy previously observed in a line of GH-transgenic zebrafish. In this sense, we evaluated the expression of genes related to the IGF system in liver and muscle of transgenics, as well as the main intracellular signaling pathways used by GH/IGF axis. Our results showed an increase in expression of igf1a, igf2a, and igf2b genes in the liver. Moreover, there was a decrease in the expression of igf1ra and an increase in muscle igf2r of transgenics, indicating a negative response of muscle tissue with respect to excess circulating IGFs. Muscle IGFs expression analyses revealed a significant increase only for igf2b, accompanied by a parallel induction of igfbp5a gene. The presence of IGFBP5a may potentiate the IGF2 action in muscle cells differentiation. Regarding JAK/STAT-related genes, we observed an alteration in the expression profile of both stat3 and stat5a in transgenic fish liver. No changes were observed in the muscle, suggesting that both tissues respond differently to GH-transgenesis. Western blotting analyses indicated an imbalance between the phosphorylation levels of the proliferative (MEK/ERK) and hypertrophic (PI3K/Akt) pathways, in favor of the latter. In summary, the results of this study suggest that the hypertrophy caused by GH-transgenesis in zebrafish may be due to circulating IGFs produced by the liver, with an important participation of muscle IGF2b. This group of IGFs appears to be favoring the hypertrophic intracellular pathway in muscle tissue of transgenic zebrafish. PMID:26718079

  14. Distribution and levels of [125I]IGF-I, [125I]IGF-II and [125I]insulin receptor binding sites in the hippocampus of aged memory-unimpaired and -impaired rats

    International Nuclear Information System (INIS)

    The insulin-like growth factors (IGF-I and IGF-II) and insulin are localized within distinct brain regions and their respective functions are mediated by specific membrane receptors. High densities of binding sites for these growth factors are discretely and differentially distributed throughout the brain, with prominent levels localized to the hippocampal formation. IGFs and insulin, in addition to their growth promoting actions, are considered to play important roles in the development and maintenance of normal cell functions throughout life. We compared the anatomical distribution and levels of IGF and insulin receptors in young (five month) and aged (25 month) memory-impaired and memory-unimpaired male Long-Evans rats as determined in the Morris water maze task in order to determine if alterations in IGF and insulin activity may be related to the emergence of cognitive deficits in the aged memory-impaired rat. In the hippocampus, [125I]IGF-I receptors are concentrated primarily in the dentate gyrus (DG) and the CA3 sub-field while high amounts of [125I]IGF-II binding sites are localized to the pyramidal cell layer, and the granular cell layer of the DG. [125I]insulin binding sites are mostly found in the molecular layer of the DG and the CA1 sub-field. No significant differences were found in [125I]IGF-I, [125I]IGF-II or [125I]insulin binding levels in any regions or laminae of the hippocampus of young vs aged rats, and deficits in cognitive performance did not relate to altered levels of these receptors in aged memory-impaired vs aged memory-unimpaired rats. Other regions, including various cortical areas, were also examined and failed to reveal any significant differences between the three groups studied.It thus appears that IGF-I, IGF-II and insulin receptor sites are not markedly altered during the normal ageing process in the Long-Evans rat, in spite of significant learning deficits in a sub-group (memory-impaired) of aged animals. Hence, recently reported

  15. Relación entre los niveles circulantes del factor de crecimiento similar a la insulina tipo I (IGF-I) y la expresión diferencial de genes relacionados con migración en células linfoides / Relatioship between circulating levels of insulin-like growth factor-I and differential expression of genes related to lymphoid cell migration

    OpenAIRE

    Cuervo Escobar, Sergio Andrei

    2011-01-01

    A partir de investigaciones realizadas en los últimos años, se ha hecho evidente la comunicación bidireccional entre los sistemas inmune y endocrino. Existe un gran cuerpo de evidencia que sugiere que el eje conformado por la hormona de crecimiento (GH) y el factor de crecimiento similar a la insulina tipo I (IGF-I) tiene un papel importante en la funcionalidad del sistema inmune. Los efectos de estas hormonas sobre los diferentes tipos celulares y tejidos pueden darse por meca...

  16. Recombinant IGF-I: Past, present and future.

    Science.gov (United States)

    Bright, George M

    2016-06-01

    Normal linear growth in humans requires GH and IGF-I. Diminished GH action resulting in reduced availability of IGF-I and IGF-binding proteins is the hallmarks of GH Insensitivity Syndromes (GHIS). The deficiencies are the perceived mechanisms for the growth failure of affected patients and the therapeutic targets for the restoration of normal growth. Early treatment attempts with pituitary-derived GH had limited effects in GHIS patients. Recombinant human insulin-like growth factor-I (rhIGF-I) treatment initially provides accelerated growth to GHIS children and provides substantial benefit. But, in general, catch up growth is less substantial with rhIGF-I treatment of GHIS than with rhGH treatment of GH Deficiency. Few classic GHIS patients have reached heights in the normal range (height SD score between -2.0 SD and +2.0 SD) with rhIGF-I monotherapy. A potential explanation is that while rhIGF-I treatment increases circulating concentrations of IGF-1 and IGFBP-3, such treatment reduces endogenous GH levels by negative feedback inhibition of pituitary GH release. In as much as both GH and IGF-I are required for good catch up growth, the loss of any residual GH signaling during IGF-I monotherapy in GHIS patients may attenuate possible catch up growth. Consistent with this explanation is the finding that, as predicted by the preclinical studies by Ross Clark, combination of rhGH & rhIGF-1 provides better growth responses than rhIGF-1 monotherapy in prepubertal children with short stature and low IGF-I levels despite normal stimulated GH responses. In the future, rhGH and rhIGF-I combination therapy can potentially improve growth outcomes over that seen with rhIGF-I monotherapy in all GHIS patients except in those with a total lack of functional GH signaling. Future alternative treatments for GHIS subjects may also include the use of post-growth hormone receptor signaling agonists which restore both GH signaling and IGF-I exposures or the addition of long-acting rh

  17. GH and IGF-I levels are positively associated with musculotendinous collagen expression: Experiments in acromegalic and GHD patients

    DEFF Research Database (Denmark)

    Doessing, Simon; Holm, Lars; Heinemeier, Katja;

    2010-01-01

    OBJECTIVE: Disproportionate growth of musculoskeletal tissue is a major cause of morbidity in both acromegalic (ACRO) and GH-deficient (GHD) patients. GH/IGF1 is likely to play an important role in the regulation of tendon and muscle collagen. We hypothesized that the local production of collagen...... is associated with the level of GH/IGF1.DESIGN AND METHODS: As primary outcomes, collagen mRNA expression and collagen protein fractional synthesis rate (FSR) were determined locally in skeletal muscle and tendon in nine ACRO and nine GHD patients. Moreover, muscle myofibrillar protein synthesis and...... tendon collagen morphology were determined.RESULTS AND CONCLUSIONS: Muscle collagen I and III mRNA expression was higher in ACRO patients versus GHD patients (P<0.05), whereas collagen protein FSR did not differ significantly between ACRO and GHD patients in muscle (P=0.21) and tendon (P=0.15). IGF1Ea...

  18. Hepatic mRNA expression and plasma levels of insulin-like growth factor-I (IGF-I in broiler chickens selected for different growth rates

    Directory of Open Access Journals (Sweden)

    Poliana Fernanda Giachetto

    2004-01-01

    Full Text Available The hepatic expression and plasma concentrations of IGF-I were investigated in three broiler chicken strains selected for different growth rates (HP-Hubbard-Pettersen, a fast growing strain; NN-Naked-neck, a strain with an intermediate growth rate and a heterozygous genotype, and C-Caipira, a slow growing crossbred strain. The chickens were studied at 1, 21 and 42 days of age and had free access to food throughout the study. Hepatic IGF-I mRNA expression was assessed by dot blot analysis using a randomly labeled chicken IGF-I cDNA as the probe and plasma IGF-I concentrations were assayed by radioimmunoassay. The hepatic levels of IGF-I mRNA increased from 1 to 21 days of age in all strains, with NN chickens showing a higher (p < 0.05 IGF-I expression than the other strains. Plasma IGF-I concentrations increased (p < 0.05 with broiler chicken age, but there were no significant differences among the strains. These results indicate that despite differences in the growth rates among the strains, the changes in the expression of IGF-I mRNA in liver and in the plasma levels of IGF-I were independent of broiler chicken strain, but varied with chicken age.

  19. Body Composition and Circulating High-Molecular-Weight Adiponectin and IGF-I in Infants Born Small for Gestational Age

    OpenAIRE

    Zegher, Francis de; Sebastiani, Giorgia; Diaz, Marta; Sánchez-Infantes, David; Lopez-Bermejo, Abel; Ibáñez, Lourdes

    2012-01-01

    Prenatal growth restraint, if followed by postnatal overweight, confers risk for adult disease including diabetes. The mechanisms whereby neonatal nutrition may modulate such risk are poorly understood. We studied the effects of nutrition (breast-feeding [BRF] vs. formula-feeding [FOF]) on weight partitioning and endocrine state (as judged by high-molecular-weight [HMW] adiponectin and IGF-I) of infants born small for gestational age (SGA). Body composition (by absorptiometry), HMW adiponecti...

  20. IGF-I bioactivity in an elderly population: Relation to insulin sensitivity, insulin levels, and the metabolic syndrome

    NARCIS (Netherlands)

    M.P. Brugts (Michael); C.M. van Duijn (Cock); L.J. Hofland (Leo); J.C.M. Witteman (Jacqueline); S.W.J. Lamberts (Steven); J.A.M.J.L. Janssen (Joop)

    2010-01-01

    textabstractOBJECTIVE - There is a complex relationship between IGF-I, IGF binding proteins, growth hormone, and insulin. The IGF-I kinase receptor activation assay (KIRA) is a novel method for measuring IGF-I bioactivity in human serum. We speculated that determination of IGF-I bioactivity might br

  1. Effects of recombinant human insulin-like growth factor-I (rhIGF-I) on total and free IGF-I concentrations, IGF-binding proteins, and glycemic response in humans.

    Science.gov (United States)

    Lieberman, S A; Bukar, J; Chen, S A; Celniker, A C; Compton, P G; Cook, J; Albu, J; Perlman, A J; Hoffman, A R

    1992-07-01

    circulating IGF-I without changing free IGF-I disposition or glycemic response. A 30-kilodalton IGFBP band, most likely IGFBP-1, appeared transiently following rhIGF-I administration, probably as a result of suppression of insulin levels. IGFBP-2, -3, and -4 were unaffected. PMID:1377706

  2. The observation of serum IGF-Ⅰ 、IGFBP-3 levels in children sex precocity%性早熟儿童IGF-Ⅰ和IGFBP-3水平的观察

    Institute of Scientific and Technical Information of China (English)

    王秀娣; 留佩宁; 项如莲

    2001-01-01

    目的:通过对胰岛素生长因子-Ⅰ(IGF-Ⅰ)、胰岛素生长因子结合蛋白-3(IGFBP-3)、生长激素(GH)及雌二醇(E2)的检测,观察性早熟儿童的生长发育轴系发育情况及与性激素的关系。方法:分别对42例真性性早熟、14例正常儿童用放射免疫及免疫放射法检测GH 、IGF-Ⅰ、IGFBP-3及E2水平。结果:真性性早熟组IGF-Ⅰ、IGFBP-3及E2水平与对照组比较差异均有非常显著性意义(P0.05)。将观察组IGF-Ⅰ、IGFBP-3、GH与E2值行相关分析,结果E2与 IGF-Ⅰ及IGFBP-3均有非常显著的相关性( P0.05) , IGF-Ⅰ与 IGFBP-3比较有显著的相关性( P<0.05)。结论:性早熟儿童生长激素介质IGF-Ⅰ、IGFBP-3水平显著升高,IGF-Ⅰ、IGFBP-3的升高与E2水平有密切的关系。%Objective:To observe the correlation between the growing-hormone axis and the sex hormone in sexual precocity by measuring the levels of IGF-Ⅰ、IGFBP-3、 GH and E2.Methods:The levels of IGF-Ⅰ、 IGFBP-3 、GH、 E2 were detected with Radioammunoassay. 42 cases of sexual precocity children were taken as the observation group,14 cases normal children as the control group.Results:The mean of IGF-Ⅰ、IGFBP-3、 E2、 GH was 293.30ng/ml、 5145.00ng/ml、10.15pg/ml、4.27ng/ml in the observation group and was 77.27ng/ml、2198.50ng/ml、3.50pg/ml 、2.33ng/ml in the control group.The levels of IGF-Ⅰ 、IGFBP-3、 E2 were significantly different between observation group and control group.There was significant correlation between IGF-Ⅰ、 IGFBP-3 and E2 in observation group, and no correlation between GH and E2.Conclusion:The levels of IGF-Ⅰ、IGFBP-3 were significantly higher in the sexual precocity children.there was significantly correlation between IGF-Ⅰ、IGFBP-3 and E2.

  3. Developmental Changes of IGF-Ⅰ mRNA Expression Level in Sheep Muscle%绵羊肌肉IGF-Ⅰ基因表达的发育性变化研究

    Institute of Scientific and Technical Information of China (English)

    黄治国; 谢庄

    2009-01-01

    [Objective] To detect the mRNA of muscle insulin-like growth factorⅠ (IGF-Ⅰ) in the early development of Kazak sheep and Xinjiang fine-wool sheep, so as to provide information for the research about the early growth and development of sheep. [Method] With real-time quantitative PCR, the muscle IGF-Ⅰ mRNA level was separately detected in two varieties of sheep at 2, 30, 60, 90 and 120 days old. Then the data was analyzed with SPSS software. [Result] The IGF-Ⅰ mRNA in sheep muscle first increased and then decreased with ages, peaking at 30 days old in Kazak sheep and at 60 days old in Xinjiang fine-wool sheep. The IGF-Ⅰ expression level of Kazak sheep had no significant difference with Xinjiang fine-wool sheep at 2 or 90 days old (P>0.05), but was lower than that of the latter with extremely significant difference (P<0.01) from 30 to 60 days old. [Conclusion] The male Kazak sheep and Xinjiang fine-wool sheep have similar model of developmental changes of muscular IGF-Ⅰ mRNA, but the expression level is different between these two species.

  4. Correlation between basal serum IGF-1 levels and functional autonomy in elderly women. (Correlación entre los niveles sericos de IGF-1 basal y autonomía funcional en las ancianas.

    Directory of Open Access Journals (Sweden)

    Rodrigo Gomes de Souza Vale

    2009-01-01

    Full Text Available Abstract The aim of the present study was to determine the degree of correlation between basal serum IGF-1 levels and functional autonomy in the performance of activities of daily living (ADL. The sample comprised 11 elderly individuals, disregarding their ADLs (age = 68.18 ± 5.19 years; body mass index (BMI = 28.89 ± 3.44 kg/m2 and not enrolled in physical exercise programs for at least 3 months. The subjects were submitted to a battery of 5 functional autonomy tests from the GDLAM protocol and blood collection to assess serum IGF-1 levels. Using Pearson’s correlation, we found a significant mean correlation coefficient (r between the 10 m walking test (10mW and IGF-1 (r = -0.690; p = 0.009 and mean correlation, but not significant between the putting on and removing a t-shirt test (PRTS and IGF-1 (r = -0.528 and between the general autonomy index (AI and IGF-1 (r = -0.417. The correlation was low in the remaining tests, but inversed. This suggests that the decline in IGF-1 with age may decrease ADL performance in the elderly. Key words: Serum IGF-1; ADL; elderly. Resumen El objetivo del presente estudio fue comprobar el nivel de la correlación entre los niveles de serum basal de IGF-1 y la autonomía funcional para la realización de las actividades de la vida diaria en personas mayores (edad = 68,18 ± 5,19 años; índice de la masa corporal, IMC = 28,89 ± 3,44 kg/m2, no participantes de los programas de ejercicios físico desde hace un mínimo de 3 meses. Los sujetos fueron sometidos a una batería de 5 tareas de autonomía funcional del protocolo GDLAM y un análisis de sangre para evaluar los niveles de serum de IGF-1. A través de la correlación de Pearson se comprobó la existencia de un coeficiente de la correlación (r medio y significativo entre el examen de la marcha 10m (C10m y el IGF-1 (r = -0,690; p=0,009 y la correlación media, pero no significativa ,entre el test de vestirse y quitarse una camiseta (VTC y el IGF-1 (r= -0

  5. 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

  6. High serum levels of growth hormone (GH) and insulin like growth factor-I (IGF-I) during high-dose GH treatment in short children born small for gestational age

    NARCIS (Netherlands)

    van Dijk, M; Mulder, P; Houdijk, M; Mulder, J; Noordam, K; Odink, RJ; Rongen-Westerlaken, C; Voorhoeve, P; Waelkens, J; Stokvis-Brantsma, J; Hokken-Koelega, A

    2006-01-01

    Context: Epidemiological studies have indicated that high serum levels of GH and IGF-I are associated with long-term risks. Objective: The objective of the study was to evaluate the changes in serum levels of GH during overnight profiles, IGF-I, and IGF binding protein 3 (IGFBP-3) in short small for

  7. High serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) during high-dose GH treatment in short children born small for gestational age.

    NARCIS (Netherlands)

    Dijk, M. van; Mulder, P.; Houdijk, M.; Mulder, J.; Noordam, K.; Odink, R.J.; Rongen-Westerlaken, C.; Voorhoeve, P.; Waelkens, J.; Stokvis-Brantsma, J.; Hokken-Koelega, A.C.

    2006-01-01

    CONTEXT: Epidemiological studies have indicated that high serum levels of GH and IGF-I are associated with long-term risks. OBJECTIVE: The objective of the study was to evaluate the changes in serum levels of GH during overnight profiles, IGF-I, and IGF binding protein 3 (IGFBP-3) in short small for

  8. High serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) during high-dose GH treatment in short children born small for gestational age

    NARCIS (Netherlands)

    M. van Dijk (Marije); P.G.H. Mulder (Paul); E.C.A.M. Houdijk (Mieke); J.C. Mulder (Jaap); K. Noordam (Kees); R.J.H. Odink (Roelof); C. Rongen-Westerlaken (Ciska); P.G. Voorhoeve (Paul); J.J.J. Waelkens (Johan); W.H. Stokvis-Brantsma; A.C.S. Hokken-Koelega (Anita)

    2006-01-01

    textabstractContext: Epidemiological studies have indicated that high serum levels of GH and IGF-I are associated with long-term risks. Objective: The objective of the study was to evaluate the changes in serum levels of GH during overnight profiles, IGF-I, and IGF binding protein 3 (IGFBP-3) in sho

  9. Preclinical Screening for Retinopathy of Prematurity Risk Using IGF1 Levels at 3 Weeks Post-Partum

    OpenAIRE

    Pérez-Muñuzuri, Alejandro; Couce-Pico, Ma 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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 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. PMID:24523937

  12. Prognostic value of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 blood levels in breast cancer.

    NARCIS (Netherlands)

    Hartog, H.; Boezen, H.M.; Jong, M.M. de; Schaapveld, M.; Wesseling, J.; Graaf, W.T.A. van der

    2013-01-01

    High circulating insulin-like growth factor 1 (IGF-1) levels are firmly established as a risk factor for developing breast cancer, especially estrogen positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is established is unknown. The authors explored the effect of IGF-1 blood

  13. Clinical significance of changes of serum IGF-II, IL-2 and SOD levels after treatment in pediatric patients with bronchial pneumonia

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical significance of changes of serum IGF-II, IL-2 and SOD levels after treatment in pediatric patients with bronchial pneumonia. Methods: Serum IGF-II, IL-2 and SOD (with RIA) levels were measured in 33 pediatric patients with bronchial pneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, serum IGF-II levels in the patients were significantly higher than those in controls (P0.05). Conclusion: Changes of serum IGF-II, IL-2 and SOD levels both before and after treatment could reflect the diseases status of the patients as well as the progress of diseases, and might be of prognostic importance in pediatric patients with bronchial pneumonia. (authors)

  14. Elevated serum IGF-I, but unaltered sex steroid levels, in healthy boys with pubertal gynaecomastia

    DEFF Research Database (Denmark)

    Mieritz, Mikkel G; Sorensen, Kaspar; Aksglaede, Lise;

    2014-01-01

    OBJECTIVE: Pubertal gynaecomastia is a very common condition. Although the underlying aetiology is poorly understood, it is generally accepted that excess of oestrogens and deficit of androgens are involved in the pathogenesis. Furthermore, adiposity as well as the GH/IGF-I axis may play a role. ...

  15. IGF-I and branchial IGF receptor expression and localization during salinity acclimation in striped bass

    DEFF Research Database (Denmark)

    Tipsmark, Christian Kølbaek; Luckenbach, John Adam; Madsen, Steffen;

    2007-01-01

    The initial response of the IGF-I system and the expression and cellular localization of IGF type-I receptor (IGF-IR) were studied in the gill of a euryhaline teleost during salinity acclimation. Exposure of striped bass (Morone saxatilis) to hyperosmotic and hypoosmotic challenges induced small...... in either plasma IGF-I, liver, or gill IGF-I mRNA, or gill IGF-IR mRNA levels. In a separate experiment, FW-acclimated fish were injected with saline or IGF-I prior to a 24-h SW challenge. Rapid regain of osmotic balance following SW transfer was hindered by IGF-I. Immunohistochemistry revealed...

  16. Intrauterine Growth Retardation (IUGR) as a Novel Condition of Insulin-Like Growth Factor-1 (IGF-1) Deficiency.

    Science.gov (United States)

    Martín-Estal, I; de la Garza, R G; Castilla-Cortázar, I

    2016-01-01

    Insulin-like growth factor 1 (IGF-1) is an anabolic hormone with several biological activities, such as proliferation, mitochondrial protection, cell survival, tissue growth and development, anti-inflammatory, antioxidant, antifibrogenic and antiaging. This hormone plays an important role in embryological and postnatal states, being essential for normal foetal and placental growth and differentiation. During gestation, the placenta is one of the major sources of IGF-1, among other hormones. This intrauterine organ expresses IGF-1 receptors and IGF-1 binding proteins (IGFBPs), which control IGF-1 activities. Intrauterine growth restriction (IUGR) is the second most frequent cause of perinatal morbidity and mortality, defined as the inability to achieve the expected weight for gestational age. Different studies have revealed that IUGR infants have placental dysfunction and low circulating levels of insulin, IGF-1, IGF-2 and IGFBPs. Such data suggest that IGF-1 deficiency in gestational state may be one of the major causes of foetal growth retardation. The aim of this review is to study the epidemiology, physiopathology and possible causes of IUGR. Also, it intends to study the possible role of the placenta as an IGF-1 target organ. The purpose is to establish if IUGR could be considered as a novel condition of IGF-1 deficiency and if its treatment with low doses of IGF-1 could be a suitable therapeutic strategy. PMID:26634242

  17. Effect of Reinforcing Kidney Replenishing qi and Promoting Blood Circulation Recipe on the Expression of IGF-1, IGFBP-1 and IGFBP-3 in liver of the Fetal Rat with FGR%补肾益气活血方对胎儿生长受限胎鼠IGF-1、IGFBP-1及IGFBP-3表达的影响

    Institute of Scientific and Technical Information of China (English)

    王琪; 熊丽萍; 陶秀良

    2011-01-01

    Objective To investigate the effect of Bushen Yiqi Huoxue (Reinforcing Kidney Replenishing qi and Promoting Blood Circulation) Decoction on the expression of IGF - 1, IGFBP - 1 and IGFBP - 3 proteins in fetal liver of Fetal growth restriction ( FGR) rat. Methods The smoke inhalation rat model was created. Thirty two pregnant Sprague - Dawley rats were randomly dividedly into four groups: control group, FGR group, group of FGR treated with Bushen Yiqi Huoxue Decoction (Chinese medicine group), group of FGR treated with arginine ( arginine group). The expression of IGF - 1, IGFBP - 1 and IGFBP - 3 proteins in fetal liver were analyzed by immunohistochemis-try. Result Compared with FGR group, the expression of IGF - 1 and IGFBP -3 in fetal liver of Chinese medicine group increased significantly (P 0. 05). Conclusion The effect of Bushen Yiqi Huoxue Decoction on preventing and treating FGR may be attributed to regulating the expression of IGF - 1, IGFBP -1 and IGFBP -3.%目的 观察补肾益气活血方对胎儿生长受限胎鼠肝脏IGF-1、IGFBP-1、IGFBP-3表达的影响,探讨补肾益气活血方治疗FGR的作用机制.方法 采用被动吸烟法建立SD大鼠FGR模型,分为正常组、FGR组、补肾益气活血方治疗组(中药组)、精氨酸治疗组(精氨酸组).采用免疫组织化学方法检测胎鼠肝脏IGF-1、IGFBP-1、IGFBP-3的表达.结果 与FGR组比较,中药组胎鼠肝脏IGF-1、IGFBP-3的表达均明显升高(P<0.05),而IGFBP-1的表达明显降低(P<0.05),并且IGF-1的表达强度高于精氨酸组(P<0.05),各项指标与正常组比较差异无统计学意义(P>0.05).结论 补肾益气活血方可能通过调节IGF-Ⅰ、IGFBP-1、IGFBP-3的表达,从而促进胎儿在宫内的生长发育.

  18. Acciones biológicas y factores determinantes de las concentraciones del factor de crecimiento similar a la insulina tipo I (IGF-1 en el caballo (Biological actions and determinant factors of the circulating concentrations of insulin-like growth factor type 1, IGF-1, in the horse

    Directory of Open Access Journals (Sweden)

    Muñoz A

    2010-06-01

    activity of the hypophysis and the somatotropic axis. In the present review, firstly, we will describe the main biological actions of the IGF-1 and secondly, we will define the main factors that could significantly influence the circulating concentrations of IGF-1. Among these factors, the most important are body size, breed, age, gender, time of blood extraction, circadianrhythms, diet, food privation, exercise and training. The effect of these factors should be assessed prior to extended clinical and research use of IGF-1 in horses.

  19. Dynamic sea level changes following changes in the thermohaline circulation

    CERN Document Server

    Levermann, A; Hofmann, M; Montoya, M; Rahmstorf, S; Levermann, Anders; Griesel, Alexa; Hofmann, Matthias; Montoya, Marisa; Rahmstorf, Stefan

    2004-01-01

    Using the coupled climate model CLIMBER-3a, we investigate changes in sea surface elevation due to a weakening of the thermohaline circulation (THC). In addition to a global sea level rise due to a warming of the deep sea, this leads to a regional dynamic sea level change which follows quasi-instantaneously any change in the ocean circulation. We show that the magnitude of this dynamic effect can locally reach up to ~1m, depending on the initial THC strength. In some regions the rate of change can be up to 20-25 mm/yr. The emerging patterns are discussed with respect to the oceanic circulation changes. Most prominent is a south-north gradient reflecting the changes in geostrophic surface currents. Our results suggest that an analysis of observed sea level change patterns could be useful for monitoring the THC strength.

  20. The effects of long-term resistance exercise on the relationship between neurocognitive performance and GH, IGF-1, and homocysteine levels in the elderly

    Directory of Open Access Journals (Sweden)

    Chia-Liang eTsai

    2015-02-01

    Full Text Available This study aimed to investigate the effects of a long-term resistance exercise intervention on executive functions in healthy elderly males, and to further understand the potential neurophysiological mechanisms mediating the changes. The study assessed forty-eight healthy elderly males randomly assigned to exercise (n=24 or control (n=24 groups. The assessment included neuropsychological and neuroelectric measures during a variant of the oddball task paradigm, as well as growth hormone (GH, insulin-like growth factor-1 (IGF-1, and homocysteine levels at baseline and after either a 12-month intervention of resistance exercise training or control period. The results showed that the control group had a significantly lower accuracy rate and smaller P3a and P3b amplitudes in the oddball condition after 12 months. The exercise group exhibited improved reaction times, sustained P3a and P3b amplitudes, increased levels of serum IGF-1, and decreased levels of serum homocysteine. The changes in IGF-1 levels were significantly correlated with the changes in reaction time and P3b amplitude of the oddball condition in the exercise group. In conclusion, significantly enhanced serum IGF-1 levels after 12 months of resistance exercise were inversely correlated with neurocognitive decline in the elderly. These findings suggest that regular resistance exercise might be a promising strategy to attenuate the trajectory of cognitive aging in healthy elderly individuals, possibly mediated by IGF-1.

  1. Analysis of IGF-1, Lp-PLA2, hs-CRP, Hcy levels in type 2 diabetes patients complicated with carotid atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Guan-Lun Ye; Zhuo-Zhang Luo; Wei-Ming Zheng

    2015-01-01

    Objective: To study the levels of IGF-1, Lp-PLA2, hs-CRP, Hcy in type 2 diabetes patients complicated with carotid atherosclerosis. Methods: 90 cases of type 2 diabetes patients complicated with carotid atherosclerosis in our hospital from May 2013 to August 2014 were enrolled in observation group and further divided into mild stenosis group, moderate stenosis group, severe stenosis group according to the judgment of color ultrasonography on carotid artery carotid artery stenosis, divided into mild sclerosis group, moderate sclerosis group, severe sclerosis group according to carotid artery plaque score. At the same time type 2 diabetic patients without complications in our hospital were enrolled in the control group. Then serums IGF-1, Lp-PLA2, hs-CRP, Hcy levels were assayed. Results: serum IGF-1, Lp-PLA2, hs-CRP, Hcy levels of observation group were higher than those of control group; as carotid artery stenosis and sclerosis degree got greater, serum IGF-1, Lp-PLA2, hs-CRP, Hcy levels were higher. Conclusion:serum IGF-1, Lp-PLA2, hs-CRP, Hcy levels in type 2 diabetes patients complicated with carotid atherosclerosis abnormally increased and it can reflect the degree of carotid stenosis and sclerosis.

  2. Assessing the role of insulin‐like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels

    Science.gov (United States)

    Bonilla, Carolina; Lewis, Sarah J.; Rowlands, Mari‐Anne; Gaunt, Tom R.; Davey Smith, George; Gunnell, David; Palmer, Tom; Donovan, Jenny L.; Hamdy, Freddie C.; Neal, David E.; Eeles, Rosalind; Easton, Doug; Kote‐Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G.; Wiklund, Fredrik; Grönberg, Henrik; Haiman, Christopher A.; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C.; Pashayan, Nora; Khaw, Kay‐Tee; Stanford, Janet L.; Blot, William J.; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon‐Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R.; Pandha, Hardev; Lathrop, Mark; Holly, Jeff M. P.

    2016-01-01

    Circulating insulin‐like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome‐wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF‐I, IGF‐II, IGFBP‐2 and IGFBP‐3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF‐II and IGFBP‐3, less so for IGF‐I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF‐II/IGFBP‐3 level‐raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF‐II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. PMID:27225428

  3. The clinical analysis of exploring essential hypertension severity through determining plasma NT-proBNP, AT II and IGF-I levels

    International Nuclear Information System (INIS)

    Objective: In order to evaluate clinical analysis of exploring essential hypertension severity through determining plasma NT-proBNP, AT II and IGF-I levels. Methods: Plasma NT-proBNP (with fluoroimmunoassay), ATII (with RIA) and IGF-I (with enzyme immunoassay) levels were measured in 265 patients with essential hypertension (EH) and 65 normal controls as well as comparable studies. Results: Plasma NT-proBNP and AT II levels in 265 patients with EH were significantly higher then those in 65 controls (P all0.05). Plasma NT-proBNP and AT II levels in 73 patients with EH I stage were tightly elevated and significantly higher then those in 65 controls (P>0.05 - <0.05), but plasma IGF-I level was significantly lower (P<0.05). Plasma NT-proBNP and AT II levels in 78 patients with EH II stage and in 78 patients with EH III stage were prominently higher than those in 65 controls (P<0.05 - <0.01), but plasma IGF-I level was very marked lower (P<0.01). Conclusion: Plasma NT-proBNP and AT II levels in patients with EH were positive correlation with EH clinical stage, while the same result was not found for plasma IGF-I level. This was showed that the severity of EH patients was closely correlation with EH clinical stage, NT-proBNP, ATII and IGF-I were probably involved in the pathophysiological process of EH. (authors)

  4. Clinical significance of serum IGF-Ⅰ,IGF-Ⅱ and IGFBP-3 in liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Yun-Lin Wu; Jing Ye; Shu Zhang; Jie Zhong; Rong-Ping Xi

    2004-01-01

    AIM: To investigate the relationship between insulin-likegrowth factor-Ⅰ, -Ⅱ (IGF-Ⅰ and IGF-Ⅱ), IGF-binding protein 3 (IGFBP-3) and Child-Pugh score in patients with liver cirrhosis, and to search for potential clinical markers of liver function. METHODS: Forty-four patients with advanced liver cirrhosis of viral origin were divided into 3 groups according to severity of cirrhosis (Child-Pugh score) and 38 healthy subjectsserved as controls. Serum levels of IGF-Ⅰ, IGF-Ⅱ and IGFBP3 were measured by immunoradiometric assay.RESULTS: Serum IGF-Ⅰ, IGF-Ⅱ and IGFBP-3 levels weresignificantly lower in patients with cirrhosis than in controls, and serum concentrations of IGF-Ⅰ, IGF-Ⅱ and IGFBP-3 were associated with the severity of liver dysfunction, and dropped sharply during the progression of liver failure. Among these 3 parameters, serum IGF-Ⅱ was the most sensitive and effective indicator for liver dysfunction. Concentrations of IGF-Ⅰ<30 ng/mL, IGF-Ⅱ<200 ng/mL and IGFBP-3 <6 ng/mL implied a negative prognosis for patients with liver cirrhosis. CONCLUSION: Serum IGF-Ⅰ, IGF-Ⅱ and IGFBP-3 may provide a new dimension in the assessment of liver dysfunction. Combined detection of serum IGF-Ⅰ, IGF-Ⅱ and IGFBP-3 with Child-Pugh score is more effective in predicting prognosis than Child-Pugh score alone.

  5. IGF-I and IGF-II effects on local IGF system and signaling pathways in gilthead sea bream (Sparus aurata) cultured myocytes.

    Science.gov (United States)

    Azizi, Sheida; Nematollahi, Mohammad Ali; Mojazi Amiri, Bagher; Vélez, Emilio J; Salmerón, Cristina; Chan, Shu Jin; Navarro, Isabel; Capilla, Encarnación; Gutiérrez, Joaquim

    2016-06-01

    The insulin-like growth factors (IGFs) have a fundamental role in a vast range of functions acting through a tyrosine-kinase receptor (IGF-IR). IGFs in muscle can affect the expression of components of the local IGF system, myogenic regulatory factors (MRFs), proliferating (proliferating cell nuclear antigen, PCNA) or differentiating molecules (myosin heavy chain, MHC) and, lead to the activation of different signaling pathways. The response of all these genes to IGFs incubation at two different times in day 4 cultured myocytes of gilthead sea bream was analyzed. Both IGFs increased the expression of IGF-I and IGFBP-5, but showed different effects on the receptors, with IGF-I suppressing the expression of both isoforms (IGF-IRa and IGF-IRb) and IGF-II up-regulating only IGF-IRb. Moreover, the protein levels of PCNA and target of rapamycin (TOR) increased after IGF-II incubation, although a decline in Myf5 and a rise in MHC gene expression was caused by IGF-I. Taken together, these results provide evidence for the importance of IGFs on controlling muscle development and growth in gilthead sea bream and suggest that each IGF may be preferentially acting through a specific IGF-IR. Moreover, the data support the hypothesis that IGF-II has a more important role during proliferation, whereas IGF-I seems to be relevant for the differentiation phase of myogenesis. PMID:26602376

  6. Reducing blood glucose levels in TIDM mice with an orally administered extract of sericin from hIGF-I-transgenic silkworm cocoons.

    Science.gov (United States)

    Song, Zuowei; Zhang, Mengyao; Xue, Renyu; Cao, Guangli; Gong, Chengliang

    2014-05-01

    In previous studies, we reported that the blood glucose levels of mice with type I diabetes mellitus (TIDM) was reduced with orally administered silk gland powder from silkworms transgenic for human insulin-like growth factor-I (hIGF-I). However, potential safety hazards could not be eliminated because the transgenic silk gland powder contained heterologous DNA, including the green fluorescent protein (gfp) and neomycin resistance (neo) genes. These shortcomings might be overcome if the recombinant hIGF-I were secreted into the sericin layer of the cocoon. In this study, silkworm eggs were transfected with a novel piggyBac transposon vector, pigA3GFP-serHS-hIGF-I-neo, containing the neo, gfp, and hIGF-I genes controlled by the sericin-1 (ser-1) promoter with the signal peptide DNA sequence of the fibrin heavy chain (Fib-H) and a helper plasmid containing the piggyBac transposase sequence under the control of the Bombyx mori actin 3 (A3) promoter, using sperm-mediated gene transfer to generate the transformed silkworms. The hIGF-I content estimated by enzyme-linked immunosorbent assay was approximately 162.7 ng/g. To estimate the biological activity of the expressed hIGF-I, streptozotocin-induced TIDM mice were orally administered sericin from the transgenic silkworm. The blood glucose levels of the mice were significantly reduced, suggesting that the extract from the transgenic hIGF-I silkworm cocoons can be used as an orally administered drug. PMID:24632065

  7. Evaluation of circulating YKL-40 levels in idiopathic interstitial pneumonias

    NARCIS (Netherlands)

    Korthagen, Nicoline M; van Moorsel, Coline H M; Zanen, Pieter; Ruven, Henk J; Grutters, Jan C

    2014-01-01

    INTRODUCTION: YKL-40 is a novel biomarker in diseases with inflammation, fibrosis and tissue remodelling. Previously, circulating YKL-40 was shown to be elevated in patients with idiopathic pulmonary fibrosis (IPF) and was associated with survival. OBJECTIVE: To compare YKL-40 serum levels between I

  8. Linkage analysis of circulating levels of adiponectin in hispanic children

    Science.gov (United States)

    Adiponectin, a hormone produced exclusively by adipose tissue, is inversely associated with insulin resistance and pro-inflammatory conditions. The aim of this study was to find quantitative trait loci (QTLs) that affect circulating levels of adiponectin in Hispanic children participating in the VVA...

  9. Human conditions of insulin-like growth factor-I (IGF-I deficiency

    Directory of Open Access Journals (Sweden)

    Puche Juan E

    2012-11-01

    Full Text Available Abstract Insulin-like growth factor I (IGF-I is a polypeptide hormone produced mainly by the liver in response to the endocrine GH stimulus, but it is also secreted by multiple tissues for autocrine/paracrine purposes. IGF-I is partly responsible for systemic GH activities although it possesses a wide number of own properties (anabolic, antioxidant, anti-inflammatory and cytoprotective actions. IGF-I is a closely regulated hormone. Consequently, its logical therapeutical applications seems to be limited to restore physiological circulating levels in order to recover the clinical consequences of IGF-I deficiency, conditions where, despite continuous discrepancies, IGF-I treatment has never been related to oncogenesis. Currently the best characterized conditions of IGF-I deficiency are Laron Syndrome, in children; liver cirrhosis, in adults; aging including age-related-cardiovascular and neurological diseases; and more recently, intrauterine growth restriction. The aim of this review is to summarize the increasing list of roles of IGF-I, both in physiological and pathological conditions, underlying that its potential therapeutical options seem to be limited to those proven states of local or systemic IGF-I deficiency as a replacement treatment, rather than increasing its level upper the normal range.

  10. Assessing the role of insulin‐like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels

    Science.gov (United States)

    Bonilla, Carolina; Lewis, Sarah J.; Rowlands, Mari‐Anne; Gaunt, Tom R.; Davey Smith, George; Gunnell, David; Palmer, Tom; Donovan, Jenny L.; Hamdy, Freddie C.; Neal, David E.; Eeles, Rosalind; Easton, Doug; Kote‐Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G.; Wiklund, Fredrik; Grönberg, Henrik; Haiman, Christopher A.; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C.; Pashayan, Nora; Khaw, Kay‐Tee; Stanford, Janet L.; Blot, William J.; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon‐Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R.; Pandha, Hardev; Lathrop, Mark; Holly, Jeff M. P.

    2016-01-01

    Circulating insulin‐like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome‐wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF‐I, IGF‐II, IGFBP‐2 and IGFBP‐3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (level‐raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF‐II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. PMID:27225428

  11. Clinical significance of measurment of changes of serum IGF-I, hs-CRP levels after treatment in patients with hyperthyroidism and hypothyroidism

    International Nuclear Information System (INIS)

    Objective: To explore the clinical significance of changes of serum IGF-I,hs-CRP levels after treatment in patients with hyperthyroidism and hypothyroidism. Methods: Serum IGF-I, hs-CRP(with RIA), and serum hs-CRP with immuno-turbidity methods levels were determined both before and after treatment in 36 cases of hyperthyroidism 30 cases of hypothyroidism as well as 35 controls. Results: Before treatment, the serum IGF-I levels in patients with hyperthyroidism were significantly higher and the levels in patients with hypothyroidism were significantly lower than those in controls (both P<0.01). After treatment for 3 months,the levels were much corrected, but still remained significantly different from those in controls (P<0.05). Before treatment serum hs-CRP levels in both groups of patients were significantly higher than those in controls (P<0.01), but after treatment,the levels were not much different from those in controls. Conclusion: Serum levels of IGF-I and hs-CRP were closely related to the disease process in patients with hyperthyroidism as well as in patients with hypothyroidism, and were much corrected after trentment.(authors)

  12. Pregnancy-induced increase in circulating IGF-I is associated with progression of diabetic retinopathy in women with type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Lene Ringholm; Laugesen, Caroline S; Juul, Anders;

    2011-01-01

    To evaluate the influence of Insulin-like Growth factor-I (IGF-I) and Placental Growth Hormone (GH) on progression of diabetic retinopathy during pregnancy in women with type 1 diabetes.......To evaluate the influence of Insulin-like Growth factor-I (IGF-I) and Placental Growth Hormone (GH) on progression of diabetic retinopathy during pregnancy in women with type 1 diabetes....

  13. Basal, But Not Pulsatile, Growth Hormone Secretion Determines the Ambient Circulating Levels of Insulin-Like Growth Factor-I

    OpenAIRE

    Faje, Alexander T.; Barkan, Ariel L.

    2010-01-01

    Context: Previous studies have shown that mean 24-h GH concentrations determine plasma IGF-I levels in patients with acromegaly. However, we have recently shown that continuous GH infusion, mimicking the interpulse GH levels, was significantly more effective than the pulsatile GH administration at increasing IGF-I concentrations.

  14. Circulating insulin-like growth factor I and cognitive function : Neuromodulation throughout the lifespan

    NARCIS (Netherlands)

    Aleman, Andre; Torres-Aleman, Ignacio

    2009-01-01

    Insulin-like growth factor I (IGF-I) is central to the somatotropic (growth hormone) axis. It promotes tissue growth and continues to have anabolic effects in adulthood. Accumulating evidence from the last decade, however, reveals that circulating levels of IGF-I also significantly affects cognitive

  15. Symptomatic Hypoglycemia Related to Inappropriately High IGF-II Serum Levels in a Patient with Desmoplastic Small Round Cell Tumor

    Directory of Open Access Journals (Sweden)

    Williams Fernandes Barra

    2010-01-01

    Full Text Available A 45-year old man was diagnosed with desmoplastic small round cell tumor (DSRCT with involvement of the peritoneum and pelvis. Disease progression was observed despite systemic chemotherapy. Six months after diagnosis, he developed severe hypoglycemia presented with seizures. He received intravenous glucose infusion and hydrocortisone with poor glycemic control, but with seizures resolution. The investigation excluded insulinoma, adrenal, liver and GH deficiencies. Laboratory showed slight rise of IGF-II and significant increase of the ratio IGF-II : IGF-I, which is pathognomonic of non-islet cell tumor hypoglycemia (NICTH. He received the diagnoses of NICTH related to IGF-II inappropriate production by DSRCT. Despite the attempt to control tumor mass and hypoglycemia, the patient died 9 months after diagnosis. NICTH related to inappropriate IGF-II secretion should be investigated in all cancer patients with refractory hypoglycemia whom insulinoma and other metabolic abnormalities were excluded from.

  16. Circulating KL-6 levels in patients with drug induced pneumonitis

    OpenAIRE

    Ohnishi, Hiroshi; Yokoyama, Akihito; Yasuhara, Yoshifumi; Watanabe, Akira; Naka, Tetsuji; Hamada, Hironobu; Abe, Masahiro; Nishimura, Kazutaka; Higaki, Jitsuo; Ikezoe, Junpei; Kohno, Nobuoki

    2003-01-01

    Background: The circulating level of KL-6/MUC1 is a sensitive marker for various interstitial lung diseases. Previous case reports have suggested that KL-6 may also be increased in some patients with drug induced pneumonitis. A study was undertaken to determine whether serum KL-6 could be a marker for particular types of drug induced pneumonitis. Methods: The findings of high resolution computed tomographic (HRCT) chest scans of 30 patients with drug induced pneumonitis were reviewed separate...

  17. Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women.

    NARCIS (Netherlands)

    Gram, Inger Torhild; Norat, Teresa; Rinaldi, Sabina; Dossus, Laure; Lukanova, Annekatrin; Téhard, B; Clavel-Chapelon, Françoise; Gils, C H van; Noord, P A H van; Peeters, Petra H M; Bueno-de-Mesquita, H Bas; Nagel, Gabriele; Linseisen, Jakob; Lahmann, Petra H; Boeing, Heiner; Palli, Domenico; Sacerdote, Carlotta; Panico, Salvatore; Tumino, Rosario; Sieri, Sabina; Dorronsoro Iraeta, Miren; Quirós, José Ramón; Navarro, Carmen A; Barricarte, Aurelio; Tormo, M-J; González, Carlos Alberto; Overvad, Kim; Paaske Johnsen, S; Olsen, Anja; Tjønneland, Anne; Travis, R; Allen, Naomi E; Bingham, Sheila A; Khaw, Kay-Tee; Stattin, P; Trichopoulou, Antonia; Kalapothaki, V; Psaltopoulou, Theodora; Casagrande, Corinne; Riboli, Elio; Kaaks, Rudolf

    2006-01-01

    OBJECTIVE: To examine the relationship between body mass index (BMI) and waist-hip ratio (WHR) with serum levels of insulin-like growth factor-I (IGF-I), and its binding protein (IGFBP)-3. DESIGN: Cross-sectional study on 2139 women participating in a case-control study on breast cancer and endogeno

  18. Body mass index, waist circumference and waist–hip ratio and serum levels of IGF-I and IGFBP-3 in European women

    NARCIS (Netherlands)

    Gram, I.T.; Norat, T.; Rinaldi, S.; Dossus, L.; Lukanova, A.; Tehard, B.; Clavel-Chapelon, F.; Gils, C.H. van; Noord, P.A.H. van; Peeters, P.H.M.; Bueno-de-Mesquita, H.B.; Nagel, G.; Linseisen, J.; Lahmann, P.H.; Boeing, H.; Palli, D.; Sacerdote, C.; Panico, S.; Tumino, R.; Sieri, S.; Dorronsoro, M.; Quirós, J.R.; Navarro, C.A.; Barricarte, A.; Tormo, M.J.; Gonzalez, C.A.; Overvad, K.; Paaske Johnsen, S.; Olsen, A.; Tjønneland, A.; Travis, R.; Allen, N.; Bingham, S.; Khaw, K-T.; Stattin, P.; Trichopoulou, A.; Kalapothaki, V.; Psaltopoulou, T.; Casagrande, C.; Riboli, E.; Kaaks, R.

    2006-01-01

    Objective: To examine the relationship between body mass index (BMI) and waist–hip ratio (WHR) with serum levels of insulinlike growth factor-I (IGF-I), and its binding protein (IGFBP)-3. Design: Cross-sectional study on 2139 women participating in a case–control study on breast cancer and endogenou

  19. Levels of serum IGF-I, MMP-7 and IGFBP-3 in colorectal cancer patients%结直肠癌患者血清中IGF-1、MMP-7和IGFBP-3水平分析

    Institute of Scientific and Technical Information of China (English)

    刘天舟; 王瑞

    2011-01-01

    Aim:To explore the levels of serum insulin-like growth factor-1 (IGF-1 ) , matrix metalloproteinase-7 (MMP-7) and insulin-like growth factor binding protein-3 (IGFBP-3) in colorectal cancer and benign colorectal disease groups, and analyse the relationship between the levels of the protein and chemotherapy efficacy. Methods:Serum IGF-1, MMP-7 and IGFBP-3 were determined by ELISA in 36 colorectal cancer patients (before and after regimen) ,30 colorectal patients with benign disease and 30 healthy controls. Results;The levels of serum MMP-7 and IGFBP-3 level in colorectal cancer patients before chemotherapy, colorectal benign disease group and healthy control group were obvious different ( F - 536.940 and 468. 740,P<0.001). The level of MMP-7 improved and IGFBP-3 dropped in colorectal cancer patients. For those obtaining CR + PR patients,the level of serum MMP-7 decreased obviously(t=6. 518,P=0.001) , and serum IGFBP-3 increased obviously after chemotherapy(t= 18. 145 ,P<0.001) . For those obtaining SD + PD patients, there was no significant difference among three groups in serum IGF-I,MMP-7 and IGFBP-3 level after chemotherapy (P>0. 05). Con-ClUSion: MMP-7 decreasing and IGFBP-3 increasing may be used to predict and evaluate the efficacy of chemotherapy.%目的:探讨胰岛素样生长因子-1(IGF-1)、人基质金属蛋白酶-7(MMP-7)和胰岛素样生长因子结合蛋白-3 (IGFBP-3)在结直肠癌患者血清中的表达及其与化疗疗效的关系.方法:采用酶联免疫吸附法(ELISA)检测36例结直肠癌患者(化疗前及化疗后)和30例结直肠良性疾病患者以及30例正常体检者血清中IGF-1、MMP-7和IGFBP-3的含量.结果:3组血清中MMP-7和IGFBP-3比较,差异有统计学意义(F=536.940和468.740,P<0.001),与其他2组比较,结直肠癌患者MMP-7水平升高,IGFBP-3水平降低(P<0.05).22例化疗有效的结直肠癌患者化疗后MMP-7水平明显降低(t=6.518,P=0.001),IGFBP-3水平明显升高(t=18.145,P<0

  20. Circulating Levels of Irisin in Hypopituitary and Normal Subjects

    Science.gov (United States)

    Pena-Bello, Lara; Pértega-Diaz, Sonia; Sangiao-Alvarellos, Susana; Outeiriño-Blanco, Elena; Eiras-Leal, Raquel; Varela-Rodriguez, Bárbara; Juiz-Valiña, Paula; Pérez-Fontán, Miguel; Cordido, María; Cordido, Fernando

    2016-01-01

    Context The recently identified myokine irisin conveys some of the benefits of exercise. Hypopituitarism with adult growth hormone deficiency (HP) is a situation characterized by decreased GH secretion and an altered body composition. Objective Our aim was to study the skeletal muscle hormone irisin in HP, and compare the results with a similar group of normal subjects. Participants and Methods Seventeen HP patients and fifty-one normal subjects of similar age and sex were studied. The diagnosis of GH deficiency was confirmed by the presence of pituitary disease and a peak GH secretion below 3 μg/L after an insulin tolerance test. The patients were adequately treated for all pituitary hormone deficits, except for GH. Fasting serum irisin was measured with an enzyme immunoassay, and HOMA-IR, QUICKI and HOMA-β were calculated. Results Fasting irisin levels (ng/ml) were similar in normal [208.42 (168.44–249.23)] and HP patients [195.13 (178.44–241.44)]. In the control group there were moderate significant positive correlations between irisin and BMI, waist circumference, leptin, fasting insulin, HOMA-IR, HOMA-β, triglycerides, and cholesterol. In the control group there were moderate significant negative correlations between irisin and IGF-I and QUICKI. In the hypopituitary group there were moderate significant positive correlations between irisin and body fat and HOMA-β. Conclusions We found similar irisin levels in GH deficiency hypopituitary patients when compared with normal subjects. The correlation between irisin and adiposity related factors suggests that that in the case of this clinical model, irisin is regulated by adiposity and not by GH. PMID:27472279

  1. Serum IGF1, IGF2, and IGFBP3 and risk of advanced colorectal adenoma

    OpenAIRE

    GAO, YING; Katki, Hormuzd; Graubard, Barry; Pollak, Michael; Martin, Michael; Tao, Yuzhen; Schoen, Robert E.; Church, Timothy; Hayes, Richard B; Greene, Mark H.; Berndt, Sonja I

    2011-01-01

    The insulin-like growth factor (IGF) signaling pathway is involved in cell proliferation and differentiation. Elevated serum IGF1 levels have been associated with increased colorectal cancer risk; however, studies of this association with colorectal adenoma are inconclusive. We examined serum IGF1, IGF2, and IGFBP3 levels in relation to risk of advanced colorectal adenoma in a case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A total of 764 advanced...

  2. Circulating docosahexaenoic acid levels are associated with fetal insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Jin-Ping Zhao

    Full Text Available BACKGROUND: Arachidonic acid (AA; C20∶4 n-6 and docosahexaenoic acid (DHA; C22∶6 n-3 are important long-chain polyunsaturated fatty acids (LC-PUFA in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally "programming" this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies. METHODS AND PRINCIPAL FINDINGS: In a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration and beta-cell function (proinsulin-to-insulin ratio in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids were lower comparing newborns of gestational diabetic (n = 24 vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01. Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = -0.37, P <0.0001. The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity. CONCLUSION: Low circulating DHA levels are associated with

  3. Free dissociable insulin-like growth factor I (IGF-I), total IGF-I and their binding proteins in girls with Turner syndrome during long-term growth hormone treatment

    NARCIS (Netherlands)

    Bannink, Ellen M. N.; Van Doorn, Jaap; Stijnen, Theo; Drop, Stenvert L. S.; Keizer-Schrama, Sabine M. P. F. de Muinck

    2006-01-01

    Objective To investigate the effect of GH treatment on free IGF-I levels in girls with Turner syndrome (TS) and to verify relationships between free IGF-I levels and total IGF-I, IGFBP-1, 2 and 3. Additionally, to analyse whether free IGF-I, total IGF-I, IGFBP-3 or its ratio were related to IGF-I bi

  4. Sports training and circulating adipokine levels 

    Directory of Open Access Journals (Sweden)

    Ryszard Plinta

    2013-01-01

    Full Text Available  The beneficial effect of regular moderate physical activity on metabolic profile is well documented. Sedentary lifestyle is a risk factor of excessive visceral fat accumulation, insulin resistance, type 2 diabetes and cardiovascular disease development. However, intensive training in athletes may be related to unfavorable changes in secretion of adipose tissue hormones and constitute a link in the pathogenesis of hormonal disturbances observed in athletes.In this paper we review the recently published data concerning the impact of sports training on circulating adipokine levels in athletes.

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

    International Nuclear Information System (INIS)

    Objective: To study the changes of serum levels of E2, IL-6, IGF-I in patients with post-menopausal osteoporosis (PMO). Methods: Serum levels of E2(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 (P2 and BMD index (r=-0. 587, - 0. 438 respectively, P2 and BMD index (r=0.569, 0.433 respectively, P2 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)

  6. Reduction of serum IGF-I levels in patients affected with Monoclonal Gammopathies of undetermined significance or Multiple Myeloma. Comparison with bFGF, VEGF and K-ras gene mutation

    Directory of Open Access Journals (Sweden)

    Pisani Francesco

    2009-03-01

    Full Text Available Abstract Background Serum levels of IGF-I in patients affected with multiple myeloma (MM have been scarcely studied. The present study is aimed to explore this point comparing 55 healthy subjects, 71 monoclonal gammopaties of uncertain significance (MGUS and 77 overt MM patients. In the same subjects, basic FGF and VEGF, have been detected. All three mediators were analyzed in function of K-ras mutation and melphalan response. Concerning IGF-I, two representative monitoring examples have also been added. Methods Cytokine determinations were performed by commercially available ELISA kits, while K12-ras mutation was investigated on genomic DNA isolated from bone marrow cell specimens by RFLP-PCR assay. Results Significant reductions of IGF-I levels were observed in MGUS and MM as compared with healthy controls. In addition, MM subjects showed significantly decreased serum IGF-I levels than MGUS. Conversely, increasing levels were observed for bFGF and VEGF, molecules significantly correlated. A multivariate analysis corrected for age and gender confirmed the significant difference only for IGF-I values (P = 0.01. K12-ras mutation was significantly associated with malignancy, response to therapy and with significantly increased serum bFGF levels. Conclusion IGF-I reduction in the transition: Controls→MGUS→MM and changes observed over time suggest that IGF-I should be furtherly studied in future clinical trials as a possible monitoring marker for MM.

  7. 支气管肺炎患儿治疗前后血清IGF-Ⅱ、IL-6、IL-8和TNF-α检测的临床意义%Clinical Significance of Determination of Changes of Serum IGF-Ⅱ,IL-6,IL-8,TNF-α Levels After Treatment in Children with Bronchopneamonia

    Institute of Scientific and Technical Information of China (English)

    冯越

    2011-01-01

    Objective To explore the clinical significance of changes of serum IGF-Ⅱ; IL-6; IL-8 and TNF-α levels after treatment in children with bronchopneamonia. Methods Serum IGF- Ⅱ; IL-6; IL-8 and TNF-a levels with RIA were detected both before and after treatment in 33 patients with children bronchopneumonia as well as in 35 controls. Results Before treatment; serum IGF-Ⅱ; IL-6; IL-8 and TNF-a levels were significantly higher in the patients than those in the controls ( P 0. 05 ) . Conclusions Seram IGF- Ⅱ; IL-6; IL-8 and TNF-a could take part in the pathogenesis of children bronchopneumonia in various ways and determination of these levels was clinically important.%目的:探讨支气管肺炎患儿治疗前后血清IGF-Ⅱ、IL-6、IL-8和TNF-α的变化及其临床意义.方法:应用放射免疫分析对33例支气管肺炎患儿进行了治疗前后血清IGF-Ⅱ、IL-6 、IL-8和TNF-α检测,并与35名正常健康儿作比较.结果:支气管肺炎患儿在治疗前血清IGF-Ⅱ、IL-6、IL-8和TNF-α水平显著地高于正常儿组(P<0.01).结论:IGF-Ⅱ、IL-6、IL-8和TNF-α以不同的方式参与了患儿的发病,其水平的检测对了解病情、指导治疗具有重要的临床价值.

  8. 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.

  9. Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits

    DEFF Research Database (Denmark)

    Teumer, Alexander; Qi, Qibin; Nethander, Maria;

    2016-01-01

    The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and canc...

  10. The relationship between diabetic retinopathy and plasma levels of IGF-1、 IGFBP-3%糖尿病视网膜病变与IGF-1及IGFBP-3水平的关系

    Institute of Scientific and Technical Information of China (English)

    张德秀; 史传衣; 雷玉明

    2001-01-01

    目的研究糖尿病视网膜病变与胰岛素样生长因子-1(IGF-1)及胰岛素样生长因子结合蛋白-3(IGFBP-3)的关系.方法用双抗夹心法酶联免疫法(ELISA)对112例非胰岛素依赖型糖尿病(NIDDM)病人及56例健康人血中的IGF-1及IGFBP-3的水平进行测定.结果NIDDM组血IGF-1,IGFBP-3水平显著低于正常人;糖尿病视网膜病变组(DR组)血IGF-1,IGFBP-3水平显著高于糖尿病无视网膜病变组(DM组);血IGF-1与IGFBP-3水平呈正相关;IGF-1与FPC呈负相关;IGFBP-3与HbAlc呈负相关.结论NIDDM病人血中IGF-1及IGFBP-3水平降低;糖尿病合并视网膜病变时,血中IGF-1及IGFBP-3水平升高.IGF-1及IGFBP-3可能参与DR的发生和发展.

  11. Insulin Like Growth Factor-1 (IGF-1 Causes Overproduction of IL-8, an Angiogenic Cytokine and Stimulates Neovascularization in Isoproterenol-Induced Myocardial Infarction in Rats

    Directory of Open Access Journals (Sweden)

    Nagaraja Haleagrahara

    2011-11-01

    Full Text Available Angiogenesis factors are produced in response to hypoxic or ischemic insult at the site of pathology, which will cause neovascularization. Insulin like growth factor-1 (IGF-1 exerts potent proliferative, angiogenic and anti-apoptotic effects in target tissues. The present study was aimed to evaluate the effects of IGF-1 on circulating level of angiogenic cytokine interleukin-8 (IL-8, in experimentally-induced myocardial ischemia in rats. Male Sprague-Dawley rats were divided into control, IGF-1 treated (2 µg/kg/day subcutaneously, for 5 and 10 days, isoproterenol (ISO treated (85 mg/kg, subcutaneously for two days and ISO with IGF-1 treated (for 5 and 10 days. Heart weight, serum IGF-1, IL-8 and cardiac marker enzymes (CK-MB and LDH were recorded after 5 and 10 days of treatment. Histopathological analyses of the myocardium were also done. There was a significant increase in serum cardiac markers with ISO treatment indicating myocardial infarction in rats. IGF-1 level increased significantly in ISO treated groups and the level of IGF-1 was significantly higher after 10 days of treatment. IL-8 level increased significantly after ISO treatment after 5 and 10 days and IGF-1 concurrent treatment to ISO rats had significantly increased IL-8 levels. Histopathologically, myocyte necrosis and nuclear pyknosis were reduced significantly in IGF-1 treated group and there were numerous areas of capillary sprouting suggestive of neovascularization in the myocardium. Thus, IGF-1 protects the ischemic myocardium with increased production of circulating angiogenic cytokine, IL-8 and increased angiogenesis.

  12. 乳腺癌患者血清IGF-I、CA153和IL-8水平检测的临床意义%Clinical Significance of Serum Levels of IGF-Ⅰ , CA153 and IL-8 in Patients with Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    林文源; 刘华; 陈琳; 刘蓉华

    2013-01-01

    Objective To explore the clinical significance of serum IGF-Ⅰ,CA153 and IL-8 levels in patients with breast cancer.Methods The serum levels of IGF-Ⅰ,CA153 and IL-8 in 36 patients with breast cancer,40 patients with benign breast patients and 35 healthy controls were determined by RIA and ELISA respectively.Results The serum levels of IGF-Ⅰ,CA153 and IL-8 in patients with breast cancer were significantly higher than those in benign breast patient and controls (P <0.01).The serum levels of IGF-Ⅰ,CA153 and IL-8 in 15 breast cancer patients with lymph node metastasis were significantly higher than those in 21 breast cancer patients without lymph nodes metastasis (P < 0.01).Conclusion The serum levels of IGF-Ⅰ,CA153 and IL-8 might be used as markers in differential diagnosis of malignant from benign diseases,also might be helpful for lymph nodes metastasis prediction.%目的 为探讨乳腺癌患者血清IGF-Ⅰ、CA153和IL-8水平的变化及临床意义.方法 对36例乳腺癌组患者、40例乳腺良性病变组患者和35名正常人,用RIA法和ELISA法分别测定血清IGF-Ⅰ、CA153和IL-8水平.结果 乳腺癌组患者血清IGF-Ⅰ、CA153和IL-8水平均高于乳腺良性病变组患者和正常组,差异有统计学意义(P<0.01);伴有淋巴结转移的乳腺癌患者血清IGF-Ⅰ、CA153和IL-8水平明显高于无淋巴结转移的乳腺癌患者,差异有统计学意义(P<0.01).结论 乳腺癌患者血清IGF-Ⅰ、CA153和IL-8水平的变化可能成为鉴别乳腺良、恶性病变的辅助指标之一,有助于判断乳腺癌有无淋巴结转移及预后.

  13. Comparison of the Effects of Resistance Exercise Orders on Number of Repetitions, Serum IGF-1, Testosterone and Cortisol Levels in Normal-Weight and Obese Men

    Science.gov (United States)

    Sheikholeslami-Vatani, Dariush; Ahmadi, Slahadin; Salavati, Rashad

    2016-01-01

    Background: Exercise order affects repetition performance and acute hormonal responses to resistance training (RT) programs. Objectives: The purpose of this study was to compare the acute effects of two different resistance exercise orders (REO) on number of repetitions and serum Insulin-like Growth Factor-1 (IGF-1), testosterone and cortisol levels in normal-weight and obese men. Materials and Methods: 25 untrained college-aged men were assigned to either obese (n = 11) or normal-weight (n = 15) groups. Subjects performed two REO protocols in 2 exercise groups. In the first group subjects began with large-muscle group and progressed to small-muscle group (Protocol A), while in the other group subjects performed the same exercise but in reverse sequence (Protocol B). Each activity was performed in 3 consecutive sets of 10 repetitions maximum to near fatigue. Results: REOs did not affect number of repetitions in none of the groups. The average rating of perceived exertion was higher for protocol B in both groups. IGF-1 and testosterone increased immediately post exercise for both protocols and in both groups, however immediately post exercise increase in IGF-1 and testosterone were lower in obese group. Cortisol response to REO was weaker in obese group. Conclusions: Performing large muscle group exercises first in RE training and progressing to small muscle group produced greater anabolic hormonal response relative to reverse sequence in normal-weight young adult men. Anabolic hormonal response to REOs was blunted in the obese group. PMID:27217934

  14. 间接判定运动员滥用人生长激素的指标的可行性研究.Ⅳ.口服肌酸、蛋白粉等营养补剂对少年男篮运动员血清hGH和IGF-I、II 及结合蛋白-3等指标的影响%Washout Study for Selection of Indirect and Potential Markers in Detection of Exogenous Growth Hormone Abuse in Athletes.Ⅳ.Effects of Oral Nutrition Supplementations on the Levels of Serum hGH、IGF-I、IGF-II、IGFBP-3 in the Juvenile Male Basketballers

    Institute of Scientific and Technical Information of China (English)

    曾凡星; 杨锡让; 王守恒; 方子龙; 谢敏豪; 杨则宜

    2001-01-01

    We observed effects of oral nutrition supplementations on the concentrations of serum hGH、IGF-I、IGF-II、IGFBP-3 in the juvenile male basketballers for one month.The subjects were divided into two groups: control group(n=8), test group(n=8).Results showed that oral creatine、protein powder and herb supplementations did not significantly influence the levels of serum IGF-II、IGFBP-3, there was a significant positive correlation between the concentration of serum IGF-I and the ratio of IGF-I/IGF-II、IGF-I/IGFBP-3.It was also found that the serum level of IGF-I in both juvenile male basketballers significantly increased in comparison with baseline after one month experiment.%16名少年男子篮球运动员分为两组:实验组(n=8)使用肌酸、蛋白粉及中药,时间为1月;对照组(n=8)不使用营养补剂。受试者每周5日进行长跑及篮球训练。结果显示:口服肌酸、蛋白粉等营养补剂实验前、后血清IGF-II和IGFBP-3浓度无明显变化,表明血清IGF-II和IGFBP-3不易受运动营养补剂的影响。口服肌酸、蛋白粉等营养补剂实验前、后,IGF-I与IGF-I/IGF-II和IGF-I/IGFBP-3比值呈高度显著性正相关。1月实验观察,两组少年运动员实验前后进行自身对照,血清IGF-I浓度明显增加;两组实验前、后分别相比较,血清IGF-I浓度无显著性差异。

  15. Concentrations, release, and disposal of insulin-like growth factor (IGF)-binding proteins (IGFBP), IGF-I, and growth hormone in different vascular beds in patients with cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Juul, A; Becker, U;

    1995-01-01

    The liver is thought to be the major source of circulating insulin-like growth factor (IGF-I) and IGF-binding protein-1 (IGFBP-1), whereas the primary production site of circulating IGFBP-3 remains unknown. As other tissues may contribute to the circulating pool of IGF-I and IGFBP, the aim of the...... present study was to assess the hepatic and renal arterio-venous difference and production rates of IGF-I, IGFBP-1, IGFBP-3, and GH in cirrhotic patients (n = 22) and matched control subjects (n = 27). IGFBP-1 and -3, IGF-I, and GH levels were measured by RIA in hepatic, renal, and peripheral veins and in...... the femoral artery. Levels of IGFBP-1 to -4 were additionally determined by Western ligand blotting. Hepatic venous IGFBP-1 was significantly increased in the cirrhotic patients (mean +/- SEM, 33.6 +/- 9.1 vs. 10.4 +/- 1.9 micrograms/L; P < 0.001), and arterio-renal-venous extraction was significant...

  16. Concentrations, release, and disposal of insulin-like growth factor (IGF)-binding proteins (IGFBP), IGF-I, and growth hormone in different vascular beds in patients with cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Juul, A; Becker, U;

    1995-01-01

    The liver is thought to be the major source of circulating insulin-like growth factor (IGF-I) and IGF-binding protein-1 (IGFBP-1), whereas the primary production site of circulating IGFBP-3 remains unknown. As other tissues may contribute to the circulating pool of IGF-I and IGFBP, the aim of the...... present study was to assess the hepatic and renal arterio-venous difference and production rates of IGF-I, IGFBP-1, IGFBP-3, and GH in cirrhotic patients (n = 22) and matched control subjects (n = 27). IGFBP-1 and -3, IGF-I, and GH levels were measured by RIA in hepatic, renal, and peripheral veins and in...... the femoral artery. Levels of IGFBP-1 to -4 were additionally determined by Western ligand blotting. Hepatic venous IGFBP-1 was significantly increased in the cirrhotic patients (mean +/- SEM, 33.6 +/- 9.1 vs. 10.4 +/- 1.9 micrograms/L; P <0.001), and arterio-renal-venous extraction was significant in...

  17. Circadian variation in serum free and total insulin-like growth factor (IGF)-I and IGF-II in untreated and treated acromegaly and growth hormone deficiency

    DEFF Research Database (Denmark)

    Skjaerbaek, Christian; Frystyk, Jan; Kaal, Andreas;

    2000-01-01

    to the nocturnal increase in IGF binding protein-1. In this study we have investigated the circadian variation in circulating free IGF-I and IGF-II in patients with acromegaly and patients with adult onset growth hormone deficiency. PATIENTS: Seven acromegalic patients were studied with and without treatment...... no significant circadian variations in free IGF-I or free IGF-II in either of the two occasions. In contrast, there was a significant circadian variation of total IGF-I after adjustment for changes in plasma volume in both treated and untreated acromegaly and GH deficiency in all cases with a peak between 0300 h...

  18. Effects of a 7-day continuous infusion of octreotide on circulating levels of growth factors and binding proteins in growth hormone (GH)-treated GH-deficient patients

    DEFF Research Database (Denmark)

    Laursen, Torben; Møller, Jens; Fisker, Sanne;

    1999-01-01

    Abstract In patients with acromegaly, clinical improvement has been reported after octreotide (OCT) treatment, even in cases of only a moderate suppression of growth hormone (GH) levels. In rats, OCT suppresses IGF-I mRNA expression and generation of serum and tissue IGF-I levels. A direct effect...

  19. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    DEFF Research Database (Denmark)

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A;

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered...

  20. Sleep extension increases IGF-I concentrations before and during sleep deprivation in healthy young men.

    Science.gov (United States)

    Chennaoui, Mounir; Arnal, Pierrick J; Drogou, Catherine; Sauvet, Fabien; Gomez-Merino, Danielle

    2016-09-01

    Sleep deprivation is known to suppress circulating trophic factors such as insulin-like growth factor (IGF)-I and brain-derived neurotrophic factor (BDNF). This experiment examined the effect of an intervention involving 6 nights of extended sleep before total sleep deprivation on this catabolic profile. In a randomized crossover design, 14 young men (age range: 26-37 years) were either in an extended (EXT; time in bed: 2100-0700 h) or habitual (HAB: 2230-0700 h) sleep condition, followed by 3 days in the laboratory with blood sampling at baseline (B), after 24 h of sleep deprivation (24h-SD), and after 1 night of recovery sleep (R). In the EXT condition compared with the HAB condition, free IGF-I levels were significantly higher at B, 24h-SD, and R (P EXT did not influence growth hormone, IGF binding protein 3, BDNF, insulin, and glucose levels. The only effect of 24 h of sleep deprivation was for insulin levels, which were significantly higher after R compared with B. In a healthy adult, additional sleep over 1 week increased blood concentrations of the anabolic factor IGF-I before and during 24 h of sleep deprivation and after the subsequent recovery night without effects on BDNF. With further research, these findings may prove to be important in guiding effective lifestyle modifications to limit physical or cognitive deficits associated with IGF-I decrease with age. PMID:27560704

  1. 补充谷氨酰胺对过度训练大鼠腹膜巨噬细胞IGF-1和MGF基因表达的影响%Supplementing Glutamine Affects the IGF-1 and MGF mRNA Levels in Peritoneal Macrophages of Overtrained Rats

    Institute of Scientific and Technical Information of China (English)

    肖卫华; 陈佩杰

    2011-01-01

    目的:了解补充谷氨酰胺对过度训练大鼠腹膜巨噬细胞胰岛素样生长因子1(IGF-1)和机械生长因子(MGF)基因表达的影响.方法:8周龄健康雄性Wistar大鼠40K,随机分为安静对照组(C)、过度训练组(E)、过度训练补充谷氨酰胺组(EG).后两组根据取材时间不同分为2组:运动后36 h取材组(E1、EG1),运动后7天取材组(E2、EG2).总计5组,每组8只,除C组外,其他4组进行ll周递增负荷跑台训练.EG组从第5周开始至第8周灌胃补充谷氨酰胺(0.8 g/kg/d),以后几周加至饮用水补充,剂量逐周加大到1.1 g/kg/d.断头处死大鼠并分离纯化腹膜巨噬细胞,采用荧光定量PCR技术测定IGF-1和MGF基因表达.结果:安静状态下巨噬细胞即可表达IGF-1和MGF.11周过度训练后36 h,巨噬细胞IGF-1、MGF表达量显著增加,分别约为安静对照组的2l倍和92倍(P<0.01).EG1组IGF-1、MGF表达显著增加,分别约为安静对照组的10倍和37倍(P<0.01),但显著低于E1组(P<0.01).停训后恢复7天,E2组、EG2组IGF-1、MGF表达量分别与E1组、EG1组相比均显著下降(P<0.01),但与C组相比差异无统计学意义.结论:静息态巨噬细胞可表达IGF-1和MGF:过度训练可增强巨噬细胞IGF-1和MGF表达,MGF表达对运动应激更敏感;补充谷氨酰胺可部分抑制巨噬细胞IGF-1和MGF对过度训练的应答.%Objective To investigate the effect of supplementation of glutamine (Gln) on the IGF-1 and MGF mRNA levels in peritoneal macrophages of rats with overtraining. Methods Forty male Wistar rats were randomly divided into following groups: sedentary group (C, n = 8) , overtraining group (E) , overtraining and supplementation of Gln group (EG) . The groups E and EG were respectively subdivided into two groups which were sacrificed 36 hours (E1, EG1, n = 8) and 7 days (E2,EG2, n = 8) after the last training. All groups except the C underwent standard treadmill training with an increasing load for 11 weeks. And group EG

  2. Paternally Inherited IGF2 Mutation and Growth Restriction.

    Science.gov (United States)

    Begemann, Matthias; Zirn, Birgit; Santen, Gijs; Wirthgen, Elisa; Soellner, Lukas; Büttel, Hans-Martin; Schweizer, Roland; van Workum, Wilbert; Binder, Gerhard; Eggermann, Thomas

    2015-07-23

    In humans, mutations in IGF1 or IGF1R cause intrauterine and postnatal growth restriction; however, data on mutations in IGF2, encoding insulin-like growth factor (IGF) II, are lacking. We report an IGF2 variant (c.191C→A, p.Ser64Ter) with evidence of pathogenicity in a multigenerational family with four members who have growth restriction. The phenotype affects only family members who have inherited the variant through paternal transmission, a finding that is consistent with the maternal imprinting status of IGF2. The severe growth restriction in affected family members suggests that IGF-II affects postnatal growth in addition to prenatal growth. Furthermore, the dysmorphic features of affected family members are consistent with a role of deficient IGF-II levels in the cause of the Silver-Russell syndrome. (Funded by Bundesministerium für Bildung und Forschung and the European Union.).

  3. PAPP-A and the IGF system.

    Science.gov (United States)

    Monget, Philippe; Oxvig, Claus

    2016-06-01

    Firstly discovered as a placental protein present abundantly in the circulation of pregnant women, pregnancy-associated plasma protein-A (PAPP-A) is widely expressed in multiple tissues. PAPP-A is a metalloproteinase that is able to specifically cleave three insulin-like growth factor binding proteins (IGFBPs): IGFBP-2, -4 and -5. PAPP-A binds tightly to glycosaminoglycans present on the surface of cells, thus functioning within tissues as a growth-promoting enzyme, releasing bioactive IGF in close proximity to the IGF receptor. Pro-MBP and stanniocalcin-2 (STC2) appear to be the main inhibitors of PAPP-A activity, by forming a covalent complex with the protease. According to in vivo experiments, IGFBP-4 is believed to be the main PAPP-A substrate to regulate IGF bioavailability. The regulation of PAPP-A includes transcriptional control of its gene, competing reactions with other IGFBPs potentially sequestering IGF from IGFBP-4 and hence antagonizing PAPP-A-mediated IGF activation, and proteolytic inhibition of PAPP-A. Finally, PAPP-A may serve as a therapeutic target to indirectly inhibit IGF signalling in tissues where this is driven by increased PAPP-A activity. By taking advantage of the intricate interaction between PAPP-A and IGFBP-4, highly specific and selective inhibition of PAPP-A is possible. PMID:27155776

  4. Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density

    Directory of Open Access Journals (Sweden)

    Chanock Stephen J

    2010-03-01

    Full Text Available Abstract Background Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a woman's life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here. Methods Samples from 964 postmenopausal Norwegian women aged 55-71 years were collected as a part of the Tromsø Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI. The main statistical analyses were conducted with the PROC HAPLOTYPE procedure within SAS/GENETICS™ (SAS 9.1.3. Results The haplotype analysis revealed six haploblocks within the studied genes. Of those, four had significant associations with circulating levels of IGF1 or IGFBP3 and/or mammographic density. One haplotype variant in the IGF1 gene was found to be associated with mammographic density. Within the IGF2 gene one haplotype variant was associated with levels of both IGF1 and IGFBP3. Two haplotype variants in the IGF2R were associated with the level of IGF1. Both variants of the IGFBP3 haplotype were associated with the IGFBP3 level and indicate regulation in cis. Conclusion Polymorphisms within the IGF1 gene and related genes were associated with plasma levels of IGF1, IGFBP3 and mammographic density in this study of postmenopausal women.

  5. Elevated levels of cell-free circulating DNA in patients with acute dengue virus infection.

    Directory of Open Access Journals (Sweden)

    Tran Thi Ngoc Ha

    Full Text Available BACKGROUND: Apoptosis is thought to play a role in the pathogenesis of severe dengue and the release of cell-free DNA into the circulatory system in several medical conditions. Therefore, we investigated circulating DNA as a potential biomarker for severe dengue. METHODS AND FINDINGS: A direct fluorometric degradation assay using PicoGreen was performed to quantify cell-free DNA from patient plasma. Circulating DNA levels were significantly higher in patients with dengue virus infection than with other febrile illnesses and healthy controls. Remarkably, the increase of DNA levels correlated with the severity of dengue. Additionally, multivariate logistic regression analysis showed that circulating DNA levels independently correlated with dengue shock syndrome. CONCLUSIONS: Circulating DNA levels were increased in dengue patients and correlated with dengue severity. Additional studies are required to show the benefits of this biomarker in early dengue diagnosis and for the prognosis of shock complication.

  6. Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome.

    Science.gov (United States)

    Lai, Yerui; Chen, Jinhua; Li, Ling; Yin, Jingxia; He, Junying; Yang, Mengliu; Jia, Yanjun; Liu, Dongfang; Liu, Hua; Liao, Yong; Yang, Gangyi

    2016-01-01

    The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID:27180914

  7. Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome

    Science.gov (United States)

    Lai, Yerui; Chen, Jinhua; Li, Ling; Yin, Jingxia; He, Junying; Yang, Mengliu; Jia, Yanjun; Liu, Dongfang; Liu, Hua; Liao, Yong; Yang, Gangyi

    2016-01-01

    The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID:27180914

  8. Circulating DNG level is negatively associated with the long-term survival of hepatocellular carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Ning Ren; Qing-Hai Ye; Lun-Xiu Qin; Bo-Heng Zhang; Yin-Kun Liu; Zhao-You Tang

    2006-01-01

    AIM: To quantify the circulating DNA in plasma from patients with hepatocellular carcinoma (HCC) and to evaluate its prognostic value.METHODS: Blood samples were collected from 79patients with HCC before operation, 20 patients with liver cirrhosis, and 20 healthy volunteers. Circulating DNA was extracted from plasma and quantified. The association between circulating DNA level and prognosis of HCC patients was evaluated.RESULTS: Compared with the healthy volunteers (17.6± 9.5 ng/mL), a significant higher circulating DNA level was found in the patients with HCC (47.1±43.7 ng/mL, P = 0.000) or with liver cirrhosis (30.0 ± 13.3 ng/mL, P = 0.002). The circulating DNA level was closely associated with tumor size (P = 0.008) and TNM stage (P = 0.040), negatively associated with the 3-year diseasefree survival (DFS) (P = 0.017) and overall survival (OS) (P = 0.001).CONCLUSION: Large or invasive tumor may release more circulating DNA, and higher level of circulating DNA may be associated with poor prognosis of HCC patients.

  9. Favorable prognostic value of SOCS2 and IGF-I in breast cancer

    International Nuclear Information System (INIS)

    Suppressor of cytokine signaling (SOCS) proteins comprise a protein family, which has initially been described as STAT induced inhibitors of the Jak/Stat pathway. Recent in vivo and in vitro studies suggest that SOCS proteins are also implicated in cancer. The STAT5 induced IGF-I acts as an endocrine and para/autocrine growth and differentiation factor in mammary gland development. Whereas high levels of circulating IGF-I have been associated with increased cancer risk, the role of autocrine acting IGF-I is less clear. The present study is aimed to elucidate the clinicopathological features associated with SOCS1, SOCS2, SOCS3, CIS and IGF-I expression in breast cancer. We determined the mRNA expression levels of SOCS1, SOCS2, SOCS3, CIS and IGF-I in 89 primary breast cancers by reverse transcriptase PCR. SOCS2 protein expression was further evaluated by immuno-blot and immunohistochemistry. SOCS2 expression inversely correlated with histopathological grade and ER positive tumors exhibited higher SOCS2 levels. Patients with high SOCS2 expression lived significantly longer (108.7 vs. 77.7 months; P = 0.015) and high SOCS2 expression proved to be an independent predictor for good prognosis (HR = 0.45, 95% CI 0.23 – 0.91, P = 0.026). In analogy to SOCS2, high IGF-I expression was an independent predictor for good prognosis in the entire patient cohort. In the subgroup of patients with lymph-node negative disease, high IGF-I was a strong predictor for favorable outcome in terms of overall survival and relapse free survival (HR = 0.075, 95% CI 0.014 – 0.388, P = 0.002). This is the first report on the favorable prognostic value of high SOCS2 expression in primary mammary carcinomas. Furthermore a strong association of high IGF-I expression levels with good prognosis was observed especially in lymph-node negative patients. Our results suggest that high expression of the STAT5 target genes SOCS2 and IGF-I is a feature of differentiated and less malignant tumors

  10. Favorable prognostic value of SOCS2 and IGF-I in breast cancer

    Directory of Open Access Journals (Sweden)

    Daxenbichler Günter

    2007-07-01

    Full Text Available Abstract Background Suppressor of cytokine signaling (SOCS proteins comprise a protein family, which has initially been described as STAT induced inhibitors of the Jak/Stat pathway. Recent in vivo and in vitro studies suggest that SOCS proteins are also implicated in cancer. The STAT5 induced IGF-I acts as an endocrine and para/autocrine growth and differentiation factor in mammary gland development. Whereas high levels of circulating IGF-I have been associated with increased cancer risk, the role of autocrine acting IGF-I is less clear. The present study is aimed to elucidate the clinicopathological features associated with SOCS1, SOCS2, SOCS3, CIS and IGF-I expression in breast cancer. Methods We determined the mRNA expression levels of SOCS1, SOCS2, SOCS3, CIS and IGF-I in 89 primary breast cancers by reverse transcriptase PCR. SOCS2 protein expression was further evaluated by immuno-blot and immunohistochemistry. Results SOCS2 expression inversely correlated with histopathological grade and ER positive tumors exhibited higher SOCS2 levels. Patients with high SOCS2 expression lived significantly longer (108.7 vs. 77.7 months; P = 0.015 and high SOCS2 expression proved to be an independent predictor for good prognosis (HR = 0.45, 95% CI 0.23 – 0.91, P = 0.026. In analogy to SOCS2, high IGF-I expression was an independent predictor for good prognosis in the entire patient cohort. In the subgroup of patients with lymph-node negative disease, high IGF-I was a strong predictor for favorable outcome in terms of overall survival and relapse free survival (HR = 0.075, 95% CI 0.014 – 0.388, P = 0.002. Conclusion This is the first report on the favorable prognostic value of high SOCS2 expression in primary mammary carcinomas. Furthermore a strong association of high IGF-I expression levels with good prognosis was observed especially in lymph-node negative patients. Our results suggest that high expression of the STAT5 target genes SOCS2 and IGF

  11. 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......BACKGROUND: IGF-I is a major regulator of growth, influenced primarily by diet in infancy and primarily by GH in childhood. Breastfed infants have lower IGF-I levels compared to formula fed and tend to be shorter. The higher protein content of infant formula has a stimulatory effect on IGF......=-0.26, P=0.043, and n=109). CONCLUSION: The results support the hypothesis that the IGF-I axis can be programmed early in life....

  12. The possible role of mRNA expression changes of GH/IGF-1/insulin axis components in subcutaneous adipose tissue in metabolic disturbances of patients with acromegaly.

    Science.gov (United States)

    Touskova, V; Klouckova, J; Durovcova, V; Lacinova, Z; Kavalkova, P; Trachta, P; Kosak, M; Mraz, M; Haluzikova, D; Hana, V; Marek, J; Krsek, M; Haluzik, M

    2016-07-18

    We explored the effect of chronically elevated circulating levels of growth hormone (GH)/insulin-like-growth-factor-1 (IGF-1) on mRNA expression of GH/IGF-1/insulin axis components and p85alpha subunit of phosphoinositide-3-kinase (p85alpha) in subcutaneous adipose tissue (SCAT) of patients with active acromegaly and compared these findings with healthy control subjects in order to find its possible relationships with insulin resistance and body composition changes. Acromegaly group had significantly decreased percentage of truncal and whole body fat and increased homeostasis model assessment-insulin resistance (HOMA-IR). In SCAT, patients with acromegaly had significantly increased IGF-1 and IGF-binding protein-3 (IGFBP-3) expression that both positively correlated with serum GH. P85alpha expression in SCAT did not differ from control group. IGF-1 and IGFBP-3 expression in SCAT were not independently associated with percentage of truncal and whole body fat or with HOMA-IR while IGFBP-3 expression in SCAT was an independent predictor of insulin receptor as well as of p85alpha expression in SCAT. Our data suggest that GH overproduction in acromegaly group increases IGF-1 and IGFBP-3 expression in SCAT while it does not affect SCAT p85alpha expression. Increased IGF-1 or IGFBP-3 in SCAT of acromegaly group do not appear to contribute to systemic differences in insulin sensitivity but may have local regulatory effects in SCAT of patients with acromegaly.

  13. The possible role of mRNA expression changes of GH/IGF-1/insulin axis components in subcutaneous adipose tissue in metabolic disturbances of patients with acromegaly.

    Science.gov (United States)

    Touskova, V; Klouckova, J; Durovcova, V; Lacinova, Z; Kavalkova, P; Trachta, P; Kosak, M; Mraz, M; Haluzikova, D; Hana, V; Marek, J; Krsek, M; Haluzik, M

    2016-07-18

    We explored the effect of chronically elevated circulating levels of growth hormone (GH)/insulin-like-growth-factor-1 (IGF-1) on mRNA expression of GH/IGF-1/insulin axis components and p85alpha subunit of phosphoinositide-3-kinase (p85alpha) in subcutaneous adipose tissue (SCAT) of patients with active acromegaly and compared these findings with healthy control subjects in order to find its possible relationships with insulin resistance and body composition changes. Acromegaly group had significantly decreased percentage of truncal and whole body fat and increased homeostasis model assessment-insulin resistance (HOMA-IR). In SCAT, patients with acromegaly had significantly increased IGF-1 and IGF-binding protein-3 (IGFBP-3) expression that both positively correlated with serum GH. P85alpha expression in SCAT did not differ from control group. IGF-1 and IGFBP-3 expression in SCAT were not independently associated with percentage of truncal and whole body fat or with HOMA-IR while IGFBP-3 expression in SCAT was an independent predictor of insulin receptor as well as of p85alpha expression in SCAT. Our data suggest that GH overproduction in acromegaly group increases IGF-1 and IGFBP-3 expression in SCAT while it does not affect SCAT p85alpha expression. Increased IGF-1 or IGFBP-3 in SCAT of acromegaly group do not appear to contribute to systemic differences in insulin sensitivity but may have local regulatory effects in SCAT of patients with acromegaly. PMID:27070751

  14. 克仑特罗对绵羊肝脏血液中IGF-Ⅰ、GH和胰岛素水平的影响%Effects of Clenbuterol on IGF-Ⅰ,GH and Insulin Level of Hepatic Blood in Sheep

    Institute of Scientific and Technical Information of China (English)

    郑元林; 韩正康; 陈杰; 艾晓杰; 刘根桃

    2001-01-01

    Four sheep installed chronic catheters in the portal vein,hepatic vein and mesenteric vein were used to study the effects of clenbuterol on metabolic hormones. The results are:①The GH level of portal vein is markedly increased during clenbuterol treatment period (0.8?mg/kg BW,twice daily for five days);②The GH level of hepatic vein with clenbuterol-treated is similar to that of control;③The IGF-Ⅰ concentration of hepatic vein is markedly elevated and IGF-Ⅰ of portal vein is maintained a higher level in clenbuterol treatment period. ④The insulin concentration of hepatic blood is decreased with clenbuterol-treated. These showed that the changes of those hormone levels in clenbuterol treatment played an important role in regulation of growth and metabolism in sheep.

  15. Association between circulating adiponectin levels and polycystic ovarian syndrome

    OpenAIRE

    Mirza, Saira Saeed; Shafique, Kashif; Shaikh, Abdul Rauf; Khan, Naveed Ali; Anwar Qureshi, Masood

    2014-01-01

    Background: Low adiponectin levels in polycystic ovarian syndrome (PCOS) have been largely attributed to obesity which is common among these patients. In addition, evidence also suggests that low adiponectin in PCOS may be related to insulin resistance (IR) in these women. However, studies on the role of adiponectin in younger and lean patients are limited. Therefore, the aim of the present study was to examine the association of adiponectin levels in young and lean women with PCOS. Me...

  16. Improving expression of recombinant human IGF-1 using IGF-1R knockout CHO cell lines.

    Science.gov (United States)

    Romand, Sandrine; Jostock, Thomas; Fornaro, Mara; Schmidt, Joerg; Ritter, Anett; Wilms, Burkhard; Laux, Holger

    2016-05-01

    Chinese Hamster Ovary (CHO) cells are widely used for the large-scale production of recombinant biopharmaceuticals. However, attempts to express IGF-1 (a mutated human Insulin-like growth factor 1 Ea peptide (hIGF-1Ea mut)) in CHO cells resulted in poor cell growth and low productivity (0.1-0.2 g/L). Human IGF-1 variants negatively impacted CHO cell growth via the IGF-1 receptor (IGF-1R). Therefore knockout (KO) of the IGF-1R gene in two different CHO cell lines as well as knockdown (KD) of IGF-1R in one CHO cell line were performed. These cell line engineering approaches decreased significantly the hIGF-1 mediated cell growth inhibition and increased productivity of both KO CHO cell lines as well as of the KD CHO cell line. A productivity increase of 10-fold at pool level and sevenfold at clone level was achieved, resulting in a titer of 1.3 g/L. This data illustrate that cell line engineering approaches are powerful tools to improve the yields of recombinant proteins which are difficult to produce in CHO cells. Biotechnol. Bioeng. 2016;113: 1094-1101. © 2015 Wiley Periodicals, Inc. PMID:26523469

  17. Circulating MKRN3 levels decline during puberty in healthy boys

    DEFF Research Database (Denmark)

    Busch, Alexander S; Hagen, Casper P; Almstrup, Kristian;

    2016-01-01

    CONTEXT: Initiation and progression of puberty requires concerted action of hypothalamic activating and inhibiting factors. Recently, cases of familial central precocious puberty have been linked to loss-of-function mutations of makorin RING-finger protein 3 (MKRN3) indicating a pivotal inhibitory.......8) years at baseline followed for 6.0 (0.5 - 7.6) years (2006 - 2014) with blood sampling every 6 months. INTERVENTION: None Main Outcome Measures: Serum levels of MKRN3: 623 samples, median (range) 12 (2 - 14) per boy. RESULTS: MKRN3 levels declined prior to onset of puberty; the geometric mean (95% CI) 5...... years prior to onset of puberty vs. last visit before onset of puberty was 216 (169 - 272) pg/ml vs. 128 (118 - 139) pg/ml (p puberty progressed. MKRN3 levels were not associated with age at onset of puberty. CONCLUSION: Declining MKRN3 prior...

  18. Circulating leptin and adiponectin levels in patients with primary hyperparathyroidism.

    Science.gov (United States)

    Delfini, Enrica; Petramala, Luigi; Caliumi, Chiara; Cotesta, Darlo; De Toma, Giorgio; Cavallaro, Giuseppe; Panzironi, Giuseppe; Diacinti, Daniele; Minisola, Savatore; D' Erasmo, Emilio; Mazzuoli, Gian Franco; Letizia, Claudio

    2007-01-01

    Primary hyperparathyroidism (PHPT) has been associated with high cardiovascular morbidity and mortality; its pathogenesis is not fully understood. Moreover, many metabolic abnormalities are frequently present in patients with PHPT. Several substances (such as leptin and adiponectin) are secreted from adipocytes, which may contribute to regulate energy homeostasis and the development of cardiovascular diseases. We examined the relationship between leptin and adiponectin levels and metabolic disorders in 67 newly diagnosed never-treated patients with PHPT and in 46 healthy subjects (HS). Twenty (29.8%) patients with PHPT presented a metabolic syndrome (as defined by Adult Treatment Panel III criteria). Serum leptin and adiponectin levels in HS were 6.28 +/- 3.3 ng/mL (range, 1.7-19.2 ng/mL) and 6.65 +/- 1.7 microg/mL (range, 3.72-10.86 microg/mL), respectively. In all patients with PHPT, the mean leptin levels (34.28 +/- 20.4 ng/mL) were significantly higher than those of HS (P < .01) and, in particular, in PHPT patients with metabolic syndrome (52.63 +/- 31.2 ng/mL) and positively correlated with body mass index, waist circumference, and cholesterol. The mean adiponectin level was significantly lower (4.34 +/- 3.5 mug/mL) only in PHPT patients with metabolic syndrome (P < .005) and negatively correlated with waist circumference and fasting glucose. We concluded that increased serum level of leptin and decreased serum level of adiponectin coexist in patients with PHPT and may represent a pathogenetic factor for cardiovascular disease in this condition.

  19. 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.

  20. Association between circulating adiponectin levels and polycystic ovarian syndrome

    NARCIS (Netherlands)

    S.S. Mirza (Saira Saeed); K. Shafique (Kashif); A.R. Shaikh (Abdul Rauf); N.A. Khan (Naveed Ali); M. Anwar Qureshi (Masood)

    2014-01-01

    textabstractBackground: Low adiponectin levels in polycystic ovarian syndrome (PCOS) have been largely attributed to obesity which is common among these patients. In addition, evidence also suggests that low adiponectin in PCOS may be related to insulin resistance (IR) in these women. However, studi

  1. Do circulating androgen levels predict competitiveness in female athletes?

    OpenAIRE

    Romfo, Marit

    2012-01-01

    Objective: In males a correlation between competitiveness and testosterone have been reported. As no such data is available in females we aimed at investigating the possible association between competitiveness and androgen levels in a sample of female top athletes.Method: Thirty one Norwegian female top athletes completed the competitiveness subscale of the Sport Orientation Questionnaire (SOQ), underwent a maximal oxygen consumption (VO2max) test with a following lactate measurement and had ...

  2. Circulating exosome levels in the diagnosis of steroid-induced osteonecrosis of the femoral head

    Science.gov (United States)

    Zhu, H-Y.; Gao, Y-C.; Wang, Y.

    2016-01-01

    Objectives Circulating exosomes represent novel biomarkers for multiple diseases. In this study, we investigated whether circulating exosome levels could be used as a diagnostic biomarker for steroid-induced osteonecrosis of the femoral head (ONFH). Methods We assessed the serum exosome level of 85 patients with steroid-induced ONFH and 115 healthy donors by Nanosight detection. We then assessed the diagnostic accuracy of serum exosomes by receiver operating characteristic curve analysis. Results The circulating exosome level of the ONFH group was significantly lower than that of control group. The area under the curve was 0.72, suggesting that the level of serum exosomes has moderate diagnostic accuracy for steroid-induced ONFH. Conclusion Circulating exosome levels are valuable in the diagnosis of steroid-induced ONFH. Cite this article: H-Y. Zhu, Y-C. Gao, Y. Wang, C-Q. Zhang. Circulating exosome levels in the diagnosis of steroid-induced osteonecrosis of the femoral head. Bone Joint Res 2016;5:276–279. DOI: 10.1302/2046-3758.56.BJR-2015-0014.R1. PMID:27357384

  3. Divergent relationship of circulating CTRP3 levels between obesity and gender: a cross-sectional study

    Science.gov (United States)

    Wagner, Roy Marshal; Sivagnanam, Kamesh; Clark, William Andrew

    2016-01-01

    C1q TNF Related Protein 3 (CTRP3) is a novel adipose tissue derived secreted factor, or adipokine, which has been linked to a number of beneficial biological effects on metabolism, inflammation, and survival signaling in a variety of tissues. However, very little is known about CTRP3 in regards to human health. The purpose of this project was to examine circulating CTRP3 levels in a clinical population, patients with symptoms requiring heart catheterization in order to identify the presence of obstructive coronary artery disease (CAD). It was hypothesized that serum CTRP3 levels would be decreased in the presence of CAD. Methods Body mass index (BMI), diabetes status, and plasma samples were collected from 100 patients who were >30 years of age and presented at the East Tennessee State University Heart Clinic with symptoms requiring heart catheterization in order to identify the presence of cardiovascular blockages (n = 52 male, n = 48 female). Circulating CTRP3 levels were quantified using commercially available ELISA. Results Circulating CTRP3 levels had no relationship to the presence of CAD regardless of gender. However, circulating concentrations of CTRP3 were significantly higher in normal weight (BMI obesity (BMI > 30) resulted in an increase in circulating CTRP3 levels in male subjects (0.74 ± 0.08 µg/ml) but showed a significant decrease in female subjects (0.58 ± 0.07 µg/ml). Additionally, there was a significant reduction in circulating CTRP3 levels in female subjects who were diagnosed with Type 2 diabetes compared with patients without (0.79 ± 0.08 vs. 0.42 ± 0.10 µg/ml). There was no relationship between diabetes status and circulating CTRP3 levels in male subjects. Conclusion Circulating CTRP3 levels had a different relationship with diabetes and obesity status between male and female patients. It is possible that circulating CTRP3 levels are controlled by hormonal status, however more research is needed to explore this relationship

  4. Correlation of levels of serum insulin-like growth factor 1 (IGF-1) and IGF bonding protein 3 (IGFBP-3) with risk of pancreas, colon cancers and rectal cancer: a Meta-analysis%血清胰岛素样生长因子-1和胰岛素样生长因子结合蛋白-3水平与胰腺癌及大肠癌发生风险相关性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    宋姗姗; 杨博逸; 孙韶龙; 孙贵范; 王宝胜

    2015-01-01

    Objective To assess the association of levels of serum insulin-like growth factor 1 (IGF-1) and IGF bonding protein 3 (IGFBP-3) with risk of pancreas,colon cancers and rectal cancer.Methods A Meta-analysis was used to analyze 20 nested case-control studies on association of serum IGF-1 and IGFBP-3 levels with risk of pancreatic cancer,colon cancers and rectal cancer.Results The pooled odds ratios (OR) with 95%CI of IGF-1 and IGFBP-3 in pancreatic cancer studies were 1.07 (95%CI:0.81-1.43) and 1.00 (95%CI:0.76-1.30),respectively.OR with 95%CI of IGF-1 and IGFBP-3 in colon cancer studies were 1.31 (95%CI:1.07-1.59) and 1.08 (95%CI:0.90-1.30),respectively.OR with 95%CI of IGF-1 and IGFBP-3 in rectal cancer studies were 0.85 (95%CI:0.55-1.30) and 0.88 (95%CI:0.59-1.32),respectively.Conclusion There is no significant correlation of serum IGF-1 or IGFBP-3 levels with pancreatic cancer and rectal cancer.High level of serum IGF-1 is associated with an elevated risk of colon cancer,but there is no indication that the change of IGFBP-3 level could influence occurrence of colon cancer.%目的 评价血清中胰岛素样生长因子-1(insulin-like growth factor 1,IGF-1)、胰岛素样生长因子结合蛋白-3(IGFbonding protein 3,IGFBP-3)水平和胰腺癌及大肠癌发生的关系.方法 利用Meta分析法对20个关于血清IGF-1、IGFBP-3水平与胰腺癌、结肠癌及直肠癌的巢式病例对照研究进行综合分析.结果 胰腺癌研究中,IGF-1合并OR值为1.07 (95%CI:0.81~1.43),IGFBP-3合并OR值为1.00 (95%CI:0.76~1.30);结肠癌研究中,IGF-1合并OR值为1.31(95%CI:1.07~1.59),IGFBP-3合并OR值为1.08(95%CI:0.90~1.30);直肠癌研究中,IGF-1合并OR值为0.85(95%CI:0.55~1.30),IGFBP-3合并OR值为0.88 (95%CI:0.59~1.32).结论 血清IGF-1及IGFBP-3水平与胰腺癌和直肠癌的相关性无统计学意义;血清中高水平的IGF-1增加结肠癌发生的风险性,但是不存在IGFBP-3水平改变影响结肠癌发生的证据.

  5. Southern hemisphere low level wind circulation statisticsfrom the Seasat scatterometer

    Directory of Open Access Journals (Sweden)

    Gad Levy

    Full Text Available Analyses of remotely sensed low-level wind vector data over the Southern Ocean are performed. Five-day averages and monthly means are created and the month-to-month variability during the winter (July-September of 1978 is investigated. The remotely sensed winds are compared to the Australian Bureau of Meteorology (ABM and the National Meteorological Center (NMC surface analyses. In southern latitudes the remotely sensed winds are stronger than what the weather services' analyses suggest, indicating underestimation by ABM and NMC in these regions. The evolution of the low-level jet and the major stormtracks during the season are studied and different flow regimes are identified. The large-scale variability of the meridional flow is studied with the aid of empirical orthogonal function (EOF analysis. The dominance of quasi-stationary wave numbers 3, 4, and 5 in the winter flow is evident in both the EOF analysis and the mean flow. The signature of an exceptionally strong blocking situation is evident in July and the special conditions leading to it are discussed. A very large intraseasonal variability with different flow regimes at different months is documented.

  6. Growth hormone dose in growth hormone-deficient adults is not associated with IGF-1 gene polymorphisms

    NARCIS (Netherlands)

    S. Meyer; S. Schaefer (Stephan); D. Ivan (Diana); L. Stolk (Lisette); P.P. Arp (Pascal); A.G. Uitterlinden (André); P.P. Nawroth (Peter); U. Plöckinger (Ursula); G.K. Stalla (Günter); U. Tuschy (Ulrich); M.M. Weber (Matthias); W.J. Weise (Wolfgang); A. Pfützner (Andreas); P. Kann (P.)

    2009-01-01

    textabstractAims: Several SNPs and a microsatellite cytosine-adenine repeat promoter polymorphisms of the IGF-1 gene have been reported to be associated with circulating IGF-1 serum concentrations. Variance in IGF-1 concentrations due to genetic variations may affect different response to growth hor

  7. Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Sorensen, Grith L; Wehner, Peder S;

    2016-01-01

    BACKGROUND: Surfactant protein D (SP-D) is a host defense molecule of the innate immune system that enhances pathogen clearance and modulates inflammatory responses. We hypothesized that circulating SP-D levels are associated with chemotherapy-induced mucositis and infectious morbidity in children...... with acute lymphoblastic leukemia (ALL). PROCEDURE: In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP-D, interleukin-6 (IL-6), C......-reactive protein, and white blood cells. Data on fever, antibiotics, and bacteremia were collected. Baseline levels of circulating SP-D were compared with healthy controls. RESULTS: Baseline values of circulating SP-D were similar to levels in healthy controls (median: 829 ng/ml vs. 657 ng/ml, respectively, P > 0...

  8. Native and Complexed IGF-1: Biodistribution and Pharmacokinetics in Infantile Neuronal Ceroid Lipofuscinosis

    Directory of Open Access Journals (Sweden)

    Tuulia Huhtala

    2012-01-01

    Full Text Available Infantile neuronal ceroid lipofuscinosis (INCL is a severe neurodegenerative disorder of childhood characterized by selective death of cortical neurons. Insulin-like growth factor 1 (IGF-1 is important in embryonic development and is considered as a potential therapeutic agent for several disorders of peripheral and central nervous systems. In circulation IGF-1 is mainly bound to its carrier protein IGFBP-3. As a therapeutic agent IGF-1 has shown to be more active as free than complexed form. However, this may cause side effects during the prolonged treatment. In addition to IGFBP-3 the bioavailability of IGF-1 can be modulated by using mesoporous silicon nanoparticles (NPs which are optimal carriers for sustained release of unstable peptide hormones like IGF-1. In this study we compared biodistribution, pharmacokinetics, and bioavailability of radiolabeled free IGF-1, IGF-1/IGFBP-3, and IGF-1/NP complexes in a Cln1-/- knockout mouse model. IGF-1/NP was mainly accumulated in liver and spleen in all studied time points, whereas minor and more constant amounts were measured in other organs compared to free IGF-1 or IGF-1/IGFBP-3. Also concentration of IGF-1/NP in blood was relatively high and stable during studied time points suggesting continuous release of IGF-1 from the particles.

  9. 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.

  10. Insulin-like growth factor (IGF)-I obliterates the pregnancy-associated protection against mammary carcinogenesis in rats: evidence that IGF-I enhances cancer progression through estrogen receptor-α activation via the mitogen-activated protein kinase pathway

    International Nuclear Information System (INIS)

    Pregnancy protects against breast cancer development in humans and rats. Parous rats have persistently reduced circulating levels of growth hormone, which may affect the activity of the growth hormone/insulin-like growth factor (IGF)-I axis. We investigated the effects of IGF-I on parity-associated protection against mammary cancer. Three groups of rats were evaluated in the present study: IGF-I-treated parous rats; parous rats that did not receive IGF-I treatment; and age-matched virgin animals, which also did not receive IGF-I treatment. Approximately 60 days after N-methyl-N-nitrosourea injection, IGF-I treatment was discontinued and all of the animal groups were implanted with a silastic capsule containing 17β-estradiol and progesterone. The 17β-estradiol plus progesterone treatment continued for 135 days, after which the animals were killed. IGF-I treatment of parous rats increased mammary tumor incidence to 83%, as compared with 16% in parous rats treated with 17β-estradiol plus progesterone only. Tumor incidence and average number of tumors per animal did not differ between IGF-I-treated parous rats and age-matched virgin rats. At the time of N-methyl-N-nitrosourea exposure, DNA content was lowest but the α-lactalbumin concentration highest in the mammary glands of untreated parous rats in comparison with age-matched virgin and IGF-I-treated parous rats. The protein levels of estrogen receptor-α in the mammary gland was significantly higher in the age-matched virgin animals than in untreated parous and IGF-I-treated parous rats. Phosphorylation (activation) of the extracellular signal-regulated kinase-1/2 (ERK1/2) and expression of the progesterone receptor were both increased in IGF-I-treated parous rats, as compared with those in untreated parous and age-matched virgin rats. Expressions of cyclin D1 and transforming growth factor-β3 in the mammary gland were lower in the age-matched virgin rats than in the untreated parous and IGF-I-treated parous

  11. Cytokines modulate the sensitivity of human fibroblasts to stimulation with insulin-like growth factor-I (IGF-I) by altering endogenous IGF-binding protein production.

    Science.gov (United States)

    Yateman, M E; Claffey, D C; Cwyfan Hughes, S C; Frost, V J; Wass, J A; Holly, J M

    1993-04-01

    Human dermal fibroblasts produce a number of insulin-like growth factor-binding proteins (IGFBPs) including the main circulating form, IGFBP-3. It has been suggested that the regulation of IGFBP secretion may play a major role in modulating insulin-like growth factor (IGF) bioactivity. We have quantified the effects of two cytokines, transforming growth factor-beta 1 (TGF-beta 1) and tumour necrosis factor-alpha (TNF-alpha) which have opposing actions on fibroblast IGFBP-3 production, and examined their subsequent role in IGF-I mitogenesis. TGF-beta 1 caused a dose-dependent increase in IGFBP-3 in serum-free fibroblast-conditioned media. TGF-beta 1 (1 microgram/l) resulted in immunoreactive IGFBP-3 levels reaching 286.5 +/- 22.4% of control after 20 h, the increase being confirmed by Western ligand blot. TNF-alpha caused a dose-dependent decrease in fibroblast IGFBP-3 secretion, 1 microgram TNF-alpha/l reducing IGFBP-3 levels to 32.1 +/- 11.% of control. This effect was not due to cytotoxicity and was not cell-density-dependent. Fibroblast proliferation was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric cytochemical bioassay. The addition of IGF-I resulted in dose-dependent growth stimulation after 48 h, the effective range being 20-100 micrograms/l. The IGF-I analogue Long-R3-IGF-I which has little affinity for the IGFBPs was approximately 20-fold more potent in this assay, and was unaffected by exogenous IGFBP-3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7684061

  12. Cross-Circulating Current Suppression Method for Parallel Three-Phase Two-Level Inverters

    DEFF Research Database (Denmark)

    Wei, Baoze; Guerrero, Josep M.; Guo, Xiaoqiang

    2015-01-01

    The parallel architecture is very popular for power inverters to increase the power level. This paper presents a method for the parallel operation of inverters in an ac-distributed system, to suppress the cross-circulating current based on virtual impedance without current-sharing bus and communi......The parallel architecture is very popular for power inverters to increase the power level. This paper presents a method for the parallel operation of inverters in an ac-distributed system, to suppress the cross-circulating current based on virtual impedance without current-sharing bus...

  13. The Expression of the IGF Family During Mouse Mammary Gland Development

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This study was to determine the patterns and levels of IGF family members' expression during postnatal mammary gland development. The authors investigated the protein expression profile of the major components of the IGF axis in murine mammary glands. All the proteins examined, IGF- Ⅰ, IGF- Ⅱ, and IGF- Ⅰ receptor (IGF- Ⅰ R) were expressed at greatly different levels and displayed unique expression profiles. IGF- Ⅱ and IGF- Ⅰ R were always expressed at significantly higher levels than IGF- Ⅰ. IGF- Ⅰ was localized in adipocytes as well as the epithelial and stromal compartments, but just distinctly expressed where mammary cells aggregated to form ducts, in virgins. The IGF- Ⅱ was localized only on the basal layer epithelial cell membranes of ducts and alveoli, with a peak level on the initiation of lactation. The higher level of IGF- Ⅰ R compared with IGF- Ⅰ was also found in adipocytes as well as in the epithelial and stromal compartments, especially during pregnancy and late lactation. The IGF- Ⅰ R pathway was obviously significant for the development of the mammary parenchyma and stroma. Overall, the comparison of the expression profiles of these different proteins would strongly suggest that they were likely to have different functions throughout the mammary gland development, and it also highlighted the potential interactions and coregulation of the members of this axis. It seems that IGF- Ⅱ was the major local modulator rather than IGF- Ⅰ by an IGF- Ⅰ R-independent pathway, especially for initiation of lactation. This study has demonstrated the importance and complexity of the IGF axis during mammary gland development and provides a valuable resource for future research in this area.

  14. Effect of recombinant porcine IGFBP-3 on IGF-I and long-R3-IGF-I-stimulated proliferation and differentiation of L6 myogenic cells.

    Science.gov (United States)

    Xi, G; Kamanga-Sollo, E; Pampusch, M S; White, M E; Hathaway, M R; Dayton, William R

    2004-09-01

    Insulin-like growth factor (IGF)-I stimulates both proliferation and differentiation of myogenic precursor cells. In vivo, IGFs are bound to one of the members of a family of six high-affinity IGF binding proteins (IGFBP 1-6) that regulate their biological activity. One of these binding proteins, IGFBP-3, affects cell proliferation via both IGF-dependent and IGF-independent mechanisms and it has generally been shown to suppress proliferation of cultured cells; however, it also may stimulate proliferation depending upon the cell type and the assay conditions. Cultured porcine embryonic myogenic cells (PEMCs) produce IGFBP-3 and its level drops significantly immediately prior to differentiation. Additionally, IGFBP-3 suppresses both IGF-I and Long-R3-IGF-I-stimulated proliferation of embryonic porcine myogenic cells. In this study, we have examined the effects of recombinant porcine IGFBP-3 (rpIGFBP-3) on IGF-I- and Long-R3-IGF-I-stimulated proliferation and differentiation of the L6 myogenic cell line. L6 cells potentially provide a good model for studying the actions of IGFBP-3 on muscle because they contain no non-muscle cells and they do not produce detectable levels of IGFBP-3. RpIGFBP-3 suppresses both IGF-I and Long-R3-IGF-I-stimulated proliferation of L6 cells, indicating that it suppresses proliferation via both IGF-dependent and IGF-independent mechanisms. Our data also show that rpIGFBP-3 causes IGF-independent suppression of proliferation without increasing the level of phosphosmad-2 in L6 cultures. Additionally, rpIGFBP-3 suppresses IGF-I-stimulated differentiation of L6 cells. In contrast, however, rpIGFBP-3 does not suppress Long-R3-IGF-I-stimulated differentiation. This suggests that rpIGFBP-3 does not have IGF-independent effects on L6 cell differentiation. PMID:15254966

  15. Interstitial fluid contains higher in vitro IGF bioactivity than serum

    DEFF Research Database (Denmark)

    Espelund, Ulrick; Søndergaard, Klaus; Bjerring, Peter;

    2012-01-01

    MEASURE: Serum and SBF concentrations of bioactive IGF (determined in vitro by specific IGF-I receptor (IGF-IR) phosphorylation assay), immunoreactive IGF and IGF binding protein (IGFBP) levels, Western ligand blotting (WLB) of IGFBPs and IGFBP-3 Western immunoblotting (WiB). RESULTS: The ability of SBF...... to phosphorylate the IGF-IR in vitro was 41±27% higher than that of serum (P=0.007 by repeated measures ANOVA). By contrast, immunoreactive IGF and IGFBP-concentrations were approximately 50% lower in SBF than in serum (all P≤0.002). A marked difference in the composition of IGFBPs between serum and...... SBF was observed, including 3-fold elevated amounts of IGFBP-3 fragments in SBF (P<0.001). For both IGF-I, IGF-II and IGFBP-2, the effect of food intake differed between serum and SBF (all P≤0.03). CONCLUSION: Despite lower concentrations, the in vitro IGF bioactivity was higher in SBF than in serum...

  16. Effects of polychlorinated biphenyls on mourning dove reproduction and circulating progesterone levels

    Energy Technology Data Exchange (ETDEWEB)

    Koval, P.J.; Peterle, T.J.; Harder, J.D.

    1987-10-01

    PCBs acquired in sublethal doses increase activation of the liver's microsomal action and hepatic mixed function oxidase (MFO) enzymes. Physiological effects of increase in the MFO system may delay, if not eliminate, avian reproductive behavior and nesting success. No evidence is yet available to clearly link PCBs to lowered levels of circulating steroids in birds. However, data concerning the effects of PCBs on avian reproduction are abundant. Increased degradation of circulating steroids might alter essential hormone dynamics associated with nesting behavior and ovulation. Alternatively, normal feedback regulation by the pituitary-gonadal axis might lead to a full compensatory response to increased MFO such that hormone profiles remain unaltered, suggesting alternative modes of action for PCBs in reproductive disorders. Therefore, the authors investigated the effect of dietary PCBs on circulating progesterone levels prior to and during egg laying in wild-trapped mourning doves (Zenaida macroura).

  17. Increasing Circulating IGFBP1 Levels Improves Insulin Sensitivity, Promotes Nitric Oxide Production, Lowers Blood Pressure, and Protects Against Atherosclerosis

    OpenAIRE

    Rajwani, Adil; Ezzat, Vivienne; Smith, Jessica; Yuldasheva, Nadira Y.; Duncan, Edward R.; Gage, Matthew; Cubbon, Richard M.; Kahn, Matthew B.; Imrie, Helen; Abbas, Afroze; Viswambharan, Hema; Aziz, Amir; Sukumar, Piruthivi; Vidal-Puig, Antonio; Sethi, Jaswinder K.

    2012-01-01

    Low concentrations of insulin-like growth factor (IGF) binding protein-1 (IGFBP1) are associated with insulin resistance, diabetes, and cardiovascular disease. We investigated whether increasing IGFBP1 levels can prevent the development of these disorders. Metabolic and vascular phenotype were examined in response to human IGFBP1 overexpression in mice with diet-induced obesity, mice heterozygous for deletion of insulin receptors (IR+/−), and ApoE−/− mice. Direct effects of human (h)IGFBP1 on...

  18. Dehydroepiandrosterone Stimulation of Osteoblastogenesis in Human MSCs Requires IGF-I Signaling.

    Science.gov (United States)

    Liang, Xiaonan; Glowacki, Julie; Hahne, Jochen; Xie, Li; LeBoff, Meryl S; Zhou, Shuanhu

    2016-08-01

    Dehydroepiandrosterone (DHEA) is an adrenal steroid that circulates in high concentrations in humans in its sulfated form, DHEAS. Clinical and epidemiological studies suggested that low DHEAS levels may be associated with low bone mass. Previously, we and others showed that the effects of DHEA on the skeleton may be conferred partly by their ability to inhibit skeletal catabolic agents, for example, bone resorptive cytokine IL-6. In this study, we tested the hypothesis that the anabolic effects of DHEA on osteoblastogenesis require IGF-I signaling pathways. Using both primary cultures and a cell line of human bone marrow-derived mesenchymal stem cells (hMSCs), we show that DHEA and other steroids stimulate osteoblastogenesis as shown by alkaline phosphatase activity and osteoblast gene induction. The stimulation by DHEA on both IGF-I gene expression and osteoblastogenesis in hMSCs requires IGF-I receptor, PI3K, p38 MAPK, or p42/44 MAPK signaling pathways. This study adds information to indicate that DHEA may be useful for treating bone diseases through its inhibition of skeletal catabolic IL-6 and stimulation of anabolic IGF-I-mediated mechanisms. J. Cell. Biochem. 117: 1769-1774, 2016. © 2015 Wiley Periodicals, Inc. PMID:26682953

  19. Simulation of the Low-Level-Jet by general circulation models

    Energy Technology Data Exchange (ETDEWEB)

    Ghan, S.J. [Pacific Northwest National Lab., Richland, WA (United States)

    1996-04-01

    To what degree is the low-level jet climatology and it`s impact on clouds and precipitation being captured by current general circulation models? It is hypothesised that a need for a pramaterization exists. This paper describes this parameterization need.

  20. Circulating 20S Proteasome Levels in Patients with Mixed Connective Tissue Disease and Systemic Lupus Erythematosus▿

    OpenAIRE

    Majetschak, Matthias; Perez, Magdalena; Sorell, Luis T.; Lam, Janet; Maldonado, Marcos E.; Hoffman, Robert W.

    2008-01-01

    The associations of circulating 20S proteasomes (c20S) with clinical and serologic disease indices in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are unknown. We present the initial report that c20S levels are elevated in MCTD and correlate with clinically relevant changes in disease activity in SLE and MCTD.

  1. Circulating levels of neuropeptides (CGRP, VIP, NPY) in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Strauss, Gitte Irene; Edvinsson, Lars; Larsen, Fin Stolze;

    2001-01-01

    The present study investigated the circulating levels and cerebral fluxes of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) and their relation to cerebral blood flow (CBF) during normoventilation and hyperventilation in patients with fulminant...

  2. 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).

  3. Analyzing the etiology of 1 496 children with short stature and establishing the predict model of growth hormonedeficiency using IGF-1 levels%1496例矮小症病因分析及基于IGF-1水平生长激素缺乏症诊断预测模型的建立

    Institute of Scientific and Technical Information of China (English)

    李晓静; 罗飞宏; 裴舟; 奚立; 叶蓉; 赵诸慧; 陆炜; 章淼滢; 郑章乾

    2012-01-01

    Objective To analysis the etiology of 1 496 short stature children and to establish the predict model of growth hormone deficiency using IGF-1 levels. Methods Anthropological and physical examination data were collected in 1 496 short children. Growth hormone levels were determined via Insulin tolerance test and Arginine test. A prediction model of growth hormone deficiency (GHD) was established by Logistic stepwise multivariate regression based on IGF-1 level. Results 659 cases (44.05%) were diagnosed as GHD, 504 cases (33.69%) were idiopathic short stature (ISS), 165 cases (11.03%) were familial short stature, 35 cases (2.33%) were constitutional delay of growth and puberty. The rests were attributed to other reasons, such as hypothyroidism, intrauterine growth retardation, Turner syndrome, multiple pituitary hormone deficiency and so on. There existed significantly statistical difference in body weight, BMI, height SDS, ALT/AST/AKP, TG/Tch, IGF-1, IGFBP-3 level between GHD and non-GHD groups. If the probability for growth hormone deficiency P, the Logistic stepwise multivariate regression model fitting model is as follows: LN[P/(1-p)] = -2.0193 + 0.0683 × age + 0.1439 × BMI + 0.021 × ALT-0.0021 × IGF-1-0.152 6 × IGFBP-3. Conclusions Endocrine disease is the most common cause of dwarfism, which is most commonly seen in GHD; GH levels were affected by multiple factors including anthropological indexes and biochemical status, it is highly suggests that serious cautions should be taken when diagnosing GHD. GHD can be briefly and accurately predicted based on IGF-1 value.%目的 探讨矮小症患儿的病因及胰岛素样生长因子 (IGF)-1与生长激素 (growth hormone,GH) 水平之间的关系,建立基于IGF-1水平的简易GH缺乏 (GHD) 诊断预测模型.方法矮小症住院患儿1 496例,采用胰岛素低血糖法和精氨酸法测定GH分泌状态,根据体格检查及实验室检查分析病因;Logistic逐步多元回归模型建立基于IGF-1

  4. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

    Science.gov (United States)

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K; Drong, Alexander W; Hayes, James E; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Del Greco M, Fabiola; Pasko, Dorota; Renström, Frida; Willems, Sara M; Mahajan, Anubha; Rose, Lynda M; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S; Ju Sung, Yun; Ramos, Yolande F; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J N; Crosslin, David R; Dale, Caroline E; Dastani, Zari; Day, Felix R; Deelen, Joris; Delgado, Graciela E; Demirkan, Ayse; Finucane, Francis M; Ford, Ian; Garcia, Melissa E; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A; Hunter, David J; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S; Jørgensen, Marit E; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P; Myers, Richard H; Männistö, Satu; Nalls, Mike A; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rice, Treva K; Brent Richards, J; Ridker, Paul M; Sattar, Naveed; Savage, David B; Söderberg, Stefan; Timpson, Nicholas J; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I A; Sarzynski, Mark A; Rao, D C; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G; Heliövaara, Markku; Knekt, Paul B; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W; van Duijn, Cornelia M; Harris, Tamara B; Bouchard, Claude; Allison, Matthew A; Chasman, Daniel I; Ohlsson, Claes; Lind, Lars; Scott, Robert A; Langenberg, Claudia; Wareham, Nicholas J; Ferrucci, Luigi; Frayling, Timothy M; Pramstaller, Peter P; Borecki, Ingrid B; Waterworth, Dawn M; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B; Eline Slagboom, P; Grallert, Harald; Spector, Tim D; Jukema, J W; Klein, Robert J; Schadt, Erik E; Franks, Paul W; Lindgren, Cecilia M; Leibel, Rudolph L; Loos, Ruth J F

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  5. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    Science.gov (United States)

    Kilpeläinen, Tuomas O.; Carli, Jayne F. Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H.; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Greco M, Fabiola Del; Pasko, Dorota; Renström, Frida; Willems, Sara M.; Mahajan, Anubha; Rose, Lynda M.; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E.; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S.; Ju Sung, Yun; Ramos, Yolande F.; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M.; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J. N.; Crosslin, David R.; Dale, Caroline E.; Dastani, Zari; Day, Felix R.; Deelen, Joris; Delgado, Graciela E.; Demirkan, Ayse; Finucane, Francis M.; Ford, Ian; Garcia, Melissa E.; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E.; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A.; Hunter, David J.; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S.; Jørgensen, Marit E.; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A.; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P.; Myers, Richard H.; Männistö, Satu; Nalls, Mike A.; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D.; Rankinen, Tuomo; Rasmussen-Torvik, Laura J.; Rathmann, Wolfgang; Rice, Treva K.; Brent Richards, J; Ridker, Paul M.; Sattar, Naveed; Savage, David B.; Söderberg, Stefan; Timpson, Nicholas J.; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R.; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I. A.; Sarzynski, Mark A.; Rao, D. C.; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G.; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G.; Heliövaara, Markku; Knekt, Paul B.; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K.; Viikari, Jorma S.; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T.; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P.; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W.; van Duijn, Cornelia M.; Harris, Tamara B.; Bouchard, Claude; Allison, Matthew A.; Chasman, Daniel I.; Ohlsson, Claes; Lind, Lars; Scott, Robert A.; Langenberg, Claudia; Wareham, Nicholas J.; Ferrucci, Luigi; Frayling, Timothy M.; Pramstaller, Peter P.; Borecki, Ingrid B.; Waterworth, Dawn M.; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B.; Eline Slagboom, P; Grallert, Harald; Spector, Tim D.; Jukema, J.W.; Klein, Robert J.; Schadt, Erik E; Franks, Paul W.; Lindgren, Cecilia M.; Leibel, Rudolph L.; Loos, Ruth J. F.

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10−6 in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10−8) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  6. Testosterone increases circulating dehydroepiandrosterone sulfate levels in the male rhesus macaque

    Directory of Open Access Journals (Sweden)

    Krystina eSorwell

    2014-06-01

    Full Text Available The adrenal steroid dehydroepiandrosterone (DHEA and its sulfate (DHEAS are two of the most abundant hormones in the human circulation. Furthermore, they are released in a circadian pattern and show a marked age-associated decline. Adult levels of DHEA and DHEAS are significantly higher in males than in females, but the reason for this sexual dimorphism is unclear. In the present study, we administered supplementary androgens (DHEA, testosterone and 5α-dihydrotestosterone [DHT] to aged male rhesus macaques (Macaca mulatta. While this paradigm increased circulating DHEAS immediately after DHEA administration, an increase was also observed following either testosterone or DHT administration, resulting in hormonal profile resembling levels observed in young males in terms of both amplitude and circadian pattern. This stimulatory effect was limited to DHEAS, as an increase in circulating cortisol was not observed. Taken together, these data demonstrate an influence of the hypothalamo-pituitary-testicular axis on adrenal function in males, possibly by sensitizing the zona reticularis to the stimulating action of adrenocorticopic hormone. This represents a plausible mechanism to explain sex differences in circulating DHEA and DHEAS levels, and may have important implications in the development of hormone therapies designed for elderly men and women.

  7. 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

    2012-02-01

    OBJECTIVE: 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). METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, IL), with P < 0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking. Blood pressure was checked at each visit in conjunction with urine analysis. The Davey & MacGillivray 1988 classification system was used in making the diagnosis of PET. RESULTS: There was no significant correlation between maternal IGF-1 or IGFBP-3 levels and gestational hypertension or PET. However, a significant positive correlation does exist between maternal IGF-2 levels and PET. CONCLUSIONS: Maternal IGF-2 has a significant positive correlation with PET.

  8. C-peptide, IGF-I, sex-steroid hormones and adiposity : a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC)

    NARCIS (Netherlands)

    Bezemer, ID; Rinaldi, S; Dossus, L; van Gils, CH; Peeters, PHM; Noord, PAH; Bueno-de-Mesquita, HB; Johnsen, SP; Overvad, K; Olsen, A; Tjonneland, A; Boeing, H; Lahmann, PH; Linseisen, J; Nagel, G; Allen, N; Roddam, A; Bingham, S; Khaw, KT; Kesse, E; Tehard, B; Clavel-Chapelon, F; Agudo, A; Ardanaz, E; Quiros, [No Value; Amiano, P; Martinez-Garcia, C; Tormo, MJ; Pala, [No Value; Panico, S; Vineis, P; Palli, D; Tumino, R; Trichopoulou, A; Baibas, N; Zilis, D; Hemon, B; Norat, T; Riboli, E; Kaaks, R

    2005-01-01

    Objectives: The risk of some cancers is positively associated with body weight, which may influence circulating levels of sex-steroid hormones, insulin and IGF-I. Interrelationships between these hormones and the associations with adiposity were evaluated in healthy women participating in the Europe

  9. Impacts of sea-level rise on estuarine circulation: An idealized estuary and San Francisco Bay

    Science.gov (United States)

    Chua, Vivien P.; Xu, Ming

    2014-11-01

    Estuaries lie at the interface of land and sea, and are particularly vulnerable to sea-level rise due to climate change that might lead to intrusion of salt water further upstream and affect circulation patterns. Climate change is also likely to have a major impact on hydrological cycles and consequently lead to changes in freshwater inflows into estuaries. An idealized estuary model is employed to investigate the effects of sea-level rise and freshwater inflows on estuarine circulation. Rising sea levels result in a stronger longitudinal salinity gradient ∂s/∂x, indicating an increase in the strength of the gravitational circulation UGC, higher longitudinal dispersion coefficients K and enhanced salinity intrusion. Under low-flow conditions, the effects of sea level rise on salinity intrusion are largest because sea-level rise has a greater impact due to weaker vertical stratification. Strong flows increase the strength of the gravitational circulation, resulting in higher vertical stratification, which leads to the nonlinear feedback between vertical mixing and stratification. The effect of sea-level rise on salinity intrusion is reduced owing to the suppression of mixing by stratification. Supporting three-dimensional simulations from northern San Francisco Bay are presented. The intrusion length scale L is used as a substitute for regulating inflows to ensure that sufficient fresh water is available to flush the Bay. Following a set of standards explicitly stated in the 1994 Bay-Delta Accord, a series of simulations is performed and we find that with sea-level rise stronger inflows are required to maintain L at the proposed locations.

  10. Obesity alters gene expression for GH/IGF-I axis in mouse mammary fat pads: differential role of cortistatin and somatostatin.

    Directory of Open Access Journals (Sweden)

    Alicia Villa-Osaba

    Full Text Available Locally produced growth hormone (GH and IGF-I are key factors in the regulation of mammary gland (MG development and may be important in breast cancer development/progression. Somatostatin (SST and cortistatin (CORT regulate GH/IGF-I axis at various levels, but their role in regulating GH/IGF-I in MGs remains unknown. Since obesity alters the expression of these systems in different tissues and is associated to MG (patho physiology, we sought to investigate the role of SST/CORT in regulating GH/IGF-I system in the MGs of lean and obese mice. Therefore, we analyzed GH/IGF-I as well as SST/CORT and ghrelin systems expression in the mammary fat pads (MFPs of SST- or CORT-knockout (KO mice and their respective littermate-controls fed a low-fat (LF or a high-fat (HF diet for 16 wks. Our results demonstrate that the majority of the components of GH/IGF-I, SST/CORT and ghrelin systems are locally expressed in mouse MFP. Expression of elements of the GH/IGF-I axis was significantly increased in MFPs of HF-fed control mice while lack of endogenous SST partially suppressed, and lack of CORT completely blunted, the up-regulation observed in obese WT-controls. Since SST/CORT are known to exert an inhibitory role on the GH/IGFI axis, the increase in SST/CORT-receptor sst2 expression in MFPs of HF-fed CORT- and SST-KOs together with an elevation on circulating SST in CORT-KOs could explain the differences observed. These results offer new information on the factors (GH/IGF-I axis involved in the endocrine/metabolic dysregulation of MFPs in obesity, and suggest that CORT is not a mere SST sibling in regulating MG physiology.

  11. A common polymorphism in the promoter of the IGF-I gene associates with increased fasting serum triglyceride levels in glucose-tolerant subjects

    DEFF Research Database (Denmark)

    Nielsen, Eva-Maria D; Hansen, Lars; Lajer, Maria;

    2004-01-01

    The aim of the present study was to examine if absence of a common allele in a microsatellite polymorphism in the insulin-like growth factor I (IGF-I) promoter was associated with type 2 diabetes and alterations in quantitative traits in glucose-tolerant subjects....

  12. Correlation between the levels of circulating adhesion molecules and atherosclerosis in type-2 diabetic normotensive patients

    Science.gov (United States)

    Vargas-Robles, Hilda; Serrano, Alberto Maceda; Lozano-Nuevo, Jose Juan; Escalante-Acosta, Bruno Alfonso

    2009-01-01

    Endothelial dysfunction is a common feature in type-2 diabetic patients and is associated with inflammation, increased levels of circulating soluble adhesion molecules and atherosclerosis. The aim of this study was to evaluate the relationship between the levels of circulating soluble adhesion molecules and the degree of atherosclerosis in normotensive type-2 diabetic patients. Results: We found significant correlations between ICAM-1 (r = 0.69, p < 0.001 95% IC 0.65 to 0.82) and VCAM-1 (r = 0.4, p < 0.03, 95% IC 0.65 to 0.82) levels and maximal carotid artery intimal-medial thickness, whereas no correlation was observed with E-selectin. Methods: We studied 30 normotensive type-2 diabetic patients in whom VCAM-1, ICAM-1 and E-selectin were measured by ELISA. Additionally, the intimal-medial thickness of both the common and internal carotid arteries was measured (B-mode ultrasound). The levels of circulating adhesion molecules and maximal carotid artery intimal-medial thicknesses were correlated using the Spearman correlation coefficient test. Statistical analysis was performed with ANOVA. Conclusion: Our results suggest that ICAM-1 and VCAM-1 are markers associated, and correlated with the degree of atherosclerosis in normotensive type-2 diabetic patients. PMID:19717975

  13. IGF-I and IGFBP2 in peripheral artery disease

    DEFF Research Database (Denmark)

    Urbonaviciene, Grazina; Frystyk, Jan; Urbonavicius, Sigitas;

    2014-01-01

    -2) in the pathogenesis of CVD disorders. The aim of this study was to examine the relationship between levels of IGF-I and IGFBP-2 with all-cause and CVD mortality in a prospective study of patients with lower-extremity peripheral artery disease (PAD). METHODS AND MATERIAL: Serum IGF-I and IGFBP-2...

  14. INSULIN-LIKE GROWTH FACTOR (IGF-1 IN CNS AND CEREBROVASCULAR AGING

    Directory of Open Access Journals (Sweden)

    William E Sonntag

    2013-07-01

    Full Text Available Insulin-like growth factor-1 (IGF-1 is an important anabolic hormone that decreases with age. In the past two decades extensive research has determined that the reduction in IGF-1 is an important component of the age-related decline in cognitive function in multiple species including humans. Deficiency in circulating IGF-1 results in impairment in processing speed and deficiencies in both spatial and working memory. Replacement of IGF-1 or factors that increase IGF-1 to old animals and humans reverses many of these cognitive deficits. Despite the overwhelming evidence for IGF-1 as an important neurotrophic agent, the specific mechanisms through which IGF-1 acts have remained elusive. Recent evidence indicates that IGF-1 is both produced by and has important actions on the cerebrovasculature as well as neurons and glia. Nevertheless, the specific regulation and actions of brain- and vascular-derived IGF-1 is poorly understood. The diverse effects of IGF-1 discovered thus far reveal a complex endocrine and paracrine system essential for integrating many of the functions necessary for brain health. Identification of the mechanisms of IGF-1 actions will undoubtedly provide critical insight into regulation of brain function in general and the causes of cognitive decline with age.

  15. 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

    acclimation. In the present study, primers for the IGF type 1 receptor from striped bass (Morone saxatilis) were designed for a real-time quantitative PCR assay. Two salinity transfer experiments were performed and the time-course of gill IGF-1R expression was examined in parallel with changes in plasma IGF-1...... concentration increased rapidly after FW transfer (6 hours and 1 day). Levels of a 37 kDa IGF binding protein (IGFBP-3 like), as measured by Western ligand blot, increased 2-fold in the plasma after transfer from FW to SW.  The cellular localization of the IGF-1R was investigated by immunohistochemistry using...

  16. Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Holst, J J; Moller, S;

    2000-01-01

    Leptin, a peptide hormone produced mainly in fat cells, appears to be important for the regulation of metabolism, insulin secretion/sensitivity and body weight. Recently, elevated plasma leptin levels have been reported in patients with arterial hypertension. Because a change in circulating leptin...... concentrations in such patients could be caused by altered rates of production or disposal, or both, the aim of the present study was to identify regions of leptin overflow into the bloodstream and of leptin extraction. Patients with arterial hypertension (n=12) and normotensive controls (n=20) were studied...... during catheterization with elective blood sampling from different vascular beds (artery, and renal, hepatic, iliac and cubital veins). Plasma leptin was determined by a radioimmunoassay. Patients with hypertension had significantly elevated levels of circulating leptin (12.8 ng/l, compared with 4.1 ng...

  17. The circulating PBEF/NAMPT/visfatin level is associated with a beneficial blood lipid profile

    OpenAIRE

    Wang, P.; Greevenbroek, van, M.M.J.; Bouwman, F.G. (F.G.); Brouwers, M.C.G.J.; Kallen, van der, B.F.; Smit, E.; Keijer, J.; Mariman, E C M

    2007-01-01

    Visfatin with the official gene name pre-B cell colony-enhancing factor 1 (PBEF) and the protein name nicotinamide phosphoribosyltransferase (NAMPT) is a recently discovered adipocyte-secreted protein that was shown by some to be associated with visceral fat and insulin resistance. To explore the link between PBEF/NAMPT/visfatin and lipid metabolism, we analyzed the relation of its plasma level with several parameters of adiposity, insulin resistance and the circulating blood lipid profile in...

  18. ELEVATED CIRCULATING LEVELS OF MACROPHAGE MIGRATION INHIBITORY FACTOR IN POLYCYSTIC OVARY SYNDROME

    OpenAIRE

    González, Frank; ROTE, Neal S.; Minium, Judi; Weaver, Amy L.; Kirwan, John P.

    2010-01-01

    Women with Polycystic Ovary Syndrome (PCOS) have chronic low level inflammation which can increase the risk of atherogenesis. We evaluated the status of circulating macrophage migration inhibitory factor (MIF), a proinflammatory cytokine involved in atherogenesis, in women with PCOS and weight-matched controls. Two-way analysis of variance models adjusted for age were fit to evaluate the effect of PCOS status (PCOS vs. controls) and weight-class (obese vs. lean) on MIF and other parameters. M...

  19. Circulating L-selectin levels and endothelial CD34 expression in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Seidelin, J B; Vainer, B; Horn, T;

    1998-01-01

    Soluble L-selectin (sL-selectin) concentrations are positively correlated with disease activity in ulcerative colitis (UC) but not in Crohn's disease (CD). This difference in sL-selectin regulation could be due to a disease specific regulation of L-selectin ligands. The aim of this study was to c...... was to compare levels of circulating sL-selectin, expression of the L-selectin ligand CD34 in the affected colon, and inflammatory bowel disease activity....

  20. Increased circulating miR-21 levels are associated with kidney fibrosis.

    Directory of Open Access Journals (Sweden)

    François Glowacki

    Full Text Available MicroRNAs (miRNAs are a class of noncoding RNA acting at a post-transcriptional level to control the expression of large sets of target mRNAs. While there is evidence that miRNAs deregulation plays a causative role in various complex disorders, their role in fibrotic kidney diseases is largely unexplored. Here, we found a strong up-regulation of miR-21 in the kidneys of mice with unilateral ureteral obstruction and also in the kidneys of patients with severe kidney fibrosis. In addition, mouse primary fibroblasts derived from fibrotic kidneys exhibited higher miR-21 expression level compared to those derived from normal kidneys. Expression of miR-21 in normal primary kidney fibroblasts was induced upon TGFβ exposure, a key growth factor involved in fibrogenesis. Finally, ectopic expression of miR-21 in primary kidney fibroblasts was sufficient to promote myofibroblast differentiation. As circulating miRNAs have been suggested as promising non-invasive biomarkers, we further assess whether circulating miR-21 levels are associated with renal fibrosis using sera from 42 renal transplant recipients, categorized according to their renal fibrosis severity, evaluated on allograft biopsies (Interstitial Fibrosis/Tubular Atrophy (IF/TA. Circulating miR-21 levels are significantly increased in patients with severe IF/TA grade (IF/TA grade 3: 3.0±1.0 vs lower grade of fibrosis: 1.5±1.2; p = 0.001. By contrast, circulating miR-21 levels were not correlated with other renal histological lesions. In a multivariate linear regression model including IF/TA grade and estimated GFR, independent associations were found between circulating miR-21 levels and IF/TA score (ß = 0.307, p = 0.03, and between miR-21 levels and aMDRD (ß = -0.398, p = 0.006. Altogether, these data suggest miR-21 has a key pathogenic role in kidney fibrosis and may represent a novel, predictive and reliable blood marker of kidney fibrosis.

  1. Elevated levels of circulating IL-18BP and perturbed regulation of IL-18 in schizophrenia

    Directory of Open Access Journals (Sweden)

    Palladino Ilaria

    2012-08-01

    Full Text Available Abstract Background The pleiotropic pro-inflammatory cytokine Interleukin (IL-18 has been proposed to play a role in schizophrenia, since elevated circulating levels of its protein and altered frequencies of genetic variants in its molecular system are reported in schizophrenic patients. Methods We analyzed 77 patients with schizophrenia diagnosis (SCZ and 77 healthy control subjects (HC for serum concentration of both IL-18 and its natural inhibitor, the IL-18 binding protein (IL-18BP. Results We confirmed that serum levels of total IL-18 are significantly increased in SCZ, as compared to HC. However, due to a highly significant increase in levels of circulating IL-18BP in SCZ, as compared to HC, the levels of free, bioactive IL-18 are not significantly different between the two groups. In addition, the relationships between the levels of IL-18 and its inhibitor, as well as between the two molecules and age appear dissimilar for SCZ and HC. In particular, the elevated levels of IL-18BP, likely a consequence of the body’s attempt to counteract the early prominent inflammation which characterizes schizophrenia, are maintained in earlier and later stages of the disease. However, the IL-18BP elevation appears ineffective to balance the IL-18 system in younger SCZ patients, while in older patients the levels of circulating bioactive IL-18 are comparable to those of HC, if not lower. Conclusions In conclusion, these findings indicate that the IL-18 system is perturbed in schizophrenia, supporting the idea that this pro-inflammatory cytokine might be part of a pathway of genetic and environmental components for vulnerability to the disease.

  2. Circulating levels of ciliary neurotrophic factor in normal pregnancy and preeclampsia

    Directory of Open Access Journals (Sweden)

    Akahori,Yoichiro

    2010-04-01

    Full Text Available

    Ciliary neurotrophic factor (CNTF has been shown to decrease food intake in mouse models of obesity and to improve insulin sensitivity. It is well known that tight regulation of glucose metabolism is essential for successful gestational outcomes (e.g. fetal growth, and that abnormal insulin resistance is associated with preeclampsia (PE. To investigate the possibility that CNTF might be involved in the regulation of insulin resistance during pregnancy, circulating levels of CNTF were assessed in non-pregnant, normal pregnant, postpartum, and pregnant women with PE. Sera from healthy non-pregnant women (n10, pregnant women (n30:1st trimester;n10, 2nd trimester n10;3rd trimester;n10, postpartum women (n10, and patients with PE (n11 were studied with Western blotting. Circulating CNTF was detected by Western blotting, and the levels of CNTF in pregnant women were decreased as compared with those in non-pregnant women, and tended to decrease as pregnancy progressed. A significant decrease was found in PE as compared with normal pregnancy. Circulating CNTF might be associated with physiological and abnormal insulin resistance during pregnancy.

  3. Circulating Cytokine Levels as Markers of Inflammation in Philadelphia Negative Myeloproliferative Neoplasms: Diagnostic and Prognostic Interest

    Directory of Open Access Journals (Sweden)

    Julie Mondet

    2015-01-01

    Full Text Available Cytokines are well known mediators of numerous physiological and pathological processes. They contribute to the regulation of normal hematopoiesis but increasing data suggest that they also have a clinical impact in some hematopoietic malignancies. In particular, there is evidence that cytokines are implicated in the functional symptoms of Philadelphia negative myeloproliferative neoplasms (Ph− MPNs, suggesting that evaluation of circulating levels of cytokines could be of clinical interest for the characterization of patients at the time of diagnosis and for disease prognosis. In this review, we present the current knowledge on alteration of circulating cytokine profiles in MPNs and their role in myelofibrosis pathogenesis. Phenotypic correlation, prognostic value of cytokines, and impact of JAK inhibitors are also discussed.

  4. Bone turnover and mineral density in adult thalassemic patients: relationships with growth hormone secretory status and circulating somatomedins.

    Science.gov (United States)

    Scacchi, Massimo; Danesi, Leila; Cattaneo, Agnese; Sciortino, Giovanna; Radin, Raffaella; Ambrogio, Alberto Giacinto; Vitale, Giovanni; D'Angelo, Emanuela; Mirra, Nadia; Zanaboni, Laura; Arvigo, Marica; Boschetti, Mara; Ferone, Diego; Marzullo, Paolo; Baldini, Marina; Cassinerio, Elena; Cappellini, Maria Domenica; Persani, Luca; Cavagnini, Francesco

    2016-08-01

    Previous evidence supports a role for growth hormone (GH)-insulin-like growth factor (IGF)-I deficiency in the pathophysiology of osteopenia/osteoporosis in adult thalassemia. Moreover, serum IGF-II has never been studied in this clinical condition. Thus, we elected to study the GH secretory status and the levels of circulating somatomedins, correlating these parameters with bone mineral density (BMD) and biochemical markers of bone turnover. A hundred and thirty-nine normal weight adult thalassemic patients (72 men and 67 women) were studied. Lumbar and femoral neck BMD were measured in 106/139 patients. Sixty-eight patients underwent growth hormone releasing hormone plus arginine testing. Measurement of baseline IGF-I and IGF-II was performed in all patients, while osteocalcin, C-terminal telopeptide of type I collagen (CTx), and urinary cross-linked N-telopeptides of type I collagen (NTx) were assayed in 95 of them. Femoral and lumbar osteoporosis/Z score below the expected range for age were documented in 61.3 and in 56.6 % of patients, respectively. Severe GH deficiency (GHD) was demonstrated in 27.9 % of cases, whereas IGF-I SDS was low in 86.3 %. No thalassemic patients displayed circulating levels of IGF-II below the reference range. GH peaks were positively correlated with femoral, but not lumbar, Z score. No correlations were found between GH peaks and osteocalcin, CTx and NTx. GH peaks were positively correlated with IGF-I values, which in their turn displayed a positive correlation with osteocalcin, CTx, and NTx. No correlations emerged between IGF-I values and either femoral or lumbar Z scores. No correlations were found between IGF-II and any of the following parameters: GH peaks, osteocalcin, CTx, NTx, femoral Z score, and lumbar Z score. Our study, besides providing for the first time evidence of a normal IGF-II production in thalassemia, contributes to a better understanding of the involvement of the somatotropin-somatomedin axis in the

  5. Insulin-like growth factors (IGFs) stimulate the release of alpha 1-antichymotrypsin and soluble IGF-II/mannose 6-phosphate receptor from MCF7 breast cancer cells.

    Science.gov (United States)

    Confort, C; Rochefort, H; Vignon, F

    1995-09-01

    The growth of hormone-responsive MCF7 human breast cancer cells is controlled by steroid hormones and growth factors. By metabolic labeling of cells grown in steroid- and growth factor-stripped serum conditions, we show that insulin-like growth factors (IGF-I and IGF-II) increase by approximately 5-fold the release of several proteins including cathepsin D, alpha 1-antichymotrypsin, and soluble forms of the multifunctional IGF-II/mannose 6-phosphate (M6P) receptor. Two soluble forms of IGF-II/M6P receptors were detected, one major (approximately 260 kilodaltons) and one minor (approximately 85 kilodaltons) that probably represents a proteolytic fragment of the larger soluble molecule. IGFs increased receptor release in a dose-dependent fashion with 50-60% of newly synthesized receptor released at 5-10 nM IGFs. The release of IGF-II/M6P receptors correlated with the levels of secreted cathepsin D in different human breast cancer cells or in rats stable transfectants that are constitutively expressing variable levels of human cathepsin D. IGFs had a stronger effect on IGF-II/M6P receptor release, whereas estradiol treatment preferentially enhanced the release of protease and antiprotease. We thus demonstrate that in human breast cancer cells, IGFs not only act as strong mitogens but also regulate release of alpha 1-antichymotrypsin, IGF-II/M6P-soluble receptor, and cathepsin D; three proteins that potentially regulate cell proliferation and/or invasion.

  6. Effect of the dry matter intake level on the sanguine profile of glucose, insulin, urea, estrogen and progesterone and concentration of IGF-I in the follicular liquid of crossbred heifers

    Directory of Open Access Journals (Sweden)

    Luiz Paulo Rigolon

    2009-02-01

    Full Text Available The aim of this work was to study effect of the dry matter intake level on the concentrations of glucose, insulin, urea, estrogen and progesterone in the blood and the level of IGF-I in the follicular liquid of heifers. Twenty seven crossbred heifers were used, in three treatments: 1.2, 1.6 and 2.6% of the live weight of dry matter intake (DMI daily. The sanguine concentrations of glucose and estrogen were higher in the animals with 1.6% of DMI and the insulin levels were higher in the animals with 2.6% of DMI. There was an increase in the sanguine levels of urea with the increase of the DMI. There was no effect of the DMI on the progesterone levels in the sanguine plasma collected from the jugular. The progesterone levels in caudal vena were higher in the animals with 2.6% of DMI. There was no effect of the DMI on the follicular levels of IGF-I.O objetivo deste trabalho foi estudar o efeito do nível de ingestão de matéria seca (IMS/% do PV sobre as concentrações sanguíneas de glicose, insulina, urea, estrógeno e progesterona e o nível de IGF-I no líquido folicular de novilhas. Vinte e sete novilhas cruzadas foram utilizadas, distribuídas em três tratamentos: 1,2%; 1,6% e 2,6% do peso vivo de ingestão de matéria seca por dia. As concentrações no plasma da veia jugular de glicose e estrógeno foram maiores nos animais com 1,6% de IMS e os níveis de insulina foram maiores nos animais com 2,6% de IMS. Houve um aumento dos níveis plasmáticos de uréia com aumento dos níveis de IMS. Não houve efeito da IMS sobre os níveis de progesterona no plasma sangüíneo coletado da jugular. No plasma sangüíneo coletado da veia cada caudal, os níveis de progesterona foram maiores (P<0,05 nos animais com 2,6% de IMS. Não houve efeito da IMS sobre os níveis foliculares de IGF-I.

  7. IGF-I concentration and changes in critically ill patients

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    Shokoufeh Hajsadeghi

    2011-01-01

    Full Text Available Background: Insulin-like growth factor 1 (IGF-I is an anabolic growth factor that affects nitrogen balance and its changing trend is not clearly understood in critically ill patients. This study was carried out to evaluate the association between serum IGF-I levels and its changing trend in critically ill patients. Methods: In this nested case-control study, all consecutive patients admitted to the medical ICU of Rasoul-e-Akram and Firuzgar hospital (Tehran, Iran from January through October 2008 were included. IGF1 concentration was meas-ured within the first 24h of ICU admission and the fourth, seventh and tenth day since admission. Patients were fol-lowed until discharge from ICU or expiration. Results: The study population consisted of 90 patients (mean age: 58.01 ± 22.56, 31 (34.4% of who died and 59 (65.6% were discharged. On admission, 43 patients (47.7% had low IGF-I levels, whereas 47 (52.3% had normal or high levels. The concentration of IGF-I was not significantly different in every 4 measurements between expired and discharged patients. Significant decrease was seen between first to fourth day IGF-I concentration (p = 0.005. Chang-ing trend was not statistically different in two groups of patients. Conclusions: There was no relation between low IGF-I concentration on admission day and increased adverse out-come, but overall these patients had lower IGF1. No clear association was found between changing trend of IGF1 and mortality. Stress on admission time may cause decreasing pattern of IGF-I in the first 4 days of admission.

  8. Circulating Resistin Levels and Risk of Colorectal Cancer: A Meta-Analysis

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    Gui Yang

    2016-01-01

    Full Text Available Objectives. Published data on resistin levels in patients with colorectal cancer (CRC were conflicting and heterogeneous. We conducted a meta-analysis of observational studies to examine the association of circulating resistin levels with carcinogenesis of the CRC. Methods. Potentially eligible studies published up to November 2015 were searched through MEDLINE, EMBASE, Science Citation Index Expanded database, CNKI, and WanFang database. The pooled weighted mean differences (WMDs with 95% confidence intervals (CIs calculated by fixed- or random-effect model were used to estimate the effects. Results. A total of 11 studies involving 965 patients were admitted in our meta-analysis. The pooled effects indicated that resistin levels were higher in CRC patients compared to healthy controls (WMD: 1.47 ng/mL; 95% CI: 0.78 to 2.16, with significant heterogeneity across the studies (I2=72%, p<0.0001. Subgroup analyses and sensitivity analyses revealed that study quality, design, sample type, and resistin assays may account for this heterogeneity. No publication bias was observed. Conclusions. Our meta-analysis suggests that increased circulating resistin levels are associated with greater risk of colorectal cancer. Given the limited number of available studies and significant heterogeneity, larger well-designed randomized studies are warranted.

  9. Circulating Resistin Levels and Risk of Colorectal Cancer: A Meta-Analysis

    Science.gov (United States)

    Yang, Gui; Fan, Wei; Luo, Baohong; Xu, Zhigao; Wang, Ping; Tang, Shihui; Xu, Peipei

    2016-01-01

    Objectives. Published data on resistin levels in patients with colorectal cancer (CRC) were conflicting and heterogeneous. We conducted a meta-analysis of observational studies to examine the association of circulating resistin levels with carcinogenesis of the CRC. Methods. Potentially eligible studies published up to November 2015 were searched through MEDLINE, EMBASE, Science Citation Index Expanded database, CNKI, and WanFang database. The pooled weighted mean differences (WMDs) with 95% confidence intervals (CIs) calculated by fixed- or random-effect model were used to estimate the effects. Results. A total of 11 studies involving 965 patients were admitted in our meta-analysis. The pooled effects indicated that resistin levels were higher in CRC patients compared to healthy controls (WMD: 1.47 ng/mL; 95% CI: 0.78 to 2.16), with significant heterogeneity across the studies (I2 = 72%, p < 0.0001). Subgroup analyses and sensitivity analyses revealed that study quality, design, sample type, and resistin assays may account for this heterogeneity. No publication bias was observed. Conclusions. Our meta-analysis suggests that increased circulating resistin levels are associated with greater risk of colorectal cancer. Given the limited number of available studies and significant heterogeneity, larger well-designed randomized studies are warranted. PMID:27642602

  10. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Andrew C.; Fasshauer, Martin; Filatova, Nika; Grundell, Linus A.; Zielinski, Elizabeth; Zhou, Jianying; Scherer, Thomas; Lindtner, Claudia; White, Phillip J.; Lapworth, Amanda L.; Llkayeva, Olka; Knippschild, Uwe; Wolf, Anna M.; Scheja, Ludger; Grove, Kevin L.; Smith, Richard D.; Qian, Weijun; Lynch, Christopher J.; Newgard, Christopher B.; Buettner, Christoph

    2014-11-04

    Circulating branched-chain amino acid (BCAA) levels are elevated in obesity and diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of protein expression and activity of branched-chain alpha keto-acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway in the liver. Selective induction of hypothalamic insulin signaling in rats as well as inducible and lifelong genetic modulation of brain insulin receptor expression in mice both demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Further, short-term overfeeding impairs the ability of brain insulin to lower circulating BCAA levels in rats. Chronic high-fat feeding in primates and obesity and/or type 2 diabetes in humans is associated with reduced BCKDH protein expression in liver, further supporting the concept that decreased hepatic BCKDH is a primary cause of increased plasma BCAA levels in insulin-resistant states. These findings demonstrate that neuroendocrine pathways control BCAA homeostasis and that hypothalamic insulin resistance can be a cause of impaired BCAA metabolism in obesity and diabetes.

  11. Chasing a ghost?--Issues with the determination of circulating levels of endotoxin in human blood.

    Science.gov (United States)

    Gnauck, Anne; Lentle, Roger Graham; Kruger, Marlena Cathorina

    2016-01-01

    Reliable quantification of bacterial products such as endotoxin is important for the diagnosis of Gram-negative infection and for the monitoring of its treatment. Further, it is important to identify patients with persistent subclinical level of bacterial products in their systemic circulation as data from animal studies also suggest this may be correlated with the onset of metabolic syndrome. In this review, we first aim to describe the principles of the Limulus amoebocyte lysate (LAL) test, an assay that is used to quantify endotoxin, and the various shortcomings that must be addressed before it can become a reliable means of quantifying endotoxin in samples derived from blood. We then review published data regarding endotoxin levels in healthy subjects and those with sepsis, inflammatory bowel disease, liver disorders and metabolic disorders such as obesity and diabetes. We also review the evidence regarding influence of macronutrients in augmenting the levels of systemic endotoxin. The results of this review show that reported mean levels of endotoxin in the systemic circulation of healthy humans and of those with various clinical disorders vary over a wide range. Further, this review shows that a significant proportion of this variation can be related to the method that was used to prepare plasma and serum samples prior to assay and its ability to reduce the effect of various blood borne factors that interfere with the LAL assay. PMID:26732012

  12. Increased Circulating Levels of Vitamin D Binding Protein in MS Patients

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    Arturo Ottavio Rinaldi

    2015-01-01

    Full Text Available Vitamin D (vitD low status is currently considered a main environmental factor in multiple sclerosis (MS etiology and pathogenesis. VitD and its metabolites are highly hydrophobic and circulate mostly bound to the vitamin D binding protein (DBP and with lower affinity to albumin, while less than 1% are in a free form. The aim of this study was to investigate whether the circulating levels of either of the two vitD plasma carriers and/or their relationship are altered in MS. We measured DBP and albumin plasma levels in 28 MS patients and 24 healthy controls. MS patients were found to have higher DBP levels than healthy subjects. Concomitant interferon beta therapy did not influence DBP concentration, and the difference with the control group was significant in both females and males. No significant correlation between DBP and albumin levels was observed either in healthy controls or in patients. These observations suggest the involvement of DBP in the patho-physiology of MS.

  13. Free insulin-like growth factor I serum levels in 1430 healthy children and adults, and its diagnostic value in patients suspected of growth hormone deficiency

    DEFF Research Database (Denmark)

    Juul, A; Holm, K; Kastrup, K W;

    1997-01-01

    fraction of the total IGF-I circulates in its free form, which is believed to be the biologically active form. However, our knowledge of the clinical or physiological value of determination of free IGF-I in serum is limited at present. In adults, the diagnostic value of total IGF-I and IGFBP-3......, unmeasurable free IGF-I values in 34 of the prepubertal children (3.3%). All individuals over 8 yr of age had measurable free IGF-I levels that amounted to approximately 1% of the total IGF-I concentrations. Free IGF-I levels were below--2 SD in 56 of 79 GHD patients (sensitivity, 71%) and above--2 SD in 24...... determinations in patients suspected of GHD has only been reported in a few studies, whereas no previous reports on the diagnostic value of free IGF-I levels in adults suspected of GHD exist. Serum levels of free IGF-I were determined in 1430 healthy children, adolescents, and adults by a newly developed...

  14. Genetic Variation in the Natriuretic Peptide System, Circulating Natriuretic Peptide Levels, and Blood Pressure

    DEFF Research Database (Denmark)

    Jeppesen, Jørgen L; Nielsen, Søren J; Torp-Pedersen, Christian;

    2012-01-01

    BackgroundIn a large collaborative study (n > 50,000), common variants in the natriuretic peptide (NP) genes were found to be associated with circulating NP levels and also with blood pressure (BP) levels based on office BP measurements (OBPMs). It is unknown if determining an individual's BP by 24...... determined by both 24-h ABPMs and OBPMs in a population consisting of 1,397 generally healthy individuals taking no BP-lowering drugs.Resultsrs632793 was significantly correlated with serum Nt-proBNP levels (r = 0.10, P = 0.0003), and participants with the A:A genotype had lower serum Nt-proBNP levels than...

  15. Circulating levels of neuropeptides (CGRP, VIP, NPY) in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Strauss, Gitte Irene; Edvinsson, L; Larsen, F S;

    2001-01-01

    The present study investigated the circulating levels and cerebral fluxes of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) and their relation to cerebral blood flow (CBF) during normoventilation and hyperventilation in patients with fulminant...... in FHF than in cirrhosis, 87 (55-218) vs. 29 (21-42) pmol/L, and 11 (6-29) vs. 5 (3-9)pmol/L, respectively. NPY was normal, none of the measures were related to CBF, and there was no detectable net brain fluxes. Hyperventilation did not alter any of the measures. CGRP and VIP in FHF seem to reflect...

  16. Research on the relationship between traditional Chinese medicine's syndrome and serum level of IGF-1 and IGFBP-3 in patients with acute cerebral infarction%急性脑梗死中风证型与血清胰岛素样生长因子-1和其结合蛋白-3水平的关系

    Institute of Scientific and Technical Information of China (English)

    俞征宙; 刘楠; 陈玉玲; 林信富

    2002-01-01

    Objective To study the relationship between traditional Chinese medicine (TCM) syndrome and serum level of IGF-1 and IGFBP-3 in patients with acute cerebral infarction (ACI).Methods 75 patients of ACI were divided into two groups by TCM` s syndrome differentiation: apolexy involving the channels (AIC) and apolexy involving the viscera (AIV).Serum level of IGF-1 and IGFBP-3 was detected by ELISA di-antibody clipping technique (DACT) and was compared with that of 30 normal controls.Results Serum level of IGF-1 and IGFBP-3 in AIC group and AIV group were significantly different from control groups;and differences between AIC group and AIV group were statistically significant.Serum level of IGF-1 and IGFBP-3 in all syndromes of AIC group and AIV group were remarkably lower than control group.Among them,syndrome of Yin-deficiency of liver and kidney and sthenia liver-yang and syndrome of blood stasis due to Qi deficiency had lower serum level of IGF-1 and IGFBP-3 than syndrome of empty and obstruction of channel.So did collapse syndrome and syndrome of mental disorder due to phlegm-fire to syndrome of wind-fire evil lucid orifices and block Yin syndrome.Conclusion There are to some extent correlation with TCM's Syndrome and serum level of IGF-1 and IGFBP-3 in patients with ACI. Serum level of IGF-1 and IGFBP-3 might be microcosmic referent markers of the damage of Qi and Yin by TCM` s syndrome differentiation.

  17. Effects of an endurance cycling competition on resting serum insulin-like growth factor I (IGF-I) and its binding proteins IGFBP-1 and IGFBP-3

    Science.gov (United States)

    Chicharro, J; Lopez-Calderon, A; Hoyos, J; Martin-Velasco, A; Villa, G; Villanua, M; Lucia, A

    2001-01-01

    Objectives—To determine whether consecutive bouts of intense endurance exercise over a three week period alters serum concentrations of insulin-like growth factor I (IGF-I) and/or its binding proteins. Methods—Seventeen professional cyclists (mean (SEM) VO2MAX, 74.7 (2.1) ml/kg/min; age, 27 (1) years) competing in a three week tour race were selected as subjects. Blood samples were collected at each of the following time points: t0 (control, before the start of competition), t1 (end of first week), and t3 (end of third week). Serum levels of both total and free IGF-I and IGF binding proteins 1 and 3 (IGFBP-1 and IGFBP-3) were measured in each of the samples. Cortisol levels were measured in nine subjects. Results—A significant (p<0.01) increase was found in total IGF-I and IGFBP-1 at both t1 and t3 compared with to (IGF-I: 110.9 (17.7), 186.8 (12.0), 196.9 (14.7) ng/ml at t0, t1, and t3 respectively; IGFBP-1: 54.6 (6.6), 80.6 (8.0), and 89.2 (7.9) ng/ml at t0, t1, and t3 respectively). A significant (p<0.01) decrease was noted in free IGF-I at t3 compared with both to and t1 (t0: 0.9 (0.1) ng/ml; t1: 0.9 (0.1) ng/ml; t3: 0.7 (0.1) ng/ml); in contrast, IGFBP-3 levels remained stable throughout the race. Conclusions—It would appear that the increase in circulating levels of both IGF-I and its binding protein IGFBP-1 is a short term (one week) endocrine adaptation to endurance exercise. After three weeks of training, total IGF-I and IGFBP-1 remained stable, whereas free IGF-I fell below starting levels. Key Words: cycling; insulin-like growth factor; exercise; endurance; binding proteins PMID:11579061

  18. Autophagy resolves early retinal inflammation in Igf1-deficient mice

    Science.gov (United States)

    Rodríguez-de la Rosa, Lourdes; Murillo-Cuesta, Silvia; Vaquero-Villanueva, Laura; Hurlé, Juan M.; Varela-Nieto, Isabel; Valverde, Ángela M.

    2016-01-01

    ABSTRACT 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

  19. Associations of Circulating Gut Hormone and Adipocytokine Levels with the Spectrum of Gastroesophageal Reflux Disease.

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    Ping-Huei Tseng

    Full Text Available The pathogenesis of gastroesophageal reflux disease (GERD is complex and poorly understood. We aim to investigate the association of various circulating peptide hormones with heterogenous manifestations of GERD.One hundred and four patients that had experienced typical GERD symptoms (heartburn and/or acid regurgitation for at least 3 episodes per week in the past 3 months were enrolled. All patients received a baseline assessment of symptom severity and frequency with the Reflux Disease Questionnaire and an upper endoscopy to classify GERD into erosive esophagitis (EE, n = 67, non-erosive esophagitis (NE, n = 37, and Barrett's esophagus (BE, n = 8. Fifty asymptomatic subjects with an endoscopically normal esophagus were recruited as the control group. Complete anthropometric measures and blood biochemistry were obtained and fasting serum levels of adipocytokines (adiponectin and leptin and gut hormones (ghrelin and peptide YY (PYY were determined by enzyme-linked immunosorbent assay in all subjects.All circulating peptide hormone levels were not statistically different between the GERD and control groups. However, GERD patients appeared to have lower PYY levels [median (25th-75th percentile, 80.1 (49.8-108.3 vs. 99.4 (65.8-131.9 pg/ml, p = 0.057] compared with control subjects. Among the GERD patients, ghrelin levels were inversely associated with the frequency and severity of acid regurgitation. In male GERD patients, EE was associated with significantly higher PYY levels [107.0 (55.0-120.8 vs. 32.8 (28.7-84.5 pg/ml, p = 0.026] but lower adiponectin levels [6.7 (5.6-9.3 vs. 9.9 (9.6-10.6 μg/ml, p = 0.034] than NE. Patients with BE had significantly lower adiponectin levels [6.0 (5.1-9.2 vs. 9.2 (7.1-11.2 μg/ml, p = 0.026] than those without BE.Humoral derangement of circulating peptide hormones might participate in inflammation and symptom perception in patients suffering from GERD. Further studies to clarify the exact role of these hormones

  20. Prognostic value of circulating catestatin levels for in-hospital heart failure in patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    冀磊

    2013-01-01

    Objective To determine whether circulating level of catestatin(CST) could provide prognostic information independently of conventional risk markers for the development of in-hospital heart failure in patients with ST-segment elevation myocardial infarction(STEMI).

  1. Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome.

    Science.gov (United States)

    Calan, Mehmet; Yilmaz, Ozgur; Kume, Tuncay; Unal Kocabas, Gokcen; Yesil Senses, Pinar; Senses, Yasar Mehmet; Temur, Muzaffer; Gursoy Calan, Ozlem

    2016-07-01

    Betatrophin is a newly identified hormone determined to be a potent inducer of pancreatic beta cell proliferation in response to insulin resistance in mice. Polycystic ovary syndrome (PCOS) is an inflammatory-based metabolic disease associated with insulin resistance. However, no evidence is available indicating whether betatrophin is involved in women with PCOS. The objective of this study was to ascertain whether betatrophin levels are altered in women with PCOS. This study was conducted in secondary referral center. This cross-sectional study included 164 women with PCOS and 164 age- and BMI-matched female controls. Circulating betatrophin levels were measured using ELISA. Metabolic and hormonal parameters were also determined. Circulating betatrophin levels were significantly elevated in women with PCOS compared with controls (367.09 ± 55.78 vs. 295.65 ± 48.97 pg/ml, P PCOS. Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 2.51 for patients in the highest quartile of betatrophin compared with those in the lowest quartile (95 % CI 1.31-4.81, P = 0.006). Multivariate regression analyses showed that HOMA-IR, hs-CRP, and free-testosterone were independent factors influencing serum betatrophin levels. Betatrophin levels were increased in women with PCOS and were associated with insulin resistance, hs-CRP, and free-testosterone in these patients. Elevated betatrophin levels were found to increase the odds of having PCOS. Further research is needed to elucidate the physiologic and pathologic significance of our findings. PMID:26832343

  2. Circulating levels of p,p'-DDE are related to prevalent hypertension in the elderly

    Energy Technology Data Exchange (ETDEWEB)

    Lind, P. Monica, E-mail: monica.lind@medsci.uu.se [Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Ulleråkersvägen 40, 751 85 Uppsala (Sweden); Penell, Johanna [Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Ulleråkersvägen 40, 751 85 Uppsala (Sweden); Salihovic, Samira; Bavel, Bert van [MTM Research Center, School of Science and Technology, Örebro University, Örebro (Sweden); Lind, Lars [Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala (Sweden)

    2014-02-01

    Background: Polychlorinated biphenyls (PCBs) and dioxin given to experimental animals increase the blood pressure. We therefore investigated if circulating levels of persistent organic pollutants (POPs) were related to hypertension in a population-based sample of men and women. Methods: One thousand and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Twenty-three POPs were analyzed using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). Hypertension was defined as a systolic blood pressure ≥140 mmHg or a diastolic blood pressure ≥90 mmHg, and/or use of antihypertensive medication. Results: Seven hundred and thirty-two subjects (72%) showed hypertension. When the POPs were treated as continuous variables and adjusted for gender only, two PCBs with a low number of chlorine atoms (PCB 105 and 118) were related to prevalent hypertension. Also the OC pesticide p,p'-DDE was related to hypertension. The strongest of these associations was seen for p,p'-DDE (OR 1.35 for a 1 SD change, 95% CI 1.17–1.56, p<0.0001). Following further adjustment also for BMI, smoking status, education level and exercise habits, only p,p'-DDE was still significantly related to hypertension (OR 1.23 for a 1 SD change, 95% CI 1.06–1.43, p=0.006). Conclusion: In this cross-sectional analysis of an elderly population, high levels of circulating levels of p,p'-DDE were associated with prevalent hypertension, further strengthening the experimental findings that POPs might influence blood pressure. - Highlights: • We evaluated the relation between POPs and hypertension. • Cross sectional data from a cohort of elderly men and women were analyzed. • The main exposure was circulating levels of 23 different POPs. • Hypertension was defined as ≥140/90 mmHg and/or antihypertensive treatment. • High levels of p,p'-DDE were associated with

  3. Circulating levels of p,p'-DDE are related to prevalent hypertension in the elderly

    International Nuclear Information System (INIS)

    Background: Polychlorinated biphenyls (PCBs) and dioxin given to experimental animals increase the blood pressure. We therefore investigated if circulating levels of persistent organic pollutants (POPs) were related to hypertension in a population-based sample of men and women. Methods: One thousand and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Twenty-three POPs were analyzed using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). Hypertension was defined as a systolic blood pressure ≥140 mmHg or a diastolic blood pressure ≥90 mmHg, and/or use of antihypertensive medication. Results: Seven hundred and thirty-two subjects (72%) showed hypertension. When the POPs were treated as continuous variables and adjusted for gender only, two PCBs with a low number of chlorine atoms (PCB 105 and 118) were related to prevalent hypertension. Also the OC pesticide p,p'-DDE was related to hypertension. The strongest of these associations was seen for p,p'-DDE (OR 1.35 for a 1 SD change, 95% CI 1.17–1.56, p<0.0001). Following further adjustment also for BMI, smoking status, education level and exercise habits, only p,p'-DDE was still significantly related to hypertension (OR 1.23 for a 1 SD change, 95% CI 1.06–1.43, p=0.006). Conclusion: In this cross-sectional analysis of an elderly population, high levels of circulating levels of p,p'-DDE were associated with prevalent hypertension, further strengthening the experimental findings that POPs might influence blood pressure. - Highlights: • We evaluated the relation between POPs and hypertension. • Cross sectional data from a cohort of elderly men and women were analyzed. • The main exposure was circulating levels of 23 different POPs. • Hypertension was defined as ≥140/90 mmHg and/or antihypertensive treatment. • High levels of p,p'-DDE were associated with prevalent hypertension

  4. Obesity suppresses circulating level and function of endothelial progenitor cells and heart function

    Directory of Open Access Journals (Sweden)

    Tsai Tzu-Hsien

    2012-07-01

    Full Text Available Abstract Background and aim This study tested the hypothesis that obesity suppresses circulating number as well as the function of endothelial progenitor cells (EPCs and left ventricular ejection fraction (LVEF. Methods High fat diet (45 Kcal% fat was given to 8-week-old C57BL/6 J mice (n = 8 for 20 weeks to induce obesity (group 1. Another age-matched group (n = 8 were fed with control diet for 20 weeks as controls (group 2. The animals were sacrificed at the end of 20 weeks after obesity induction. Results By the end of study period, the heart weight, body weight, abdominal fat weight, serum levels of total cholesterol and fasting blood sugar were remarkably higher in group 1 than in group 2 (all p Conclusions Obesity diminished circulating EPC level, impaired the recovery of damaged endothelium, suppressed EPC angiogenesis ability and LVEF, and increased LV remodeling.

  5. The local expression and abundance of insulin-like growth factor (IGF) binding proteins in skeletal muscle are regulated by age and gender but not local IGF-I in vivo.

    Science.gov (United States)

    Oliver, William T; Rosenberger, Judy; Lopez, Rusmely; Gomez, Adam; Cummings, Kathleen K; Fiorotto, Marta L

    2005-12-01

    We wished to determine whether sustained IGF-I production in skeletal muscle increases local IGF binding protein (IGFBP) abundance, thereby mitigating the long-term stimulation of muscle growth by IGF-I. Muscle growth of transgenic mice that overexpress IGF-I in muscle (SIS2) and of wild-type (Wt) mice was compared. At 3, 5, 10, and 20 wk of age, hind-limb muscle weights and IGFBP-3, -4, -5, and -6 mRNA and protein abundances were quantified. Additional mice were injected with IGF-I or LR3-IGF-I, and phosphorylation of the type 1 IGF receptor (IGF-1R) was compared. Muscle mass was 20% greater in SIS2 compared with Wt mice by 10 wk of age (P LR3-IGF-I stimulated IGF-1R phosphorylation to a greater extent than IGF-I at both 5 and 10 wk of age (P 0.21). Thus, variations in local IGF-I levels do not appear to regulate muscle IGFBP expression. The age- and gender-specific differences in muscle IGFBP expression are not sufficient to alter the response of the muscle to the IGFs but may impact the IGF-independent effects of these IGFBPs. PMID:16166219

  6. Association of circulating omentin-1 level with arterial stiffness and carotid plaque in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Yoo Hye

    2011-11-01

    Full Text Available Abstract Background Adipokines contribute directly to the atherosclerotic process, connecting metabolic disorders such as obesity and diabetes to cardiovascular disease. Omentin-1 is a recently discovered novel adipokine, so data about the relationship of this adipokine to vascular health in type 2 diabetes is limited. Methods We enrolled 60 people with type 2 diabetes, with or without carotid plaque, and 30 participants with normal glucose tolerance. We measured serum omentin-1, high-sensitivity C-reactive protein (hsCRP levels, and the homeostasis model assessment of insulin resistance (HOMA-IR, as well as other cardiovascular risk factors. Vascular health was assessed by brachial ankle pulse wave velocity (baPWV and carotid intima-media thickness (IMT. Results Serum omentin-1 levels were significantly decreased in type 2 diabetes patients compared to normal glucose controls and was further reduced in type 2 diabetes patients with carotid plaque compared to those without carotid plaque. Multiple stepwise regression analysis showed that age, systolic blood pressure, history of use of statins, angiotensin receptor blockers or angiotensin-converting enzyme inhibitors, and serum omentin-1 level were independent factors determining baPWV in people with type 2 diabetes (r2 = 0.637. Furthermore, in multivariate logistic regression analysis, circulating omentin-1 level was an independent decisive factor for the presence of carotid plaque in type 2 diabetes patients, even after adjusting for age, gender, body mass index, systolic blood pressure, fasting blood glucose, low density lipoprotein cholesterol, and history of smoking and medication (odds ratio, 0.621; 95% confidence interval, 0.420-0.919; P = 0.017. Conclusions Circulating omentin-1 level was independently correlated with arterial stiffness and carotid plaque in type 2 diabetes, even after adjusting for other cardiovascular risk factors and detailed medication history.

  7. The Association Between IGF-I and Insulin Resistance

    DEFF Research Database (Denmark)

    Friedrich, Nele; Thuesen, Betina; Jørgensen, Torben;

    2012-01-01

    the association between IGF-I level and insulin resistance in a Danish general population.RESEARCH DESIGN AND METHODSIncluded were 3,354 adults, aged 19-72 years, from the cross-sectional Health2006 study. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index to estimate insulin...... with intermediate (Q3) IGF-I levels. These associations remained statistically significant after the exclusion of subjects with type 2 diabetes and by using the updated computer HOMA2-IR model.CONCLUSIONSLow- and high-normal IGF-I levels are both related to insulin resistance. The biological mechanism......OBJECTIVEIGF-I has an almost 50% amino acid sequence homology with insulin and elicits nearly the same hypoglycemic response. Studies showed that low and high IGF-I levels are related to impaired glucose tolerance and to a higher risk of type 2 diabetes. The aim of the current study was to evaluate...

  8. The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone

    DEFF Research Database (Denmark)

    Rasmussen, M H; Frystyk, Jan; Andersen, T;

    1994-01-01

    The aim of this study was to characterize the association between serum insulin-like growth factor-1 (IGF-1) and obesity, as well as fat distribution, before and during moderate energy restriction (1,200 kcal/d). In 51 females and nine males having a body mass index (BMI) between 27 and 39 kg/m2......, relationships between serum IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, growth hormone (GH), blood glucose, and anthropometric measurements of body fat were examined. The patients were studied before treatment and again after 8 and 16 weeks of dieting. Visceral adipose tissue (AT) was estimated...... = .02) weeks of dietary treatment. Both serum IGF-1 and insulin levels were positively correlated with serum IGFBP-3 levels (r = .34, P = .009 and r = .34, P = .008, respectively). We conclude that IGF-1 levels in obese females reflect the intraabdominal fat mass rather than obesity per se. IGF-1...

  9. 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.

  10. Longitudinal assessment of circulating insulin-like peptide 3 levels in healthy peripubertal girls

    DEFF Research Database (Denmark)

    Hagen, Casper P; Mieritz, Mikkel G; Nielsen, John E;

    2015-01-01

    OBJECTIVE: To elucidate the natural course of circulating insulin-like peptide 3 (INSL3) levels according to puberty as well as its relation to other reproductive hormones. DESIGN: Population-based cohort study. SETTING: Not applicable. PATIENT(S): Healthy peripubertal girls (n = 10) examined every......), and T and androstenedione (liquid chromatography-tandem mass spectrometry). RESULT(S): Serum levels of INSL3 varied considerably between girls (range, 0.01-0.27 ng/mL) and within each girl as puberty progressed; intraindividual variation, median (range) 102% (65%-143%). Insulin-like peptide 3 increased...... of antral follicles. CONCLUSION(S): Insulin-like peptide 3 increased in late puberty, albeit inter- and intraindividual variations were substantial. Immunohistochemistry and intraindividual variation, as well as relations to other ovarian hormones, reveal that INSL3 in girls is a unique and specific marker...

  11. Long-term stability and circadian variation in circulating levels of surfactant protein D

    DEFF Research Database (Denmark)

    Hoegh, Silje Vermedal; Sorensen, Grith Lykke; Tornoe, Ida;

    2010-01-01

    to be used as a biomarker for disease e.g. in COPD. We aimed to investigate the variation of circulating SP-D in healthy individuals in and between days for 6 months. In addition, we studied the SP-D response to a standardized physical exercise programme. SP-D was measured in serum using a 5-layered ELISA...... pre-exercise level of SP-D was 746 ng/ml (95% CI: 384-2035), and immediately after cessation of physical activity the median SP-D level was 767 ng/ml (95% CI: 367-1885) (P=0.248). Our findings underscore the importance of standardized blood sampling conditions in future studies on the potential role...... of SP-D as a biomarker. Importantly, stable measures of systemic SP-D over a prolonged period support that SP-D is suitable for biomarker studies....

  12. High Circulating Adrenaline Levels at Admission Predict Increased Mortality After Trauma

    DEFF Research Database (Denmark)

    Johansson, Pär Ingemar; Stensballe, Jakob; Rasmussen, Lars Simon;

    2012-01-01

    partial thromboplastin time, international normalized ratio, hematology, biochemistry, circulating adrenaline and noradrenaline, 11 biomarkers of tissue and endothelial damage, glycocalyx degradation, natural anticoagulation and fibrinolysis (histone-complexed DNA fragments, high-mobility group box 1......:: The adrenaline level was increased in nonsurvivors (p = 0.026), it was independently associated with increased activated partial thromboplastin time (p = 0.034) and syndecan-1 (p = 0.007), a marker of glycocalyx degradation, and it correlated with biomarkers of tissue and endothelial damage (histone......-complexed DNA, high-mobility group box 1, soluble thrombomodulin) and hyperfibrinolysis (tissue-type plasminogen activator, d-dimer). Furthermore, nonsurvivors had higher syndecan-1, tissue factor pathway inhibitor, and d-dimer levels (all p adrenaline was independently associated with 30...

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Impact of remote oceanic forcing on Gulf of Alaska sea levels and mesoscale circulation

    Science.gov (United States)

    Melsom, Arne; Metzger, E. Joseph; Hurlburt, Harley E.

    2003-11-01

    We examine the relative importance of regional wind forcing and teleconnections by an oceanic pathway for impact on interannual ocean circulation variability in the Gulf of Alaska. Any additional factors that contribute to this variability, such as freshwater forcing from river runoff, are disregarded. The study is based on results from numerical simulations, sea level data from tide gauge stations, and sea surface height anomalies from satellite altimeter data. At the heart of this investigation is a comparison of ocean simulations that include and exclude interannual oceanic teleconnections of an equatorial origin. Using lagged correlations, the model results imply that 70-90% of the interannual coastal sea level variance in the Gulf of Alaska can be related to interannual sea levels at La Libertad, Equador. These values are higher than the corresponding range from sea level data, which is 25-55%. When oceanic teleconnections from the equatorial Pacific are excluded in the model, the explained variance becomes about 20% or less. During poleward propagation the coastally trapped sea level signal in the model is less attenuated than the observed signal. In the Gulf of Alaska we find well-defined sea level peaks in the aftermath of El Niño events. The interannual intensity of eddies in the Gulf of Alaska also peaks after El Niño events; however, these maxima are less clear after weak and moderate El Niño events. The interannual variations in eddy activity intensity are predominantly governed by the regional atmospheric forcing.

  15. Plasma macrophage colony-stimulating factor levels during cardiopulmonary bypass with extracorporeal circulation

    Directory of Open Access Journals (Sweden)

    Y. Denizot

    1996-01-01

    Full Text Available Leukocytosis and thrombocytopenia occur during cardiopulmonary bypass (CPB with extracorporeal circulation (ECC. Elevated circulating concentrations of macrophage colony-stimulating factor (M-CSF are reported during thrombocytopenia and leukopenia of different origins. We have assessed M-CSF concentrations in 40 patients undergoing CPB with ECC. Plasma M-CSF concentrations were stable during ECC and increased at the 6th (7.3 ± 0.7 IU/μg protein and 24th (8.6 ± 0.8 IU/μg protein postoperative hour compared with pre-ECC values (4.9 ± 0.5 IU/μg protein. A deep thrombocytopenia was found during ECC and until the 24th postoperative hour. A drop of leukocyte counts was found during ECC followed by an increase after ECC weaning. While no correlation was found between M-CSF concentrations and the leukocyte counts, M-CSF values were positively correlated with platelet counts only before and during ECC. Thus, M-CSF is not implicated in the thrombocytopenia and the leukopenia generated during CPB with ECC. However the elevated levels of M-CSFa few hours after the end of ECC might play a role in the inflammatory process often observed after CPB.

  16. A two-time-level split-explicit ocean circulation model (MASNUM) and its validation

    Institute of Scientific and Technical Information of China (English)

    HAN Lei

    2014-01-01

    A two-time-level, three-dimensional numerical ocean circulation model (named MASNUM) was estab-lished with a two-level, single-step Eulerian forward-backward time-differencing scheme. A mathematical model of large-scale oceanic motions was based on the terrain-following coordinated, Boussinesq, Reyn-olds-averaged primitive equations of ocean dynamics. A simple but very practical Eulerian forward-back-ward method was adopted to replace the most preferred leapfrog scheme as the time-differencing method for both barotropic and baroclinic modes. The forward-backward method is of second-order of accuracy, computationally efficient by requiring only one function evaluation per time step, and free of the compu-tational mode inherent in the three-level schemes. This method is superior to the leapfrog scheme in that the maximum time step of stability is twice as large as that of the leapfrog scheme in staggered meshes thus the computational efficiency could be doubled. A spatial smoothing method was introduced to control the nonlinear instability in the numerical integration. An ideal numerical experiment simulating the propa-gation of the equatorial Rossby soliton was performed to test the amplitude and phase error of this new model. The performance of this circulation model was further verified with a regional (northwest Pacific) and a quasi-global (global ocean simulation with the Arctic Ocean excluded) simulation experiments. These two numerical experiments show fairly good agreement with the observations. The maximum time step of stability in these two experiments were also investigated and compared between this model and that model which adopts the leapfrog scheme.

  17. Low Circulating Protein C Levels Are Associated with Lower Leg Ulcers in Patients with Diabetes

    Directory of Open Access Journals (Sweden)

    K. Whitmont

    2013-01-01

    Full Text Available Activated protein C (APC promotes angiogenesis and reepithelialisation and accelerates healing of diabetic ulcers. The aim of this study was to determine the relationship between the incidence of lower leg ulcers and plasma levels of APC's precursor, protein C (PC, in diabetic patients. Patients with diabetes who had a lower leg ulcer(s for >6 months (n=36 were compared with age-, type of diabetes-, and sex-matched subjects with diabetes but without an ulcer (n=36, controls. Total PC was assessed using a routine PC colorimetric assay. There was a significantly (P<0.001 lower level of plasma PC in patients with ulcers (103.3 ± 22.7, mean ± SD compared with control (127.1±34.0 subjects, when corrected for age and matched for gender and type of diabetes. Ulcer type (neuropathic, ischaemic, or mixed was not a significant covariate for plasma PC levels (P=0.35. There was no correlation between PC levels and gender, type of diabetes, HbA1c, or C-reactive protein in either group. In summary, decreased circulating PC levels are associated with, and may predispose to, lower leg ulceration in patients with diabetes.

  18. The gyre-scale circulation of the North Atlantic and sea level at Brest

    Directory of Open Access Journals (Sweden)

    P. L. Woodworth

    2010-02-01

    Full Text Available The relationship between the gyre-scale circulation of the North Atlantic, represented by air pressure near to the centre of the sub-tropical gyre, and sea level measured at the eastern boundary of the ocean has been investigated using records commencing in the middle of the 18th century. These time series are twice as long as those employed in an earlier study of this relationship. Near-continuous values of annual mean sea level and mean high water from Brest, and air pressure fields for the eastern North Atlantic derived from terrestrial instrumental pressure records and ship logbook information, have been used to demonstrate that sea level on the eastern boundary does indeed appear to be related to air pressure at the centre of the gyre (subject to reservations concerning short sub-sections of data near to the ends of the records. These findings confirm the earlier conclusions but over much longer timescales. This relationship can explain at least part of the century timescale accelerations in European sea level records obtained from tide gauge and saltmarsh data. This finding has important implications for interpretation of the observed sea level rise and acceleration on the European Atlantic coast, suggesting that redistribution of water could play an important role instead of (or as well as change in ocean volume.

  19. Production of immunoreactive insulin-like growth factor-I (IGF-I) and IGF-I binding proteins by human lung tumours.

    OpenAIRE

    Reeve, J. G.; Payne, J. A.; Bleehen, N. M.

    1990-01-01

    The production of insulin-like growth factor I (IGF-I) and IGF-I binding proteins (BPs) by human lung tumour cell lines in vitro has been examined and the levels of these substances in the serum of lung cancer patients investigated. While small cell lung cancer (SCLC) cell lines secreted both IGF-I and BPs, non-small cell lung cancer (NSCLC) cell lines secreted BPs only. No evidence of increased serum IGF-I levels was obtained in a cohort of 52 lung cancer patients having SCLC and NSCLC histo...

  20. Liver-derived IGF-I regulates cortical bone mass but is dispensable for the osteogenic response to mechanical loading in female mice.

    Science.gov (United States)

    Svensson, Johan; Windahl, Sara H; Saxon, Leanne; Sjögren, Klara; Koskela, Antti; Tuukkanen, Juha; Ohlsson, Claes

    2016-07-01

    Low circulating IGF-I is associated with increased fracture risk. Conditional depletion of IGF-I produced in osteoblasts or osteocytes inhibits the bone anabolic effect of mechanical loading. Here, we determined the role of endocrine IGF-I for the osteogenic response to mechanical loading in young adult and old female mice with adult, liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice, serum IGF-I reduced by ≈70%) and control mice. The right tibia was subjected to short periods of axial cyclic compressive loading three times/wk for 2 wk, and measurements were performed using microcomputed tomography and mechanical testing by three-point bending. In the nonloaded left tibia, the LI-IGF-I(-/-) mice had lower cortical bone area and increased cortical porosity, resulting in reduced bone mechanical strength compared with the controls. Mechanical loading induced a similar response in LI-IGF-I(-/-) and control mice in terms of cortical bone area and trabecular bone volume fraction. In fact, mechanical loading produced a more marked increase in cortical bone mechanical strength, which was associated with a less marked increase in cortical porosity, in the LI-IGF-I(-/-) mice compared with the control mice. In conclusion, liver-derived IGF-I regulates cortical bone mass, cortical porosity, and mechanical strength under normal (nonloaded) conditions. However, despite an ∼70% reduction in circulating IGF-I, the osteogenic response to mechanical loading was not attenuated in the LI-IGF-I(-/-) mice.

  1. Associations of serum insulin-like growth factor-I and insulin-like growth factor-binding protein 3 levels with biomarker-calibrated protein, dairy product and milk intake in the Women's Health Initiative.

    Science.gov (United States)

    Beasley, Jeannette M; Gunter, Marc J; LaCroix, Andrea Z; Prentice, Ross L; Neuhouser, Marian L; Tinker, Lesley F; Vitolins, Mara Z; Strickler, Howard D

    2014-03-14

    It is well established that protein-energy malnutrition decreases serum insulin-like growth factor (IGF)-I levels, and supplementation of 30 g of whey protein daily has been shown to increase serum IGF-I levels by 8 % after 2 years in a clinical trial. Cohort studies provide the opportunity to assess associations between dietary protein intake and IGF axis protein levels under more typical eating conditions. In the present study, we assessed the associations of circulating IGF axis protein levels (ELISA, Diagnostic Systems Laboratories) with total biomarker-calibrated protein intake, as well as with dairy product and milk intake, among postmenopausal women enrolled in the Women's Health Initiative (n 747). Analyses were carried out using multivariate linear regression models that adjusted for age, BMI, race/ethnicity, education, biomarker-calibrated energy intake, alcohol intake, smoking, physical activity and hormone therapy use. There was a positive association between milk intake and free IGF-I levels. A three-serving increase in milk intake per d (approximately 30 g of protein) was associated with an estimated average 18·6 % higher increase in free IGF-I levels (95 % CI 0·9, 39·3 %). However, total IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were not associated with milk consumption and nor were there associations between biomarker-calibrated protein intake, biomarker-calibrated energy intake, and free IGF-I, total IGF-I or IGFBP-3 levels. The findings of the present study carried out in postmenopausal women are consistent with clinical trial data suggesting a specific relationship between milk consumption and serum IGF-I levels, although in the present study this association was only statistically significant for free, but not total, IGF-I or IGFBP-3 levels.

  2. Identifying growth hormone-regulated enhancers in the Igf1 locus.

    Science.gov (United States)

    Alzhanov, Damir; Mukherjee, Aditi; Rotwein, Peter

    2015-11-01

    Growth hormone (GH) plays a central role in regulating somatic growth and in controlling multiple physiological processes in humans and other vertebrates. A key agent in many GH actions is the secreted peptide, IGF-I. As established previously, GH stimulates IGF-I gene expression via the Stat5b transcription factor, leading to production of IGF-I mRNAs and proteins. However, the precise mechanisms by which GH-activated Stat5b promotes IGF-I gene transcription have not been defined. Unlike other GH-regulated genes, there are no Stat5b sites near either of the two IGF-I gene promoters. Although dispersed GH-activated Stat5b binding elements have been mapped in rodent Igf1 gene chromatin, it is unknown how these distal sites might function as potential transcriptional enhancers. Here we have addressed mechanisms of regulation of IGF-I gene transcription by GH by generating cell lines in which the rat Igf1 chromosomal locus has been incorporated into the mouse genome. Using these cells we find that physiological levels of GH rapidly and potently activate Igf1 gene transcription while stimulating physical interactions in chromatin between inducible Stat5b-binding elements and the Igf1 promoters. We have thus developed a robust experimental platform for elucidating how dispersed transcriptional enhancers control Igf1 gene expression under different biological conditions. PMID:26330488

  3. Clinical Significance of Changes on Serum TGF-Ⅱ, IL-8 and TNF-α Levels in Patients with Acute Cerebral Infarction%ACI患者血清IGF-Ⅱ、IL-8和TNF-α水平的变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    朱德义; 刘家喜

    2012-01-01

    Objective To explore the clinical significance of changes on serum ICF- Ⅱ ,IL-8 and TNF-α levels in patients with a-cute cerebral infaction. Methods Serum IGF-Ⅱ ,IL-S and TNF-α levels were determined with radioimmunoassay(RIA)in 33 patients with acute cerebral infarction and 35 normal controls. ReslutS The serum IGF- Ⅱ ,IL-8 and TNF-α in patients with acute cerebral infarction were significantly higher than those in controls (P<0.01) , the serum IGF- Ⅱ levels were positive correlation with serum IL-8, TNF-a levels (r =0.5712, 0.6018, P<0.01 ). Conclusion Detection of changes of serum IGF- Ⅱ, IL-8and TNF-α levels can be help to assess the progress and prognosis of the disease, also such laboratory items offer to realise the pathosis and therapeutic effect possess definite clinical value.%目的:探讨急性脑梗死(ACI)患者血清IGF-Ⅱ、IL-8和TNF-α水平的变化及临床意义.方法:采用放射免疫分析对33例ACI患者进行了血清IGF-Ⅱ、IL-2和TNF-α检测,并与35名正常健康人作比较.结果:ACI患者血清IGF-Ⅱ、IL-2和TNF-α水平均非常显著地高于正常人组(P<0.01),且血清IGF-Ⅱ水平与IL-8和TNF-α水平呈正相关(r=0.5712、0.6018,P<0.01).结论:检测ACI患者血清IGF-Ⅱ、IL-2和TNF-α水平变化,对观察疾病的预后和疗效具有确切的临床价值.

  4. Increased circulating urocortin-3 levels is associated with polycystic ovary syndrome.

    Science.gov (United States)

    Temur, Muzaffer; Yilmaz, Özgür; Aksun, Saliha; Özün Özbay, Pelin; Calan, Mehmet; Küme, Tuncay; Karakulak, Murat; Korkmaz, Hüseyin Anıl

    2016-01-01

    This study was aimed to compare serum urocortin-3 (UCN3) levels in women with polycystic ovary syndrome (PCOS) and healthy women, and establish what role UCN3 levels play in PCOS. Fifty-two patients with PCOS and 55 healthy women were included in the study, matched for age and body mass index. Fasting blood glucose (FBG), insulin, hs-CRP, UCN3 and free-testosterone levels of the all participants were measured. HOMA-IR was used to calculate the insulin resistance. Circulating UCN3 levels were significantly increased in women with PCOS than in control subjects (54.49 ± 5.77 versus 51.28 ± 5.86 pmol/l, p = 0.005). Serum insulin, hs-CRP and HOMA-IR levels were higher in women with PCOS than in control group. UCN3 levels positively correlated with hs-CRP in PCOS group (r = 0.391, p = 0.004). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curves were 0.732 (95% CI 0.634-0.830, p optimal cut-off value of UCN3 for detecting PCOS was ≥51.46 pmol/l, at which the sensitivity was 75% and specificity was 68%. Our results suggest that there is a potential link between PCOS and UCN3 levels. The results of this study support the presence of increased UCN3 levels for the association of inflammation with PCOS. PMID:26488073

  5. Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

    Science.gov (United States)

    Strajhar, P; Schmid, Y; Liakoni, E; Dolder, P C; Rentsch, K M; Kratschmar, D V; Odermatt, A; Liechti, M E

    2016-03-01

    Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance.

  6. Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

    Science.gov (United States)

    Strajhar, P; Schmid, Y; Liakoni, E; Dolder, P C; Rentsch, K M; Kratschmar, D V; Odermatt, A; Liechti, M E

    2016-03-01

    Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance. PMID:26849997

  7. Impact of PTEN on the expression of insulin-like growth factors (IGFs) and IGF-binding proteins in human gastric adenocarcinoma cells

    International Nuclear Information System (INIS)

    PTEN is a tumor suppressor gene that is frequently mutated or deleted in a variety of human cancers including human gastric cancer. PTEN functions primarily as a lipid phosphatase and plays a key role in the regulation of the PI3 kinase/Akt pathway, thereby modulating cell proliferation and cell survival. On the other hand, the IGF system plays an important role in cell proliferation and cell survival via the PI3 kinase/Akt and MAP kinase pathways in many cancer cells. To characterize the impact of PTEN on the IGF-IGFR-IGFBP axis in gastric cancer, we overexpressed PTEN using an adenovirus gene transfer system in human gastric adenocarcinoma cells, SNU-484 and SNU-663, which lack PTEN. Overexpression of PTEN inhibited serum-induced as well as IGF-I-induced cell proliferation as compared to control cells. PTEN overexpression resulted in a significant decrease in the expression of IGF-I, -II, and IGF-IR. Interestingly, amongst the six IGFBPs, only IGFBP-3 was upregulated by PTEN, whereas IGFBP-4 and -6 were reduced. The IGFBP-3 promoter activity assay and Western immunoblotting demonstrate that PTEN regulates IGFBP-3 at the transcriptional level. In addition, the PI3 kinase inhibitor, LY294002, upregulates IGFBP-3 expression but downregulates IGF-I and IGF-II, indicating that PTEN controls IGFBP-3 and IGFs by an Akt-dependent pathway. These findings suggest that PTEN may inhibit antiapoptotic IGF actions not only by blocking the IGF-IGFR-induced Akt activity, but also by regulating expression of components of the IGF system, in particular, upregulation of IGFBP-3, which is known to exert antiproliferative effects through IGF-dependent and IGF-independent mechanisms in cancer cells

  8. Aquifer-Circulating Water Curtain Cultivation System To Recover Groundwater Level And Temperature

    Science.gov (United States)

    Kim, Y.; Ko, K.; Chon, C.; Oh, S.

    2011-12-01

    Groundwater temperature, which generally ranges 14 to 16 degree of Celsius all year long, can be said to be 'constant' compared to the amplitude of daily variation of air temperature or surface water. Water curtain cultivating method utilizes this 'constant' groundwater temperature to warm up the inside of greenhouse during winter night by splash groundwater on the roof of inner greenhouse. The area of water curtain cultivation system have increased up to 107.5 square kilometers as of 2006 since when it is first introduced to South Korea in 1984. Groundwater shortage problem became a great issue in a concentrated water curtain cultivation area because the pumped and splashed groundwater is abandoned to nearby stream and natural recharge rate is reduced by greenhouses. The amount of groundwater use for water curtain cultivation system in South Korea is calculated to be 587 million cubic meters which is 35% of national agricultural use of groundwater. A new water curtain cultivation system coupled with aquifer circulating of the splashed groundwater and greenhouse roof-top rainwater harvesting is developed and applied to field site in Nonsan-si, Chungnam province to minimize groundwater shortage problem and recover groundwater level. The aquifer circulating water curtain cultivation system is consist of a pumping well and a injection well of 80 m deep, groundwater transfer and splashing system, recovery tank and rainwater collecting waterway. The distance between injection and pumping well is 15 m and an observation well is installed in the middle of the wells. To characterize hydrogeological properties of this site, hydraulic test such as pumping tests and tracer tests with dye tracer, thermal tracer and ion tracer. Once the integrated system is constructed in this site, hydraulic head in all the wells and temperature of air, recovery tank and groundwater in all the wells are monitored during the operation for 3months in winter season. Hydraulic test and tracer

  9. Circulating levels of the interleukin (IL)-4 receptor and of IL-18 in patients with Plasmodium falciparum malaria.

    Science.gov (United States)

    Perkmann, Thomas; Winkler, Heidi; Graninger, Wolfgang; Kremsner, Peter G; Winkler, Stefan

    2005-02-21

    Circulating levels of sIL-4R, IL-18 and IFN-gamma were studied by ELISA in 36 Gabonese patients with Plasmodium falciparum malaria (29 children, 7 adults). Drug induced clearance of parasitemia, studied in 22 patients with mild disease, was accompanied by a rapid decrease of sIL-4R and IFN-gamma to normal values and an increase of circulating IL-18, suggesting the downregulation of a type 2 biased immune response and a dissociated type 1 responsiveness while resolving parasitemia. Comparing subgroups with hyperparasitemia/severe anemia and mild malaria, children with severe malaria had significant higher levels of sIL-4R and IFN-gamma, whereas IL-18 levels were not statistically different. Furthermore, among those children, higher levels of circulating IL-18 correlated with a lower degree of parasitemia.

  10. GRP94 Regulates Circulating Cholesterol Levels through Blockade of PCSK9-Induced LDLR Degradation

    Directory of Open Access Journals (Sweden)

    Steve Poirier

    2015-12-01

    Full Text Available Clearance of circulating low-density lipoprotein cholesterol (LDLc by hepatic LDL receptors (LDLR is central for vascular health. Secreted by hepatocytes, PCSK9 induces the degradation of LDLR, resulting in higher plasma LDLc levels. Still, it remains unknown why LDLR and PCSK9 co-exist within the secretory pathway of hepatocytes without leading to complete degradation of LDLR. Herein, we identified the ER-resident GRP94, and more precisely its client-binding C-terminal domain, as a PCSK9-LDLR inhibitory binding protein. Depletion of GRP94 did not affect calcium homeostasis, induce ER stress, nor did it alter PCSK9 processing or its secretion but greatly increased its capacity to induce LDLR degradation. Accordingly, we found that hepatocyte-specific Grp94-deficient mice have higher plasma LDLc levels correlated with ∼80% reduction in hepatic LDLR protein levels. Thus, we provide evidence that, in physiological conditions, binding of PCSK9 to GRP94 protects LDLR from degradation likely by preventing early binding of PCSK9 to LDLR within the ER.

  11. Circulating Antigens Levels in Different Clinical Forms of the Schistosoma mansoni Infection

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    Yerkes Pereira e Silva

    1999-01-01

    Full Text Available With the aim to evaluate the circulating cathodic antigen (CCA levels in relation to the different clinical phases of Schistosoma sp. infection a sandwich ELISA using monoclonal antibody 5H11 was performed. The sera of three groups of 25 Brazilian patients with acute, intestinal and hepatosplenic forms of S. mansoni infection were tested and compared to a non-infected control group. Patients and control groups were matched for age and sex and the number of eggs per gram of feces was equally distributed among the three patient groups. Sensitivity of 100%, 72%, 52% of the assay was observed for the intestinal, hepatosplenic and acute toxemic groups respectively. The specificity was 100%. Intestinal and hepatosplenic groups presented CCA levels significantly higher in comparison to those observed for acute patients (F-ratio = 2,524; p = 0.000 and F-ratio = 6,314; p = 0.015 respectively. There was no significant difference of CCA serum levels between hepatosplenic and intestinal groups (F-ratio = 1,026; p = 0.316.

  12. Climate-Induced Variability of Sea Level in Stockholm: Influence of Air Temperature and Atmospheric Circulation

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    This study is focused on climate-induced variation of sea level in Stockholm during 1873-1995. After the effect of the land uplift is removed, the residual is characterized and related to large-scale temperature and atmospheric circulation. The residual shows an overall upward trend, although this result depends on the uplift rate used. However, the seasonal distribution of the trend is uneven. There are even two months (June and August) that show a negative trend. The significant trend in August may be linked to fresh water input that is controlled by precipitation. The influence of the atmospheric conditions on the sea level is mainly manifested through zonal winds, vorticity and temperature. While the wind is important in the period January-May, the vorticity plays a main role during June and December. A successful linear multiple-regression model linking the climatic variables (zonal winds, vorticity and mean air temperature during the previous two months) and the sea level is established for each month. An independent verification of the model shows that it has considerable skill in simulating the variability.

  13. Relationship of circulating hyaluronic acid levels to disease control in asthma and asthmatic pregnancy.

    Science.gov (United States)

    Eszes, Noémi; Toldi, Gergely; Bohács, Anikó; Ivancsó, István; Müller, Veronika; Rigó, János; Losonczy, György; Vásárhelyi, Barna; Tamási, Lilla

    2014-01-01

    Uncontrolled asthma is a risk factor for pregnancy-related complications. Hyaluronic acid (HA), a potential peripheral blood marker of tissue fibrosis in various diseases, promotes eosinophil survival and plays a role in asthmatic airway inflammation as well as in physiological processes necessary to maintain normal pregnancy; however the level of circulating HA in asthma and asthmatic pregnancy is unknown. We investigated HA levels in asthmatic patients (N = 52; asthmatic pregnant (AP) N = 16; asthmatic non-pregnant (ANP) N = 36) and tested their relationship to asthma control. Serum HA level was lower in AP than in ANP patients (27 [24.7-31.55] vs. 37.4 [30.1-66.55] ng/mL, p = 0.006); the difference attenuated to a trend after its adjustment for patients' age (p = 0.056). HA levels and airway resistance were positively (r = 0.467, p = 0.004), HA levels and Asthma Control Test (ACT) total score inversely (r = -0.437, p = 0.01) associated in ANP patients; these relationships remained significant even after their adjustments for age. The potential value of HA in the determination of asthma control was analyzed using ROC analysis which revealed that HA values discriminate patients with ACT total score ≥20 (controlled patients) and asthma control, as it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Decrease of HA level in pregnancy may be the consequence of pregnancy induced immune tolerance.

  14. Circulating microRNAs correlated with the level of coronary artery calcification in symptomatic patients

    Science.gov (United States)

    Liu, Wei; Ling, Shukuan; Sun, Weijia; Liu, Tong; Li, Yuheng; Zhong, Guohui; Zhao, Dingsheng; Zhang, Pengfei; Song, Jinping; Jin, Xiaoyan; Xu, Zi; Song, Hailin; Li, Qi; Liu, Shujuan; Chai, Meng; Dai, Qinyi; He, Yi; Fan, Zhanming; Zhou, Yu Jie; Li, Yingxian

    2015-01-01

    The purpose of this study was to find the circulating microRNAs (miRNAs) co-related with the severity of coronary artery calcification (CAC), and testify whether the selected miRNAs could reflect the obstructive coronary artery disease in symptomatic patients. Patients with chest pain and moderated risk for coronary artery disease (CAD) were characterized with coronary artery calcium score (CACS) from cardiac computed tomography (CT). We analyzed plasma miRNA levels of clinical matched 11 CAC (CACS > 100) and 6 non-CAC (CACS = 0) subjects by microarray profile. Microarray analysis identified 34 differentially expressed miRNAs between CAC and non CAC groups. Eight miRNAs (miR-223, miR-3135b, miR-133a-3p, miR-2861, miR-134, miR-191-3p, miR-3679-5p, miR-1229 in CAC patients) were significantly increased in CAC plasma in an independent clinical matched cohort. Four miRNAs (miR-2861, 134, 1229 and 3135b) were correlated with the degree of CAC. Validation test in angiographic cohort showed that miR-134, miR-3135b and miR-2861 were significantly changed in patients with obstructive CAD . We identified three significantly upregulated circulating miRNAs (miR-134, miR-3135b and 2861) correlated with CAC while detected obstructive coronary disease in symptomatic patients. PMID:26537670

  15. Evaluation of circulating levels and renal clearance of natural amino acids in patients with Cushing's disease.

    Science.gov (United States)

    Faggiano, A; Pivonello, R; Melis, D; Alfieri, R; Filippella, M; Spagnuolo, G; Salvatore, F; Lombardi, G; Colao, A

    2002-02-01

    Although the hypercortisolism-induced impairment of protein homeostasis is object of several studies, a detailed evaluation of the complete amino acid profile of patients with Cushing's syndrome (CS) has never been performed. The aim of the current open transversal controlled study was to evaluate serum and urinary concentrations as well as renal clearance of the complete series of natural amino acids and their relationship with glucose tolerance in patients with Cushing's disease (CD). Twenty patients with CD (10 active and 10 cured) and 20 sex- and age-matched healthy controls entered the study. Measurement of serum and urinary levels of the complete series of natural amino acids was performed in all patients analyzed by cationic exchange high performance liquid cromatography (HPLC) after 2 weeks of a standardized protein intake regimen. The renal clearance (renal excretion rate) of each amino acid was calculated on the basis of the serum and urinary concentrations of creatinine and the specific amino acid. Fasting glucose and insulin levels, glucose and insulin response to standard glucose load, insulinogenic and homeostasis model insulin resistance (Homa-R) indexes were also evaluated and correlated to the circulating levels and renal clearances of each amino acid. Significantly higher serum (p<0.01) and urinary (p<0.05) levels of alanine and cystine, lower serum and higher urinary levels of leucine, isoleucine and valine (p<0.05) and higher renal excretion rates of leucine, isoleucine and valine (p<0.01) were found in patients with active CD than in patients cured from the disease and in controls. No difference was found between cured patients and controls. Creatinine clearance was similar in active and cured patients and in controls. In patients with active CD, urinary cortisol levels were significantly correlated to urinary cystine levels (r=0.85; p<0.01) and renal excretion rate of leucine (r=-0.76; p<0.05), isoleucine (r=-0.76; p<0.05) and valine (r=-0

  16. Exploring Secondary Students' Epistemological Features Depending on the Evaluation Levels of the Group Model on Blood Circulation

    Science.gov (United States)

    Lee, Shinyoung; Kim, Heui-Baik

    2014-01-01

    The purpose of this study is to identify the epistemological features and model qualities depending on model evaluation levels and to explore the reasoning process behind high-level evaluation through small group interaction about blood circulation. Nine groups of three to four students in the eighth grade participated in the modeling practice.…

  17. Efficacy of anti-insulin like growth factor I receptor (IGF-IR) monoclonal antibody cixutumumab in mesothelioma is highly correlated with IGF-IR sites/cell

    OpenAIRE

    Kalra, Neetu; Zhang, Jingli; Yu, Yunkai; Ho, Mitchell; Merino, Maria; Cao, Liang; Hassan, Raffit

    2012-01-01

    Insulin growth factor-I receptor (IGF-IR) is expressed in mesothelioma and therefore an attractive target for therapy. The anti-tumor activity of cixutumumab, a humanized monoclonal antibody to IGF-IR, in mesothelioma and relationship to IGF-IR expression was investigated using eight early passage tumor cells obtained from patients, nine established cell lines and an in vivo human mesothelioma tumor xenograft model. Although IGF-IR expression at the mRNA and protein level was present in all m...

  18. Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors

    Directory of Open Access Journals (Sweden)

    Diesch Claude

    2009-11-01

    Full Text Available Abstract Background With the aim to simplify cancer management, cancer research lately dedicated itself more and more to discover and develop non-invasive biomarkers. In this connection, circulating cell-free DNA (ccf DNA seems to be a promising candidate. Altered levels of ccf nuclear DNA (nDNA and mitochondrial DNA (mtDNA have been found in several cancer types and might have a diagnostic value. Methods Using multiplex real-time PCR we investigated the levels of ccf nDNA and mtDNA in plasma samples from patients with malignant and benign breast tumors, and from healthy controls. To evaluate the applicability of plasma ccf nDNA and mtDNA as a biomarker for distinguishing between the three study-groups we performed ROC (Receiver Operating Characteristic curve analysis. We also compared the levels of both species in the cancer group with clinicopathological parameters. Results While the levels of ccf nDNA in the cancer group were significantly higher in comparison with the benign tumor group (P P P P = 0.022. The level of ccf nDNA was also associated with tumor-size (2 cmP = 0.034. Using ROC curve analysis, we were able to distinguish between the breast cancer cases and the healthy controls using ccf nDNA as marker (cut-off: 1866 GE/ml; sensitivity: 81%; specificity: 69%; P P Conclusion Our data suggests that nuclear and mitochondrial ccf DNA have potential as biomarkers in breast tumor management. However, ccf nDNA shows greater promise regarding sensitivity and specificity.

  19. Evidence from a randomized trial that simvastatin, but not ezetimibe, upregulates circulating PCSK9 levels.

    Directory of Open Access Journals (Sweden)

    Heiner K Berthold

    Full Text Available BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9 is a secreted inhibitor of the low-density lipoprotein (LDL receptor and an important regulator of LDL metabolism. Elevated PCSK9 levels have been associated with cardiovascular risk. The purpose of this study was to investigate how ezetimibe and simvastatin, alone and in combination, affect PCSK9 circulating concentrations. METHODS: A single center, randomized, open-label parallel 3-group study in healthy men (mean age 32±9 years, body mass index 25.7±3.2 kg/m(2 was performed. Each group of 24 subjects was treated for 14 days with either simvastatin 40 mg/d, ezetimibe 10 mg/d, or with both drugs. Multivariate analysis was used to investigate parameters influencing the change in PCSK9 concentrations under treatment. RESULTS: The baseline plasma PCSK9 concentrations in the total cohort were 52±20 ng/mL with no statistically significant differences between the groups. They were increased by 68±85% by simvastatin (P = 0.0014, by 10±38% by ezetimibe (P = 0.51 and by 67±91% by simvastatin plus ezetimibe (P = 0.0013. The increase in PCSK9 was inversely correlated with baseline PCSK9 concentrations (Spearman's R = -0.47, P<0.0001 and with the percent change in LDL cholesterol concentrations (Spearman's R = -0.30, P<0.01. In multivariate analyses, only baseline PCSK9 concentrations (β = -1.68, t = -4.04, P<0.0001, percent change in LDL cholesterol from baseline (β = 1.94, t = 2.52, P = 0.014, and treatment with simvastatin (P = 0.016, but not ezetimibe (P = 0.42, significantly influenced changes in PCSK9 levels. Parameters without effect on PCSK9 concentration changes were age, body mass index, body composition, thyroid function, kidney function, glucose metabolism parameters, adipokines, markers of cholesterol synthesis and absorption, and molecular markers of cholesterol metabolism. CONCLUSIONS: Ezetimibe does not increase

  20. IGF-binding proteins in type 1 diabetes are more severely altered in the presence of complications

    Directory of Open Access Journals (Sweden)

    Ashok eSharma

    2016-01-01

    Full Text Available Aims: Reduced levels of free and total insulin-like growth factor 1 (IGF-I have been observed in Type-1 Diabetes (T1D patients. The bioavailability of IGF-I from the circulation to the target cells is controlled by multifunctional IGF binding proteins (IGFBPs. The aim of this study was to profile serum IGFBPs in T1D and its complications.Design: We measured the IGFBP levels in 3662 patient serum samples from our ongoing Phenome and Genome of Diabetes Autoimmunity (PAGODA study. IGFBP levels of four different groups of T1D patients (with 0, 1, 2, ≥3 complications were compared with healthy controls. Results: Three serum IGFBPs (IGFBP-1, 2 and 6 are significantly higher in T1D patients and these alterations are greater in the presence of diabetic complications. IGFBP-3 is lower in patients with diabetic complications. Analyses using quintiles revealed that risk of T1D complications increases with increasing concentrations of IGFBP-2 (5th quintile ORs: 18-60, p<10-26, IGFBP-1 (5th quintile ORs: 8-20, p<10-15 and IGFBP-6 (5th quintile ORs: 3-148, p<10-3. IGFBP-3 has a negative association with T1D complications (5th quintile ORs: 0.12-0.25, p<10-5. Conclusions: we found that elevated serum levels of IGFBP-1, 2 and 6 were associated with T1D and its complications and IGFBP-3 level was found to be decreased in T1D with complications. Given the known role of these IGFBPs, the overall impact of these alterations suggest a negative effect on IGF signaling.

  1. On the relation between Meridional Overturning Circulation and sea-level gradients in the Atlantic

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    H. Kienert

    2012-04-01

    Full Text Available On the basis of model simulations, we examine what information on changes in the strength of the Atlantic Meridional Overturning Circulation (AMOC can be extracted from associated changes in sea surface height (SSH, specifically from a broad Atlantic north-south gradient as has been suggested previously in the literature. Since a relation between AMOC and SSH changes can only be used as an AMOC diagnostic if it is valid independently of the specific forcing, we consider three different forcing types: increase of CO2 concentration, freshwater fluxes to the northern convection sites and the modification of Southern Ocean winds. We concentrate on a timescale of 100 yr. We find approximately linear and numerically similar relations between a sea-level difference within the Atlantic and the AMOC for freshwater as well as wind forcing. However, the relation is more complex in response to atmospheric CO2 increase, which precludes this sea-level difference as an AMOC diagnostic under climate change. Finally, we show qualitatively to what extent changes in SSH and AMOC strength that are caused by simultaneous application of different forcings correspond to the sum of the changes due to the individual forcings, a potential prerequisite for more complex SSH-based AMOC diagnostics.

  2. Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings.

    Science.gov (United States)

    Garcia, J F; Ebbe, S N; Hollander, L; Cutting, H O; Miller, M E; Cronkite, E P

    1982-05-01

    Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 microliters of sample, the essay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples show a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases in circulating Ep levels in physiological and clinical conditions known to be associated with stimulation of suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RIA inthe hematology clinic, which will most certainly be expanded with its more extensive use. PMID:7069267

  3. Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, J.F. (Lawrence Berkeley Lab., CA); Ebbe, S.N.; Hollander, L.; Cutting, H.O.; Miller, M.E.; Cronkite, E.P.

    1982-05-01

    Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 ..mu..l of sample, the assay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples show a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RA in the hematology clinic, which will most certainly be expanded with its more extensive use.

  4. Haplotypes of vitamin D receptor modulate the circulating levels of lead in exposed subjects

    Energy Technology Data Exchange (ETDEWEB)

    Rezende, Vania B. [State University of Campinas, Department of Pharmacology, Faculty of Medical Sciences, Campinas, SP (Brazil); Barbosa, Fernando [University of Sao Paulo, Department of Clinical, Toxicological and Food Science Analysis, Faculty of Pharmaceutical Sciences of Ribeirao Preto, Ribeirao Preto, SP (Brazil); Montenegro, Marcelo F.; Sandrim, Valeria C.; Tanus-Santos, Jose E. [University of Sao Paulo, Ribeirao Preto, Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, Ribeirao Preto, SP (Brazil); Gerlach, Raquel F. [University of Sao Paulo, Department of Morphology, Estomatology and Physiology, Dental School of Ribeirao Preto, Ribeirao Preto, SP (Brazil)

    2008-01-15

    Genetic factors influence whole blood lead (Pb-B) concentrations in lead exposed subjects. This study aimed at examining the combined effects (haplotype analysis) of three polymorphisms (BsmI, ApaI and FokI) in vitamin D receptor (VDR) gene on Pb-B and on the concentrations of lead in plasma (Pb-P), which is more relevant to lead toxicity, in 150 environmentally exposed subjects. Genotypes were determined by RFLP, and Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. Subjects with the bb (BsmI polymorphism) or ff (FokI polymorphism) genotypes have lower B-Pb than subjects in the other genotype groups. Subjects with the aa (ApaI polymorphism) or ff genotypes have lower P-Pb than subjects in the other genotype groups. Lower Pb-P, Pb-B, and %Pb-P/Pb-B levels were found in subjects with the haplotype combining the a, b, and f alleles for the ApaI, BsmI, and FokI polymorphisms, respectively, compared with the other haplotype groups, thus suggesting that VDR haplotypes modulate the circulating levels of lead in exposed subjects. (orig.)

  5. Differential regulation of IGF-binding proteins in rabbit costal chondrocytes by IGF-I and dexamethasone.

    Science.gov (United States)

    Koedam, J A; Hoogerbrugge, C M; Van Buul-Offers, S C

    2000-06-01

    Cartilage is a primary target tissue for the IGFs. The mitogenic activity of these peptides is regulated by a family of high-affinity IGF-binding proteins (IGFBP-1 to -6). We characterized the IGFBPs produced by cultured chondrocytes derived from rib cartilage of prepubertal rabbits. Culture medium, which had been conditioned by these cells for 48 h showed bands of 22 kDa, 24 kDa and a 31/32 kDa doublet by Western ligand blotting with [(125)I]IGF-II. When the cells were grown in the presence of increasing amounts of IGF-I or IGF-II, the 31/32 kDa doublet increased in intensity (reaching a plateau of about 11-fold stimulation between 2 and 10 nM IGF-I). The 22 kDa and 24 kDa bands increased only slightly while a 26 kDa band became faintly visible. By Western immunoblotting the 31/32 kDa doublet was identified as IGFBP-5. An IGF-I analog with reduced affinity for IGFBPs, Long-R3 IGF-I, also induced IGFBP-5, while insulin was less effective (2.2-fold stimulation at 10 nM). IGF-I protected IGFBP-5 against proteolytic degradation by conditioned medium. IGF-I also enhanced the level of IGFBP-5 mRNA. LY294002, a specific inhibitor of the intracellular signaling molecule phosphatidylinositol 3-kinase, inhibited stimulation of IGFBP-5 by IGF-I. Dexamethasone suppressed IGFBP-5 (by 70% at 20 nM) but, at the same time, a 39/41 kDa doublet (presumably IGFBP-3) was induced. IGFBP-5 has been shown in several cell types to enhance the mitogenic activity of IGF-I. IGFBP-3 generally acts as a growth inhibitor. Therefore, the differential effects of dexamethasone on these regulatory proteins could account, at least in part, for the growth-arresting effect of this glucocorticoid. PMID:10828839

  6. Detection and adequacy evaluation of erythrocyte glutathione transferase on levels of circulating toxins in hemodialysis patients.

    Science.gov (United States)

    Yin, Rui; Qiu, Hui; Zuo, Huaiyun; Cui, Min; Zhai, Nailiang; Zheng, Hongguang; Zhang, Dewei; Huo, Ping; Hong, Min

    2016-08-01

    To explore detection and adequacy evaluation of erythrocyte glutathione S transferase (GST) on levels of circulating toxins in hemodialysis patients in Qinhuangdao region in China, this study divided 84 cases of long-term, end-stage hemodialysis patients into 2 groups: one group of 33 cases of adequate hemodialysis (spKt/V ≥ 1.3) and another group of 51 cases of inadequate hemodialysis (spKt/V GST, creatinine, high sensitivity C-reactive protein (hs-CRP), transferrin saturation (TSAT), parathyroid hormone (PTH), interleukin-2,6,8 (IL-2,6,8) and tumor necrosis factor-a (TNF-a) in the hemodialysis group were significantly higher than those in the control group (P GST, IL-2, 6, 8, and TNF-a levels in the inadequate hemodialysis group were significantly higher than in the adequate hemodialysis group (P GST and spKt/V, IL-2, IL-6, IL-8, and TNF-a have a positive correlation (P 0.05). There were 23 patients with levels of spKt/V ≥ 1.3 after adjusting the dialysis solution for 51 cases of inadequate hemodialysis patients, and the GST level after the adjustment was significantly lower than that before the adjustment, but still higher than that in the adequate dialysis group. This concludes that the maintenance of hemodialysis in patients has certain relevance on spKt/V and associated inflammatory factors. Through the study, it can be determined that GST can effectively respond to adequate hemodialysis, which has a guiding significance on adjusting the blood dialysis solution in clinical practice. PMID:27121915

  7. Circulating levels of human salusin-β, a potent hemodynamic and atherogenesis regulator.

    Directory of Open Access Journals (Sweden)

    Kazumi Fujimoto

    Full Text Available Using bioinformatics analysis, we previously identified salusin-β, an endogenous bioactive peptide with diverse physiological activities. Salusin-β is abundantly expressed in the neuroendocrine system and in systemic endocrine cells/macrophages. Salusin-β acutely regulates hemodynamics and chronically induces atherosclerosis, but its unique physicochemical characteristics to tightly adhere to all types of plastic and glassware have prevented elucidation of its precise pathophysiological role. To quantitate plasma total salusin-β concentrations, we produced rabbit and chicken polyclonal antibodies against the C- and N-terminal end sequences, circumvented its sticky nature, and successfully established a sandwich enzyme-linked immunosorbent assay (ELISA. Salusin-β was abundantly present in the plasma of healthy volunteers, ranging from 1.9 to 6.6 nmol/L. Reverse phase-high performance liquid chromatography analysis showed that a single immunoreactive salusin-β peak coincided with synthetic authentic salusin-β. Plasma salusin-β concentrations were unaffected by postural changes and by potent vasopressin release stimuli, such as hypertonic saline infusion or smoking. However, salusin-β concentrations showed significant circadian variation; concentrations were high during the daytime and reached the lowest concentrations in the early morning. Plasma salusin-β levels in subjects with diabetes mellitus, coronary artery disease, and cerebrovascular disease showed distinctly higher levels than healthy controls. Patients with panhypopituitarism combined with complete central diabetes insipidus also showed significantly higher plasma salusin-β levels. Therefore, the ELISA system developed in this study will be useful for evaluating circulating total salusin-β levels and for confirming the presence of authentic salusin-β in human plasma. The obtained results suggest a limited contribution of the neuroendocrine system to peripheral total salusin

  8. Peripheral elevation of IGF-1 fails to alter Abeta clearance in multiple in vivo models.

    Science.gov (United States)

    Lanz, Thomas A; Salatto, Christopher T; Semproni, Anthony R; Marconi, Michael; Brown, Tracy M; Richter, Karl E G; Schmidt, Kari; Nelson, Frederick R; Schachter, Joel B

    2008-03-01

    Increasing beta-amyloid (Abeta) clearance may alter the course of Alzheimer's disease progression and attenuate amyloid plaque pathology. Insulin-like growth factor I (IGF-1) augmentation has been suggested to increase Abeta clearance by facilitating transport of Abeta out of the brain. The availability of safe agents that increase IGF-1 levels therefore makes IGF-1 elevation an attractive target for disease modifying therapy in AD. The present series of studies sought to replicate published paradigms in which peripheral IGF-1 administration lowered brain Abeta acutely, with reduction in plaque pathology after chronic treatment. Thus Abeta levels were measured in several animal models following treatments that elevated IGF-1. Administration of IGF-1 to young or old rats for up to 3 days had no effect on Abeta levels in brain, CSF, or plasma. In adult beagles, 4 days of dosing with the growth hormone secretagogue, CP-424391, doubled baseline plasma IGF-1 levels, yet failed to alter CSF or plasma Abeta. 5-day treatment of young Tg2576 mice with IGF-1 produced robust elevations of IGF-1 levels in plasma, but no effects on Abeta were detected in brain, CSF, or plasma. Finally, 11-month-old Tg2576 mice were implanted with subcutaneous minipumps delivering IGF-1 for 1 month. No significant changes in Abeta (by ELISA or Western blot), plaque pathology, or phospho-tau epitopes were detected. These results do not demonstrate acute or chronic actions of peripherally administered IGF-1 on Abeta levels or the phosphorylation state of tau and therefore do not suggest any disease-modifying benefits of IGF-1 restorative therapy for AD through these mechanisms.

  9. 急性一氧化碳中毒后迟发性脑病患者血清胰岛素样生长因子-1水平及其临床意义研究%Serum IGF-1 Level in Patients with Delayed Encephalopathy after Acute Carbon Monoxide Poisoning and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    顾家鹏; 李艳丽; 王冀康; 张萍; 顾仁骏; 李静; 潘登; 衣学伟; 史玫; 高琦

    2013-01-01

    Objective To investigate the dynamic changes of level of serum insulin - like growth factor - 1 ( IGF - 1 ) and its clinical significance in patients with delayed encephalopathy after acute carbon monoxide poisoning ( DEACMP ). Methods 33 DEACMP patients were selected form November 2007 to Jun 2008, IGF - 1 level was assayed with enzyme - linked im-munno - sorbent assay ( ELISA ). Their condition changes were evaluated with Activity of Daily Living Scale ( ADL ), Information - Memory - Concentration Test ( IMCT ) and Hasegawa's Dementia Scale ( HDS ). The above indexes were compared with those of 32 acute carbon monoxide poisoning ( ACMP ) patients without occurrence of DEACMP ( ACMP group ) and of 32 healthy subjects ( control group ). Results ( 1 ) IGF - 1 at acute stage was significantly lower in DEACMP group [ ( 136. 10 ±51. 51 ) μg/L ] than in control group [ ( 192. 91 ± 145. 97 ) μg/L, P 0. 05 ). IGF - 1 was higher at recovery stage [ ( 187. 69 ±92. 46 ) μg/L ] than at acute stage in DEACMP group, the difference was significant (P <0. 05 ). (2) ADL, HDS, IMCT at acute stage was significantly different from those at recovery stage in DEACMP group ( P < 0. 05 ). ( 3 ) IGF - 1 was negatively correlated with ADL in DEACMP group ( r = - 0. 377 , P = 0. 03 ). Conclusion IGF - 1, protecting probably DEACMP patients from brain damage, may be used as one of indexes for clinical outcomes and therapeutic effectiveness assessment.%目的 研究急性一氧化碳中毒后迟发性脑病(DEACMP)患者血清胰岛素样生长因子-1(IGF-1)水平的动态变化及其临床意义.方法 选择2007年11月-2008年6月在我院住院的33例DEACMP患者,采用酶联免疫吸附法动态测定血清IGF-1水平,用日常生活能力量表(ADL)、长谷川痴呆量表(HDS)、常识-记忆-注意测验(IMCT)动态评估DEACMP患者的病情变化,并与32例急性一氧化碳中毒(ACMP)后未发生DEACMP的患者(ACMP组)和32例健康体检者(正常对照组)的

  10. Nutritional Regulation of IGFs in Channel Catfish

    Science.gov (United States)

    We examined changes in hepatic IGF-I and IGF-II mRNA, insulin like growth factor binding proteins (IGFBP-1 and IGFBP-2) mRNA, muscle IGF-I and IGF-II mRNA in fed (fed daily for 45 days) and restricted (not fed for 30 days followed by feeding for 15 days) channel catfish. By day 30, liver IGF-I mRNA...

  11. Circulating levels of chromatin fragments are inversely correlated with anti-dsDNA antibody levels in human and murine systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Jørgensen, Mariann H; Rekvig, Ole Petter; Jacobsen, Rasmus S;

    2011-01-01

    Anti-dsDNA antibodies represent a central pathogenic factor in Lupus nephritis. Together with nucleosomes they deposit as immune complexes in the mesangial matrix and along basement membranes within the glomeruli. The origin of the nucleosomes and when they appear e.g. in circulation is not known...... an inverse correlation between anti-dsDNA antibodies and the DNA concentration in the circulation in both murine and human serum samples. High titer of anti-DNA antibodies in human sera correlated with reduced levels of circulating chromatin, and in lupus prone mice with deposition within glomeruli....... The inverse correlation between DNA concentration and anti-dsDNA antibodies may reflect antibody-dependent deposition of immune complexes during the development of lupus nephritis in autoimmune lupus prone mice. The measurement of circulating DNA in SLE sera by using qPCR may indicate and detect...

  12. Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kan Casina WS

    2012-12-01

    Full Text Available Abstract Background There is a critical need for improved diagnostic markers for high grade serous epithelial ovarian cancer (SEOC. MicroRNAs are stable in the circulation and may have utility as biomarkers of malignancy. We investigated whether levels of serum microRNA could discriminate women with high-grade SEOC from age matched healthy volunteers. Methods To identify microRNA of interest, microRNA expression profiling was performed on 4 SEOC cell lines and normal human ovarian surface epithelial cells. Total RNA was extracted from 500 μL aliquots of serum collected from patients with SEOC (n = 28 and age-matched healthy donors (n = 28. Serum microRNA levels were assessed by quantitative RT-PCR following preamplification. Results microRNA (miR-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers. miR-103, miR-92a and miR -638 had relatively invariant expression across all ovarian cell lines, and with small-nucleolar C/D box 48 (RNU48 were assessed in RNA extracted from serum as candidate endogenous normalizers. No correlation between serum levels and age were observed (age range 30-79 years for any of these microRNA or RNU48. Individually, miR-200a, miR-200b and miR-200c normalized to serum volume and miR-103 were significantly higher in serum of the SEOC cohort (P  Conclusions We identified serum microRNAs able to discriminate patients with high grade SEOC from age-matched healthy controls. The addition of these microRNAs to current testing regimes may improve diagnosis for women with SEOC.

  13. Age dependency of serum insulin - like growth factor (IGF-1 in healthy Turkish adolescents and adults.

    Directory of Open Access Journals (Sweden)

    Tiryakioaylu O

    2003-12-01

    Full Text Available BACKGROUND: Serum levels of insulin-like growth factor-1 (IGF-1 reflect endogenous growth hormone (GH secretion in healthy subjects. Measurements of IGF-1 are useful for diagnosis and follow-up of patients with acromegaly and the diagnosis of GH deficiency in children. AIMS: To assess age dependency and normal ranges of serum IGF-1 levels in healthy Turkish population. SETTING AND DESIGN: We therefore studied 272 healthy adolescents and adults between 15-75 years of age. None had diabetes or other endocrine disease or had received estrogen therapy. MATERIAL AND METHODS: Height, weight, body mass index (BMI and waist-hip ratio were measured in all subjects. Serum samples were obtained during morning hours and IGF-1 was measured by radioimmunoassay. STATISTICAL ANALYSIS: The age-dependent reference range for serum IGF-1 concentrations was calculated by simple least linear regression analysis: the regression line represents the means with 95 percent confidence intervals. Correlation analysis was also done. RESULTS: Ageing was negatively related to serum levels of IGF-1 (P= 0.0001, r=-0.931 with a mean decrease (youngest vs. oldest. IGF-1 levels increased during adolescence, with the highest mean values during puberty. After puberty, a subsequent decline in serum levels of IGF-1 was apparent. There were also a significant difference according to gender; females had significantly higher levels (357.909+/-219.167 mg/L than males (307.962+/-198.41 mg/L (P=0.012. IGF-1 levels were correlated with body height (P=0.001, r=0.223, body weight (P=0.002,r=-0.188 and BMI (P=0.039, r=0.128. CONCLUSION: IGF-1 serum levels increase in adolescents with a peak in puberty, whereafter IGF-1 levels return to prepubertal levels.

  14. Effect of changes in circulating amylase levels on amylase output in bile.

    Science.gov (United States)

    Grendell, J H; Rothman, S S

    1982-07-01

    The relation between plasma and biliary amylase activity and their relationship to the functional state of the pancreas were studied in anesthetized rabbits. Repetitive intravenous injections of cholecystokinin resulted in a 25-fold rise in the secretion of amylase via the pancreatic duct, followed at first by a 50% increase in plasma amylase concentration and later by a 270% increase in biliary amylase concentration. There was then a gradual, roughly synchronous decline in both plasma and biliary values toward basal level despite a continued highly augmented rate of pancreatic ductal secretion. "Near-total" pancreatectomy completely abolished the effect. These observations are consistent with a cholecystokinin-induced basolateral secretion of amylase from pancreas into blood and its subsequent movement from blood into bile down a concentration gradient. The output of amylase in bile, however, was quite small and does not suggest that biliary transport of amylase has an important function either as a means of secreting and recycling digestive enzyme into the gut or as a major excretory pathway for circulating amylase in the rabbit.

  15. IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma

    OpenAIRE

    Svalina, Matthew N; Ken Kikuchi; Jinu Abraham; Sangeet Lal; Davare, Monika A.; Settelmeyer, Teagan P.; Young, Michael C.; Jennifer L. Peckham; Yoon-Jae Cho; Michalek, Joel E.; Hernandez, Brian S.; Noah E. Berlow; Melanie Jackson; Guillaume, Daniel J.; Selden, Nathan R.

    2016-01-01

    Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving pro...

  16. Waist circumference does not predict circulating adiponectin levels in sub-Saharan women

    Directory of Open Access Journals (Sweden)

    Gautier Jean-François

    2007-10-01

    Full Text Available Abstract Background Because of previously reported ethnic differences in determinants and markers of obesity and related metabolic disorders, we sought to investigate circulating levels of adiponectin and their correlates in a sub-Saharan African (sSA population. Subjects and Methods We studied 70 non-diabetic volunteers (33M/37F living in Yaoundé, Cameroon, aged 24–69 yr, with BMI 20–42 kg/m2. In all participants we measured waist circumference and total body fat by bioimpedance, and obtained a fasting venous blood sample for measurement of plasma glucose, serum insulin and adiponectin concentrations. We performed a euglycaemic hyperinsulinaemic clamp in 1/4 subjects, and HOMAIR was used as surrogate of fasting insulin sensitivity index since it best correlates to clamp measurements. Results Males had lower adiponectin levels than females (8.8 ± 4.3 vs. 11.8 ± 5.5 μg/L. There was no significant correlation between adiponectin and total body fat (rs = -0.03; NS, whereas adiponectin was inversely correlated with waist circumference (rs = -0.39; p = 0.001. Adiponectin correlated negatively with insulin resistance (rs = -0.35; p = 0.01. In a regression analysis using fasting adiponectin concentration as the dependent variable, and age, HOMAIR, waist circumference, and fat mass as predictors, waist circumference (β = -3.30; p = 0.002, fat mass (β = -2.68; p = 0.01, and insulin resistance (β = -2.38; p = 0.02 but not age (β = 1.11; p = 0.27 were independent predictors of adiponectin. When considering gender, these relations persisted with the exception of waist circumference in females. Conclusion Adiponectin correlates in this study population are comparable to those observed in Caucasians with the exception of waist circumference in women. The metabolic significance of waist circumference is therefore questioned in sSA women.

  17. Circulating interleukin-8 levels explain breast cancer osteolysis in mice and humans.

    Science.gov (United States)

    Kamalakar, Archana; Bendre, Manali S; Washam, Charity L; Fowler, Tristan W; Carver, Adam; Dilley, Joshua D; Bracey, John W; Akel, Nisreen S; Margulies, Aaron G; Skinner, Robert A; Swain, Frances L; Hogue, William R; Montgomery, Corey O; Lahiji, Parshawn; Maher, Jacqueline J; Leitzel, Kim E; Ali, Suhail M; Lipton, Alan; Nicholas, Richard W; Gaddy, Dana; Suva, Larry J

    2014-04-01

    Skeletal metastases of breast cancer and subsequent osteolysis connote a dramatic change in the prognosis for the patient and significantly increase the morbidity associated with disease. The cytokine interleukin 8 (IL-8/CXCL8) is able to directly stimulate osteoclastogenesis and bone resorption in mouse models of breast cancer bone metastasis. In this study, we determined whether circulating levels of IL-8 were associated with increased bone resorption and breast cancer bone metastasis in patients and investigated IL-8 action in vitro and in vivo in mice. Using breast cancer patient plasma (36 patients), we identified significantly elevated IL-8 levels in bone metastasis patients compared with patients lacking bone metastasis (pIL-8 and increased bone resorption (pIL-8 expression. In vitro, human MDA-MB-231 and MDA-MET breast cancer cell lines secrete two distinct IL-8 isoforms, both of which were found to stimulate osteoclastogenesis. However, the more osteolytic MDA-MET-derived full length IL-8(1-77) had significantly higher potency than the non-osteolytic MDA-MB-231-derived IL-8(6-77), via the CXCR1 receptor. MDA-MET breast cancer cells were injected into the tibia of nude mice and 7days later treated daily with a neutralizing IL-8 monoclonal antibody. All tumor-injected mice receiving no antibody developed large osteolytic bone tumors, whereas 83% of the IL-8 antibody-treated mice had no evidence of tumor at the end of 28days and had significantly increased survival. The pro-osteoclastogenic activity of IL-8 in vivo was confirmed when transgenic mice expressing human IL-8 were examined and found to have a profound osteopenic phenotype, with elevated bone resorption and inherently low bone mass. Collectively, these data suggest that IL-8 plays an important role in breast cancer osteolysis and that anti-IL-8 therapy may be useful in the treatment of the skeletal related events associated with breast cancer.

  18. The association of circulating adiponectin levels with pancreatic cancer risk : A study within the prospective EPIC cohort

    NARCIS (Netherlands)

    Grote, Verena A.; Rohrmann, Sabine; Dossus, Laure; Nieters, Alexandra; Halkjaer, Jytte; Tjonneland, Anne; Overvad, Kim; Stegger, Jakob; Chabbert-Buffet, Nathalie; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Francoise; Teucher, Birgit; Becker, Susen; Montonen, Jukka; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Vineis, Paolo; Mattiello, Amalia; Argueelles, Marcial; Duell, Eric J.; Molina-Montes, Esther; Larranaga, Nerea; Chirlaque, Maria-Dolores; Gurrea, Aurelio Barricarte; Jeurnink, Suzanne M.; Peeters, Petra H. M.; Ye, Weimin; Sund, Malin; Lindkvist, Bjoern; Johansen, Dorthe; Khaw, Kay-Tee; Wareham, Nick; Crowe, Francesca L.; Romieu, Isabelle; Rinaldi, Sabina; Jenab, Mazda; Romaguera, Dora; Michaud, Dominique S.; Riboli, Elio; Bueno-de-Mesquita, H. Bas; Kaaks, Rudolf

    2012-01-01

    Excess body weight and type 2 diabetes mellitus, risk factors of pancreatic cancer, are characterized by decreased levels of adiponectin. In addition to anti-inflammatory and anti-proliferative actions, adiponectin has an important role in regulating glucose metabolism, i.e., decreasing circulating

  19. Associations between joint effusion in the knee and gene expression levels in the circulation: A meta-analysis

    NARCIS (Netherlands)

    Y.F.M. Ramos (Yolande); M.J. Peters (Marjolein); W. den Hollander (Wouter); D. Schiphof (Dieuwke); A. Hofman (Albert); A.G. Uitterlinden (André); E.H.G. Oei (Edwin); P.E. Slagboom (Eline); M. Kloppenburg (Margreet); J.L. Bloem (Johan); S.M. Bierma-Zeinstra (Sita); I. Meulenbelt (Ingrid); J.B.J. van Meurs (Joyce)

    2016-01-01

    textabstractObjective: To identify molecular biomarkers for early knee osteoarthritis (OA), we examined whether joint effusion in the knee associated with different gene expression levels in the circulation. Materials and Methods: Joint effusion grades measured with magnetic resonance (MR) imaging a

  20. Changes in circulating levels of fibroblast growth factor 23 induced by short-term dietary magnesium deficiency in rats.

    Science.gov (United States)

    Matsuzaki, Hiroshi; Katsumata, Shinichi; Maeda, Yoshiaki; Kajita, Yasutaka

    2016-06-01

    Fibroblast growth factor 23 (FGF23) is a potent regulator of phosphorus (P) and vitamin D metabolism. Long-term dietary magnesium (Mg) deficiency increases circulating levels of FGF23, whereas the effects of short-term dietary Mg deficiency are unclear. Thus, the present study investigated whether short-term dietary Mg deficiency affects circulating levels of FGF23. We also assessed changes in renal mRNA expression of vitamin D metabolizing enzymes and type II sodium-phosphate (Na/Pi) cotransporters, since these are regulated by FGF23. Rats were fed a control diet (control group) or an Mg-deficient diet (Mg-deficient group) for 2, 4 or 7 days. Serum Mg levels were significantly lower in the Mg-deficient group than in the control group at all time points. Serum FGF23 levels were significantly higher in the Mg-deficient group than in the control group at day 7. The 25-hydroxyvitamin D-24-hydroxylase (24(OH)ase) mRNA levels were significantly higher in the Mg-deficient group than in the control group at day 7 . No significant differences in types IIa and IIc Na/Pi cotransporter mRNA levels were observed between the control and Mg-deficient groups. These results suggest that dietary Mg deficiency causes a rapid increase in circulating levels of FGF23 and renal 24(OH)ase mRNA levels. PMID:27624533

  1. Insulin-like growth factors (IGFs) stimulate the release of alpha 1-antichymotrypsin and soluble IGF-II/mannose 6-phosphate receptor from MCF7 breast cancer cells.

    Science.gov (United States)

    Confort, C; Rochefort, H; Vignon, F

    1995-09-01

    The growth of hormone-responsive MCF7 human breast cancer cells is controlled by steroid hormones and growth factors. By metabolic labeling of cells grown in steroid- and growth factor-stripped serum conditions, we show that insulin-like growth factors (IGF-I and IGF-II) increase by approximately 5-fold the release of several proteins including cathepsin D, alpha 1-antichymotrypsin, and soluble forms of the multifunctional IGF-II/mannose 6-phosphate (M6P) receptor. Two soluble forms of IGF-II/M6P receptors were detected, one major (approximately 260 kilodaltons) and one minor (approximately 85 kilodaltons) that probably represents a proteolytic fragment of the larger soluble molecule. IGFs increased receptor release in a dose-dependent fashion with 50-60% of newly synthesized receptor released at 5-10 nM IGFs. The release of IGF-II/M6P receptors correlated with the levels of secreted cathepsin D in different human breast cancer cells or in rats stable transfectants that are constitutively expressing variable levels of human cathepsin D. IGFs had a stronger effect on IGF-II/M6P receptor release, whereas estradiol treatment preferentially enhanced the release of protease and antiprotease. We thus demonstrate that in human breast cancer cells, IGFs not only act as strong mitogens but also regulate release of alpha 1-antichymotrypsin, IGF-II/M6P-soluble receptor, and cathepsin D; three proteins that potentially regulate cell proliferation and/or invasion. PMID:7649082

  2. Relationship of circulating cell-free DNA levels to cell-free fetal DNA levels, clinical characteristics and laboratory parameters in preeclampsia

    Directory of Open Access Journals (Sweden)

    Mézes Miklós

    2009-01-01

    Full Text Available Abstract Background The aim of our study was to examine whether increased circulating total cell-free DNA levels are related to the clinical characteristics and standard laboratory parameters of preeclamptic patients, to markers of inflammation, endothelial activation or injury, oxidative stress and to cell-free fetal DNA levels. Methods Circulating total cell-free DNA was measured by real-time quantitative PCR in plasma samples obtained from 67 preeclamptic and 70 normotensive pregnant women. Standard laboratory parameters, C-reactive protein, plasma von Willebrand factor antigen, plasma fibronectin, plasma malondialdehyde and cell-free fetal DNA levels were also determined. Results and Conclusion Circulating total cell-free and fetal deoxyribonucleic acid levels were significantly elevated in pregnancies complicated by preeclampsia (median: 11.395 vs. 32.460 and 0.001 vs. 0.086 pg/μl; P < .001. The quantity of plasma total cell-free DNA did not correlate with most of the laboratory parameters, except for serum aspartate aminotransferase and alanine aminotransferase activities (correlation coefficient: 0.31; P = 0.012 and 0.46; P < .001. There was no correlation with clinical characteristics, including body mass index. The releases of both free fetal and total cell-free deoxyribonucleic acid were found to be affected in preeclampsia. Hepatocellular necrosis seems to be responsible - at least partly - for increased circulating total DNA levels in preeclampsia, as suggested by the significant correlation with liver enzyme activities.

  3. The relationship of the levels of IGF-1, IGFBP-3, LEP of birth weight and huge child birth%IGF-1、IGFBP-3与新生儿出生体重及巨大儿出生率的关系研究

    Institute of Scientific and Technical Information of China (English)

    梁辉标; 陈丽; 蓝晓林

    2015-01-01

    目的 探讨胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白3(IGFBP-3)与新生儿出生体重及巨大儿出生率的关系.方法 应用ELISA法测定85例正常妊娠(正常组)、80例妊娠糖尿病组(GDM组)及80例胎儿宫内发育迟缓(IUCR组)足月分娩时母血及脐血中IGF-1、IGFBP-3水平,观察三组新生儿出生体重,并分析IGF-1、IGFBP-3与巨大儿的关系.结果 正常组、GDM组及IUCR组母血IGF-1、IGFBP-3水平无统计学差异(P>0.05).GDM组脐血中IGF-1、IGFBP-3水平显著高于正常组及IUCR组(P<0.05),而正常组脐血中IGF-1、IGFBP-3水平显著高于IUCR组(P<0.05).GDM组新生儿出生体重显著重于对照组及IUCR组(P<0.05),而巨大儿出生率高于对照组及IUCR组(P<0.05).与低出生体重儿及正常体重儿相比,巨大儿脐血中IGF-1、 IGFBP-3水平显著较高(P<0.05),而正常体重儿脐血中IGF-1、IGFBP-3水平高于低出生体重儿(P<0.05).结论 脐血中IGF-1、 IGFBP-3水平对胎儿宫内发育具有重要的调节作用,可能是胎盘中影响胎儿生长发育的重要因子,并与IUGR及巨大儿形成有密切的关系.

  4. Circulating Levels of IL-1B+IL-6 Cause ER Stress and Dysfunction in Islets From Prediabetic Male Mice

    OpenAIRE

    O'Neill, Christina M.; Lu, Christine; Corbin, Kathryn L.; Sharma, Poonam R.; Dula, Stacey B.; Carter, Jeffrey D.; Ramadan, James W.; Xin, Wenjun; Lee, Jae K.; Nunemaker, Craig S.

    2013-01-01

    Elevated levels of circulating proinflammatory cytokines are associated with obesity and increased risk of type 2 diabetes, but the mechanism is unknown. We tested whether proinflammatory cytokines IL-1B+IL-6 at low picogram per milliliter concentrations (consistent with serum levels) could directly trigger pancreatic islet dysfunction. Overnight exposure to IL-1B+IL-6 in islets isolated from normal mice and humans disrupted glucose-stimulated intracellular calcium responses; cytokine-induced...

  5. High intakes of skimmed milk, but not meat, increase serum IGF-I and IGFBP-3 in eight-year-old boys

    DEFF Research Database (Denmark)

    Hoppe, Camilla; Mølgaard, C; Juul, A;

    2004-01-01

    To examine whether a high protein intake (PI) from either milk or meat, at a level often seen in late infancy, could increase s-IGF-I and s-IGF-I/s-IGFBP-3 in healthy, prepubertal children. IGF-I levels are positively associated with growth velocity in children and some studies suggest that a high...

  6. Light stimuli control neuronal migration by altering of insulin-like growth factor 1 (IGF-1) signaling.

    Science.gov (United States)

    Li, Ying; Komuro, Yutaro; Fahrion, Jennifer K; Hu, Taofang; Ohno, Nobuhiko; Fenner, Kathleen B; Wooton, Jessica; Raoult, Emilie; Galas, Ludovic; Vaudry, David; Komuro, Hitoshi

    2012-02-14

    The role of genetic inheritance in brain development has been well characterized, but little is known about the contributions of natural environmental stimuli, such as the effect of light-dark cycles, to brain development. In this study, we determined the role of light stimuli in neuronal cell migration to elucidate how environmental factors regulate brain development. We show that in early postnatal mouse cerebella, granule cell migration accelerates during light cycles and decelerates during dark cycles. Furthermore, cerebellar levels of insulin-like growth factor 1 (IGF-1) are high during light cycles and low during dark cycles. There are causal relationships between light-dark cycles, speed of granule cell migration, and cerebellar IGF-1 levels. First, changes in light-dark cycles result in corresponding changes in the fluctuations of both speed of granule cell migration and cerebellar IGF-1 levels. Second, in vitro studies indicate that exogenous IGF-1 accelerates the migration of isolated granule cells through the activation of IGF-1 receptors. Third, in vivo studies reveal that inhibiting the IGF-1 receptors decelerates granule cell migration during light cycles (high IGF-1 levels) but does not alter migration during dark cycles (low IGF-1 levels). In contrast, stimulating the IGF-1 receptors accelerates granule cell migration during dark cycles (low IGF-1 levels) but does not alter migration during light cycles (high IGF-1 levels). These results suggest that during early postnatal development light stimuli control granule cell migration by altering the activity of IGF-1 receptors through modification of cerebellar IGF-1 levels.

  7. Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation

    DEFF Research Database (Denmark)

    Pedersen, Henrik Duelund; Falk, Bo Torkel; Häggström, Jens;

    2005-01-01

    Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations...... has been found in several studies. In dogs with HF, few studies have focused on IGF-1. We examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR) caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King Charles Spaniels (CKCSs) with a broad range...... of asymptomatic MR (median serum IGF-1: 76.7 µg/L; 25-75 percentile, 59.8-104.9 µg/L). As expected, standard body weight and percentage under- or overweight correlated directly with IGF-1. MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28 dogs with severe MR and stable, treated...

  8. 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.

  9. 鸭发育早期骨骼肌异步发育和IGF-I/MSTN-A mRNA 表达的相关性%Correlation of the Relative Levels of Insulin-Like Growth Factor - I and Myostatin mRNA Expression and Asynchronous Development of Skeletal Muscles Development in Ducks During Early Development

    Institute of Scientific and Technical Information of China (English)

    胡艳; 刘宏祥; 单艳菊; 姬改革; 束婧婷; 徐文娟; 朱春红; 陶志云; 李慧芳

    2016-01-01

    Objective] The present experiment was conducted to study the mRNA expression characterization of insulin-like growth factor 1 (IGF-I) and myostatin A (MSTN-A), the developmental pattern in duck skeletal muscles and their correlation during embryogenesis and post-hatching development in different breeds of ducks.[Method]We have compared the ontogeny of body weight, the weight of pectoralis major (PM) and lateral gastrocnemius muscle (LM) and the mRNA expression of insulin-like growth factor-I (IGF-I) and myostatin A (MSTN-A) at the embryonic days 13, 17, 21, 25, 27 and the neonatal age of 7 days of Gaoyou duck and Jinding duck.[Result]During embryogenesis and post-hatching development, the weight of PM and LM showed an extreme significant difference by duck variety and time. The mRNA expression of IGF-I and MSTN-A in duck breast/leg muscles had significantly negative correlations with body weight and weight of skeletal muscle, but had a positive correlation with breast/leg muscles index. During early development, there were extremely significant positive correlations between the mRNA expression of IGF-I and MSTN-A, and there were peaks in the mRNA expression of IGF-I and MSTN-A at embryonic age of 13 days. The turning points of IGF-I mRNA expression in duck PM were matched with PM growth, and but not for LM. During duck myogenesis, the profile of MSTN-A expression showed synchronization with growth of skeletal muscle and the peaks of proliferation in changes of myofiber characters, and the differences of the IGF-I/MSTN-A mRNA ratio in PM between the two myoblasts. The IGF-I/MSTN-A mRNA ratio in PM and LM were significantly higher with a similar trend in the breeds matched the timing of varieties difference in PM weight.[Conclusion] During embryogenesis and post-hatching development, the duck PM and LM developed in an asynchronous pattern. The relative levels of IGF-I and MSTN mRNA may participate to set muscle growth rate along development.%【目的】选择生长

  10. 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.

  11. 动物GH/IGF-Ⅰ轴调控机制的研究进展%Advances on the Regulation Mechanism of Growth Hormone/IGF- Ⅰ Axis

    Institute of Scientific and Technical Information of China (English)

    顾志良; 王慧娟; 郁建锋

    2011-01-01

    生长轴是动物体内下丘脑—垂体—靶器官一系列激素及其受体所组成的神经内分泌系统.通过提高生长轴中生长激素(GH)和胰岛素样生长因子-Ⅰ (IGF-Ⅰ)水平,促进增重、提高饲料转化率和改善肉品质,是畜禽生长调控的一种新途径.GH通过IGF-Ⅰ介导调节动物生长和细胞分化等,文章综述了GH/IGF-Ⅰ轴的组成、功能,以及GH调控IGF-Ⅰ表达的分子机理.%The growth axis is a neuroendocrine system, which is composed of series of hormones and their receptors from the hypothalamus-pituitary-target organ in xrivo of animals. Increasing the GH and IGF- I levels in the growth axis, to promote weight gain, feed conversion rate and improve meat quality, which is a new approach of animal growth regulation. GH mediated by IGF- I regulates animal growth and cell differentiation. We will discuss the constitution and function of GH/IGF-I axis, and mechanism of growth hormone regulation of IGF- I expression in this review.

  12. Steam drum level dynamics in a multiple loop natural circulation system of a pressure-tube type BWR

    International Nuclear Information System (INIS)

    Advanced Heavy Water Reactor (AHWR) is a pressure tube type boiling water reactor employing natural circulation as the mode of heat removal under all the operating conditions. Main Heat Transport System (MHTS) of AHWR is essentially a multi-loop natural circulation system with all the loops connected to each other. Each loop of MHTS has a steam drum that provides for gravity based steam-water separation. Steam drum level is a very critical parameter especially in multi-loop natural circulation systems as large departures from the set point may lead to ineffective separation of steam-water or may affect the driving head. However, such a system is susceptible to steam drum level anomalies under postulated asymmetrical operating conditions among the different quadrants of the core like feedwater flow distribution anomaly among the steam drums or power anomaly among the core quadrants. Analyses were carried out to probe such scenarios and unravel the underlying dynamics of steam drum level using system code RELAP5/Mod3.2. In addition, a scheme to obviate such problem in a passive manner without dependence on level controller was examined. It was concluded that steam drums need to be connected in the liquid as well as steam space to make the system tolerant to asymmetrical operating conditions.

  13. Smoking decreases the level of circulating CD34+ progenitor cells in young healthy women - a pilot study

    Directory of Open Access Journals (Sweden)

    Baumann Gert

    2010-05-01

    Full Text Available Abstract Background Decreased levels of circulating bone marrow-derived progenitor cells have been associated with risk factors and cardiovascular diseases. Smoking is the most important modifiable risk factor for atherosclerosis in young women. The aim of this pilot study was to assess in healthy premenopausal women without other risk factors for cardiovascular disease the influence of nicotine abuse on the number of circulating progenitor cells in relation to endothelial function. Methods The number of endothelial progenitor cells, measured as colony-forming units in a cell-culture assay (EPC-CFU and the number of circulating CD34 + and CD34 + /CD133 + cells, measured by flow cytometry, was estimated in 32 women at the menstrual phase of the menstrual cycle. In addition, flow-mediated dilation (FMD was assessed as a marker for vascular function. In a subgroup of these women (n = 20, progenitor cells were also investigated at the mid-follicular and luteal phases of the menstrual cycle. Results Compared to non-smokers, the abundance of circulating CD34 + cells was significantly lower in smoking women in the menstrual, mid-luteal, and mid-follicular phases of the menstrual cycle. The number of CD34 + progenitor cells was revealed to have significant positive correlation with FMD in young healthy women, whereas CD34 + /CD133 + progenitor cells and EPC-CFU showed no significant correlation. Conclusion The number of CD34 + progenitor cells positively correlates with FMD in young healthy women and is decreased by smoking.

  14. GH/IGF-I axis and matrix adaptation of the musculotendinous tissue to exercise in humans

    DEFF Research Database (Denmark)

    Heinemeier, K M; Mackey, Abigail; Doessing, S;

    2012-01-01

    cells (satellite cells), as increased satellite cell numbers are found in human muscle with increased GH/IGF-I levels, despite no change in myofibrillar protein synthesis. Although advanced age is associated with both a reduction in the GH/IGF-I axis activity, and in skeletal muscle mass (sarcopenia...

  15. IGF-1R inhibition induces schedule-dependent sensitization of human melanoma to temozolomide.

    Science.gov (United States)

    Ramcharan, Roger; Aleksic, Tamara; Kamdoum, Wilfride Petnga; Gao, Shan; Pfister, Sophia X; Tanner, Jordan; Bridges, Esther; Asher, Ruth; Watson, Amanda J; Margison, Geoffrey P; Woodcock, Mick; Repapi, Emmanouela; Li, Ji-Liang; Middleton, Mark R; Macaulay, Valentine M

    2015-11-24

    Prior studies implicate type 1 IGF receptor (IGF-1R) in mediating chemo-resistance. Here, we investigated whether IGF-1R influences response to temozolomide (TMZ), which generates DNA adducts that are removed by O6-methylguanine-DNA methyltransferase (MGMT), or persist causing replication-associated double-strand breaks (DSBs). Initial assessment in 10 melanoma cell lines revealed that TMZ resistance correlated with MGMT expression (r = 0.79, p = 0.009), and in MGMT-proficient cell lines, with phospho-IGF-1R (r = 0.81, p = 0.038), suggesting that TMZ resistance associates with IGF-1R activation. Next, effects of IGF-1R inhibitors (IGF-1Ri) AZ3801 and linsitinib (OSI-906) were tested on TMZ-sensitivity, cell cycle progression and DSB induction. IGF-1Ri sensitized BRAF wild-type and mutant melanoma cells to TMZ in vitro, an effect that was independent of MGMT. Cells harboring wild-type p53 were more sensitive to IGF-1Ri, and showed schedule-dependent chemo-sensitization that was most effective when IGF-1Ri followed TMZ. This sequence sensitized to clinically-achievable TMZ concentrations and enhanced TMZ-induced apoptosis. Simultaneous or prior IGF-1Ri caused less effective chemo-sensitization, associated with increased G1 population and reduced accumulation of TMZ-induced DSBs. Clinically relevant sequential (TMZ → IGF-1Ri) treatment was tested in mice bearing A375M (V600E BRAF, wild-type p53) melanoma xenografts, achieving peak plasma/tumor IGF-1Ri levels comparable to clinical Cmax, and inducing extensive intratumoral apoptosis. TMZ or IGF-1Ri caused minor inhibition of tumor growth (gradient reduction 13%, 25% respectively), while combination treatment caused supra-additive growth delay (72%) that was significantly different from control (p < 0.01), TMZ (p < 0.01) and IGF-1Ri (p < 0.05) groups. These data highlight the importance of scheduling when combining IGF-1Ri and other targeted agents with drugs that induce replication-associated DNA damage. PMID

  16. Abnormal sex chromosome constitution and longitudinal growth: serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-3, luteinizing hormone, and testosterone in 109 males with 47,XXY, 47,XYY, or sex-determining region of the Y chromosome (SRY)-positive 46,XX karyotypes

    DEFF Research Database (Denmark)

    Aksglaede, L.; Skakkebaek, N.E.; Juul, A.

    2008-01-01

    CONTEXT: Growth is a highly complex process regulated by the interaction between sex steroids and the GH IGF-axis. However, other factors such as sex chromosome-related genes play independent roles. AIM: The aim of the study was to evaluate the role of abnormal chromosome constitution for longitu...

  17. mRNA expression patterns for GH, PRL, SL, IGF-I and IGF-II during altered feeding status in rabbitfish, Siganus guttatus.

    Science.gov (United States)

    Ayson, Felix G; de Jesus-Ayson, Evelyn Grace T; Takemura, Akihiro

    2007-01-15

    Feeding time is a major synchronizer of many physiological rhythms in many organisms. Alteration in the nutritional status, specifically fasting, also affects the secretion rhythms of growth hormone (GH) and insulin-like growth factor-I (IGF-I). In this study, we investigated whether the expression patterns for the mRNAs of GH, prolactin (PRL) and somatolactin (SL) in the pituitary gland, and insulin-like growth factor I and II (IGF-I and IGF-II) in the liver of juvenile rabbitfish (Siganus guttatus) follow a rhythm according to feeding time and whether these hormone rhythms changes with starvation. Hormone mRNA levels were determined by real time PCR. The daily expression pattern for the mRNAs of GH, PRL and SL was not altered whether food was given in the morning (10:00 h) or in the afternoon (15:00 h). The daily GH mRNA expression pattern, however, was affected when food was not available for 3 days. In contrast, the daily expression pattern for IGF-I mRNA reaches its peak at roughly 5-6h after feeding. This pattern, however, was not observed with IGF-II mRNA. During 15-day starvation, GH mRNA levels in starved fish were significantly higher than the control fish starting on the 9th day of starvation until day 15. The levels returned to normal after re-feeding. In contrast to GH, PRL mRNA levels in starved fish were significantly lower than the control group starting on the 6th day of starvation until 3 days after re-feeding. SL mRNA levels were not significantly different between the control and starved group at anytime during the experiment. Both IGF-I and IGF-II mRNA levels in starved group were significantly higher than the control fish on the 3rd and 6th day of starvation. mRNA levels of both IGF-I and II in the starved fish decreased starting on the 9th day of starvation. While IGF-I mRNA levels in the starved group continued to decrease as starvation progressed, IGF-II mRNA levels were not significantly different from the control during the rest of the

  18. Crosstalk between adiponectin and IGF-IR in breast cancer

    Directory of Open Access Journals (Sweden)

    Loredana eMauro

    2015-07-01

    Full Text Available Obesity is a chronic and multifactorial disorder that is reaching epidemic proportions. It is characterized by an enlarged mass of adipose tissue caused by a combination of size increase of preexisting adipocytes (hypertrophy and de novo adipocyte differentiation (hyperplasia. Obesity is related to many metabolic disorders like hypertension, type 2 diabetes, metabolic syndrome, cardiovascular disease, and it is associated with an increased risk of cancer development in different tissues including breast. Adipose tissue is now regarded as not just a storage reservoir for excess energy, but rather as an endocrine organ, secreting a large number of bioactive molecules called adipokines. Among these, adiponectin represents the most abundant adipose tissue-excreted protein, which exhibits insulin-sensitizing, anti-inflammatory and antiatherogenic properties. The serum concentrations of adiponectin are inversely correlated with body mass index. Recently, low levels of plasma adiponectin have been associated with an increased risk for obesity-related cancers and development of more aggressive phenotype, concomitantly with alterations in the bioavailability of Insulin-like Growth Factor-I (IGF-I and IGF-I Receptor (IGF-IR signaling pathways. In this review we discuss the cross-talk between adiponectin/AdipoR1 and IGF-I/IGF-IR in breast cancer.

  19. Effect of recombinant porcine IGF-binding protein-3 on proliferation of embryonic porcine myogenic cell cultures in the presence and absence of IGF-I.

    Science.gov (United States)

    Pampusch, M S; Kamanga-Sollo, E; White, M E; Hathaway, M R; Dayton, W R

    2003-02-01

    IGF-binding protein (IGFBP)-3 is produced by cultured porcine embryonic myogenic cell (PEMC) cultures and is secreted into the medium. Levels of secreted IGFBP-3 and IGFBP-3 mRNA are significantly reduced during differentiation and increase after differentiation is complete, suggesting that IGFBP-3 may play some role in myogenesis and/or in changes in myogenic cell proliferation that accompany differentiation. IGFBP-3 reportedly may either suppress or stimulate proliferation of cultured cells depending on cell type. Additionally, IGFBP-3 has been shown to affect proliferation via both IGF-dependent and IGF-independent mechanisms in some cell types but not all. Currently, the effect, if any, of IGFBP-3 on myogenic cell proliferation is not known. Consequently, the goal of this study was to assess the IGF-I-dependent and IGF-I-independent actions of recombinant porcine IGFBP-3 on proliferation of cultured porcine myogenic cells. To facilitate these investigations, we have expressed porcine IGFBP-3 in the baculovirus system, purified and characterized the expressed recombinant porcine IGFBP-3 (rpIGFBP-3), and produced and characterized an anti-porcine IGFBP-3 antibody that neutralizes the biological activity of porcine IGFBP-3. rpIGFBP-3 suppressed IGF-I-stimulated proliferation of PEMCs in a concentration-dependent manner with equimolar concentrations of IGF-I and rpIGFBP-3, resulting in complete suppression of IGF-I-stimulated proliferation. rpIGFBP-3 also suppressed Long-R3-IGF-I-stimulated proliferation of PEMC, indicating that rpIGFBP-3 possesses IGF-independent activity in this cell system. These data have established that IGFBP-3 has the potential to affect proliferation of PEMCs during critical periods of muscle development that may impact ultimate muscle mass achievable postnatally. PMID:12553871

  20. Effects of dietary genistein on GH/IGF-I axis of Nile tilapia Oreochromis niloticus

    Science.gov (United States)

    Chen, Dong; Wang, Wei; Ru, Shaoguo

    2016-09-01

    There is considerable concern that isoflavones, such as genistein in fish feed composed of soybean protein, aff ects somatic growth in fish. Our previous works demonstrated that 30 and 300 μg/g dietary genistein had no significant eff ect on growth performance in Nile tilapia ( Oreochromis niloticus), but the higher level of genistein (3 000 μg/g) significantly depressed growth. This study was conducted to further examine the eff ects of dietary genistein on the endocrine disruption on growth hormone/insulin-like growth factor-I (GH/IGF-I) axis in Nile tilapia ( O. niloticus). Juvenile fish were fed by hand twice daily to satiation with one of four isonitrogenous and isoenergetic diets, each containing either 0, 30, 300 or 3 000 μg/g genistein. Following an 8-week feeding period, plasma GH and IGF-I levels were investigated by radioimmunoassay and gene expression levels of gh, ghrelin, gnrhs, ghr, npy, npyrs, pacap, ghrs, i gf-I, igf-Ir, and igfbp3 were examined by real-time PCR. The results show that no significant change in plasma GH and IGF-I levels in fish fed with diets containing 30 μg/g and 300 μg/g genistein. mRNA expression of genes along the GH/IGF-I axis remained unaff ected, except for igf-Ir, which was stimulated by the 300 μg/g genistein diet. While in fish fed the 3 000 μg/g genistein diet, the plasma GH and IGF-I levels decreased, and mRNA expression of gh, ghr2, npyr1, igf-I, and igf-Ir were also significantly depressed. In contrast, npy and igfbp3 mRNA expression were enhanced. This study provides convincing evidence for growth impediment by genistein by disturbing the GH/IGF-I axis in Nile tilapia O. niloticus.

  1. The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy

    Science.gov (United States)

    Adams, G. R.; Haddad, F.

    1996-01-01

    Insulin-like growth factor-1 (IGF-1) is known to have anabolic effects on skeletal muscle cells. This study examined the time course of muscle hypertrophy and associated IGF-1 peptide and mRNA expression. Data were collected at 3, 7, 14, and 28 days after surgical removal of synergistic muscles of both normal and hypophysectomized (HX) animals. Overloading increased the plantaris (Plant) mass, myofiber size, and protein-to-body weight ratio in both groups (normal and HX; P Muscle IGF-1 peptide levels peaked at 3 (normal) and 7 (HX) days of overloading with maximum 4.1-fold (normal) and 6.2-fold (HX) increases. Increases in muscle IGF-1 preceded the hypertrophic response. Total DNA content of the overloaded Plant increased in both groups. There was a strong positive relationship between IGF-1 peptide and DNA content in the overloaded Plant from both groups. These results indicate that 1) the muscles from rats with both normal and severely depressed systemic levels of IGF-1 respond to functional overload with an increase in local IGF-1 expression and 2) this elevated IGF-1 may be contributing to the hypertrophy response, possibly via the mobilization of satellite cells to provide increases in muscle DNA.

  2. A multi-level adaptation model of circulation for the western Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Shaji, C.; Bahulayan, N.; Dube, S.K.; Rao, A.D.

    topography is also included in diagnostic models. Many diagnostic calculations of seasonal mean currents in the non-equatorial regions of the world oceans have been carried out by Sarkisyan and his co-workers [1–4]. These calculations show that, on average..., the baroclinic currents do not decay very rapidly with depth. Even at greater depths, the horizontal gradient of density is one of the main factors that control the large scale circulation in the ocean. Mellor et al. [5] has carried out the diagnostic calculation...

  3. IGF-1, IGFBP-3, and nutritional factors in young black and white men: the CARDIA Male Hormone Study.

    Science.gov (United States)

    Colangelo, Laura A; Chiu, Brian C-H; Liu, Kiang; Kopp, Peter A; Gann, Peter H; Gapstur, Susan M

    2005-01-01

    Nutritional factors might play a role in regulating serum levels of insulin-like growth factors (IGFs), which are associated with some cancers. We examined the associations of nutritional factors with IGF-1 and IGF binding protein-3 (IGFBP-3). Serum IGF-1 and IGFBP-3 levels and dietary intake were measured in 459 black and 682 white male subjects of the Coronary Artery Risk Development in Young Adults study at the Year 7 (1992-1993) exam. Analysis of covariance and multivariable linear regression were used to assess associations of IGFs with dietary factors by race. IGF-1 was positively associated with magnesium in both black and white men (P = 0.008 and 0.05, respectively). Calcium was positively significantly related to IGF-1 in black men (P = 0.04) and marginally so in white men (P = 0.09). In black men, IGFBP-3 was positively associated with magnesium (P = 0.02), and one serving of milk per day was associated with an 8.23-ng/ml higher IGF-1 concentration (P = 0.05). Tests for interaction, however, revealed no differences between blacks and whites in the associations of nutrients with IGF-1 or IGFBP-3. In conclusion, the associations of dietary factors with serum IGF-1 and IGFBP-3 observed in our study corroborate those from other studies and generally do not differ between black and white men.

  4. High circulating levels of tumor necrosis factor-alpha in centenarians are not associated with increased production in T lymphocytes

    DEFF Research Database (Denmark)

    Sandmand, Marie; Bruunsgaard, Helle; Kemp, Kåre;

    2003-01-01

    BACKGROUND: Aging is characterized by increased inflammatory activity reflected by increased plasma levels of proinflammatory cytokines, concomitant with an altered cytokine profile of T lymphocytes. High plasma levels of tumor necrosis factor (TNF)-alpha are strongly associated with morbidity...... and mortality in elderly humans. However, the cellular source and mechanisms for the increased circulating TNF-alpha levels are unknown. OBJECTIVE: The aim of the present study was to investigate if high plasma levels of TNF-alpha are associated with increased production of TNF-alpha by T lymphocytes in elderly...... humans. METHODS: TNF-alpha production by CD4+ and CD8+ T lymphocytes was measured by flow cytometry following stimulation with phorbol 12-myristate 13-acetate and ionomycin in 28 young controls, 14, 81-year-olds and 25 centenarians. RESULTS: Plasma levels of TNF-alpha increased with increasing age...

  5. HIV-1/HAART-Related Lipodystrophy Syndrome (HALS Is Associated with Decreased Circulating sTWEAK Levels.

    Directory of Open Access Journals (Sweden)

    Miguel López-Dupla

    Full Text Available Obesity and HIV-1/HAART-associated lipodystrophy syndrome (HALS share clinical, pathological and mechanistic features. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK is a multifunctional cytokine that plays an important role in obesity and related diseases. We sought to explore the relationship between HALS and circulating levels of soluble (s TWEAK and its scavenger receptor sCD163.This was a cross-sectional multicenter study of 120 HIV-1-infected patients treated with a stable HAART regimen; 56 with overt HALS and 64 without HALS. Epidemiological and clinical variables were determined. Serum levels of sTWEAK and sCD163 levels were measured by ELISA. Results were analyzed with Student's t-test, Mann-Whitney U and χ2 test. Pearson and Spearman correlation were used to estimate the strength of association between variables.Circulating sTWEAK was significantly decreased in HALS patients compared with non-HALS patients (2.81±0.2 vs. 2.94±0.28 pg/mL, p = 0.018. No changes were observed in sCD163 levels in the studied cohorts. On multivariate analysis, a lower log sTWEAK concentration was independently associated with the presence of HALS (OR 0.027, 95% CI 0.001-0.521, p = 0.027.HALS is associated with decreased sTWEAK levels.

  6. The IGF-Axis and Diabetic Retinopathy Before and After Gastric Bypass Surgery

    DEFF Research Database (Denmark)

    Brynskov, Troels; Laugesen, Caroline Schmidt; Floyd, Andrea Karen;

    2016-01-01

    BACKGROUND: Laparoscopic gastric bypass (LGB) abruptly causes remission of type 2 diabetes (T2D). Such dramatic metabolic changes have previously been found to cause worsening of diabetic retinopathy (DR) and circulating insulin-like growth factor I (IGF-I) has been suggested as a causal mediator...

  7. Maternal deprivation has sexually dimorphic long-term effects on hypothalamic cell-turnover, body weight and circulating hormone levels.

    Science.gov (United States)

    Viveros, María-Paz; Llorente, Ricardo; Díaz, Francisca; Romero-Zerbo, Silvana Y; Bermudez-Silva, Francisco J; Rodríguez de Fonseca, Fernando; Argente, Jesús; Chowen, Julie A

    2010-11-01

    Maternal deprivation (MD) has numerous outcomes, including modulation of neuroendocrine functions. We previously reported that circulating leptin levels are reduced and hypothalamic cell-turnover is affected during MD, with some of these effects being sexually dimorphic. As leptin modulates the development of hypothalamic circuits involved in metabolic control, we asked whether MD has long-term consequences on body weight, leptin levels and the expression of neuropeptides involved in metabolism. Rats were separated from their mother for 24h starting on postnatal day (PND) 9 and sacrificed at PNDs 13, 35 and 75. In both sexes MD reduced body weight, but only until puberty, while leptin levels were unchanged at PND 35 and significantly reduced at PND 75. Adiponectin levels were also reduced at PND 75 in females, while testosterone levels were reduced in males. At PND 13, MD modulated cell-turnover markers in the hypothalamus of males, but not females and increased nestin, a marker of immature neurons, in both sexes, with males having higher levels than females and a significantly greater rise in response to MD. There was no effect of MD on hypothalamic mRNA levels of the leptin receptor or metabolic neuropeptides or the mRNA levels of leptin and adiponectin in adipose tissue. Thus, MD has long-term effects on the levels of circulating hormones that are not correlated with changes in body weight. Furthermore, these endocrine outcomes are different between males and females, which could be due to the fact that MD may have sexually dimorphic effects on hypothalamic development.

  8. IGF-1 (Insulin-Like Growth Factor -1) Test

    Science.gov (United States)

    ... 1) may be used to help: Identify growth hormone (GH) deficiency; it is not diagnostic of a GH ... day, making it a useful indicator of average GH levels. IGF-1 may be ordered with other pituitary hormone tests, such as prolactin or FSH and LH , ...

  9. Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability.

    Science.gov (United States)

    Dauber, Andrew; Muñoz-Calvo, María T; Barrios, Vicente; Domené, Horacio M; Kloverpris, Soren; Serra-Juhé, Clara; Desikan, Vardhini; Pozo, Jesús; Muzumdar, Radhika; Martos-Moreno, Gabriel Á; Hawkins, Federico; Jasper, Héctor G; Conover, Cheryl A; Frystyk, Jan; Yakar, Shoshana; Hwa, Vivian; Chowen, Julie A; Oxvig, Claus; Rosenfeld, Ron G; Pérez-Jurado, Luis A; Argente, Jesús

    2016-01-01

    Mutations in multiple genes of the growth hormone/IGF-I axis have been identified in syndromes marked by growth failure. However, no pathogenic human mutations have been reported in the six high-affinity IGF-binding proteins (IGFBPs) or their regulators, such as the metalloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) that is hypothesized to increase IGF-I bioactivity by specific proteolytic cleavage of IGFBP-3 and -5. Multiple members of two unrelated families presented with progressive growth failure, moderate microcephaly, thin long bones, mildly decreased bone density and elevated circulating total IGF-I, IGFBP-3, and -5, acid labile subunit, and IGF-II concentrations. Two different homozygous mutations in PAPPA2, p.D643fs25* and p.Ala1033Val, were associated with this novel syndrome of growth failure. In vitro analysis of IGFBP cleavage demonstrated that both mutations cause a complete absence of PAPP-A2 proteolytic activity. Size-exclusion chromatography showed a significant increase in IGF-I bound in its ternary complex. Free IGF-I concentrations were decreased. These patients provide important insights into the regulation of longitudinal growth in humans, documenting the critical role of PAPP-A2 in releasing IGF-I from its BPs. PMID:26902202

  10. Epigenetic DNA methylation in the promoters of the Igf1 receptor and insulin receptor genes in db/db mice.

    Science.gov (United States)

    Nikoshkov, Andrej; Sunkari, Vivekananda; Savu, Octavian; Forsberg, Elisabete; Catrina, Sergiu-Bogdan; Brismar, Kerstin

    2011-04-01

    We have investigated promoter methylation of the Insr, Igf1 and Igf1r genes in skeletal and cardiac muscles of normal and diabetic db/db mice. No differences in Insr promoter methylation were found in the heart and skeletal muscles and no methylation was detected in the Igf1 promoter in skeletal muscle. In skeletal muscle, db/db males exhibited a 7.4-fold increase in Igf1r promoter methylation, which was accompanied by a 1.8-fold decrease in Igf1r mRNA levels, compared with controls. More than 50% of the detected methylation events were concentrated within an 18 bp sequence that includes one of the Sp1 binding sites. We conclude that the methylation level and pattern of the Igf1r promoter in skeletal muscle is related to gender and the diabetic state. PMID:21474992

  11. Homocysteine harasses the imprinting expression of IGF2 and H19 by demethylation of differentially methylated region between IGF2/H19 genes

    Institute of Scientific and Technical Information of China (English)

    Lijuan Li; Jing Xie; Meng Zhang; Shuren Wang

    2009-01-01

    Homocysteine (Hcy) can induce proliferation of vascular smooth muscle cells (VSMCs), which is a key event in the genesis of the lesions of atherosclerosis. Insulinlike growth factor 2 (IGF2) and 1119 are two important regulating molecules of cell proliferation. The role of Hcy in the proliferation of smooth muscle cell by regulating IGF2 and HI9 has not been shown or analyzed so far. This study aims to investigate the potential impact of Hcy on gene imprinting of IGF2 and 1-119.Cultured human umbilical VSMCs were treated with different concentrations of Hcy. The DNA methylation status of VSMCs was assayed by nested methylationspecific polymerase chain reaction (PCR). The mRNA levels of H19, IGF2, and CCCTC-binding factor (CTCF) were detected by reverse transcription PCR,and the protein expression of IGF2 by Western blotting. The results showed that the Hcy treatment resulted in hypomethylation of the sixth CTCF-binding site upstream of 1119 of VSMCs. The expression of H19 was increased, whereas the IGF2 mRNA and protein were decreased, the CTCF expression increased with the increase in Hcy concentration. These data indicated that Hcy could induce hypomethylation of the sixth CTCF-binding sites upstream of 1119, which is an important regulating area for the imprinting expression of IGF2 and 1119. The increased CTCF expression may be a potential mechanism for the demethylation modification of DNA, which resulted from the Hcy treatment.

  12. A combination of l-arabinose and chromium lowers circulating glucose and insulin levels after an acute oral sucrose challenge

    Directory of Open Access Journals (Sweden)

    Perricone Nicholas V

    2011-05-01

    Full Text Available Abstract Background A growing body of research suggests that elevated circulating levels of glucose and insulin accelerate risk factors for a wide range of disorders. Low-risk interventions that could suppress glucose without raising insulin levels could offer significant long-term health benefits. Methods To address this issue, we conducted two sequential studies, the first with two phases. In the first phase of Study 1, baseline fasting blood glucose was measured in 20 subjects who consumed 70 grams of sucrose in water and subsequently completed capillary glucose measurements at 30, 45, 60 and 90 minutes (Control. On day-2 the same procedure was followed, but with subjects simultaneously consuming a novel formula containing l-arabinose and a trivalent patented food source of chromium (LA-Cr (Treatment. The presence or absence of the LA-Cr was blinded to the subjects and testing technician. Comparisons of changes from baseline were made between Control and Treatment periods. In the second phase of Study 1, 10 subjects selected from the original 20 competed baseline measures of body composition (DXA, a 43-blood chemistry panel and a Quality of Life Inventory. These subjects subsequently took LA-Cr daily for 4 weeks completing daily tracking forms and repeating the baseline capillary tests at the end of each of the four weeks. In Study 2, the same procedures used in the first phase were repeated for 50 subjects, but with added circulating insulin measurements at 30 and 60 minutes from baseline. Results In both studies, as compared to Control, the Treatment group had significantly lower glucose responses for all four testing times (AUC = P P = Conclusions As compared to a placebo control, consumption of a LA-Cr formula after a 70-gram sucrose challenge was effective in safely lowering both circulating glucose and insulin levels. Trial Registration Clinical Trials.gov, NCT0110743

  13. Genetic variations altering FSH action affect circulating hormone levels as well as follicle growth in healthy peripubertal girls

    DEFF Research Database (Denmark)

    Busch, Alexander Siegfried; Hagen, Casper; Almstrup, Kristian;

    2016-01-01

    Abstract STUDY QUESTION: Do variants of the genes encoding follicle stimulating hormone (FSH) beta subunit (B) and FSH receptor (R) impact circulating reproductive hormone levels and ovarian follicle maturation in healthy peripubertal girls? SUMMARY ANSWER: FSHB and FSHR genetic variants exert...... (2006-2014, a cross-sectional and ongoing longitudinal study) and the Copenhagen Mother-Child Cohort (1997-2002, including transabdominal ultrasound (TAUS) of the ovaries in a subset of 91 peripubertal girls). PARTICIPANTS/MATERIALS, SETTING, METHODS: Clinical examinations, including pubertal breast...

  14. Decreased Circulating C3 Levels and Mesangial C3 Deposition Predict Renal Outcome in Patients with IgA Nephropathy

    OpenAIRE

    Seung Jun Kim; Hyang Mo Koo; Beom Jin Lim; Hyung Jung Oh; Dong Eun Yoo; Dong Ho Shin; Mi Jung Lee; Fa Mee Doh; Jung Tak Park; Tae-Hyun Yoo; Shin-Wook Kang; Kyu Hun Choi; Hyeon Joo Jeong; Seung Hyeok Han

    2012-01-01

    BACKGROUND AND AIMS: Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN). However, the role of complement in the pathogenesis or progression of IgAN is uncertain. In this observational cohort study, we aimed to identify the clinical implications of circulating C3 levels and mesangial C3 deposition and to investigate their utility as predictors of renal outcomes in patients with IgAN. METHODS: A total of 343 patients with biopsy-proven IgAN were enrolled betw...

  15. Serum IGF-1 affects skeletal acquisition in a temporal and compartment-specific manner.

    Directory of Open Access Journals (Sweden)

    Hayden-William Courtland

    Full Text Available Insulin-like growth factor-1 (IGF-1 plays a critical role in the development of the growing skeleton by establishing both longitudinal and transverse bone accrual. IGF-1 has also been implicated in the maintenance of bone mass during late adulthood and aging, as decreases in serum IGF-1 levels appear to correlate with decreases in bone mineral density (BMD. Although informative, mouse models to date have been unable to separate the temporal effects of IGF-1 depletion on skeletal development. To address this problem, we performed a skeletal characterization of the inducible LID mouse (iLID, in which serum IGF-1 levels are depleted at selected ages. We found that depletion of serum IGF-1 in male iLID mice prior to adulthood (4 weeks decreased trabecular bone architecture and significantly reduced transverse cortical bone properties (Ct.Ar, Ct.Th by 16 weeks (adulthood. Likewise, depletion of serum IGF-1 in iLID males at 8 weeks of age, resulted in significantly reduced transverse cortical bone properties (Ct.Ar, Ct.Th by 32 weeks (late adulthood, but had no effect on trabecular bone architecture. In contrast, depletion of serum IGF-1 after peak bone acquisition (at 16 weeks resulted in enhancement of trabecular bone architecture, but no significant changes in cortical bone properties by 32 weeks as compared to controls. These results indicate that while serum IGF-1 is essential for bone accrual during the postnatal growth phase, depletion of IGF-1 after peak bone acquisition (16 weeks is compartment-specific and does not have a detrimental effect on cortical bone mass in the older adult mouse.

  16. Thermal hydraulic aspects of steam drum level control philosophy for the natural circulation based heavy water reactor

    International Nuclear Information System (INIS)

    From safety considerations advanced nuclear reactors rely more and more on passive systems such as natural circulation for primary heat removal. A natural circulation based water reactor is relatively larger in size so as to reduce flow losses and channel type for proper flow distribution. From the size of steam drum considerations it has to be multi loop but has a common inlet header. Normally the turbine follows the reactor. This paper addresses the thermal hydraulic aspects of the steam drum pressure and level control philosophy for a four drum, natural circulation based, channel type boiling water advanced reactor. Three philosophies may be followed for drum control viz. individual drum control, one control drum approach and an average of all the four drums. For drum pressure control, the steam flow to the turbine is be regulated. A single point pressure control is better than individual drum pressure control. This is discussed in the paper. But the control point has to be at a place down steam the point where all steam line from individual drum meet. This may lead to different pressure in all the four drums depending on the power produced in the respective loops. The difference in pressure cannot be removed even if the four drums are directly connected through pipes. Also the pressure control scheme with/without interconnection is discussed. For level, the control of individual drum may not be normally possible because of common inlet header. As the frictional pressure drops in the large diameter downcomers are small as compared to elevation pressure drops, the level in all the steam drum tend to equalize. Consequently a single representative drum level may be chosen as a control variable for controlling level in all the four drums. But in case, where all the four loops are producing different powers and single point pressure control is effective, the scheme may not work satisfactorily. the level in a drum may depend on the power produced in the loop

  17. The level of circulating endothelial progenitor cells may be associated with the occurrence and recurrence of chronic subdural hematoma

    Directory of Open Access Journals (Sweden)

    Yan Song

    2013-01-01

    Full Text Available OBJECTIVES: The onset of chronic subdural hematoma may be associated with direct or indirect minor injuries to the head or a poorly repaired vascular injury. Endothelial progenitor cells happen to be one of the key factors involved in hemostasis and vascular repair. This study was designed to observe the levels of endothelial progenitor cells, white blood cells, platelets, and other indicators in the peripheral blood of patients diagnosed with chronic subdural hematoma to determine the possible relationship between the endothelial progenitor cells and the occurrence, development, and outcomes of chronic subdural hematoma. METHOD: We enrolled 30 patients with diagnosed chronic subdural hematoma by computer tomography scanning and operating procedure at Tianjin Medical University General Hospital from July 2009 to July 2011. Meanwhile, we collected 30 cases of peripheral blood samples from healthy volunteers over the age of 50. Approximately 2 ml of blood was taken from veins of the elbow to test the peripheral blood routine and coagulation function. The content of endothelial progenitor cells in peripheral blood mononuclear cells was determined by flow cytometry. RESULTS: The level of endothelial progenitor cells in peripheral blood was significantly lower in preoperational patients with chronic subdural hematomas than in controls. There were no significant differences between the two groups regarding the blood routine and coagulation function. However, the levels of circulating endothelial progenitor cells were significantly different between the recurrent group and the non-recurrent group. CONCLUSIONS: The level of circulating endothelial progenitor cells in chronic subdural hematoma patients was significantly lower than the level in healthy controls. Meanwhile, the level of endothelial progenitor cells in recurrent patients was significantly lower than the level in patients without recurrence. Endothelial progenitor cells may be related to the

  18. Virtual Screening of Specific Insulin-Like Growth Factor 1 Receptor (IGF1R Inhibitors from the National Cancer Institute (NCI Molecular Database

    Directory of Open Access Journals (Sweden)

    Yu-Xin Li

    2012-12-01

    Full Text Available Insulin-like growth factor 1 receptor (IGF1R is an attractive drug target for cancer therapy and research on IGF1R inhibitors has had success in clinical trials. A particular challenge in the development of specific IGF1R inhibitors is interference from insulin receptor (IR, which has a nearly identical sequence. A few potent inhibitors that are selective for IGF1R have been discovered experimentally with the aid of computational methods. However, studies on the rapid identification of IGF1R-selective inhibitors using virtual screening and confidence-level inspections of ligands that show different interactions with IGF1R and IR in docking analysis are rare. In this study, we established virtual screening and binding-mode prediction workflows based on benchmark results of IGF1R and several kinase receptors with IGF1R-like structures. We used comprehensive analysis of the known complexes of IGF1R and IR with their binding ligands to screen specific IGF1R inhibitors. Using these workflows, 17 of 139,735 compounds in the NCI (National Cancer Institute database were identified as potential specific inhibitors of IGF1R. Calculations of the potential of mean force (PMF with GROMACS were further conducted for three of the identified compounds to assess their binding affinity differences towards IGF1R and IR.

  19. On Evaluating circulation and temperature stratification under changing water levels in Lake Mead with a 3D hydrodynamic model

    Science.gov (United States)

    Li, Y.; Acharya, K.; Chen, D.; Stone, M.; Yu, Z.; Young, M.; Zhu, J.; Shafer, D. S.; Warwick, J. J.

    2009-12-01

    Sustained drought in the western United States since 2000 has led to a significant drop (about 35 meters) in the water level of Lake Mead, the largest reservoir by volume in United States. The drought combined with rapid urban development in southern Nevada and emergence of invasive species has threatened the water quality and ecological processes in Lake Mead. A three-dimensional hydrodynamic model, Environmental Fluid Dynamics Code (EFDC), was applied to investigate lake circulation and temperature stratification in parts of Lake Mead (Las Vegas Bay and Boulder Basin) under changing water levels. Besides the inflow from Las Vegas Wash and the Colorado River, the model considered atmospheric changes as well as the boundary conditions restricted by the operation of Hoover Dam. The model was calibrated and verified by using observed data including water level, velocity, and temperature from 2003 and 2005. The model was applied to study the hydrodynamic processes at water level 366.8 m (year 2000) and at water level 338.2 m (year 2008). The high-stage simulation described the pre-drought lake hydrodynamic processes while the low-stage simulation highlighted the drawdown impact on such processes. The results showed that both inflow and wind-driven mixing process played major roles in the thermal stratification and lake circulation in both cases. However, the atmospheric boundary played a more important role than inflow temperature on thermal stratification of Lake Mead during water level decline. Further, the thermal stratification regime and flow circulation pattern in shallow lake regions (e.g.., the Boulder Basin area) were most impacted. The temperature of the lake at the high-stage was more sensitive to inflow temperatures than at low-stage. Furthermore, flow velocities decreased with the decreasing water level due to reduction in wind impacts, particularly in shallow areas of the lake. Such changes in temperature and lake current due to present drought have a

  20. Characteristics of binding of insulin-like growth factor (IGF)-I and IGF-II analogues to the type 1 IGF receptor determined by BIAcore analysis.

    Science.gov (United States)

    Forbes, Briony E; Hartfield, Perry J; McNeil, Kerrie A; Surinya, Kathy H; Milner, Steven J; Cosgrove, Leah J; Wallace, John C

    2002-02-01

    Insulin-like growth factor (IGF) binding to the type 1 IGF receptor (IGF1R) elicits mitogenic effects, promotion of differentiation and protection from apoptosis. This study has systematically measured IGF1R binding affinities of IGF-I, IGF-II and 14 IGF analogues to a recombinant high-affinity form of the IGF1R using BIAcore technology. The analogues assessed could be divided into two groups: (a) those designed to investigate binding of IGF-binding protein, which exhibited IGF1R-binding affinities similar to those of IGF-I or IGF-II; (b) those generated to probe IGF1R interactions with greatly reduced IGF1R-binding affinities. The relative binding affinities of IGF-I analogues and IGF-I for the IGF1R determined by BIAcore analysis agreed closely with existing data from receptor-binding assays using cells or tissue membranes, demonstrating that BIAcore technology is a powerful tool for measuring affinities of IGFs for IGF1R. In parallel studies, IGF1R-binding affinities were related to ability to protect against serum withdrawal-induced apoptosis in three different assays including Hoechst 33258 staining, cell survival, and DNA fragmentation assays using the rat pheochromocytoma cell line, PC12. In this model system, IGF-I and IGF-II at low nanomolar concentrations are able to prevent apoptosis completely. We conclude that ability to protect against apoptosis is directly related to ability to bind the IGF1R. PMID:11846798

  1. Serum leptin levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in normal pregnancy and preeclampsia

    Directory of Open Access Journals (Sweden)

    Karádi István

    2011-09-01

    Full Text Available Abstract Objective In this study, we determined circulating levels of C-reactive protein, several cytokines, chemokines, adhesion molecules and angiogenic factors along with those of leptin in healthy non-pregnant and pregnant women and preeclamptic patients, and investigated whether serum leptin levels were related to the clinical characteristics and measured laboratory parameters of the study participants. Methods Sixty preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Levels of leptin and transforming growth factor (TGF-beta1 in maternal sera were assessed by ELISA. Serum levels of interleukin (IL-1beta, IL-1 receptor antagonist (IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, interferon-gamma-inducible protein (IP-10, monocyte chemotactic protein (MCP-1, intercellular adhesion molecule (ICAM-1 and vascular cell adhesion molecule (VCAM-1 were determined by multiplex suspension array. Serum C-reactive protein (CRP concentrations were measured by an autoanalyzer. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1 and biologically active placental growth factor (PlGF levels were determined by electrochemiluminescence immunoassay. For statistical analyses, non-parametric methods were applied. Results There were significant differences in most of the measured laboratory parameters among the three study groups except for serum IL-1beta and TGF-beta1 levels. Serum leptin levels were significantly higher in preeclamptic patients and healthy pregnant women than in healthy non-pregnant women. Additionally, preeclamptic patients had significantly higher leptin levels as compared to healthy pregnant women. Serum leptin levels were independently associated with BMI in healthy non-pregnant women. In healthy pregnant women, both BMI and serum CRP concentrations showed significant positive linear

  2. Assessment of γ-H2AX levels in circulating tumor cells from patients receiving chemotherapy

    Directory of Open Access Journals (Sweden)

    Alejandra eGarcia-Villa

    2012-10-01

    Full Text Available Circulating tumor cells (CTCs are prognostic markers in a variety of solid tumor malignancies. The potential of CTCs to be used as a liquid biopsy to monitor a patient’s condition and predict drug response and resistance is currently under investigation. Using a negative depletion, enrichment methology, CTCs isolated from the peripheral blood of breast cancer patients with stage IV breast cancer undergoing DNA damaging therapy with platinum based therapy were enriched. The enriched cell suspensions, were stained with an optimized labeling protocol targeting: nuclei, cytokeratins 8, 18, and 19, the surface marker CD45, and the presence of the protein ɣ-H2AX. As a direct or indirect result of platinum therapy, double strand break of DNA initiates phosphorylation of the histone H2AX, at serine 139; this phosphorylated form is referred to as ɣ-H2AX. In addition to ɣ-H2AX staining in specific locations with the cell nuclei, consistent with previous reports and referred to as foci, more general staining in the cell cytoplamim was also observed in some cells suggesting the potential of cell apoptosis. Our study underscores the utility and the complexity of investigating CTCs as predictive markers of response to various therapies. Additional studies are ongoing to evaluate the diverse γ-H2AX staining patterns we report here which needs to be further correlated with patient outcomes

  3. TSH-Mediated TNFα Production in Human Fibrocytes Is Inhibited by Teprotumumab, an IGF-1R Antagonist.

    Directory of Open Access Journals (Sweden)

    Hong Chen

    Full Text Available Fibrocytes (FC are bone marrow-derived progenitor cells that are more abundant and infiltrate the thyroid and orbit in Graves orbitopathy (GO. FCs express high levels of thyrotropin receptor (TSHR and insulin-like growth factor-1 receptor (IGF-1R. These receptors are physically and functionally associated, but their role in GO pathogenesis is not fully delineated. Treatment of FCs with thyroid stimulating hormone (TSH or M22 (activating antibody to TSHR induces the production of numerous cytokines, including tumor necrosis factor α (TNFα. Teprotumumab (TMB is a human monoclonal IGF-1R blocking antibody currently in clinical trial for GO and inhibits TSHR-mediated actions in FCs.To characterize the molecular mechanisms underlying TSH-induced TNFα production by FCs, and the role of IGF-1R blockade by TMB.FCs from healthy and GD patients were treated with combinations of TSH, M22, MG132 and AKTi (inhibitors of NF-κB and Akt, respectively, and TMB. TNFα protein production was measured by Luminex and flow cytometry. Messenger RNA expression was quantified by real time PCR.Treatment with TSH/M22 induced TNFα protein and mRNA production by FCs, both of which were reduced when FCs were pretreated with MG132 and AKTi (p<0.0001. TMB decreased TSH-induced TNFα protein production in circulating FCs from mean fluorescent index (MFI value of 2.92 to 1.91, and mRNA expression in cultured FCs from 141- to 52-fold expression (p<0.0001. TMB also decreased M22-induced TNFα protein production from MFI of 1.67 to 1.12, and mRNA expression from 6- to 3-fold expression (p<0.0001.TSH/M22 stimulates FC production of TNFα mRNA and protein. This process involves the transcription factor NF-κB and its regulator Akt. Blocking IGF-1R attenuates TSH/M22-induced TNFα production. This further delineates the interaction of TSHR and IGF1-R signaling pathways. By modulating the proinflammatory properties of FCs such as TNFα production, TMB may be a promising

  4. Single ingestion of soy β-conglycinin induces increased postprandial circulating FGF21 levels exerting beneficial health effects.

    Science.gov (United States)

    Hashidume, Tsutomu; Kato, Asuka; Tanaka, Tomohiro; Miyoshi, Shoko; Itoh, Nobuyuki; Nakata, Rieko; Inoue, Hiroyasu; Oikawa, Akira; Nakai, Yuji; Shimizu, Makoto; Inoue, Jun; Sato, Ryuichiro

    2016-01-01

    Soy protein β-conglycinin has serum lipid-lowering and anti-obesity effects. We showed that single ingestion of β-conglycinin after fasting alters gene expression in mouse liver. A sharp increase in fibroblast growth factor 21 (FGF21) gene expression, which is depressed by normal feeding, resulted in increased postprandial circulating FGF21 levels along with a significant decrease in adipose tissue weights. Most increases in gene expressions, including FGF21, were targets for the activating transcription factor 4 (ATF4), but not for peroxisome proliferator-activated receptor α. Overexpression of a dominant-negative form of ATF4 significantly reduced β-conglycinin-induced increases in hepatic FGF21 gene expression. In FGF21-deficient mice, β-conglycinin effects were partially abolished. Methionine supplementation to the diet or primary hepatocyte culture medium demonstrated its importance for activating liver or hepatocyte ATF4-FGF21 signaling. Thus, dietary β-conglycinin intake can impact hepatic and systemic metabolism by increasing the postprandial circulating FGF21 levels. PMID:27312476

  5. Mean sea surface heights of the South and East China Seas from ocean circulation model and geodetic leveling

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The mean sea surface heights (sea surface topography) of the South China, East China, Yellow and Bohai Seas are derived from an ocean general circulation model and surface air pressure. The circulation model covers the global oceans, with fine grid (1/6°) covering the East Asian marginal seas and coarse grid (3°) covering the rest part of the global oceans. The result shows that the China 1985 National Altitude Datum is 24.7 cm above the mean sea surface height of the world oceans. The mean sea surface in the coastal ocean adjacent to China is higher in the south than in the north. Intercomparison of the model results with the geodetic leveling measurements at 28 coastal tidal stations shows a standard deviation of 4.8 cm and a fitting coefficient of 95.3%. After correction through linear regression, the standard deviation is reduced to 4.5 cm. This indicates that the accuracy of rmodel results is sufficient for practical application. Based on the model results, the mean sea surface heights for the study area with a resolution of 1/6 degree are given. This result also links the mean sea levels at islands with those on the mainland coast and gives the mean sea surface heights at tidal stations in the Taiwan Island, the Dongsha Islands, the Xisha Islands and the Nansha Islands relative to the China 1985 National Altitude Datum.

  6. Circulating levels of pegvisomant and endogenous growth hormone during prolonged pegvisomant therapy in patients with acromegaly

    DEFF Research Database (Denmark)

    Madsen, Michael; Fisker, Sanne; Feldt-Rasmussen, Ulla;

    2014-01-01

    OBJECTIVE: To investigate whether pegvisomant treatment in acromegaly induces gradual elevations in endogenous serum growth hormone (GH) levels and whether serum pegvisomant levels predict the therapeutic outcome. PATIENTS AND METHODS: Seventeen patients (6 women), mean age 46·3 years (range: 23...... correlated with baseline growth hormone levels, whereas no associations between serum pegvisomant and either dose, gender, age or body weight were found. CONCLUSIONS: (1) Serum GH levels increased initially, but remained stable during prolonged pegvisomant treatment in patients with acromegaly, (2) serum...

  7. Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women

    International Nuclear Information System (INIS)

    Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk. - Highlights: • Low level cadmium exposure may interfere with the levels of steroid hormones. • Cadmium exposure was associated with increased serum testosterone concentrations. • Cadmium exposure was associated with decreased estradiol/testosterone ratio. • Cadmium exposure may have implications for breast-cancer promotion

  8. Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Imran; Engström, Annette; Vahter, Marie [Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden); Skerfving, Staffan; Lundh, Thomas [Division of Occupational and Environmental Medicine, University Hospital, Lund (Sweden); Lidfeldt, Jonas [Department of Community Health, Malmö University Hospital, Malmö (Sweden); Samsioe, Göran [Department of Gynecology and Obstetrics, University Hospital, Lund (Sweden); Halldin, Krister [Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden); Åkesson, Agneta, E-mail: agneta.akesson@ki.se [Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden)

    2014-10-15

    Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk. - Highlights: • Low level cadmium exposure may interfere with the levels of steroid hormones. • Cadmium exposure was associated with increased serum testosterone concentrations. • Cadmium exposure was associated with decreased estradiol/testosterone ratio. • Cadmium exposure may have implications for breast-cancer promotion.

  9. Circulating cortisol levels after exogenous cortisol administration are higher in women using hormonal contraceptives: data from two preliminary studies.

    Science.gov (United States)

    Gaffey, Allison E; Wirth, Michelle M; Hoks, Roxanne M; Jahn, Allison L; Abercrombie, Heather C

    2014-07-01

    Exogenous cortisol administration has been used to test the influence of glucocorticoids on a variety of outcomes, including memory and affect. Careful control of factors known to influence cortisol and other endogenous hormone levels is central to the success of this research. While the use of hormonal birth control (HBC) is known to exert many physiological effects, including decreasing the salivary cortisol response to stress, it is unknown how HBC influences circulating cortisol levels after exogenous cortisol administration. To determine those effects, we examined the role of HBC on participants' cortisol levels after receiving synthetic cortisol (hydrocortisone) in two separate studies. In Study 1, 24 healthy women taking HBC and 26 healthy men were administered a 0.1 mg/kg body weight intravenous dose of hydrocortisone, and plasma cortisol levels were measured over 3 h. In Study 2, 61 participants (34 women; 16 were on HBC) received a 15 mg hydrocortisone pill, and salivary cortisol levels were measured over 6 h. Taken together, results from these studies suggest that HBC use is associated with a greater cortisol increase following cortisol administration. These data have important methodological implications: (1) when given a controlled dose of hydrocortisone, cortisol levels may increase more dramatically in women taking HBC versus women not on HBC or men; and (2) in studies manipulating cortisol levels, women on hormonal contraceptives should be investigated as a separate group.

  10. 宫内生长迟缓儿血清GH、IGF-1、IGFBP-3和瘦素水平及临床意义%Serum levels of GH, IGF-1, IGFBP-3 and leptin in the intrauterine growth retarded newborns and their clinical significance

    Institute of Scientific and Technical Information of China (English)

    潘革; 李惠玲; 林广; 马南花; 韦香妮; 王彩珊; 王淑萍

    2007-01-01

    [目的] 探讨宫内生长迟缓(intrauterine growth retarded,IUGR)新生儿血清生长激素(growth hormone,GH)、胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)、胰岛素样生长因子结合蛋白-3(insulin-like growth factor binding protein-3,IGFBP-3)、瘦素的浓度水平及临床意义.[方法] 选择出生48~72 h的IUGR新生儿62例和足月适于胎龄儿(appropriate for gestional age,AGA)37例与早产AGA36例,其中IUGR分为重度IUGR组(29例),轻度IUGR组(33例)和足月小于胎龄儿(small for gestional age,SGA)32例与早产SGA30例;分别于上午9时抽取静脉血,分离血清.采用放射免疫法测定GH、IGF-1、IGFBP-3和瘦素. [结果] ①足月SGA和足月AGA组血清GH、IGF-1、IGFBP-3、瘦素浓度(μg/L)分别为6.58±1.42和24.32±3.59,11.89±3.01和37.12±6.4,82.3±19.66和256.55±33.62,2.75±0.66和7.58±1.26;早产SGA和早产AGA组血清GH、IGF-1、IGFBP-3、瘦素浓度(μg/L)分别为8.18±2.55和13.83±3.98,13.59±4.83和21.05±3.44,93.48±16.44和157.33±39.34,3.21±0.61和4.9±0.83,各组比较有显著差异(P<0.05或P<0.01).②轻度和重度IUGR组血清GH、IGF-1、IGFBP-3、瘦素浓度(μg/L)分别为5.82±1.02和8.67±2.07,9.96±2.19和14.56±3.87,77.48±20.51和99.13±7.16,2.61±0.63和3.31±0.51,两组比较差异均有显著性(P<0.01).[结论] 新生儿血清GH、IGF-1、IGFBP-3、瘦素浓度水平与胎儿生长发育有密切关系,是调节胎儿宫内生长发育的重要因素.

  11. Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls

    DEFF Research Database (Denmark)

    Nielsen, Lotte B; Wang, Cheng; Sørensen, Kaspar;

    2012-01-01

    This study aims to identify key miRNAs in circulation, which predict ongoing beta-cell destruction and regeneration in children with newly diagnosed Type 1 Diabetes (T1D). We compared expression level of sera miRNAs from new onset T1D children and age-matched healthy controls and related the mi......RNAs expression levels to beta-cell function and glycaemic control. Global miRNA sequencing analyses were performed on sera pools from two T1D cohorts (n = 275 and 129, resp.) and one control group (n = 151). We identified twelve upregulated human miRNAs in T1D patients (miR-152, miR-30a-5p, miR-181a, miR-24, mi...

  12. Adipose Tissue-Derived Stem Cell Secreted IGF-1 Protects Myoblasts from the Negative Effect of Myostatin

    Directory of Open Access Journals (Sweden)

    Sebastian Gehmert

    2014-01-01

    Full Text Available Myostatin, a TGF-β family member, is associated with inhibition of muscle growth and differentiation and might interact with the IGF-1 signaling pathway. Since IGF-1 is secreted at a bioactive level by adipose tissue-derived mesenchymal stem cells (ASCs, these cells (ASCs provide a therapeutic option for Duchenne Muscular Dystrophy (DMD. But the protective effect of stem cell secreted IGF-1 on myoblast under high level of myostatin remains unclear. In the present study murine myoblasts were exposed to myostatin under presence of ASCs conditioned medium and investigated for proliferation and apoptosis. The protective effect of IGF-1 was further examined by using IGF-1 neutralizing and receptor antibodies as well as gene silencing RNAi technology. MyoD expression was detected to identify impact of IGF-1 on myoblasts differentiation when exposed to myostatin. IGF-1 was accountable for 43.6% of the antiapoptotic impact and 48.8% for the proliferative effect of ASCs conditioned medium. Furthermore, IGF-1 restored mRNA and protein MyoD expression of myoblasts under risk. Beside fusion and transdifferentiation the beneficial effect of ASCs is mediated by paracrine secreted cytokines, particularly IGF-1. The present study underlines the potential of ASCs as a therapeutic option for Duchenne muscular dystrophy and other dystrophic muscle diseases.

  13. Regulation of human trophoblast GLUT1 glucose transporter by insulin-like growth factor I (IGF-I.

    Directory of Open Access Journals (Sweden)

    Marc U Baumann

    Full Text Available Glucose transport to the fetus across the placenta takes place via glucose transporters in the opposing faces of the barrier layer, the microvillous and basal membranes of the syncytiotrophoblast. While basal membrane content of the GLUT1 glucose transporter appears to be the rate-limiting step in transplacental transport, the factors regulating transporter expression and activity are largely unknown. In view of the many studies showing an association between IGF-I and fetal growth, we investigated the effects of IGF-I on placental glucose transport and GLUT1 transporter expression. Treatment of BeWo choriocarcinoma cells with IGF-I increased cellular GLUT1 protein. There was increased basolateral (but not microvillous uptake of glucose and increased transepithelial transport of glucose across the BeWo monolayer. Primary syncytial cells treated with IGF-I also demonstrated an increase in GLUT1 protein. Term placental explants treated with IGF-I showed an increase in syncytial basal membrane GLUT1 but microvillous membrane GLUT1 was not affected. The placental dual perfusion model was used to assess the effects of fetally perfused IGF-I on transplacental glucose transport and syncytial GLUT1 content. In control perfusions there was a decrease in transplacental glucose transport over the course of the perfusion, whereas in tissues perfused with IGF-I through the fetal circulation there was no change. Syncytial basal membranes from IGF-I perfused tissues showed an increase in GLUT1 content. These results demonstrate that IGF-I, whether acting via microvillous or basal membrane receptors, increases the basal membrane content of GLUT1 and up-regulates basal membrane transport of glucose, leading to increased transepithelial glucose transport. These observations provide a partial explanation for the mechanism by which IGF-I controls nutrient supply in the regulation of fetal growth.

  14. Increased Circulating Levels of Alpha-Ketoglutarate in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Berlanga, Alba; Guiu-Jurado, Esther; Martinez, Salomé; Armengol, Sandra; Sabench, Fàtima; Ras, Rosa; Hernandez, Mercè; Aguilar, Carmen; Colom, Josep; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2016-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, ranging from simple steatosis to cirrhosis. However, simple steatosis (SS) and steatohepatitis (NASH) cannot yet be distinguished by clinical or laboratory features. The aim of this study was to assess the relationship between alpha-ketoglutarate and the degrees of NAFLD in morbidly obese patients. Materials and Methods We used a gas chromatography-quadruple time-of-flight-mass spectrometry analysis to quantify alpha-ketoglutarate in serum from normal-weight subjects (n = 30) and morbidly obese women (n = 97) with or without NAFLD. Results We found that serum levels of alpha-ketoglutarate were significantly higher in morbidly obese women than in normal-weight women. We showed that circulating levels of alpha-ketoglutarate were lower in lean controls and morbidly obese patients without NAFLD. We also found that alpha-ketoglutarate serum levels were higher in both SS and NASH than in normal liver of morbidly obese patients. However, there was no difference between SS and NASH. Moreover, we observed that circulating levels of alpha-ketoglutarate were associated with glucose metabolism parameters, lipid profile, hepatic enzymes and steatosis degree. In addition, diagnostic performance of alpha-ketoglutarate has been analyzed in NAFLD patients. The AUROC curves from patients with liver steatosis exhibited an acceptable clinical utility. Finally, we showed that the combination of biomarkers (AST, ALT and alpha-ketoglutarate) had the highest accuracy in diagnosing liver steatosis. Conclusion These findings suggest that alpha-ketoglutarate can determine the presence of non-alcoholic fatty liver in morbidly obese patients but it is not valid a biomarker for NASH. PMID:27123846

  15. The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy

    Science.gov (United States)

    Adams, G. R.; Haddad, F.

    1996-01-01

    Insulin-like growth factor-1 (IGF-1) is known to have anabolic effects on skeletal muscle cells. This study examined the time course of muscle hypertrophy and associated IGF-1 peptide and mRNA expression. Data were collected at 3, 7, 14, and 28 days after surgical removal of synergistic muscles of both normal and hypophysectomized (HX) animals. Overloading increased the plantaris (Plant) mass, myofiber size, and protein-to-body weight ratio in both groups (normal and HX; P peptide levels peaked at 3 (normal) and 7 (HX) days of overloading with maximum 4.1-fold (normal) and 6.2-fold (HX) increases. Increases in muscle IGF-1 preceded the hypertrophic response. Total DNA content of the overloaded Plant increased in both groups. There was a strong positive relationship between IGF-1 peptide and DNA content in the overloaded Plant from both groups. These results indicate that 1) the muscles from rats with both normal and severely depressed systemic levels of IGF-1 respond to functional overload with an increase in local IGF-1 expression and 2) this elevated IGF-1 may be contributing to the hypertrophy response, possibly via the mobilization of satellite cells to provide increases in muscle DNA.

  16. Circulating levels of platelet α-granule cytokines in trauma patients

    DEFF Research Database (Denmark)

    Windeløv, Nis Agerlin; Ostrowski, Sisse Rye; Johansson, Per Ingemar;

    2015-01-01

    TGs), transforming growth factor-β1 (TGFβ1) and the pro-inflammatory platelet factor 4 (PF4) cytokines. We also measured soluble glycoprotein VI (sGPVI), procoagulant platelet microparticles (PMPs) and white blood cell (WBC) counts, and evaluated in vitro platelet function in primary and secondary haemostasis...... p PMPs levels correlated with TGFβ1 and PF4 whereas we found no significant association between cytokine levels and measures of haemostasis. By multivariate regression, a high WBC count was associated with high levels of TGFβ1 (p = 0.01) and β...

  17. FNDC5 expression and circulating irisin levels are modified by diet and hormonal conditions in hypothalamus, adipose tissue and muscle.

    Science.gov (United States)

    Varela-Rodríguez, B M; Pena-Bello, L; Juiz-Valiña, P; Vidal-Bretal, B; Cordido, F; Sangiao-Alvarellos, S

    2016-01-01

    Irisin is processed from fibronectin type III domain-containing protein 5 (FNDC5). However, a controversy exists concerning irisin origin, regulation and function. To elucidate the relationship between serum irisin and FNDC5 mRNA expression levels, we evaluated plasma irisin levels and FNDC5 gene expression in the hypothalamus, gastrocnemius muscle and different depots of adipose tissue in models of altered metabolism. In normal rats, blood irisin levels diminished after 48-h fast and with leptin, insulin and alloxan treatments, and serum irisin concentrations increased in diabetic rats after insulin treatment and acute treatments of irisin increased blood insulin levels. No changes were observed during long-term experiments with different diets. We suggested that levels of circulating irisin are the result of the sum of the irisin produced by different depots of adipose tissue and skeletal muscle. This study shows for the first time that there are differences in FNDC5 expression depending on white adipose tissue depots. Moreover, a considerable decrease in visceral and epididymal adipose tissue depots correlated with increased FNDC5 mRNA expression levels, probably in an attempt to compensate the decrease that occurs in their mass. Hypothalamic FNDC5 expression did not change for any of the tested diets but increased with leptin, insulin and metformin treatments suggesting that the regulation of central and peripheral FNDC5/irisin expression and functions are different. PMID:27432282

  18. A Statistically-Based Low-Level Cloud Scheme and Its Tentative Application in a General Circulation Model

    Institute of Scientific and Technical Information of China (English)

    DAI Fushan; YU Rucong; ZHANG Xuehong; YU Yongqiang

    2005-01-01

    In this study, a statistical cloud scheme is first introduced and coupled with a first-order turbulence scheme with second-order turbulence moments parameterized by the timescale of the turbulence dissipation and the vertical turbulent diffusion coefficient. Then the ability of the scheme to simulate cloud fraction at different relative humidity, vertical temperature profile, and the timescale of the turbulent dissipation is examined by numerical simulation. It is found that the simulated cloud fraction is sensitive to the parameter used in the statistical cloud scheme and the timescale of the turbulent dissipation. Based on the analyses, the introduced statistical cloud scheme is modified. By combining the modified statistical cloud scheme with a boundary layer cumulus scheme, a new statistically-based low-level cloud scheme is proposed and tentatively applied in NCAR (National Center for Atmospheric Research) CCM3 (Community Climate Model version3). It is found that the simulation of low-level cloud fraction is markedly improved and the centers with maximum low-level cloud fractions are well simulated in the cold oceans off the western coasts with the statistically-based low-level cloud scheme applied in CCM3. It suggests that the new statistically-based low-level cloud scheme has a great potential in the general circulation model for improving the low-level cloud parameterization.

  19. Natural circulation steam generator model for optimal steam generator water level control

    International Nuclear Information System (INIS)

    Several authors have cited the control of steam generator water level as an important problem in the operation of pressurized water reactor plants. In this paper problems associated with steam generator water level control are identified, and advantages of modern estimation and control theory in dealing with these problems are discussed. A new state variable steam generator model and preliminary verification results using data from the loss of fluid test (LOFT) plant are also presented

  20. Helicobacter pylori prevalence and circulating micronutrient levels in a low-income United States population

    OpenAIRE

    Epplein, Meira; Signorello, Lisa B.; Zheng, Wei; Cai, Qiuyin; Hargreaves, Margaret K.; Michel, Angelika; Pawlita, Michael; Fowke, Jay H.; Correa, Pelayo; Blot, William J.

    2011-01-01

    High prevalence of Helicobacter pylori, the leading cause of gastric cancer, and low levels of micronutrients have been observed in many developing countries, and the question remains as to the whether an association between the two exists. The present study seeks to further our understanding of this potential connection in the Southern Community Cohort Study, representing a low-income population in the United States. Blood levels of antibodies to Helicobacter pylori proteins were assessed us...

  1. Circulating irisin levels are not affected by coffee intake: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Patricia R Peter

    Full Text Available Irisin, secreted by skeletal muscle and possibly fat, is hypothesized to play an important role in modulating energy expenditure, obesity and metabolism. Coffee consumption also increases energy expenditure and leads to positive metabolic effects, but whether these effects are mediated by irisin remains unknown. The objective of this study was to determine the association between baseline irisin levels and the metabolic profile in humans and to investigate whether consumption of caffeinated coffee alters irisin levels. To this end, a secondary analysis was performed investigating irisin levels at baseline and after eight weeks in 32 healthy, overweight coffee drinkers who were randomized to consumption of 5 cups per day of instant caffeinated coffee, decaffeinated coffee, or water. Spearman correlation and analysis of covariance analyses were performed to identify possible associations. Irisin levels were positively correlated with waist circumference (r = 0.41, p = 0.02, fat mass (r = 0.44, p = 0.01 and CRP (r = 0.47, p = 0.007. Though there was a trend towards increased levels of irisin over time in the caffeinated coffee group (+1.8% when compared to the placebo group (24% this did not reach statistical significance (p = 0.75 for the trend. This first randomized trial failed to reveal any effects of coffee consumption on irisin levels, but a larger trial, appropriately sized on the basis of data provided by this study, is needed to conclusively investigate such a relationship.Clinicaltrials.gov NCT00305097.

  2. Antimicrobial activity of various immunomodulators: independence from normal levels of circulating monocytes and natural killer cells. Technical report

    Energy Technology Data Exchange (ETDEWEB)

    Morahan, P.S.; Dempsey, W.L.; Volkman, A.; Connor, J.

    1986-01-01

    The effects of /sup 89/Sr treatment on the natural host resistance of CD-1 mice and the enhancement of resistance by immunomodulators to infection with Listeria monocytogenes or herpes simplex virus type 2 (HSV-2) were determined. In the CD-1 mouse, single-dose treatment with /sup 89/Sr caused a profound decrease in the number of circulating monocytes (Mo), lymphocytes, and polymorphonuclear leukocytes (PMN) within 1 week. There was also marked functional impairment of the Mo inflammatory response, as well as markedly decreased spontaneous and activatable cytoxicity by splenic natural killer (NK) cells. Despite this profound cellular suppression, there was no significant change in natural resistance of CD-1 mice to L. monocytogenes of HSV-2 infection. Furthermore, prophylactic treatment of mice with the biologic immunomodulator Corynebacterium parvum or the synthetic immunomodulators maleic anhydride-divinyl ether or avridine in liposomes resulted in comparable enhancement of resistance in /sup 89/Sr-treated and normal mice. These data indicate that natural and immunomodulator-enhanced resistance of CD-1 mice to microbail infections do not depend on normal levels of Mo, PMN, or NK cells. The resistance enhancement may rely on activated tissue macrophages. In contrast to the early changes in circulating leukocytes, the residenet peritoneal cell populations were not markedly altered until after day 30. There then was a distinct decline in lymphocytes and a gradual decline in activated tissue macrophages.

  3. Pre-diagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations

    DEFF Research Database (Denmark)

    Fedirko, Veronika; Duarte-Salles, Talita; Bamia, Christina;

    2014-01-01

    size or smoking status. Conclusion: In this prospective study on Western European populations, serum levels of 25(OH)D were inversely associated with risk of hepatocellular carcinoma. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest......-hydroxyvitamin D [25(OH)D] serum levels and risk of hepatocellular carcinoma in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n = 138) diagnosed between 1992 and 2010 was matched to one control by...... age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRR) of hepatocellular carcinoma associated with continuous (per 10 nmol/L) or...

  4. Circulating levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with incisional hernia

    DEFF Research Database (Denmark)

    Henriksen, Nadia A; Sørensen, Lars T; Jorgensen, Lars N;

    2013-01-01

    Incisional hernia formation is a common complication to laparotomy and possibly associated with alterations in connective tissue metabolism. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are closely involved in the metabolism of the extracellular matrix. Our...... aim was to study serum levels of multiple MMPs and TIMPs in patients with and without incisional hernia. Out of 305 patients who underwent laparotomy, 79 (25.9%) developed incisional hernia over a median follow-up period of 3.7 years. Pooled sera from a subset (n = 72) of these patients were screened...... for MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, MMP-13, TIMP-1, TIMP-2, and TIMP-4 using a multiplex sandwich fluorescent immunoassay supplemented with gelatin zymography. The screening indicated differences in serum MMP-9 and TIMP-1 levels. Consequently, MMP-9 and TIMP-1 levels were...

  5. Systematic review and meta-analysis of circulating S100B blood levels in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Katina Aleksovska

    Full Text Available S100B is a calcium-binding protein secreted in central nervous system from astrocytes and other glia cells. High blood S100B levels have been linked to brain damage and psychiatric disorders. S100B levels have been reported to be higher in schizophrenics than healthy controls. To quantify the relationship between S100B blood levels and schizophrenia a systematic literature review of case-control studies published on this topic within July 3rd 2014 was carried out using three bibliographic databases: Medline, Scopus and Web of Science. Studies reporting mean and standard deviation of S100B blood levels both in cases and controls were included in the meta-analysis. The meta-Mean Ratio (mMR of S100B blood levels in cases compared to controls was used as a measure of effect along with its 95% Confidence Intervals (CI. 20 studies were included totaling for 994 cases and 785 controls. Schizophrenia patients showed 76% higher S100B blood levels than controls with mMR = 1.76 95% CI: 1.44-2.15. No difference could be found between drug-free patients with mMR = 1.84 95%CI: 1.24-2.74 and patients on antipsychotic medication with mMR = 1.75 95% CI: 1.41-2.16. Similarly, ethnicity and stage of disease didn't affect results. Although S100B could be regarded as a possible biomarker of schizophrenia, limitations should be accounted when interpreting results, especially because of the high heterogeneity that remained >70%, even after carrying out subgroups analyses. These results point out that approaches based on traditional categorical diagnoses may be too restrictive and new approaches based on the characterization of new complex phenotypes should be considered.

  6. Alternative splicing and expression of the insulin-like growth factor (IGF-1) gene in osteoblasts under mechanical stretch

    Institute of Scientific and Technical Information of China (English)

    XIAN Chengyu; WANG Yuanliang; ZHANG Bingbing; TANG Liling; PAN Jun; LUO Yanfeng; JIANG Peng; LI Dajun

    2006-01-01

    Insulin-like growth factor 1 (IGF-1) promotes osteoblasts differentiation and bone formation,and its expression is induced by mechanical stretch,thus IGF-1 has been considered an effector molecule that links mechanical stimulation and local tissue responses. In this study, a mechanical stretching device was designed to apply physiological level static or cyclic stretching stimulation to osteoblasts.Different isoforms of IGF-1 mRNA were amplified by RT-PCR from the cells using respective primers and these amplified products were sequenced. An isoform of IGF-1 splicing product was found to be selectively produced by osteoblasts under stretching stimulation. This IGF-1 isoform had identical sequence with the mechano growth factor (MGF) which was originally identified in muscle cells. Regulations of the expression of the liver-type IGF (L.IGF-1) and MGF in osteoblasts under stretch stimulation were further studied using semi-quantitative RT-PCR.Stretch stimulation was found to promot the expression of IGF-1 (L.IGF-1 and MGF), and for both isoforms expression was more effectively stimulated by cyclic stretch than static stretch. MGF was detected only in osteoblasts subjected to mechanical stretch,suggesting MGF was a stretch sensitive growth factor.Expression of MGF peaked earlier than that of L.IGF-1, which was similar to their regulation in muscie and suggested similar roles of MGF and L.IGF-1in bone as in muscle cells. The functions of MGF and L.IGF-1 in osteoblasts shall be established by further experimental studies.

  7. Dual-level parallelism exploitation with OpenMP in coastal ocean circulation modeling

    OpenAIRE

    González Tallada, Marc; Ayguadé Parra, Eduard; Martorell Bofill, Xavier; Labarta Mancho, Jesús José; Luong, P V

    2002-01-01

    Two alternative dual-level parallel implementations of the Multiblock Grid Princeton Ocean Model (MGPOM) are compared in this paper. The first one combines the use of two programming paradigms: message passing with the Message Passing Interface (MPI) and shared memory with OpenMP (version called MPI-OpenMP); the second uses only OpenMP (version called OpenMP-Only). MGPOM is a multiblock grid code that enables the exploitation of two levels of parallelism. The MPI-OpenMP implementation use...

  8. rhIGF-1 Therapy for Growth Failure and IGF-1 Deficiency in Congenital Disorder of Glycosylation Ia (PMM2 Deficiency

    Directory of Open Access Journals (Sweden)

    Bradley S. Miller MD, PhD

    2013-09-01

    Full Text Available Background. Congenital disorders of glycosylation (CDG are a group of rare disorders in which glycosylation required for proper protein-protein interactions and protein stability is disrupted, manifesting clinically with multiple system involvement and growth failure. The insulin-like growth factor (IGF system plays an important role in childhood growth and has been shown to be dysfunctional with low IGF-1 levels in children with CDG type Ia (PMM2 deficiency. Case report. A 3-year-old Caucasian male with failure to thrive was diagnosed with PMM2-CDG at 5 months of age. Initially, his length and weight were less than −2 standard deviation score, IGF-1 <25 ng/mL (normal 55-327 ng/mL, IGFBP-3 1.0 µg/mL (normal 0.7-3.6 ng/mL, and acid-labile subunit 1.3 mg/L (normal 0.7-7.9 mg/L. Despite aggressive feeding, he continued to show poor linear growth and weight gain. At 17 months, he underwent an IGF-1 generation test with growth hormone (0.1 mg/kg/d for 7 days; baseline IGF-1of 27 ng/mL (normal 55-327 ng/mL stimulated to only 33 ng/mL. Recombinant human IGF-1 (rhIGF-1 therapy (up to 130 µg/kg/dose twice daily was initiated at 21 months of age resulting in an excellent linear growth response with height increasing from −2.73 to −1.39 standard deviation score over 22 months. IGF-1 and IGFBP-3 levels also increased. Conclusion. This is the first case report of rhIGF-1 therapy in a patient with PMM2-CDG. The child had an excellent linear growth response. These results provide additional in vivo evidence for IGF dysfunction in PMM2-CDG and suggest that rhIGF-1 may be a novel treatment for growth failure in PMM2-CDG.

  9. Decreased Circulating Interleukin-35 Levels Are Related to Interleukin-4-Producing CD8+ T Cells in Patients with Allergic Asthma.

    Science.gov (United States)

    Wang, Wei; Li, Ping; Yang, Jiong

    2015-08-01

    Interleukin (IL)-35 is a newly discovered suppressive cytokine and has been shown to alleviate inflammatory and autoimmune diseases. The purpose of this study was to investigate immunomodulatory capacity of IL-35 in patients with allergic asthma. IL-35 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) were detected by quantitative real-time PCR (qPCR). The frequencies of cytotoxic T cells (Tc)1, Tc2 and Tc17 cells were measured by flow cytometry. Plasma levels of IL-35, interferon (IFN)-γ, IL-4, and IL-17 were examined by enzyme-linked immunosorbent assay (ELISA). The correlations between plasma IL-35 levels and Tc1, Tc2, and Tc17 cytokine production in allergic asthmatics (n = 25) and healthy controls (n = 12) were analyzed by Pearson's test. IL-35 protein and mRNA expression levels were down-regulated in allergic asthmatics compared with healthy controls. The frequencies of Tc2 and Tc17 cells were significantly increased in patients with asthma, and the frequency of Tc1 cells did not differ between asthmatic patients and healthy controls. Similarly, plasma levels of IL-4 and IL-17 were significantly increased in asthmatic patients, while there was no difference in IFN-γ levels between allergic asthma patients and healthy controls. More importantly, plasma IL-35 protein levels were negatively correlated with the frequency of IL-4-producing CD8+ T (Tc2) cells and with the IL-4 level in patients with allergic asthma. Our results suggest that decreased circulating IL-35 levels could contribute to the pathogenesis of allergic asthma by regulating CD8+ T cells. PMID:26547705

  10. Elevated circulating stromal-derived factor-1 levels in sickle cell disease

    NARCIS (Netherlands)

    Landburg, P P; Nur, E; Maria, N; Brandjes, D P M; Biemond, B J; Schnog, J B; Duits, A J

    2009-01-01

    Inflammation and angiogenesis are of importance in the pathophysiology of sickle cell disease (SCD). Recently, the chemokine stromal-derived factor-1 (SDF-1) has been shown to be a key mediator of angiogenesis and inflammation. In this study we determined serum SDF-1 levels in consecutive adult sick

  11. Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3

    DEFF Research Database (Denmark)

    Juul, A; Kastrup, K W; Pedersen, S A;

    1997-01-01

    Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) reflect the endogenous GH secretion in healthy children and exhibit little diurnal variation, which makes them good diagnostic markers for screening of GH deficiency (GHD) in short children, although so...

  12. Circulating levels of endothelin-1 in a homogenous Gulf Arab population with untreated essential hypertension

    International Nuclear Information System (INIS)

    Rectal variations are reported in the natural history of high-tension. For example hypertension is significantly more prevalent in blacks than whites. Endothelial cells are important regulators of vasculars tone and homeostasis, in part through secretions of vasoactive substances including endothelin-I (ET-1), a small peptide with potent vaspressor actions in black hypertensive and normotensive whites. Since ET-I might play a significant role to the development and severity of hypertension in the indigenous Arab population of United Arab Emirates; we investigated the circulatory levels of ET-1 in the homogenous population. ET-I levels were measured in plasma samples from 60 unteated hypertensive Arabs and compared with 60 age and sex matched normotensive controls. ET-I levels were significantly higher in hypertensive (10.1+-pmol/L) than normtensives (mean 2.2+-0.5 pmol/L). Body mass index (BMI) was slightly higher among the hypertensive. For all subjects these levels significantly (P<0.001) correlated with systolic blood pressure and less significantly (P<0.05) with diastolic blood pressure and body weight. The correlation with ET-1 and both systolic and diastolic blood pressure with persistently significant after adjusting for BMI. Plasma concentration of ET-I are significantly higher in hypertensive Gulf Arabs as compared with reported levels in which hypertensives and ET-I could be a risk factor for cardiovascular diseases in this population. The endothelial sate might be particularly important with respect to hypertension in this racial group and merits further study. (author)

  13. Bioavailable IGF-1 and its Relation to the Metabolic Syndrome in a Bi-Ethnic Population of Men and Women.

    Science.gov (United States)

    Koegelenberg, A S E; Schutte, R; Smith, W; Schutte, A E

    2016-02-01

    Insulin-like growth factor 1 (IGF-1), an insulin sensitivity and vasculoprotective factor, associates negatively with the metabolic syndrome. However, IGF-1 is reduced by factors such as inflammation, oxidative stress and liver dysfunction. We investigated the relationship between bioavailable IGF-1 and the number of metabolic syndrome components and determined whether this relationship is independent of inflammation, oxidative stress and gamma glutamyl transferase (γ-GT; a marker of liver dysfunction). This study included 907 black and white participants stratified by sex (aged 43.0±11.8 years). Among them 63 participants had fasting glucose levels of ≥+7.0+mmol/l and/or used diabetes medication. Via standard methods we determined waist circumference, fasting glucose, triglycerides, high-density lipoprotein cholesterol and blood pressure. We also determined high-sensitivity C-reactive protein (CRP), reactive oxygen species (ROS), γ-GT, IGF-1 and insulin-like growth factor binding protein 3 (IGFBP-3). IGF-1/IGFBP-3 was used as an estimate of bioavailable IGF-1. Total IGF-1 was similar between men and women (p=0.10), however, bioavailable IGF-1 was lower in women (prelationship was dependent on oxidative stress, liver dysfunction and inflammation, suggesting underlying processes by which the metabolic syndrome attenuates IGF-1. PMID:26348017

  14. Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3

    DEFF Research Database (Denmark)

    Juul, A; Kastrup, K W; Pedersen, S A;

    1997-01-01

    .e. 45% of patients treated with GH during childhood because of isolated GHD had a normal GH response when retested in adulthood. Multiple regression analysis revealed that peak GH levels were dependent on the degree of hypopituitarism, body mass index, and duration of disease. IGF-I levels were below -2...... significantly dependent on peak GH levels and the number of other pituitary axes affected. In this analysis, duration of disease was significantly associated with both IGF-I and IGFBP-3, whereas body mass index was significantly associated with IGFBP-3, but not with IGF-I. We conclude that IGF-I and IGFBP-3...... determinations predict the outcome of a GH provocative test in adults suspected of GHD and believe that IGF-I as well as IGFBP-3 serum concentrations are valuable diagnostic parameters in the evaluation of GHD in adults with childhood-onset disease. We suggest that children who have been treated with GH should...

  15. IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma.

    Science.gov (United States)

    Svalina, Matthew N; Kikuchi, Ken; Abraham, Jinu; Lal, Sangeet; Davare, Monika A; Settelmeyer, Teagan P; Young, Michael C; Peckham, Jennifer L; Cho, Yoon-Jae; Michalek, Joel E; Hernandez, Brian S; Berlow, Noah E; Jackson, Melanie; Guillaume, Daniel J; Selden, Nathan R; Bigner, Darell D; Nazemi, Kellie J; Green, Sarah C; Corless, Christopher L; Gultekin, Sakir; Mansoor, Atiya; Rubin, Brian P; Woltjer, Randall; Keller, Charles

    2016-01-01

    Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma. PMID:27255663

  16. Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats

    Science.gov (United States)

    Adams, G. R.; McCue, S. A.

    1998-01-01

    Insulin-like growth factor I (IGF-I) peptide levels have been shown to increase in overloaded skeletal muscles (G. R. Adams and F. Haddad. J. Appl. Physiol. 81: 2509-2516, 1996). In that study, the increase in IGF-I was found to precede measurable increases in muscle protein and was correlated with an increase in muscle DNA content. The present study was undertaken to test the hypothesis that direct IGF-I infusion would result in an increase in muscle DNA as well as in various measurements of muscle size. Either 0.9% saline or nonsystemic doses of IGF-I were infused directly into a non-weight-bearing muscle of rats, the tibialis anterior (TA), via a fenestrated catheter attached to a subcutaneous miniosmotic pump. Saline infusion had no effect on the mass, protein content, or DNA content of TA muscles. Local IGF-I infusion had no effect on body or heart weight. The absolute weight of the infused TA muscles was approximately 9% greater (P muscles. IGF-I infusion resulted in significant increases in the total protein and DNA content of TA muscles (P hypertrophied TA was similar to that of the contralateral muscles. These results suggest that IGF-I may be acting to directly stimulate processes such as protein synthesis and satellite cell proliferation, which result in skeletal muscle hypertrophy.

  17. Insulin and IGF-1 regularize energy metabolites in neural cells expressing full-length mutant huntingtin.

    Science.gov (United States)

    Naia, Luana; Ribeiro, Márcio; Rodrigues, Joana; Duarte, Ana I; Lopes, Carla; Rosenstock, Tatiana R; Hayden, Michael R; Rego, A Cristina

    2016-08-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder linked to the expression of mutant huntingtin. Bioenergetic dysfunction has been described to contribute to HD pathogenesis. Thus, treatment paradigms aimed to ameliorate energy deficits appear to be suitable candidates in HD. In previous studies, we observed protective effects of insulin growth factor-1 (IGF-1) in YAC128 and R6/2 mice, two HD mouse models, whereas IGF-1 and/or insulin halted mitochondrial-driven oxidative stress in mutant striatal cells and mitochondrial dysfunction in HD human lymphoblasts. Here, we analyzed the effect of IGF-1 versus insulin on energy metabolic parameters using striatal cells derived from HD knock-in mice and primary cortical cultures from YAC128 mice. STHdh(Q111/Q111) cells exhibited decreased ATP/ADP ratio and increased phosphocreatine levels. Moreover, pyruvate levels were increased in mutant cells, most probably in consequence of a decrease in pyruvate dehydrogenase (PDH) protein expression and increased PDH phosphorylation, reflecting its inactivation. Insulin and IGF-1 treatment significantly decreased phosphocreatine levels, whereas IGF-1 only decreased pyruvate levels in mutant cells. In a different scenario, primary cortical cultures derived from YAC128 mice also displayed energetic abnormalities. We observed a decrease in both ATP/ADP and phosphocreatine levels, which were prevented following exposure to insulin or IGF-1. Furthermore, decreased lactate levels in YAC128 cultures occurred concomitantly with a decline in lactate dehydrogenase activity, which was ameliorated with both insulin and IGF-1. These data demonstrate differential HD-associated metabolic dysfunction in striatal cell lines and primary cortical cultures, both of which being alleviated by insulin and IGF-1. PMID:26876526

  18. Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

    DEFF Research Database (Denmark)

    Vassiliadis, E.; Oliveira, C. P.; Alvares-da-Silva, M. R.;

    2012-01-01

    Aim: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. Methods: A monoclonal antibody against the sequence RLRSSVPGV-citrulline ......Aim: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. Methods: A monoclonal antibody against the sequence RLRSSVPGV......-citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl4) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. Results: In CCl4-treated...

  19. Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

    DEFF Research Database (Denmark)

    Vassiliadis, Efstathios; Oliveira, Claudia P; Alvares-da-Silva, Mario R;

    2012-01-01

    AIM: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. METHODS: A monoclonal antibody against the sequence RLRSSVPGV-citrulline ......AIM: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. METHODS: A monoclonal antibody against the sequence RLRSSVPGV......-citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl(4)) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. RESULTS: In CCl(4...

  20. Impact of obesity control on circulating level of endothelial progenitor cells and angiogenesis in response to ischemic stimulation

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    Chen Yung-Lung

    2012-07-01

    Full Text Available Abstract Background and aim We tested the hypothesis that obesity reduced circulating number of endothelial progenitor cells (EPCs, angiogenic ability, and blood flow in ischemic tissue that could be reversed after obesity control. Methods 8-week-old C57BL/6J mice (n = 27 were equally divided into group 1 (fed with 22-week control diet, group 2 (22-week high fat diet, and group 3 (14-week high fat diet, followed by 8-week control diet. Critical limb ischemia (CLI was induced at week 20 in groups 2 and 3. The animals were sacrificed at the end of 22 weeks. Results Heart weight, body weight, abdominal fat weight, serum total cholesterol level, and fasting blood sugar were highest in group 2 (all p  Conclusion Obesity suppressed abilities of angiogenesis and recovery from CLI that were reversed by obesity control.

  1. Association of circulating irisin levels with normal weight obesity, glycemic and lipid profile

    OpenAIRE

    Mehrabian, Sarvenaz; Taheri, Ehsaneh; Karkhaneh, Maryam; Qorbani, Mostafa; Hosseini, Saeed

    2016-01-01

    Background Irisin, a recently identified myokine/adipokine, has potential role in type 2 diabetes and obesity. Normal weight obesity (NWO) is associated with a significantly higher risk of developing metabolic syndrome and cardiometabolic dysfunction. The aim of this study was to investigate association of irisin level with NWO, glycemicand lipid profile in women. Methods In this matchedcase-control study, 38 subjects with NWO (body mass index (BMI)  30) as case and 26 controls (BMI

  2. The Inhomogeneous Tropospheric Warming as the driver of Tropical Sea Level Pressure and Walker Circulation Changes

    OpenAIRE

    Bayr, Tobias; Dommenget, Dietmar

    2013-01-01

    In this presentation we follow the idea to split up the global warming signal in a spatial homogeneous warming and in a spatial inhomogeneous warming. In Bayr and Dommenget (2012) the changes of the tropical sea level pressure (SLP) due to inhomo-geneous tropospheric warming in climate change, which is mostly the land-sea warming contrast, was investigated in a multi model ensemble. The amplitude of the inhomogeneous tropospheric warming is roughly 10 times smaller than the total warming of t...

  3. Bancroftian filariasis: circulating B-1 cells decreased in microfilaria carriers and correlate with immunoglobulin M levels.

    Science.gov (United States)

    Mishra, R; Sahoo, P K; Mishra, S; Achary, K G; Dwibedi, B; Kar, S K; Satapathy, A K

    2014-05-01

    B-1 cells play an important role in the outcome of infection in schistosomiasis, pneumonia and experimental filariasis. However, no information exists regarding status of B-1 cells in clinical manifestations of human filariasis. We investigated the levels of B-1 cells from the total B cells by flow cytometry. Significantly low levels of B-1 cells and IgM antibodies were detected against a wide variety of autoantigens in microfilariae carriers as compared to endemic controls and patients with chronic pathology. A positive correlation was found between IgM antibodies to actin and ss-DNA. Absorption of plasma with soluble actin, myosin and lipopolysaccharides (LPS) resulted in significant removal of antifilarial antibodies. Affinity-purified anti-ss-DNA antibodies were found to be reactive to filarial antigens and various autoantigens. Further, a positive correlation was found between polyreactive antibodies and B-1 cells in filarial-infected human subjects. After antifilarial treatment, levels of IgM antibodies to ss-DNA, actin, LPS and filarial antigen increased significantly indicating a role of polyreactive naturally occurring antibodies in filarial infection. Our findings add to the existing evidence that the B-cell defect in BALB.Xid mice account for susceptibility to murine filarial infection and indicate an important role for these antibodies in providing host protection against filarial infection.

  4. Enhanced efficacy of IGF1R inhibition in pediatric glioblastoma by combinatorial targeting of PDGFRα/β

    DEFF Research Database (Denmark)

    Bielen, Aleksandra; Perryman, Lara; Box, Gary M;

    2011-01-01

    Pediatric glioblastoma (pGBM), although rare, is one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. We have identified IGF1R to be a potential therapeutic target in pGBM due to gene amplification and high levels of IGF2 expre...

  5. Sex Hormones in Allergic Conjunctivitis: Altered Levels of Circulating Androgens and Estrogens in Children and Adolescents with Vernal Keratoconjunctivitis

    Directory of Open Access Journals (Sweden)

    Marta Sacchetti

    2015-01-01

    Full Text Available Purpose. Vernal keratoconjunctivitis (VKC is a chronic allergic disease mainly affecting boys in prepubertal age and usually recovering after puberty. To evaluate a possible role of sex hormones in VKC, serum levels of sex hormones in children and adolescents with VKC were assessed. Methods. 12 prepubertal and 7 early pubertal boys with active VKC and 6 male patients with VKC in remission phase at late pubertal age and 48 healthy age and sex-matched subjects were included. Serum concentration of estrone, 17 beta-estradiol, dehydroepiandrosterone-sulfate, total testosterone and free testosterone, dihydrotestosterone (DHT, cortisol, delta-4-androstenedione, follicle-stimulating hormone, luteinizing hormone, and sex-hormones binding globuline (SHBG were evaluated. Results. Serum levels of Estrone were significantly increased in all groups of patients with VKC when compared to healthy controls (P<0.001. Prepubertal and early pubertal VKC showed a significant decrease in DHT (P=0.007 and P=0.028, resp. and SHBG (P=0.01 and P=0.002, resp. when compared to controls and serum levels of SHBG were increased in late pubertal VKC in remission phase (P=0.007. Conclusions and Relevance. VKC patients have different circulating sex hormone levels in different phases of the disease and when compared to nonallergic subjects. These findings suggest a role played by sex hormones in the pathogenesis and/or activity of VKC.

  6. Circulating Glutamate and Taurine Levels Are Associated with the Generation of Reactive Oxygen Species in Paroxysmal Atrial Fibrillation

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    Shintaro Takano

    2016-01-01

    Full Text Available Atrial fibrillation (AF is the most common cardiac arrhythmia, but its proarrhythmic mechanism remains to be elucidated. Glutamate (Glu and taurine (Tau are present in the myocardium at substantially higher concentrations than in the plasma, suggesting their active role in myocardium. Here, we tested the hypothesis that the metabolism of Glu and Tau is altered in association with the generation of reactive oxygen species (ROS in patients with AF. Fifty patients with paroxysmal AF and 50 control subjects without a history of AF were consecutively enrolled. Circulating Glu and Tau levels were measured and correlations between Glu/Tau and ROS levels were examined. Glu/Tau content was significantly higher in patients with AF versus controls (Glu: 79.2±23.9 versus 60.5±25.2 nmol/L; Tau: 78.8±19.8 versus 68.5±20.8 nmol/L; mean ± standard deviation (SD, p<0.001 for both. Glu/Tau levels also showed an independent association with AF by multiple logistic regression analysis. Glu and Tau levels both showed significant positive associations with plasma hydroperoxide concentrations. These data suggest a novel pathophysiological role of Glu and Tau in association with ROS production in paroxysmal AF, providing new insights into the elevated amino acid content in cardiac disease.

  7. Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways

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    Radhakrishnan Sridhar

    2010-05-01

    Full Text Available Abstract Background Obesity is a global phenomenon and is associated with various types of cancer, including colon cancer. There is a growing interest for safe and effective bioactive compounds that suppress the risk for obesity-promoted colon cancer. Resveratrol (trans-3, 4', 5,-trihydroxystilbene, a stilbenoid found in the skin of red grapes and peanuts suppresses many types of cancers by regulating cell proliferation and apoptosis through a variety of mechanisms, however, resveratrol effects on obesity-promoted colon cancer are not clearly established. Methods We investigated the anti-proliferative effects of resveratrol on HT-29 and SW480 human colon cancer cells in the presence and absence of insulin like growth factor-1 (IGF-1; elevated during obesity and elucidated the mechanisms of action using IGF-1R siRNA in HT-29 cells which represents advanced colon carcinogenesis. Results Resveratrol (100-150 μM exhibited anti-proliferative properties in HT-29 cells even after IGF-1 exposure by arresting G0/G1-S phase cell cycle progression through p27 stimulation and cyclin D1 suppression. Treatment with resveratrol suppressed IGF-1R protein levels and concurrently attenuated the downstream Akt/Wnt signaling pathways that play a critical role in cell proliferation. Targeted suppression of IGF-1R using IGF-1R siRNA also affected these signaling pathways in a similar manner. Resveratrol treatment induced apoptosis by activating tumor suppressor p53 protein, whereas IGF-1R siRNA treatment did not affect apoptosis. Our data suggests that resveratrol not only suppresses cell proliferation by inhibiting IGF-1R and its downstream signaling pathways similar to that of IGF-1R siRNA but also enhances apoptosis via activation of the p53 pathway. Conclusions For the first time, we report that resveratrol suppresses colon cancer cell proliferation and elevates apoptosis even in the presence of IGF-1 via suppression of IGF-1R/Akt/Wnt signaling pathways and

  8. Changes in IGF-I and its Binding Proteins Are Associated with Diabetes in Older Adults

    Science.gov (United States)

    Aneke, Chino S.; Parrinello, Christina M.; Rajpathak, Swapnil N.; Rohan, Thomas E.; Strotmeyer, Elsa S.; Kritchevsky, Stephen B.; Psaty, Bruce M.; Bůžková, Petra; Kizer, Jorge R.; Newman, Anne B.; Strickler, Howard D.; Kaplan, Robert C.

    2015-01-01

    Objectives Little is known about long-term changes in insulin-like growth Factor (IGF) proteins and glycemic status. We hypothesized that changes in IGF proteins are exaggerated in participants with type 2 diabetes or worsening glycemia versus those that remain normoglycemic over a 9-year follow-up period. Design Retrospective analysis of cohort study. Setting Participants were recruited from four States: North Carolina, California, Maryland and Pennsylvania. Participants 897 participants enrolled in CHS All Stars, a cohort study of community dwelling adults aged ≥65 years. Measurements Plasma IGF-I, IGFBP-1, and IGFBP-3 levels were assessed and ADA cut-points for IGT, IFG, and diabetes were used to classify participants at baseline (1996–1997) and follow-up (2005–2006). Results At baseline, mean age was 76.3 years (± 3.6) and 18.5% had diabetes. Individuals with IFG alone and IGT+IFG had the highest levels of IGF-I and lowest levels of IGFBP-1, compared to individuals with normoglycemia or diabetes. The greatest percent change in IGF levels occurred in those who had diabetes at baseline (9-year changes: −9.3% for IGF-I, 59.7% for IGFBP-1, −13.4% for IGFBP-3); the smallest in individuals who remained normoglycemic at follow-up (9-year changes: −3.7% for IGF-I, 25.6% for IGFBP-1, −6.4% for IGFBP-3); and intermediate changes in those who were normoglycemic but developed IFG at follow-up. Conclusion Our results demonstrate that degrees of glycemic impairment are associated with varying levels of changes in IGF proteins. The exaggerated changes observed in the diabetes group have been previously shown to be associated with heart failure, cancer and non-cancer mortality. PMID:25989565

  9. Circulating ADAM17 Level Reflects Disease Activity in Proteinase-3 ANCA-Associated Vasculitis.

    Science.gov (United States)

    Bertram, Anna; Lovric, Svjetlana; Engel, Alissa; Beese, Michaela; Wyss, Kristin; Hertel, Barbara; Park, Joon-Keun; Becker, Jan U; Kegel, Johanna; Haller, Hermann; Haubitz, Marion; Kirsch, Torsten

    2015-11-01

    ANCA-associated vasculitides are characterized by inflammatory destruction of small vessels accompanied by enhanced cleavage of membrane-bound proteins. One of the main proteases responsible for ectodomain shedding is disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). Given its potential role in aggravating vascular dysfunction, we examined the role of ADAM17 in active proteinase-3 (PR3)-positive ANCA-associated vasculitis (AAV). ADAM17 concentration was significantly increased in plasma samples from patients with active PR3-AAV compared with samples from patients in remission or from other controls with renal nonvascular diseases. Comparably, plasma levels of the ADAM17 substrate syndecan-1 were significantly enhanced in active AAV. We also observed that plasma-derived ADAM17 retained its specific proteolytic activity and was partly located on extracellular microparticles. Transcript levels of ADAM17 were increased in blood samples of patients with active AAV, but those of ADAM10 or tissue inhibitor of metalloproteinases 3, which inhibits ADAMs, were not. We also performed a microRNA (miR) screen and identified miR-634 as significantly upregulated in blood samples from patients with active AAV. In vitro, miR-634 mimics induced a proinflammatory phenotype in monocyte-derived macrophages, with enhanced expression and release of ADAM17 and IL-6. These data suggest that ADAM17 has a prominent role in AAV and might account for the vascular complications associated with this disease. PMID:25788529

  10. Tailored antihypertensive drug therapy prescribed to older women attenuates circulating levels of interleukin-6 and tumor necrosis factor-α

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    Toledo JO

    2015-01-01

    Full Text Available Juliana O Toledo,1 Clayton F Moraes,2,3 Vinícius C Souza,2 Audrey C Tonet-Furioso,2 Luís CC Afonso,4 Cláudio Córdova,3 Otávio T Nóbrega1,2 1Graduate Program in Health Sciences, 2Graduate Program in Medical Sciences, University of Brasília, Brasília, 3Graduate Program in Gerontology, Catholic University of Brasília, Brasília, 4Research Center in Biological Sciences, Federal University of Ouro Preto, Ouro Preto, Brazil Objective: To test the hypothesis that antihypertensive drug therapy produces anti-inflammatory effects in clinical practice, this study investigated circulating levels of selected proinflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and interferon-γ [INF-γ] in response to multivariate drug directions for blood pressure (BP control.Methods: Prospective study involving 110 hypertensive, community-dwelling older women with different metabolic disorders. A short-term BP-lowering drug therapy was conducted according to current Brazilian guidelines on hypertension, and basal cytokine levels were measured before and after intervention.Results: Interventions were found to represent current hypertension-management practices in Brazil and corresponded to a significant reduction in systolic and diastolic BP levels in a whole-group analysis, as well as when users and nonusers of the most common therapeutic classes were considered separately. Considering all patients, mean IL-6 and TNF-α levels showed a significant decrease in circulating concentrations (P<0.01 at the endpoint compared with baseline, whereas the mean INF-γ level was not significantly different from baseline values. In separate analyses, only users of antagonists of the renin–angiotensin system and users of diuretics exhibited the same significant treatment-induced reduction in serum IL-6 and TNF-α observed in the whole group.Conclusion: Our data demonstrates that a clinically guided antihypertensive treatment is effective in

  11. 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

  12. Association of High Vitamin D Status with Low Circulating Thyroid-Stimulating Hormone Independent of Thyroid Hormone Levels in Middle-Aged and Elderly Males

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    Qingqing Zhang

    2014-01-01

    Full Text Available Background. A recent study has reported that high circulating 25-hydroxyvitamin D [25(OHD] is associated with low circulating thyroid-stimulating hormone (TSH levels, but only in younger individuals. The goal of the present study was to explore the relationship between vitamin D status and circulating TSH levels with thyroid autoimmunity and thyroid hormone levels taken into consideration in a population-based health survey of middle-aged and elderly individuals. Methods. A total of 1,424 Chinese adults, aged 41–78 years, were enrolled in this cross-sectional study. Serum levels of 25(OHD, TSH, thyroid hormones, and thyroid autoantibodies were measured. Results. The prevalence of vitamin D insufficiency was 94.29% in males and 97.22% in females, and the prevalence of vitamin D deficiency was 55.61% in males and 69.64% in females. Vitamin D status was not associated with positive thyroid autoantibodies after controlling for age, gender, body mass index, and smoking status. Higher 25(OHD levels were associated with lower TSH levels after controlling for age, FT4 and FT3 levels, thyroid volume, the presence of thyroid nodule(s, and smoking status in males. Conclusion. High vitamin D status in middle-aged and elderly males was associated with low circulating TSH levels independent of thyroid hormone levels.

  13. Circulating MicroRNA-223 Serum Levels Do Not Predict Sepsis or Survival in Patients with Critical Illness

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    Fabian Benz

    2015-01-01

    Full Text Available Background and Aims. Dysregulation of miR-223 was recently linked to various diseases associated with systemic inflammatory responses such as type 2 diabetes, cancer, and bacterial infections. However, contradictory results are available on potential alterations of miR-223 serum levels during sepsis. We thus aimed to evaluate the diagnostic and prognostic value of miR-223 serum concentrations in patients with critical illness and sepsis. Methods. We used i.v. injection of lipopolysaccharide (LPS as well as cecal pole ligation and puncture (CLP for induction of polymicrobial sepsis in mice and measured alterations in serum levels of miR-223. These results from mice were translated into a large and well-characterized cohort of critically ill patients admitted to the medical intensive care unit (ICU. Finally, results from analysis in patients were correlated with clinical data and extensive sets of routine and experimental biomarkers. Results. Although LPS injection induced moderately elevated serum miR-223 levels in mice, no significant alterations in miR-223 serum levels were found in mice after CLP-induced sepsis. In accordance with these results from animal models, serum miR-223 levels did not differ between critically ill patients and healthy controls. However, ICU patients with more severe disease (APACHE-II score showed moderately reduced circulating miR-223. Strikingly, no differences in miR-223 levels were found in critically ill patients with or without sepsis, and serum levels of miR-223 did not correlate with classical markers of inflammation or bacterial infection. Finally, low miR-223 serum levels were moderately associated with an unfavorable prognosis of patients during the ICU treatment but did not predict long-term mortality. Conclusion. Recent reports on alterations in miR-223 serum levels during sepsis revealed contradictory results, preventing a potential use of this miRNA in clinical routine. We clearly show that miR-223 serum

  14. Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors.

    Science.gov (United States)

    Yi, Buqing; Nichiporuk, Igor; Nicolas, Michel; Schneider, Stefan; Feuerecker, Matthias; Vassilieva, Galina; Thieme, Detlef; Schelling, Gustav; Choukèr, Alexander

    2016-06-01

    Increasing evidence indicates that chronic stress, such as social isolation, plays an important role in the development of a variety of psychiatric and somatic disorders. Meanwhile, chronic stress imposed by prolonged isolation and confinement in the spacecraft is also one of the major concerns for the health of future interplanetary space travelers. Preclinical studies suggest that the peripheral endocannabinoid (eCB) system is involved in the regulation of the stress response and eCB signaling is implicated in the pathogenesis of stress-related diseases. However, there are only few human studies addressing this topic, of which most focusing on patients who have already developed a certain type of disorder. It remains unknown whether chronic stress may affect eCB signaling in healthy humans. A 520-d isolation and confinement study simulating a flight to Mars provided an extraordinary chance to study the effects of prolonged stress in healthy humans. During the study period, the participants lived in confinement and could not meet their families, friends, or strangers for more than 500 days. We examined the impact of chronic exposure to isolation and confinement through monitoring their psychological state, brain cortical activity, sympathetic adrenal-medullary system response and eCB signaling response. We observed reduced positive emotion ratings, decreased brain cortical activities and high levels of catecholamine release, indicating that prolonged exposure to isolation and confinement stressors may bring about changes both psychologically and physiologically. Importantly, for eCB signaling response, blood concentrations of eCB 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), were significantly reduced (p<0.001), suggesting that dysregulation of 2-AG signaling might be specifically implicated in the response to chronic stressors.

  15. Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors.

    Science.gov (United States)

    Yi, Buqing; Nichiporuk, Igor; Nicolas, Michel; Schneider, Stefan; Feuerecker, Matthias; Vassilieva, Galina; Thieme, Detlef; Schelling, Gustav; Choukèr, Alexander

    2016-06-01

    Increasing evidence indicates that chronic stress, such as social isolation, plays an important role in the development of a variety of psychiatric and somatic disorders. Meanwhile, chronic stress imposed by prolonged isolation and confinement in the spacecraft is also one of the major concerns for the health of future interplanetary space travelers. Preclinical studies suggest that the peripheral endocannabinoid (eCB) system is involved in the regulation of the stress response and eCB signaling is implicated in the pathogenesis of stress-related diseases. However, there are only few human studies addressing this topic, of which most focusing on patients who have already developed a certain type of disorder. It remains unknown whether chronic stress may affect eCB signaling in healthy humans. A 520-d isolation and confinement study simulating a flight to Mars provided an extraordinary chance to study the effects of prolonged stress in healthy humans. During the study period, the participants lived in confinement and could not meet their families, friends, or strangers for more than 500 days. We examined the impact of chronic exposure to isolation and confinement through monitoring their psychological state, brain cortical activity, sympathetic adrenal-medullary system response and eCB signaling response. We observed reduced positive emotion ratings, decreased brain cortical activities and high levels of catecholamine release, indicating that prolonged exposure to isolation and confinement stressors may bring about changes both psychologically and physiologically. Importantly, for eCB signaling response, blood concentrations of eCB 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), were significantly reduced (p<0.001), suggesting that dysregulation of 2-AG signaling might be specifically implicated in the response to chronic stressors. PMID:26780604

  16. An elevated level of circulating galanin promotes developmental expression of myelin basic protein in the mouse brain.

    Science.gov (United States)

    Lyubetska, H; Zhang, L; Kong, J; Vrontakis, M

    2015-01-22

    Myelinogenesis is a scheduled process that is regulated by the intrinsic properties of the cell and extracellular signals. Galanin (GAL) is a bioactive neuropeptide that is widely distributed throughout the nervous system. Chronic increase in circulating GAL levels protects the demyelination processes. Furthermore, GAL is synthesized in myelin-producing glial cells, such as oligodendrocytes and its expression level is at its highest between postnatal days 10 and 40. In the present study, we use our GAL transgenic mouse model to examine the effects of GAL on postnatal myelinogenesis in the CNS. Although we observed no difference in the proliferation of oligodendrocyte precursor cells, we found that GAL has a strong pro-myelinating effect. The transgenic mice at postnatal day 10 appeared to undergo myelinogenesis at an accelerated rate, as demonstrated by the increase in myelin basic protein (MBP) synthesis. The immunohistochemical results are consistent with our preliminary findings that suggest that GAL is a regulator of myelination and may be one of the myelination promoters. This finding is especially important for studies focusing on endogenous molecules for treating myelin-related diseases, such as multiple sclerosis and other leukodystrophies.

  17. Decreased Circulating Interleukin-35 Levels Are Related to Interleukin-4-Producing CD8+ T Cells in Patients with Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2015-10-01

    Full Text Available  Interleukin (IL-35 is a newly discovered suppressive cytokine and has been shown to alleviate  inflammatory  and  autoimmune  diseases.  The  purpose  of  this  study  was  to investigate immunomodulatory capacity of IL-35 in patients with allergic asthma.IL-35 mRNA expression levels in peripheral blood mononuclear cells (PBMCs were detected  by  quantitative  real-time  PCR  (qPCR.  The  frequencies  of  cytotoxic  T  cells (Tc1,Tc2  and  Tc17  cells  were  measured  by  flow  cytometry.  Plasma  levels  of  IL-35, interferon (IFN-γ, IL-4, and IL-17 were examined by enzyme-linked immunosorbent assay (ELISA. The correlations between plasma IL-35 levels and Tc1, Tc2, and Tc17 cytokine production in allergic asthmatics (n = 25 and healthy controls (n = 12 were analyzed by Pearson’s test.IL-35 protein and mRNA expression levels were down-regulated in allergic asthmaticscompared with healthy controls. The frequencies of Tc2 and Tc17 cells were significantly increased in patients with asthma, and the frequency of Tc1 cells did not differ between asthmatic patients and healthy controls. Similarly, plasma levels of IL-4 and IL-17 were significantly increased in asthmatic patients, while there was no difference in IFN-γ levels between allergic asthma patients  and  healthy  controls.  More importantly,  plasma  IL-35 protein levels were negatively correlated with the frequency of IL-4-producing CD8+ T (Tc2 cells and with the IL-4 level in patients with allergic asthma.Our results suggest that decreased circulating IL-35 levels could contribute to the pathogenesis of allergic asthma by regulating CD8+ T cells. 

  18. IGF-IR targeted therapy: Past, present and future

    NARCIS (Netherlands)

    J.A.M.J.L. Janssen (Joseph); A.J. Varewijck (Aimee)

    2014-01-01

    textabstractThe IGF-I receptor (IGF-IR) has been studied as an anti-cancer target. However, monotherapy trials with IGF-IR targeted antibodies or with IGF-IR specific tyrosine kinase inhibitors have, overall, been very disappointing in the clinical setting. This review discusses potential reasons wh

  19. Binding Inhibition Between Igf1r and Igf1 by Catechin of Black Tea

    Directory of Open Access Journals (Sweden)

    Lina Firdausi

    2012-12-01

    Full Text Available The natural compound of black tea is used as an alternative of obesity therapies in the world; particularly, the catechin family in tea leaves which has bioactive compounds such as EC, EGC and EGCG. Their bioactivity contributes to inhibit the ligand of Insulin-Like Growth Factor I Receptor (Igf-1r binding-region to Igf-1 protein. To elucidate the inhibiton of Igf-1 expression and proliferating of Rattus norvegicus strain wistar adipose cell using black tea solution. The research used Rattus norvegicus strain wistar. After a 90-day treatment, the adipose tissues were picked up from the viscera of each experimental animal, and then the adipose tissues were embedded by paraffin. The paraffin sections were determined through immunohistochemistry with anti-Igf-1 antiserum, and were also analyzed through hematoxylin-eosin. A protein sequence of Igf-1, Igf-1r, and 3D structure of EC, EGC and EGCG from Gene Bank sites were used during in silico analysis. The sequences were aligned by BLAST program to identify the conserve and variable domain of IGF-1 protein isoforms. The 3D structures of IGF-1 and IGF-1R were constructed using Phyre program. The ligand among the 3D structures of IGF-1, IGF-1R and catechin compounds were analyzed using Hex 5.1 docking program. The data showed that the Igf-1 expression of adipose cells was reduced at 0,03 g/ml BTS and 0,045 g/ml BTS treatments. The result of BLAST analysis showed that IGF-1 (a, b, c, and d isoforms conserved a domain from amino acid no 22 until 134; and this region was a variable region. The EGCG bound L1 domain of IGF-1R with E-total -235.3 KJ/mol which was lower than EC (-208,4 KJ/mol and EGC (-142 KJ/mol. The total energy of IGF-1 (a, b, c, but not d isoform which interacted with EGCG was around -223.7 KJ/mol, EC is -205.6 KJ/mol and EGC was -191.7 KJ/mol. However, EC, EGC and EGCG was only able to prevent the interaction between the L1 of IGF-1R with IGF-1 protein, but not the opposite.

  20. IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients

    Directory of Open Access Journals (Sweden)

    Herrmann Richard

    2010-01-01

    Full Text Available Abstract Background Insulin-like growth factor-1 (IGF-I signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately. Methods We used an ex vivo culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. In vitro data were correlated with in vivo findings by comparing the results with published expression datasets on human cancer biopsies. Results Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (P = 0.029 - Norway/Stanford and P = 7.96e-09 - NKI dataset. Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (P = 0.007 - Bhattacharjee and P = 0.008 - Garber dataset. Conclusion Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies. See the related commentary by Werner and Bruchim: http://www.biomedcentral.com/1741-7015/8/2

  1. Circulating High-Molecular-Weight (HMW) Adiponectin Level Is Related with Breast Cancer Risk Better than Total Adiponectin: A Case-Control Study.

    Science.gov (United States)

    Guo, Ming-ming; Duan, Xue-ning; Cui, Shu-de; Tian, Fu-guo; Cao, Xu-chen; Geng, Cui-zhi; Fan, Zhi-min; Wang, Xiang; Wang, Shu; Jiang, Hong-chuan; Zhang, Jian-guo; Jin, Feng; Tang, Jin-hai; Liang, Hong; Yang, Zhen-lin; Wang, Hai-bo; Wang, Qi-tang; Li, Guo-lou; Li, Liang; Zhu, Shi-guang; Zuo, Wen-shu; Liu, Li-yuan; Wang, Lu; Ma, Dan-dan; Liu, Shu-chen; Xiang, Yu-juan; Liu, Lu; Ye, Chun-miao; Zhou, Wen-zhong; Wang, Fei; Yu, Li-xiang; Ma, Zhong-bing; Yu, Zhi-gang

    2015-01-01

    The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMIbreast cancer risk (P=0.034, 0.0116). This study showed different forms of circulating adiponectin levels might play different roles in breast cancer risk. A higher circulating HMW adiponectin is associated with a decreased breast cancer risk, especially in postmenopausal, without family history of breast cancer or BMI>=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed.

  2. Characterization data of gilthead sea bream (Sparus aurata IGF-I receptors (IGF-IRa/Rb

    Directory of Open Access Journals (Sweden)

    Emilio J. Vélez

    2016-03-01

    Full Text Available In this data article we describe the coding sequence of two IGF-IR paralogues (IGF-IRa and IGF-IRb obtained from gilthead sea bream embryos. The putative protein architecture (domains and other important motifs was determined and, amino acid sequences alignment and phylogenetic analysis of both receptors together with IGF-IR orthologues from different vertebrates was performed. Additionally, a semi-quantitative conventional PCR was done to analyze the mRNA expression of both receptors in different tissues of gilthead sea bream. These data will assist in further physiological studies in this species. In this sense, the expression of both receptors during ontogeny in muscle as well as the differential effects of IGF-I and IGF-II on their regulation during in vitro myogenesis has been recently studied (doi: 10.1016/j.ygcen.2015.11.011; [1].

  3. Differential Roles of Insulin and IGF-1 Receptors in Adipose Tissue Development and Function.

    Science.gov (United States)

    Boucher, Jeremie; Softic, Samir; El Ouaamari, Abdelfattah; Krumpoch, Megan T; Kleinridders, Andre; Kulkarni, Rohit N; O'Neill, Brian T; Kahn, C Ronald

    2016-08-01

    To determine the roles of insulin and insulin-like growth factor 1 (IGF-1) action in adipose tissue, we created mice lacking the insulin receptor (IR), IGF-1 receptor (IGF1R), or both using Cre-recombinase driven by the adiponectin promoter. Mice lacking IGF1R only (F-IGFRKO) had a ∼25% reduction in white adipose tissue (WAT) and brown adipose tissue (BAT), whereas mice lacking both IR and IGF1R (F-IR/IGFRKO) showed an almost complete absence of WAT and BAT. Interestingly, mice lacking only the IR (F-IRKO) had a 95% reduction in WAT, but a paradoxical 50% increase in BAT with accumulation of large unilocular lipid droplets. Both F-IRKO and F-IR/IGFRKO mice were unable to maintain body temperature in the cold and developed severe diabetes, ectopic lipid accumulation in liver and muscle, and pancreatic islet hyperplasia. Leptin treatment normalized blood glucose levels in both groups. Glucose levels also improved spontaneously by 1 year of age, despite sustained lipodystrophy and insulin resistance. Thus, loss of IR is sufficient to disrupt white fat formation, but not brown fat formation and/or maintenance, although it is required for normal BAT function and temperature homeostasis. IGF1R has only a modest contribution to both WAT and BAT formation and function.

  4. G Allele of the IGF2 ApaI Polymorphism Is Associated With Judo Status.

    Science.gov (United States)

    Itaka, Toshio; Agemizu, Kenichiro; Aruga, Seiji; Machida, Shuichi

    2016-07-01

    Itaka, T, Agemizu, K, Aruga, S, and Machida, S. G allele of the IGF2 ApaI polymorphism is associated with judo status. J Strength Cond Res 30(7): 2043-2048, 2016-Previous studies have reported that the insulin-like growth factor 2 (IGF2) ApaI polymorphism is associated with body mass index, fat mass, and grip strength. Competitive judo requires high levels of strength and power. The purpose of this study was to investigate the association between the IGF2 ApaI and ACTN3 R577X polymorphisms and judo status. The subjects were 156 male judo athletes from a top-level university in Japan. They were divided into 3 groups based on their competitive history: international-level athletes, national-level athletes, and others. Genomic DNA was extracted from the saliva of each athlete, and the maximal isometric strength of the trunk muscles and handgrip strength were measured. Genotyping by polymerase chain reaction-restriction fragment length polymorphism was used to detect IGF2 (rs680) and α-actinin-3 (ACTN3) (rs1815739) gene polymorphisms. The genotype frequencies of the 2 gene polymorphisms were compared among the 3 groups of judo athletes and controls. International-level judo athletes showed a higher frequency of the GG + GA genotype of the IGF2 gene than that of the national-level athletes and others. There was an inverse linear correlation between the frequency of the IGF2 AA genotype and level of judo performance (p = 0.041). Back muscle strength relative to height and weight was higher in subjects with the GG + GA genotype than in those with the AA genotype. Conversely, the ACTN3 R577X polymorphism was not associated with judo status. Additionally, no differences were found in back muscle or handgrip strength among the ACTN3 genotypes. In conclusion, the results indicate that the IGF2 gene polymorphism may be associated with judo status. PMID:26677828

  5. Bioactive rather than total IGF-I is involved in acute responses to nutritional interventions in CAPD patients

    NARCIS (Netherlands)

    M.P. Brugts (Michael); H.L. Tjiong (Hoey Lan); T. Rietveld (Trinet); J.L.D. Wattimena (Josias); J.W.O. van den Berg (Willem); M.W.J.A. Fieren (Marien); J.A.M.J.L. Janssen (Joseph)

    2010-01-01

    textabstractBackground. Inadequate food intake plays an important role in the development of malnutrition in continuous ambulatory peritoneal dialysis (CAPD) patients.Aim of the study. The aim of the study was to investigate in CAPD patients whether circulating insulin-like growth factor-I (IGF-I) b

  6. Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Honglei; Peng, Wujian; Shen, Xuemei; Huang, Yunhui; Ouyang, Xin; Dai, Yong [Clinical Medical Research Center, Second Clinical Medical College, Shenzhen People' s Hospital, Jinan University, Shenzhen, Guangdong (China)

    2012-10-19

    Circulating microRNAs (miRNAs) may represent a potential noninvasive molecular biomarker for various pathological conditions. Moreover, the detection of circulating miRNAs can provide important novel disease-related information. In particular, inflammation-associated miR-155 and endothelial-enriched miR-126 are reported to be associated with vascular homeostasis. Vascular damage is a common event described in end-stage renal disease (ESRD). We hypothesized that miR-155 and miR-126 may be detectable in the circulation and serve as potential biomarkers for risk stratification. In this study, we assessed miR-155 and miR-126 in the plasma of 30 ESRD patients and 20 healthy controls using real-time quantification RT-PCR. The circulating levels of miR-155 and miR-126 were significantly reduced in patients with ESRD compared to healthy controls. However, there was no significant difference of circulating miR-155 and miR-126 levels between prehemodialysis and posthemodialysis patients. Furthermore, both circulating miR-126 and miR-155 correlated positively with estimated glomerular filtration rate (miR-126: r = 0.383, P = 0.037; miR-155: r = 0.494, P = 0.006) and hemoglobin (miR-126: r = 0.515, P = 0.004; miR-155: r = 0.598, P < 0.001) and correlated inversely with phosphate level (miR-126: r = -0.675, P < 0.001; miR-155: r = -0.399, P = 0.029). Pearson's correlation was used to compare circulating levels of miRNAs with clinical parameters. These results suggested that circulating miR-155 and miR-126 might be involved in the development of ESRD. Further studies are needed to demonstrate the role of circulating miR-155 and miR-126 as candidate biomarkers for risk estimation.

  7. The effects of thyroid hormone on insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) expression in the neonatal rat: prolonged high expression of IGFBP-2 in methimazole-induced congenital hypothyroidism.

    Science.gov (United States)

    Näntö-Salonen, K; Glasscock, G F; Rosenfeld, R G

    1991-11-01

    In the rat a developmental switch in the serum insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) profile takes place during the first 3 postnatal weeks. The fetal expression pattern of high IGF-II and IGFBP-2 is replaced by the adult pattern of low levels of IGF-II and IGFBP-2 and high levels of IGF-I and IGFBP-3. The regulatory mechanisms mediating these changes are unknown, but may include perinatal changes in endocrine function. To study the effects of thyroid function and the perinatal thyroid secretory burst on IGF and IGFBP expression, we established a rat model of congenital hypothyroidism, leading to marked postnatal growth retardation during the perinatal period. The hypothyroid animals lacked the steep rise in serum IGF-I levels normally occurring during the third week of life, showing only a modest rise to approximately 50% of control levels. The pattern of serum IGF-II decline in hypothyroid animals was slightly different from that in controls, with lower IGF-II levels during the second week of life and a slower decline down to the very low final levels. The hypothyroid pups continued to express high levels of IGFBP-2 up to the age of 19 days, while the control animals, after a slow initial decline, showed an abrupt fall of IGFBP-2 serum levels during the third week of life. Liver IGFBP-2 mRNA levels reflected the serum changes, with elevated IGFBP-2 mRNA in hypothyroid animals. The expression of other IGFBPs did not differ from that in the control group. At the age of 18 days, serum GH levels in the hypothyroid animals were approximately one third of control GH levels, which suggests a role for GH as a possible mediator of thyroid hormone actions on the IGF system. The changes in growth parameters and in the IGF and IGFBP profile of hypothyroid pups could be abolished by thyroid hormone replacement from birth. We conclude that thyroid hormone is, directly or indirectly, essential for some of the neonatal changes in IGF and IGFBP profiles

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Lee, Ha Won; Cheng, Jie; Kovbasnjuk, Olga; Donowitz, Mark; Guggino, William B

    2013-01-01

    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.

  10. IGF1-R inhibition and liposomal doxorubicin: Progress in preclinical evaluation for the treatment of adrenocortical carcinoma.

    Science.gov (United States)

    Beuschlein, Felix; Jakoby, Judith; Mentz, Susanne; Zambetti, Gerard; Jung, Sara; Reincke, Martin; Süss, Regine; Hantel, Constanze

    2016-06-15

    Adrenocortical carcinoma (ACC) is a tumor with poor prognosis and limited therapeutic options. Therefore, in addition to multi-chemotherapeutic regimens IGF-1 receptor (IGF-1R) targeting approaches have been evaluated including immunoliposomal (IL) preparations utilizing an IGF-1R inhibiting antibody. In the current study, we extended our experiments by long-term treatment regimens in the classical adrenocortical NCIH295R xenograft model as well as by short-term experiments in two novel xenograft models, which all displayed different levels of IGF-1R and IGF-2 expression. Interestingly, these experiments reveal sub-group dependent differences in therapeutic outcome, reflecting clinical observations and indicate, thus, that implementation of this panel of tumor models might be helpful for clinical translation of novel therapeutic regimens in the future. PMID:26994514

  11. IGF-II transgenic mice display increased aberrant colon crypt multiplicity and tumor volume after 1,2-dimethylhydrazine treatment

    Directory of Open Access Journals (Sweden)

    Oesterle Doris

    2006-01-01

    Full Text Available Abstract In colorectal cancer insulin-like growth factor II (IGF-II is frequently overexpressed. To evaluate, whether IGF-II affects different stages of tumorigenesis, we induced neoplastic alterations in the colon of wild-type and IGF-II transgenic mice using 1,2-dimethylhydrazine (DMH. Aberrant crypt foci (ACF served as markers of early lesions in the colonic mucosa, whereas adenomas and carcinomas characterized the endpoints of tumor development. DMH-treatment led initially to significantly more ACF in IGF-II transgenic than in wild-type mice. This increase in ACF was especially prominent for those consisting of ≥three aberrant crypts (AC. Nevertheless, adenomas and adenocarcinomas of the colon, present after 34 weeks in both genetic groups, were not found at different frequency. Tumor volumes, however, were significantly higher in IGF-II transgenic mice and correlated with serum IGF-II levels. Immunohistochemical staining for markers of proliferation and apoptosis revealed increased cell proliferation rates in tumors of IGF-II transgenic mice without significant affection of apoptosis. Increased proliferation was accompanied by elevated localization of β-catenin in the cytosol and cell nuclei and reduced appearance at the inner plasma membrane. In conclusion, we provide evidence that IGF-II, via activation of the β-catenin signaling cascade, promotes growth of ACF and tumors without affecting tumor numbers.

  12. IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer

    Science.gov (United States)

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M.; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui; Yang, Lily

    2016-05-01

    Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.

  13. IGF-Ⅰ、IGFBP与肺癌

    Institute of Scientific and Technical Information of China (English)

    张燕; 梅同华

    2002-01-01

    胰岛素样生长因子-Ⅰ(IGF-Ⅰ)具有类似胰岛素的代谢作用和促有丝分裂作用.IGF-Ⅰ的生物学活性受胰岛素样生长因子结合蛋白(IGFBP,包括IGFBP-1~6)的调节.近年的研究表明测量肺癌各种标本的IGF-Ⅰ、IGFBP的水平有助于肺癌的早期诊断、病理分期,IGF-Ⅰ抑制剂和IGFBP-3,6增强剂可望成为肺癌的有用的治疗手段.

  14. Optimisation of an immunohistochemistry method for the determination of androgen receptor expression levels in circulating tumour cells

    International Nuclear Information System (INIS)

    AZD3514 inhibits and down regulates the androgen receptor (AR) and has undergone clinical trials in prostate cancer. To provide proof-of-mechanism (POM) in patients, an immunohistochemistry (IHC) method for determination of AR in circulating tumour cells (CTC) was developed and validated. After an assessment of specificity validation focused on intra- and inter-operator reproducibility utilising a novel modification of incurred sample reanalysis (ISR). β-Content γ-confidence tolerance intervals (BCTI) and Cohen’s Kappa (κ) were employed in statistical analysis of results. In a first set of IHC reproducibility experiments, almost perfect agreement was recorded (κ=0.94) when two different operators scored CTC as overall positive or negative for AR. However, BCTI analysis identified a specific bias in scoring staining intensity, where one operator favoured moderate over strong assignments, whereas the reverse was the case with the second operator. After a period of additional training involving deployment of a panel of standardised images, a second set of validation experiments were conducted. These showed correction of the inter-operator bias by BCTI with κ for scoring intensity increasing from 0.59 to 0.81, indicative of almost perfect agreement. By application of BCTI to the validation of IHC, operator bias and therefore poor reproducibility can be identified, characterised and corrected to achieve a level of error normally associated with a quantitative biomarker assay, such as an ELISA. The methodological approach described herein can be applied to any generic IHC technique

  15. Striatal GDNF Production Is Independent to Circulating Estradiol Level Despite Pan-Neuronal Activation in the Female Mouse

    Science.gov (United States)

    Enterría-Morales, Daniel; López-López, Ivette; López-Barneo, José; d’Anglemont de Tassigny, Xavier

    2016-01-01

    Gender difference in Parkinson’s disease (PD) suggests that female sex steroids may promote dopaminergic neuron survival and protect them from degeneration. The glial cell line-derived neurotrophic factor (GDNF) is believed to be dopaminotrophic; thus it is considered as a potential therapeutic target in PD. Additionally, GDNF is endogenously synthetized in the caudate/putamen of humans and striatum in rodents. A neuroprotective role of estrogens on the nigrostriatal pathway via the stimulation of GDNF has been proposed. Since the GDNF-producing parvalbumin (Parv) interneurons express the estrogen receptor alpha in the mouse striatum, we sought to determine whether ectopic estrogenic compound modulates the GDNF synthesis in mice. Using an ovariectomized-estradiol (E2) replacement regimen, which reliably generates a rise of plasma estradiol, we assessed the effects of different levels of E2 on the activation of striatal neuronal populations, and GDNF production. A strong correlation was found between plasma E2 and the expression of the immediate early gene cFos in the striatum, as well as in other cortical regions. However, moderate and high E2 treatments failed to induce any striatal GDNF mRNA and protein synthesis. High E2 only stimulates cFos induction in a low percentage of striatal Parv neurons whereas the majority of cFos-positive cells are medium spiny neurons. Activation of these projecting neurons by E2 suggests a role of circulating sex steroids in the modulation of striatal neural pathways. PMID:27741271

  16. A Python Implementation of an Intermediate-Level Tropical Circulation Model and Implications for How Modeling Science is Done

    Science.gov (United States)

    Lin, J. W. B.

    2015-12-01

    Historically, climate models have been developed incrementally and in compiled languages like Fortran. While the use of legacy compiledlanguages results in fast, time-tested code, the resulting model is limited in its modularity and cannot take advantage of functionalityavailable with modern computer languages. Here we describe an effort at using the open-source, object-oriented language Pythonto create more flexible climate models: the package qtcm, a Python implementation of the intermediate-level Neelin-Zeng Quasi-Equilibrium Tropical Circulation model (QTCM1) of the atmosphere. The qtcm package retains the core numerics of QTCM1, written in Fortran, to optimize model performance but uses Python structures and utilities to wrap the QTCM1 Fortran routines and manage model execution. The resulting "mixed language" modeling package allows order and choice of subroutine execution to be altered at run time, and model analysis and visualization to be integrated in interactively with model execution at run time. This flexibility facilitates more complex scientific analysis using less complex code than would be possible using traditional languages alone and provides tools to transform the traditional "formulate hypothesis → write and test code → run model → analyze results" sequence into a feedback loop that can be executed automatically by the computer.

  17. Circulating levels of adiponectin, resistin, and visfatin after mud-bath therapy in patients with bilateral knee osteoarthritis.

    Science.gov (United States)

    Fioravanti, Antonella; Giannitti, Chiara; Cheleschi, Sara; Simpatico, Antonella; Pascarelli, Nicola Antonio; Galeazzi, Mauro

    2015-11-01

    adiponectin and resistin but not the circulating levels of visfatin. In view of the recent evidences about the involvement of adiponectin and resistin in the pathogenesis and progression of OA, the decrease of these adipokines after mud-bath therapy may play a protective role in the course of the disease. However, it remains to be clarified which of the mechanisms of action of MBT may have determined the changes in serum levels of adiponectin and resistin that we observed.

  18. Circulating levels of adiponectin, resistin, and visfatin after mud-bath therapy in patients with bilateral knee osteoarthritis

    Science.gov (United States)

    Fioravanti, Antonella; Giannitti, Chiara; Cheleschi, Sara; Simpatico, Antonella; Pascarelli, Nicola Antonio; Galeazzi, Mauro

    2015-11-01

    Adipocytokines, including adiponectin, resistin, and visfatin may play an important role in the pathophysiology of osteoarthritis (OA). Spa therapy is one of the most commonly used non-pharmacological approaches for OA, but its mechanisms of action are not completely known. The aim of the present study was to assess whether a cycle of mud-bath therapy (MBT) influences the serum levels of adiponectin, resistin, and visfatin in patients with knee OA. As part of a prospective randomized, single blind-controlled trial evaluating the efficacy of MBT in knee OA, we included in this study 95 outpatients. One group ( n = 49) received a cycle of MBT at the spa center of Chianciano Terme (Italy) in addition to the usual treatment, and one group (control group; n = 46) continued their regular care routine alone. Patients were assessed at basal time and at the end of the study (15 days) for clinical and biochemical parameters. Clinical assessments included spontaneous pain on a visual analog scale (VAS) score and the Western Ontario and McMaster Universities index (WOMAC) subscores for knee OA evaluated as total pain score (W-TPS), total stiffness score (W-TSS), and total physical function score (W-TPFS). Adiponectin, resistin and visfatin serum levels were assessed by enzyme immunoassay methods. At the end of the mud-bath therapy, serum adiponectin levels showed a significant decrease ( p MBT group at the end of the study and a significant increase in the control patients ( p MBT. Furthermore, we tested the relationships between demographic and clinical parameters and adipocytokine concentrations measured in the MBT group at basal and at the end of the study. In conclusion, the present study shows that a cycle of MBT can modify serum levels of adiponectin and resistin but not the circulating levels of visfatin. In view of the recent evidences about the involvement of adiponectin and resistin in the pathogenesis and progression of OA, the decrease of these adipokines after mud

  19. 低声压级次声对缺血再灌注损伤大鼠脑组织胰岛素样生长因子-1的影响%Effects of infrasound with low sound pressure level on the content of IGF-1 in brain of rats with focal cerebral ischemia-refusion injury

    Institute of Scientific and Technical Information of China (English)

    李川; 范建中; 吴红瑛; 魏轶

    2008-01-01

    目的 观察低声压级次声对局灶性脑缺血再灌注损伤的影响及其作用机制.方法 用线栓法制备右侧大脑中动脉栓塞-再灌注大鼠模型,以Infrasound 8TM次声治疗仪产生的次声作为处理因素.将32只大鼠随机假手术组(n=8)、造模组(n=8)、次声组(n=16),次声组按每天作用时间分为20 min组及120 min组.每组8只.动态观察(2 h、1 d、3 d和7 d)各组神经功能状态.7 d后大鼠断头取脑,采用免疫组化技术观察缺血侧大脑皮层胰岛素样生长因子-1(IGF-1)变化.结果 与模型组相比,次声120 min组神经症状改善明显(P<0.05).次声120 min组缺血侧大脑皮质IGF-1表达明显增加,与模型组比较差异有统计学意义(P<0.01).结论 低声压级次声(120 min/d,7 d)对大鼠局灶性脑缺血再灌注损伤具有保护作用,其机制与增加IGF-1表达有关.%Objective To study the effects and mechanisms of infrasound with low sound pressure level on focal cerebral ischemia-refusion injury. Methods Focal cerebral ischemia was produced by 2 hours of occlusion of the middle cerebral artery in rats. lnfrasound generated by infrasound 8TM device was used as treatment factor. Thirty-two Sprague-Dawley rats were divided into three groups: sham group (n=8), model group (n=8) and in-frasound group (n=16) , and the infrasound group was subdivided into 20- and 120-min infrasound groups, with 8 rats in each group. Neurological symptoms was assessed at 2 h, 1 d, 3 d and 7 d, respectively. These rats were sacrificed after 7 days of infrasound treatment and their brains were harvested. The number of IGF-1 posive cells of ischemia cortex was counted by using immunohistochemical technique. Results Compared with model group, neurological symptoms of rats in 120-min infrasound group was significantly improved (P<0.05); the number of IGF-1 positive cells of ischemia cortex in 120-min infrasound group increased significantly as compared with that in model group (P<0

  20. Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy.

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    Seung Jun Kim

    Full Text Available BACKGROUND AND AIMS: Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN. However, the role of complement in the pathogenesis or progression of IgAN is uncertain. In this observational cohort study, we aimed to identify the clinical implications of circulating C3 levels and mesangial C3 deposition and to investigate their utility as predictors of renal outcomes in patients with IgAN. METHODS: A total of 343 patients with biopsy-proven IgAN were enrolled between January 2000 and December 2008. Decreased serum C3 level (hypoC3 was defined as C3 <90 mg/dl. The study endpoint was end-stage renal disease (ESRD and a doubling of the baseline serum creatinine (D-SCr. RESULTS: Of the patients, there were 66 patients (19.2% with hypoC3. During a mean follow-up of 53.7 months, ESRD occurred in 5 patients (7.6% with hypoC3 compared with 9 patients (3.2% with normal C3 levels (P = 0.11. However, 12 patients (18.2% with hypoC3 reached D-SCr compared with 17 patients (6.1% with normal C3 levels [Hazard ratio (HR, 3.59; 95% confidence interval (CI, 1.33-10.36; P = 0.018]. In a multivariable model in which serum C3 levels were treated as a continuous variable, hypoC3 significantly predicted renal outcome of D-SCr (per 1 mg/dl increase of C3; HR, 0.95; 95% CI, 0.92-0.99; P = 0.011. The risk of reaching renal outcome was significantly higher in patients with mesangial C3 deposition 2+ to 3+ than in patients without deposition (HR 9.37; 95% CI, 1.10-80.26; P = 0.04. CONCLUSIONS: This study showed that hypoC3 and mesangial C3 deposition were independent risk factors for progression, suggesting that complement activation may play a pathogenic role in patients with IgAN.

  1. Circulating microparticles and plasma levels of soluble E- and P-selectins in patients with systemic sclerosis

    DEFF Research Database (Denmark)

    Iversen, Lars; Østergaard, O; Ullman, S;

    2013-01-01

    Microparticles (MPs) may be involved in the pathogenesis of systemic sclerosis (SSc), which includes vasculopathy, endothelial cell activation, and coagulation activation. Circulating MPs from SSc patients were characterized and their relationship with soluble markers of vascular activation inves...

  2. Altered circulating levels of matrix metalloproteinases and inhibitors associated with elevated type 2 cytokines in lymphatic filarial disease.

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    Rajamanickam Anuradha

    Full Text Available BACKGROUND: Infection with Wuchereria bancrofti can cause severe disease characterized by subcutaneous fibrosis and extracellular matrix remodeling. Matrix metalloproteinases (MMPs are a family of enzymes governing extracellular remodeling by regulating cellular homeostasis, inflammation, and tissue reorganization, while tissue-inhibitors of metalloproteinases (TIMPs are endogenous regulators of MMPs. Homeostatic as well as inflammation-induced balance between MMPs and TIMPs is considered critical in mediating tissue pathology. METHODS: To elucidate the role of MMPs and TIMPs in filarial pathology, we compared the plasma levels of a panel of MMPs, TIMPs, other pro-fibrotic factors, and cytokines in individuals with chronic filarial pathology with (CP Ag+ or without (CP Ag- active infection to those with clinically asymptomatic infections (INF and in those without infection (endemic normal [EN]. Markers of pathogenesis were delineated based on comparisons between the two actively infected groups (CP Ag+ compared to INF and those without active infection (CP Ag- compared to EN. RESULTS AND CONCLUSION: Our data reveal that an increase in circulating levels of MMPs and TIMPs is characteristic of the filarial disease process per se and not of active infection; however, filarial disease with active infection is specifically associated with increased ratios of MMP1/TIMP4 and MMP8/TIMP4 as well as with pro-fibrotic cytokines (IL-5, IL-13 and TGF-β. Our data therefore suggest that while filarial lymphatic disease is characterized by a non-specific increase in plasma MMPs and TIMPs, the balance between MMPs and TIMPs is an important factor in regulating tissue pathology during active infection.

  3. Expression of FGF-2 and IGF-1 in diabetic rats with fracture

    Institute of Scientific and Technical Information of China (English)

    Qing-Quan Chen; Wan-Ming Wang

    2014-01-01

    Objective: To observe the change of fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1 (IGF-1) in serum and bone callus after fracture in diabetic rats, and to explore molecular biological mechanism of healing of diabetic fracture. Methods: Thirty male SD rats were designed into normal (n=15) and control (n=15) groups randomly. Venous blood was extracted on the lst, 2nd, 4th, 6th, 8th week after surgery. It was certificated and the serum was obtained. Left lower extremity was observed by X- ray. Bone callus at broken ends was observed under light microscope. Expressions of FGF-2 and IGF-1 in tissue were detected by immunohistochemistry method, and ELISA was used to detect expression of FGF-2 and IGF-1 in serum. Results:The results showed a significant increase in the density and area of newly formed bone in the distraction gaps of normal rats compared to control rats. Increased cell proliferation was also found in the distraction gaps of normal rats versus control rats. There was significant difference in serum levels of FGF-2 and IGF-1 between two groups. Conclusions: The decrease of FGF-2 and IGF-1 both in the serum and in the fracture region is one of the reasons for bad bone healing or delayed union in rats’ fracture with diabetes. There are some synergistic effects possibly between FGF-2 and IGF-1.

  4. Osmoregulatory actions of the GH/IGF axis in non-salmonid teleosts

    Science.gov (United States)

    Mancera, J.M.; McCormick, S.D.

    1998-01-01

    Salmonid fishes provided the first findings on the influence of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis on osmoregulation in teleost fishes. Recent studies on non-salmonid species, however, indicate that this physiological action of the GH/IGF-I axis is not restricted to salmonids or anadromous fishes. GH-producing cells in the pituitary of fish acclimated to different salinities show different degrees of activation depending on the species studied. Plasma GH levels either increase or do not change after transfer of fish from freshwater to seawater. Treatment with GH or IGF-I increases salinity tolerance and/or increases gill Na+,K+-ATPase activity of killifish (Fundulus heteroclitus), tilapia (Oreochromis mossambicus and Oreochromis niloticus) and striped bass (Morone saxatilis). As in salmonids, a positive interaction between GH and cortisol for improving hypoosmoregulatory capacity has been described in tilapia (O. mossambicus). Research on the osmoregulatory role of the GH/IGF-I axis is derived from a small number of teleost species. The study of more species with different osmoregulary patterns will be necessary to fully clarify the osmoregulatory role of GH/IGF-I axis in fish. The available data does suggest, however, that the influence of the GH/IGF-I axis on osmoregulation may be a common feature of euryhalinity in teleosts. Copyright (C) 1998 Elsevier Science Inc.

  5. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    International Nuclear Information System (INIS)

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma

  6. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Er-Wen [Guangzhou Institute of Forensic Science, Guangzhou (China); Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Xue, Sheng-Jiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Li, Xiao-Yan [Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Suo-Wen [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Cheng, Jian-Ding; Zheng, Jin-Xiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong [Guangzhou Institute of Forensic Science, Guangzhou (China); Li, Jie, E-mail: mdlijie@sina.com [Department of Anaesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, Chao, E-mail: liuchaogaj@21cn.com [Guangzhou Institute of Forensic Science, Guangzhou (China)

    2014-05-02

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.

  7. Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats

    Science.gov (United States)

    Adams, G. R.; McCue, S. A.

    1998-01-01

    Insulin-like growth factor I (IGF-I) peptide levels have been shown to increase in overloaded skeletal muscles (G. R. Adams and F. Haddad. J. Appl. Physiol. 81: 2509-2516, 1996). In that study, the increase in IGF-I was found to precede measurable increases in muscle protein and was correlated with an increase in muscle DNA content. The present study was undertaken to test the hypothesis that direct IGF-I infusion would result in an increase in muscle DNA as well as in various measurements of muscle size. Either 0.9% saline or nonsystemic doses of IGF-I were infused directly into a non-weight-bearing muscle of rats, the tibialis anterior (TA), via a fenestrated catheter attached to a subcutaneous miniosmotic pump. Saline infusion had no effect on the mass, protein content, or DNA content of TA muscles. Local IGF-I infusion had no effect on body or heart weight. The absolute weight of the infused TA muscles was approximately 9% greater (P protein and DNA content of TA muscles (P DNA-to-protein ratio of the hypertrophied TA was similar to that of the contralateral muscles. These results suggest that IGF-I may be acting to directly stimulate processes such as protein synthesis and satellite cell proliferation, which result in skeletal muscle hypertrophy.

  8. IGF-1 protects tubular epithelial cells during injury via activation of ERK/MAPK signaling pathway

    Science.gov (United States)

    Wu, Zengbin; Yu, Yang; Niu, Lei; Fei, Aihua; Pan, Shuming

    2016-01-01

    Injury of renal tubular epithelial cells can induce acute renal failure and obstructive nephropathy. Previous studies have shown that administration of insulin-like growth factor-1 (IGF-1) ameliorates the renal injury in a mouse unilateral ureteral obstruction (UUO) model, whereas the underlying mechanisms are not completely understood. Here, we addressed this question. We found that the administration of IGF-1 significantly reduced the severity of the renal fibrosis in UUO. By analyzing purified renal epithelial cells, we found that IGF-1 significantly reduced the apoptotic cell death of renal epithelial cells, seemingly through upregulation of anti-apoptotic protein Bcl-2, at protein but not mRNA level. Bioinformatics analyses and luciferase-reporter assay showed that miR-429 targeted the 3′-UTR of Bcl-2 mRNA to inhibit its protein translation in renal epithelial cells. Moreover, IGF-1 suppressed miR-429 to increase Bcl-2 in renal epithelial cells to improve survival after UUO. Furthermore, inhibition of ERK/MAPK signaling pathway in renal epithelial cells abolished the suppressive effects of IGF-1 on miR-429 activation, and then the enhanced effects on Bcl-2 in UUO. Thus, our data suggest that IGF-1 may protect renal tubular epithelial cells via activation of ERK/MAPK signaling pathway during renal injury. PMID:27301852

  9. Experimental Alcohol-Related Peripheral Neuropathy: Role of Insulin/IGF Resistance

    Directory of Open Access Journals (Sweden)

    James Gilchrist

    2012-08-01

    Full Text Available The mechanisms of alcohol-related peripheral neuropathy (ALPN are poorly understood. We hypothesize that, like alcohol-related liver and brain degeneration, ALPN may be mediated by combined effects of insulin/IGF resistance and oxidative stress. Adult male Long Evans rats were chronically pair-fed with diets containing 0% or 37% ethanol (caloric, and subjected to nerve conduction studies. Chronic ethanol feeding slowed nerve conduction in the tibial (p = 0.0021 motor nerve, and not plantar sensory nerve, but it did not affect amplitude. Histological studies of the sciatic nerve revealed reduced nerve fiber diameters with increased regenerative sprouts, and denervation myopathy in ethanol-fed rats. qRT-PCR analysis demonstrated reduced mRNA levels of insulin, IGF-1, and IGF-2 polypeptides, IGF-1 receptor, and IRS2, and ELISAs revealed reduced immunoreactivity for insulin and IGF-1 receptors, IRS-1, IRS-4, myelin-associated glycoprotein, and tau in sciatic nerves of ethanol-fed rats (all p < 0.05 or better. The findings suggest that ALPN is characterized by (1 slowed conduction velocity with demyelination, and a small component of axonal degeneration; (2 impaired trophic factor signaling due to insulin and IGF resistance; and (3 degeneration of myelin and axonal cytoskeletal proteins. Therefore, ALPN is likely mediated by molecular and signal transduction abnormalities similar to those identified in alcoholic liver and brain degeneration.

  10. Circulating level of microRNA-126 may be a potential biomarker for recovery from smoking-related vascular damage in middle-aged habitual smokers

    Directory of Open Access Journals (Sweden)

    Tomonori Sugiura

    2015-06-01

    Conclusions: Endothelial damage was improved and plasma levels of circulating miR-126 were increased after 8 weeks of smoking cessation. These findings suggested a potential use of miR-126 as a biomarker for recovery from smoking-induced vascular damage.

  11. Assessment of circulating sex steroid levels in prepubertal and pubertal boys and girls by a novel ultrasensitive gas chromatography-tandem mass spectrometry method

    DEFF Research Database (Denmark)

    Courant, Frédérique; Aksglæde, Lise; Antignac, Jean-Philippe;

    2010-01-01

    Estrogens and androgens play key roles for pubertal onset and sexual maturation. Most currently used immunoassays are not sensitive enough to accurately measure the low circulating levels of sex steroids in children without any signs of puberty. However, this does not exclude that sex steroids ha...

  12. Circulating alpha-klotho levels are not disturbed in patients with type 2 diabetes with and without macrovascular disease in the absence of nephropathy

    NARCIS (Netherlands)

    van Ark, Joris; Hammes, Hans-Peter; van Dijk, Marcory C. R. F.; Vervloet, Marc G.; Wolffenbuttel, Bruce H. R.; van Goor, Harry; Hillebrands, Jan-Luuk

    2013-01-01

    Background: Diabetes is associated with a high incidence of macrovascular disease (MVD), including peripheral and coronary artery disease. Circulating soluble-Klotho (sKlotho) is produced in the kidney and is a putative anti-aging and vasculoprotective hormone. Reduced Klotho levels may therefore in

  13. Assessment of circulating sex steroid levels in prepubertal and pubertal boys and girls by a novel ultrasensitive gas chromatography-tandem mass spectrometry method

    DEFF Research Database (Denmark)

    Courant, Frédérique; Aksglæde, Lise; Antignac, Jean-Philippe;

    2010-01-01

    Estrogens and androgens play key roles for pubertal onset and sexual maturation. Most currently used immunoassays are not sensitive enough to accurately measure the low circulating levels of sex steroids in children without any signs of puberty. However, this does not exclude that sex steroids have...... important biological roles in prepubertal children....

  14. Apoptosis-related deregulation of proteolytic activities and high serum levels of circulating nucleosomes and DNA in blood correlate with breast cancer progression

    International Nuclear Information System (INIS)

    As cell-free circulating DNA exists predominantly as mono- and oligonucleosomes, the focus of the current study was to examine the interplay of circulating nucleosomes, DNA, proteases and caspases in blood of patients with benign and malignant breast diseases. The concentrations of cell-free DNA and nucleosomes as well as the protease and caspase activities were measured in serum of patients with benign breast disease (n = 20), primary breast cancer (M0, n = 31), metastatic breast cancer (M1, n = 32), and healthy individuals (n = 28) by PicoGreen, Cell Death Detection ELISA, Protease Fluorescent Detection Kit and Caspase-Glo®3/7 Assay, respectively. Patients with benign and malignant tumors had significantly higher levels of circulating nucleic acids in their blood than healthy individuals (p = 0.001, p = 0.0001), whereas these levels could not discriminate between benign and malignant lesions. Our analyses of all serum samples revealed significant correlations of circulating nucleosome with DNA concentrations (p = 0.001), nucleosome concentrations with caspase activities (p = 0.008), and caspase with protease activities (p = 0.0001). High serum levels of protease and caspase activities associated with advanced tumor stages (p = 0.009). Patients with lymph node-positive breast cancer had significantly higher nucleosome levels in their blood than node-negative patients (p = 0.004). The presence of distant metastases associated with a significant increase in serum nucleosome (p = 0.01) and DNA levels (p = 0.04), and protease activities (p = 0.008). Our findings demonstrate that high circulating nucleic acid concentrations in blood are no indicators of a malignant breast tumor. However, the observed changes in apoptosis-related deregulation of proteolytic activities along with the elevated serum levels of nucleosomes and DNA in blood are linked to breast cancer progression

  15. Perioperative prostate specific antigen levels among coronary artery bypass grafting patients: Does extracorporeal circulation and body temperature induce prostate specific antigen levels alterations?

    Science.gov (United States)

    Patris, Emmanuel; Giakoumidakis, Konstantinos; Patris, Vasileios; Kuduvalli, Manoj; Argiriou, Mihalis; Charitos, Christos; Kalaitzis, Christos; Touloupidis, Stavros

    2015-01-01

    Purpose: The purpose of this study is to compare the perioperative total prostate specific antigen (tPSA) levels among coronary artery bypass grafting (CABG) patients with and without extracorporeal circulation (ECC), to investigate the changes overtime of tPSA in each group separately and to determine the effect of body core temperature on tPSA levels. Materials and Methods: A prospective study was conducted. Our sample was allocated to: (a) Seven patients who underwent off pump CABG (Group I) and (b) 16 CABG patients with ECC (Group II). The levels of tPSA were measured preoperatively (baseline), intra-operatively and at the 4th postoperative day. We compared the two groups on their tPSA levels and we investigated the changes of tPSA overtime in each group separately. Results: Intra-operative serum samples were obtained in significantly lower body temperature in patients of Group II than in those of Group I (31°C vs. 36.9°C, P < 0.001). In each group separately, postoperative tPSA levels were increased significantly compared to the baseline values (2.55 ng/ml vs. 0.39 ng/ml for Group I, P = 0.005 and 4.36 ng/ml vs. 0.77 for Group II, P < 0.001). CABG patients with ECC had significantly lower intra-operative tPSA levels than the baseline values (0.67 ng/ml vs. 0.77 ng/ml, P = 0.008). We did not observe significant differences of tPSA levels between the two groups. Conclusions: CABG surgery affects similarly the perioperative tPSA independently the involvement of ECC. Although all patients had significantly higher early postoperative tPSA levels, only those who underwent CABG with ECC had exceeded normal values and significantly decreased intra-operative tPSA. Hypothermia seems to be the causal factor of tPSA reduction. PMID:25657546

  16. Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance.

    Directory of Open Access Journals (Sweden)

    Sophie R Sayers

    Full Text Available Enteroendocrine L-cells synthesise and release the gut hormone glucagon-like peptide-1 (GLP-1 in response to food transit. Deletion of the tumour suppressor kinase LKB1 from proglucagon-expressing cells leads to the generation of intestinal polyps but no change in circulating GLP-1 levels. Here, we explore the role of the downstream kinase AMP-activated protein kinase (AMPK in these cells.Loss of AMPK from proglucagon-expressing cells was achieved using a preproglucagon promoter-driven Cre (iGluCre to catalyse recombination of floxed alleles of AMPKα1 and α2. Oral and intraperitoneal glucose tolerance were measured using standard protocols. L-cell mass was measured by immunocytochemistry. Hormone and peptide levels were measured by electrochemical-based luminescence detection or radioimmunoassay.Recombination with iGluCre led to efficient deletion of AMPK from intestinal L- and pancreatic alpha-cells. In contrast to mice rendered null for LKB1 using the same strategy, mice deleted for AMPK displayed an increase (WT: 0.05 ± 0.01, KO: 0.09±0.02%, p<0.01 in L-cell mass and elevated plasma fasting (WT: 5.62 ± 0.800 pg/ml, KO: 14.5 ± 1.870, p<0.01 and fed (WT: 15.7 ± 1.48pg/ml, KO: 22.0 ± 6.62, p<0.01 GLP-1 levels. Oral, but not intraperitoneal, glucose tolerance was significantly improved by AMPK deletion, whilst insulin and glucagon levels were unchanged despite an increase in alpha to beta cell ratio (WT: 0.23 ± 0.02, KO: 0.33 ± 0.03, p<0.01.AMPK restricts L-cell growth and GLP-1 secretion to suppress glucose tolerance. Targeted inhibition of AMPK in L-cells may thus provide a new therapeutic strategy in some forms of type 2 diabetes.

  17. Insulin-like growth factor-I (IGF-I) protects cultured equine Leydig cells from undergoing apoptosis.

    Science.gov (United States)

    Yoon, M J; Roser, J F

    2010-12-01

    Leydig cells located in the interstitial space of the testicular parenchyma produce testosterone which plays a critical role in the maintenance and restoration of spermatogenesis in many species, including horses. For normal spermatogenesis, maintaining Leydig cells is critical to provide an optimal and constant level of testosterone. Recently, an anti-apoptotic effect of IGF-I in testicular cells in rats has been reported, but a similar effect of IGF-I on equine Leydig cells remains to be elucidated. If IGF-I also protects stallion testicular cells from undergoing apoptosis, then IGF-I may have potential as a treatment regime to prevent testicular degeneration. The present study was designed to evaluate the anti-apoptotic effect of IGF-I on cultured equine Leydig cells. Testes were collected from 5 post-pubertal stallions (2-4 years old) during routine castrations. A highly purified preparation of equine Leydig cells was obtained from a discontinuous Percoll gradient. Purity of equine Leydig cells was assessed using histochemical 3β-HSD staining. Equine Leydig cells and selected doses of recombinant human IGF-1 (rhIGF-I; Parlow A.F., National Hormone and Peptide Program, Harbor-UCLA Medical Center) were added to wells of 24 or 96 well culture plates in triplicate and cultured for 24 or 48 h under 95% air:5% CO(2) at 34°C. After 24 or 48 h incubation, apoptotic rate was assessed using a Cell Death Detection ELISA kit. Significantly lower apoptotic rates were observed in equine Leydig cells cultured with 5, 10, or 50ng/ml of rhIGF-I compared with control cells cultured without rhIGF-I for 24h. Exposure to 1, 5, 10 or 50 ng/ml of rhIGF-I significantly decreased apoptotic rate in equine Leydig cells cultured for 48 h. After 48 h incubation, cells were labeled with Annexin V and propodium iodine to determine the populations of healthy, apoptotic, and necrotic cells by counting stained cells using a Nikon Eclipse inverted fluorescence microscope. As a percentage of

  18. Heterodimerization of glycosylated insulin-like growth factor-1 receptors and insulin receptors in cancer cells sensitive to anti-IGF1R antibody.

    Directory of Open Access Journals (Sweden)

    Jun Gyu Kim

    Full Text Available Identification of predictive biomarkers is essential for the successful development of targeted therapy. Insulin-like growth factor 1 receptor (IGF1R has been examined as a potential therapeutic target for various cancers. However, recent clinical trials showed that anti-IGF1R antibody and chemotherapy are not effective for treating lung cancer.In order to define biomarkers for predicting successful IGF1R targeted therapy, we evaluated the anti-proliferation effect of figitumumab (CP-751,871, a humanized anti-IGF1R antibody, against nine gastric and eight hepatocellular cancer cell lines. Out of 17 cancer cell lines, figitumumab effectively inhibited the growth of three cell lines (SNU719, HepG2, and SNU368, decreased p-AKT and p-STAT3 levels, and induced G 1 arrest in a dose-dependent manner. Interestingly, these cells showed co-overexpression and altered mobility of the IGF1R and insulin receptor (IR. Immunoprecipitaion (IP assays and ELISA confirmed the presence of IGF1R/IR heterodimeric receptors in figitumumab-sensitive cells. Treatment with figitumumab led to the dissociation of IGF1-dependent heterodimeric receptors and inhibited tumor growth with decreased levels of heterodimeric receptors in a mouse xenograft model. We next found that both IGF1R and IR were N-linked glyosylated in figitumumab-sensitive cells. In particular, mass spectrometry showed that IGF1R had N-linked glycans at N913 in three figitumumab-sensitive cell lines. We observed that an absence of N-linked glycosylation at N913 led to a lack of membranous localization of IGF1R and figitumumab insensitivity.The data suggest that the level of N-linked glycosylated IGF1R/IR heterodimeric receptor is highly associated with sensitivity to anti-IGF1R antibody in cancer cells.

  19. Luteolin decreases IGF-II production and downregulates insulin-like growth factor-I receptor signaling in HT-29 human colon cancer cells

    Directory of Open Access Journals (Sweden)

    Lim Do

    2012-01-01

    Full Text Available Abstract Background Luteolin is a 3',4',5,7-tetrahydroxyflavone found in various fruits and vegetables. We have shown previously that luteolin reduces HT-29 cell growth by inducing apoptosis and cell cycle arrest. The objective of this study was to examine whether luteolin downregulates the insulin-like growth factor-I receptor (IGF-IR signaling pathway in HT-29 cells. Methods In order to assess the effects of luteolin and/or IGF-I on the IGF-IR signaling pathway, cells were cultured with or without 60 μmol/L luteolin and/or 10 nmol/L IGF-I. Cell proliferation, DNA synthesis, and IGF-IR mRNA levels were evaluated by a cell viability assay, [3H]thymidine incorporation assays, and real-time polymerase chain reaction, respectively. Western blot analyses, immunoprecipitation, and in vitro kinase assays were conducted to evaluate the secretion of IGF-II, the protein expression and activation of IGF-IR, and the association of the p85 subunit of phophatidylinositol-3 kinase (PI3K with IGF-IR, the phosphorylation of Akt and extracellular signal-regulated kinase (ERK1/2, and cell division cycle 25c (CDC25c, and PI3K activity. Results Luteolin (0 - 60 μmol/L dose-dependently reduced the IGF-II secretion of HT-29 cells. IGF-I stimulated HT-29 cell growth but did not abrogate luteolin-induced growth inhibition. Luteolin reduced the levels of the IGF-IR precursor protein and IGF-IR transcripts. Luteolin reduced the IGF-I-induced tyrosine phosphorylation of IGF-IR and the association of p85 with IGF-IR. Additionally, luteolin inhibited the activity of PI3K activity as well as the phosphorylation of Akt, ERK1/2, and CDC25c in the presence and absence of IGF-I stimulation. Conclusions The present results demonstrate that luteolin downregulates the activation of the PI3K/Akt and ERK1/2 pathways via a reduction in IGF-IR signaling in HT-29 cells; this may be one of the mechanisms responsible for the observed luteolin-induced apoptosis and cell cycle arrest.

  20. Proteomic Screening and Lasso Regression Reveal Differential Signaling in Insulin and Insulin-like Growth Factor I (IGF1) Pathways.

    Science.gov (United States)

    Erdem, Cemal; Nagle, Alison M; Casa, Angelo J; Litzenburger, Beate C; Wang, Yu-Fen; Taylor, D Lansing; Lee, Adrian V; Lezon, Timothy R

    2016-09-01

    Insulin and insulin-like growth factor I (IGF1) influence cancer risk and progression through poorly understood mechanisms. To better understand the roles of insulin and IGF1 signaling in breast cancer, we combined proteomic screening with computational network inference to uncover differences in IGF1 and insulin induced signaling. Using reverse phase protein array, we measured the levels of 134 proteins in 21 breast cancer cell lines stimulated with IGF1 or insulin for up to 48 h. We then constructed directed protein expression networks using three separate methods: (i) lasso regression, (ii) conventional matrix inversion, and (iii) entropy maximization. These networks, named here as the time translation models, were analyzed and the inferred interactions were ranked by differential magnitude to identify pathway differences. The two top candidates, chosen for experimental validation, were shown to regulate IGF1/insulin induced phosphorylation events. First, acetyl-CoA carboxylase (ACC) knock-down was shown to increase the level of mitogen-activated protein kinase (MAPK) phosphorylation. Second, stable knock-down of E-Cadherin increased the phospho-Akt protein levels. Both of the knock-down perturbations incurred phosphorylation responses stronger in IGF1 stimulated cells compared with insulin. Overall, the time-translation modeling coupled to wet-lab experiments has proven to be powerful in inferring differential interactions downstream of IGF1 and insulin signaling, in vitro.

  1. Production of immunoreactive insulin-like growth factor I and response to exogenous IGF-I in small cell lung cancer cell lines

    International Nuclear Information System (INIS)

    Small cell lung cancer (SCLC) cell lines were examined for the presence of insulin-like growth factor I-related protein (IGF-I) in cell pellets and culture media. IGF-I immunoreactivity was detected in 11/14 pellets, ranging from 12 to 76 mIU/mg soluble protein. The IGF-I levels in the cell pellets showed a correlation to the corresponding culture media. IGF-I binding sites were found in all tested cell lines. The maximum binding (Bmax) ranged from 131 to 1,230 fmol/mg protein and the dissociation constant (KD) from 0.89 to 5.21 nM. The incorporation of [3H]thymidine in the presence of recombinant human IGF-I resulted in a clearly increased DNA synthesis in two of seven cell lines. Thus, IGF-I may be an important growth factor in SCLC

  2. Insulin-like growth factor I (IGF-I) is a more potent regulator of gene expression than insulin in primary human myoblasts and myotubes

    DEFF Research Database (Denmark)

    Palsgaard, J.; Brown, A.E.; Jensen, M.;

    2009-01-01

    regulation was investigated in primary human skeletal muscle cells before and after differentiation. Cell cultures were treated with 100 nM insulin, IGF-I or nothing for 4h, and gene expression was subsequently determined using the Affymetrix microarray platform. Insulin and IGF-I receptor levels were......Conventionally, insulin is believed to induce a metabolic response, and IGF-I a mitogenic/differentiation response in vivo. However, several studies indicate that the roles of insulin and IGF-I may not be that easy to separate. In this study, insulin and IGF-I specificity in terms of gene......-I receptors as determined by radioligand binding assays. In the myotubes, we did not identify any ligand specificity in terms of functional categories. The major difference between the two ligands was their respective potencies in gene regulation, which was higher for IGF-I than for insulin. This was true for...

  3. Effects of fasting on IGF-I, IGF-II, and IGF-binding protein mRNA concentrations in channel catfish (Ictalurus punctatus)

    Science.gov (United States)

    The effects of fasting on IGF-I, IGF-II, and IGF-binding proteins (IGFBPs) in channel catfish were examined. Fed control fish (Fed) were compared to fish that had been fasted for 30 days followed by 15 days of additional feeding (Restricted). Sequence alignment and similarity to orthologous protei...

  4. HIF2A and IGF2 Expression Correlates in Human Neuroblastoma Cells and Normal Immature Sympathetic Neuroblasts

    Directory of Open Access Journals (Sweden)

    Sofie Mohlin

    2013-03-01

    Full Text Available During normal sympathetic nervous system (SNS development, cells of the ganglionic lineage can malignantly transform and develop into the childhood tumor neuroblastoma. Hypoxia-inducible transcription factors (HIFs mediate cellular responses during normal development and are central in the adaptation to oxygen shortage. HIFs are also implicated in the progression of several cancer forms, and high HIF-2α expression correlates with disseminated disease and poor outcome in neuroblastoma. During normal SNS development, HIF2A is transiently expressed in neuroblasts and chromaffin cells. SNS cells can, during development, be distinguished by distinct gene expression patterns, and insulin-like growth factor 2 (IGF2 is a marker of sympathetic chromaffin cells, whereas sympathetic neuroblasts lack IGF2 expression. Despite the neuronal derivation of neuroblastomas, we show that neuroblastoma cell lines and specimens express IGF2 and that expression of HIF2A and IGF2 correlates, with the strongest correlation in high-stage tumors. In neuroblastoma, both IGF2 and HIF2A are hypoxia-driven and knocking down IGF2 at hypoxia resulted in downregulated HIF2A levels. HIF-2α and IGF2 were strongly expressed in subsets of immature neuroblastoma cells, suggesting that these two genes could be co-expressed also at early stages of SNS development. We show that IGF2 is indeed expressed in sympathetic chain ganglia at embryonic week 6.5, a developmental stage when HIF-2α is present. These findings provide a rationale for the unexpected IGF2 expression in neuroblastomas and might suggest that IGF2 and HIF2A positive neuroblastoma cells are arrested at an embryonic differentiation stage corresponding to the stage when sympathetic chain ganglia begins to coalesce.

  5. Resveratrol inhibits collagen I synthesis by suppressing IGF-1R activation in intestinal fibroblasts

    Science.gov (United States)

    Li, Ping; Liang, Mei-Lan; Zhu, Ying; Gong, Yao-Yao; Wang, Yun; Heng, Ding; Lin, Lin

    2014-01-01

    AIM: To investigate whether resveratrol (3,4,5-trihydroxy-trans-stilbene) inhibits collagen I synthesis induced by insulin growth factor-1 (IGF-1) in intestinal fibroblasts, and to explore the possible molecular mechanisms. METHODS: Male Sprague-Dawley rats were randomly divided into two groups: a control group and a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis group. After 21 d of TNBS administration, the degree of inflammation and fibrosis in colon was measured by HE staining and Masson’s trichrome staining. Western blotting was used to examine collagen I, IGF-1 and silent information regulator 1 (SIRT1) protein expression in colitis tissues. Western blotting and quantitative real-time polymerase chain reaction were used to characterize collagen I protein and col1a2 mRNA expression in mouse intestinal fibroblasts and CCD-18Co cells treated with IGF-1. A MEK inhibitor (U0126) was used to determine whether IGF-1-induced collagen I expression was mediated by extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent mechanism. Effects of resveratrol on collagen I protein level, insulin growth factor-1 receptor (IGF-1R) and ERK1/2 phosphorylation levels were also examined after IGF-1 treatment in fibroblasts. To evaluate whether SIRT1 was necessary for the anti-fibrosis effect of resveratrol, cells were transfected with SIRT1-specific small interfering RNAs, wild-type SIRT1, and deacetylase-inactive mutant SIRT1. RESULTS: Collagen I and IGF-1 expression was increased, and SIRT1 expression was decreased (0.67 ± 0.04 vs 1.05 ± 0.07, P < 0.001) in TNBS-induced colitis compared with the control group. In vitro, IGF-1 could induce collagen I expression, mainly through the ERK 1/2 signal pathway. Resveratrol reduced basal and IGF-1-induced collagen I gene and protein expression in intestinal fibroblasts. Overexpression of wild-type SIRT1, not deacetylase-inactive mutant SIRT1, decreased expression of collagen

  6. Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine.

    Science.gov (United States)

    Suman, Shubhankar; Kumar, Santosh; Fornace, Albert J; Datta, Kamal

    2016-01-01

    Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as (56)Fe ions, which due to its high linear energy transfer (high-LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as γ rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specific in vivo molecular data. We investigated long-term effects of (56)Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week-old C57BL/6J mice were exposed to 1.6 Gy of (56)Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1, and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum, and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract. PMID:27558773

  7. Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine.

    Science.gov (United States)

    Suman, Shubhankar; Kumar, Santosh; Fornace, Albert J; Datta, Kamal

    2016-01-01

    Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as (56)Fe ions, which due to its high linear energy transfer (high-LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as γ rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specific in vivo molecular data. We investigated long-term effects of (56)Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week-old C57BL/6J mice were exposed to 1.6 Gy of (56)Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1, and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum, and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract.

  8. Circulating levels of chromatin fragments are inversely correlated with anti-dsDNA antibody levels in human and murine systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Jørgensen, Mariann H; Rekvig, Ole Petter; Jacobsen, Rasmus S;

    2011-01-01

    Anti-dsDNA antibodies represent a central pathogenic factor in Lupus nephritis. Together with nucleosomes they deposit as immune complexes in the mesangial matrix and along basement membranes within the glomeruli. The origin of the nucleosomes and when they appear e.g. in circulation is not known....... Serum samples from autoimmune (NZBxNZW)F1 mice, healthy BALB/c mice, patients with SLE, RA and normal healthy individuals were analyzed for presence and amount of circulating anti-dsDNA antibodies and nucleosomal DNA. Here we use a quantitative PCR to measure circulating DNA in sera. We demonstrate...

  9. Prolactin anterior pituitary expression and circulating levels are reduced in obese and diabetic rats: role of TGF-β and TNF-α.

    Science.gov (United States)

    Lemini, María; Ruiz-Herrera, Xarubet; Ledesma-Colunga, María G; Díaz-Lezama, Nundehui; De Los Ríos, Ericka A; López-Barrera, Fernando; Méndez, Isabel; Martínez de la Escalera, Gonzalo; Macotela, Yazmín; Clapp, Carmen

    2015-05-01

    The levels of the hormone prolactin (PRL) are reduced in the circulation of patients with Type 2 diabetes and in obese children, and lower systemic PRL levels correlate with an increased prevalence of diabetes and a higher risk of metabolic syndrome. The secretion of anterior pituitary (AP) PRL in metabolic diseases may be influenced by the interplay between transforming growth factor β (TGF-β) and tumor necrosis factor α (TNF-α), which inhibit and can stimulate AP PRL synthesis, respectively, and are known contributors to insulin resistance and metabolic complications. Here, we show that TGF-β and TNF-α antagonize the effect of each other on the expression and release of PRL by the GH4C1 lactotrope cell line. The levels of AP mRNA and circulating PRL decrease in high-fat diet-induced obese rats in parallel with increased and reduced AP levels of TGF-β and TNF-α mRNA, respectively. Likewise, AP expression and circulating levels of PRL are reduced in streptozotocin-induced diabetic rats and are associated with higher AP expression and protein levels of TGF-β and TNF-α. The opposing effects of the two cytokines on cultured AP cells, together with their altered expression in the AP of obese and diabetic rats suggest they are linked to the reduced PRL production and secretion characteristics of metabolic diseases.

  10. The proto-oncogene product c-Crk associates with insulin receptor substrate-1 and 4PS. Modulation by insulin growth factor-I (IGF) and enhanced IGF-I signaling.

    Science.gov (United States)

    Beitner-Johnson, D; Blakesley, V A; Shen-Orr, Z; Jimenez, M; Stannard, B; Wang, L M; Pierce, J; LeRoith, D

    1996-04-19

    The Crk proto-oncogene product is an SH2 and SH3 domain-containing adaptor protein which we have previously shown to become rapidly tyrosine phosphorylated in response to stimulation with insulin-like growth factor I (IGF-I) in NIH-3T3 cells. In order to further characterize the role of Crk in the IGF-I signaling pathway, NIH-3T3 and 293 cells were stably transfected with an expression vector containing the Crk cDNA. The various resultant 3T3-Crk clones expressed Crk at approximately 2-15-fold higher levels than parental 3T3 cells. In 3T3-Crk cells, Crk immunoreactivity was detected in insulin receptor substrate-1 (IRS-1) immunoprecipitates. Stimulation with IGF-I resulted in a dissociation of Crk protein from IRS-1. In contrast, the association of the related adaptor protein Grb2 with IRS-1 was enhanced by IGF-I stimulation. Similar results were obtained in stably transfected 293-Crk cells, which express both IRS-1 and the IRS-1-related signaling protein 4PS. In these cells, IRS-1 and 4PS both associated with Crk, and this association was also decreased by IGF-I treatment, whereas the association of Grb2 with IRS-1 and 4PS was enhanced by IGF-I. Overexpression of Crk also enhanced IGF-I-induced mitogenesis of NIH-3T3 cells, as measured by [3H]thymidine incorporation. The levels of IGF-I-induced mitogenesis were proportional to the level of Crk expression. These results suggest that Crk is a positive effector of IGF-I signaling, and may mediate its effects via interaction with IRS-1 and/or 4PS.

  11. Characterisation of adiponectin multimers and the IGF axis in humans with a heterozygote mutation in the tyrosine kinase domain of the insulin receptor gene

    DEFF Research Database (Denmark)

    Højlund, Kurt; Beck-Nielsen, Henning; Flyvbjerg, Allan;

    2012-01-01

    Objective: Low levels of adiponectin, IGF-binding protein (IGFBP)-1, and IGFBP-2, and high levels of leptin correlate with several indices of insulin resistance and risk of type 2 diabetes. However, in insulin receptoropathies plasma adiponectin is paradoxically increased despite severe insulin r...... in insulin receptor deficient individuals.......Objective: Low levels of adiponectin, IGF-binding protein (IGFBP)-1, and IGFBP-2, and high levels of leptin correlate with several indices of insulin resistance and risk of type 2 diabetes. However, in insulin receptoropathies plasma adiponectin is paradoxically increased despite severe insulin...... an euglycemic-hyperinsulinemic clamp were examined for plasma adiponectin multimers, leptin, total IGF-I, IGF-II, free IGF-I, IGFBP-1 and IGFBP-2.Results: Despite 10-fold elevated fasting insulin and marked insulin resistance in Arg1174Gln-carriers, the levels of total adiponectin, leptin, IGFBP-1 and IGFBP-2...

  12. Common genetic variation in the SERPINF1 locus determines overall adiposity, obesity-related insulin resistance, and circulating leptin levels.

    Directory of Open Access Journals (Sweden)

    Anja Böhm

    , obesity-related insulin resistance, and circulating leptin levels.

  13. Insulin-Like Growth Factor I Serum Levels Influence Ischemic Stroke Outcome

    NARCIS (Netherlands)

    De Smedt, Ann; Brouns, Raf; Uyttenboogaart, Maarten; De Raedt, Sylvie; Moens, Maarten; Wilczak, Nadine; Luijckx, Gert-Jan; De Keyser, Jacques

    2011-01-01

    Background and Purpose-Insulin-like growth factor I (IGF-I) is neuroprotective in animal models of stroke. We investigated whether serum IGF-I levels in patients with acute ischemic stroke influence stroke severity and outcome. Methods-Concentrations of IGF-I and IGF binding protein 3 were measured

  14. Increased Obesity-Associated Circulating Levels of the Extracellular Matrix Proteins Osteopontin, Chitinase-3 Like-1 and Tenascin C Are Associated with Colon Cancer

    Science.gov (United States)

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Izaguirre, Maitane; Hernández-Lizoain, José Luis; Baixauli, Jorge; Martí, Pablo; Valentí, Víctor; Moncada, Rafael; Silva, Camilo; Salvador, Javier; Frühbeck, Gema

    2016-01-01

    Background Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM) remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC), promoting a microenvironment favorable for tumor growth. Methods Serum samples obtained from 79 subjects [26 lean (LN) and 53 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (44 without CC and 35 with CC). Anthropometric measurements as well as circulating metabolites and hormones were determined. Circulating concentrations of the ECM proteins osteopontin (OPN), chitinase-3-like protein 1 (YKL-40), tenascin C (TNC) and lipocalin-2 (LCN-2) were determined by ELISA. Results Significant differences in circulating OPN, YKL-40 and TNC concentrations between the experimental groups were observed, being significantly increased due to obesity (P<0.01) and colon cancer (P<0.05). LCN-2 levels were affected by obesity (P<0.05), but no differences were detected regarding the presence or not of CC. A positive association (P<0.05) with different inflammatory markers was also detected. Conclusions To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics. PMID:27612200

  15. 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

    Directory of Open Access Journals (Sweden)

    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.

  16. Fetal Circulation

    Science.gov (United States)

    ... Pressure High Blood Pressure Tools & Resources Stroke More Fetal Circulation Updated:Jul 8,2016 click to enlarge The ... fetal heart. These two bypass pathways in the fetal circulation make it possible for most fetuses to survive ...

  17. Adiponectin levels are associated with the number and activity of circulating endothelial progenitor cells in patients with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang YING; Dan-dan ZHONG; Geng XU; Miao-yan CHEN; Qing-yu CHEN

    2009-01-01

    Objective: To study the relationship between plasma adiponectin concentration and the functional activities of circulating endothelial progenitor cells (EPCs) in patients with coronary artery disease (CAD). Methods: Circulating EPCs were enumerated as AC133+/KDR+ cells via flow cytometry and identified by co-staining with Dii-acLDL and fluorescein isothiocy-anate (FITC)-conjugated lectin under a fluorescent microscope. The migratory capacity of EPCs was measured by modified Boyden chamber assay. Adhesion capacity was performed to count adherent cells after replating EPCs on six-well culture dishes coated with fibronectin. Results: The number of circulating EPCs (AC133+/KDR+ cells) decreased significantly in CAD patients, compared with control subjects [(74.2±12.3) vs (83.5±12.9) cells/ml blood, P<0.0\\]. In addition, the number of EPCs also decreased in CAD patients after ex vivo cultivation [(54.4±8.6) vs (71.9±11.6) EPCs/field, P<0.01]. Both circulating EPCs and differentiated EPCs were positively correlated with plasma adiponectin concentration. The functional activities of EPCs from CAD patients, such as migratory and adherent capacities, were also impaired, compared with control subjects, and positively correlated with plasma adiponectin concentration. Conclusion: The study demonstrates that the impairment of the number and functional activities of EPCs in CAD patients is correlated with their lower plasma adiponectin concentrations.

  18. Circulating vitamin D binding protein levels are not associated with relapses or with vitamin D status in multiple sclerosis

    NARCIS (Netherlands)

    Smolders, J.J.F.M.; Peelen, E.; Thewissen, M.; Menheere, P.; Damoiseaux, J.; Hupperts, R.

    2014-01-01

    BACKGROUND: A low vitamin D status has been associated with multiple sclerosis (MS). Most circulating vitamin D metabolites are bound to vitamin D binding protein (DBP). OBJECTIVES: The purpose of this study was to explore whether there is an association between MS and DBP. METHODS: We compared DBP

  19. Transcription Factor ZBED6 Mediates IGF2 Gene Expression by Regulating Promoter Activity and DNA Methylation in Myoblasts

    OpenAIRE

    Huang, Yong-Zhen; Liang-zhi ZHANG; Lai, Xin-Sheng; Li, Ming-xun; Sun, Yu-Jia; Li, Cong-jun; Lan, Xian-yong; Lei, Chu-Zhao; Zhang, Chun-Lei; Zhao, Xin; Chen, Hong

    2014-01-01

    Zinc finger, BED-type containing 6 (ZBED6) is an important transcription factor in placental mammals, affecting development, cell proliferation and growth. In this study, we found that the expression of the ZBED6 and IGF2 were upregulated during C2C12 differentiation. The IGF2 expression levels were negatively associated with the methylation status in beef cattle (P < 0.05). A luciferase assay for the IGF2 intron 3 and P3 promoter showed that the mutant-type 439 A-SNP-pGL3 in driving reporter...

  20. Insulin-like growth factor-1 (IGF-1) promotes myoblast proliferation and skeletal muscle growth of embryonic chickens via the PI3K/Akt signalling pathway.

    Science.gov (United States)

    Yu, Minli; Wang, Huan; Xu, Yali; Yu, Debing; Li, Dongfeng; Liu, Xiuhong; Du, Wenxing

    2015-08-01

    During embryonic development, IGF-1 fulfils crucial roles in skeletal myogenesis. However, the involvement of IGF-1-induced myoblast proliferation in muscle growth is still unclear. In the present study, we have characterised the role of IGF-1 in myoblast proliferation both in vitro and in vivo and have revealed novel details of how exogenous IGF-1 influences myogenic genes in chicken embryos. The results show that IGF-1 significantly induces the proliferation of cultured myoblasts in a dose-dependent manner. Additionally, the IGF-1 treatment significantly promoted myoblasts entering a new cell cycle and increasing the mRNA expression levels of cell cycle-dependent genes. However, these effects were inhibited by the PI3K inhibitor LY294002 and the Akt inhibitor KP372-1. These data indicated that the pro-proliferative effect of IGF-1 was mediated in response to the PI3K/Akt signalling pathway. Moreover, we also showed that exogenous IGF-1 stimulated myoblast proliferation in vivo. IGF-1 administration obviously promoted the incorporation of BrdU and remarkably increased the number of PAX7-positive cells in the skeletal muscle of chicken embryos. Administration of IGF-1 also significantly induced the upregulation of myogenic factors gene, the enhancement of c-Myc and the inhibition of myostatin (Mstn) expression. These findings demonstrate that IGF-1 has strong activity as a promoter of myoblast expansion and muscle fiber formation during early myogenesis. Therefore, this study offers insight into the mechanisms responsible for IGF-1-mediated stimulation of embryonic skeletal muscle development, which could have important implications for the improvement of chicken meat production.

  1. Na+ transport across rumen epithelium of hay-fed sheep is acutely stimulated by the peptide IGF-1 in vitro.

    Science.gov (United States)

    Shen, Zanming; Martens, Holger; Schweigel-Röntgen, Monika

    2012-04-01

    An energy-rich diet leads to enhanced ruminal Na(+) absorption, which is associated with elevated plasma insulin-like growth factor 1 (IGF-1) levels and an increased number of IGF-1 receptors in rumen papillae. This study examined the in vitro effect of IGF-1 on Na(+) transport across the rumen epithelium of hay-fed sheep, in which the IGF-1 concentration in plasma is lower than in concentrate-fed animals. At concentrations ranging from 20 to 100 μg l(-1), serosal LR3-IGF-1, a recombinant analogue of IGF-1, rapidly (within 30 min) stimulated the mucosal-to-serosal Na(+) flux (J(ms)Na) and consequently the net Na(+) flux (J(net)Na). Compared with controls, J(net)Na increased by about 60% (P LR3-IGF-1 (20 μg l(-1)). The IGF-1-induced increment of J(ms)Na and J(net)Na was inhibited by mucosal amiloride (1 mmol l(-1)). Neither IGF-1 nor amiloride altered tissue conductance or the short-circuit current of the isolated rumen epithelium. These data support the assumption that the stimulating effect of serosally applied IGF-1 on Na(+) transport across the rumen epithelium is mediated by Na(+)-H(+) exchange (NHE). A further study was performed with cultured rumen epithelial cells and a fluorescent probe (BCECF) to estimate the rate of pH(i) recovery after acid loading. The pH(i) of isolated rumen epithelial cells was 6.43 ± 0.15 after butyrate loading and recovered by 0.26 ± 0.02 pH units (15 min)(-1). Application of LR3-IGF-1 (20 μg l(-1)) significantly increased the rate of pH(i) recovery to 0.33 ± 0.02 pH units (15 min)(-1). Amiloride administration reduced the recovery rate in both control and IGF-1-stimulated cells. These results show, for the first time, that an acute effect of IGF-1 on Na(+) absorption across rumen epithelium results from increased NHE activity. Insulin-like growth factor 1 is thus important for the fast functional adaptation of ruminal Na(+) transport via NHE. PMID:22227200

  2. Lower Circulating C1q/TNF-Related Protein-3 (CTRP3 Levels Are Associated with Obesity: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Risa M Wolf

    Full Text Available C1q/TNF-related protein-3 (CTRP3 is a novel adipokine that lowers blood glucose levels, reduces liver triglyceride synthesis, and is protective against hepatic steatosis in diet-induced obese mouse models. We hypothesized that higher circulating serum levels of CTRP3 would be associated with a lean body mass index (BMI and a more favorable metabolic profile in humans. The aim of this study was to investigate CTRP3 levels in lean individuals compared to obese individuals.This was a cross-sectional study of obese (n=44 and lean control patients (n=60. Fasting metabolic parameters were measured in all patients and serum CTRP3 levels were measured by ELISA.BMI of the lean group was 21.9 ± 0.2 kg/m2 and obese group was 45.2 ± 1.1 kg/m2. We found significantly lower circulating levels of CTRP3 in obese individuals (405 ± 8.3 vs. 436 ± 6.7 ng/mL, p=0.004 compared to the lean group. Serum CTRP3 levels were inversely correlated with BMI (p=0.001, and triglycerides (p<0.001, and significantly associated with gender (p<0.01, ethnicity (p=0.05, HDL-cholesterol (p<0.01, and adiponectin (p<0.01. We found BMI (p<0.01, gender (p<0.01, and ethnicity (p<0.05 to be significant predictors of CTRP3 levels when controlling for age in multiple regression analysis.CTRP3 is a beneficial adipokine whose circulating levels are significantly lower in obese individuals. Obesity causes dysregulation in adipokine production, including the down-regulation of CTRP3. Lower CTRP3 levels may contribute to the pathophysiology of metabolic disorders associated with obesity. Optimizing CTRP3 levels through novel therapies may improve obesity and its comorbidities.

  3. Validation of serum IGF-I as a biomarker to monitor the bioactivity of exogenous growth hormone agonists and antagonists in rabbits

    Directory of Open Access Journals (Sweden)

    Maximilian Bielohuby

    2014-11-01

    Full Text Available The development of new growth hormone (GH agonists and growth hormone antagonists (GHAs requires animal models for pre-clinical testing. Ideally, the effects of treatment are monitored using the same pharmacodynamic marker that is later used in clinical practice. However, intact rodents are of limited value for this purpose because serum IGF-I, the most sensitive pharmacodynamic marker for the action of GH in humans, shows no response to treatment with recombinant human GH and there is little evidence for the effects of GHAs, except when administered at very high doses or when overexpressed. As an alternative, more suitable model, we explored pharmacodynamic markers of GH action in intact rabbits. We performed the first validation of an IGF-I assay for the analysis of rabbit serum and tested precision, sensitivity, linearity and recovery using an automated human IGF-I assay (IDS-iSYS. Furthermore, IGF-I was measured in rabbits of different strains, age groups and sexes, and we monitored IGF-I response to treatment with recombinant human GH or the GHA Pegvisomant. For a subset of samples, we used LC-MS/MS to measure IGF-I, and quantitative western ligand blot to analyze IGF-binding proteins (IGFBPs. Although recovery of recombinant rabbit IGF-I was only 50% in the human IGF-I assay, our results show that the sensitivity, precision (1.7–3.3% coefficient of variation and linearity (90.4–105.6% were excellent in rabbit samples. As expected, sex, age and genetic background were major determinants of IGF-I concentration in rabbits. IGF-I and IGFBP-2 levels increased after single and multiple injections of recombinant human GH (IGF-I: 286±22 versus 434±26 ng/ml; P<0.01 and were highly correlated (P<0.0001. Treatment with the GHA lowered IGF-I levels from the fourth injection onwards (P<0.01. In summary, we demonstrated that the IDS-iSYS IGF-I immunoassay can be used in rabbits. Similar to rodents, rabbits display variations in IGF-I depending on

  4. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer

    Science.gov (United States)

    Pailler, E.; Auger, N.; Lindsay, C. R.; Vielh, P.; Islas-Morris-Hernandez, A.; Borget, I.; Ngo-Camus, M.; Planchard, D.; Soria, J.-C.; Besse, B.; Farace, F.

    2015-01-01

    Background Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Patients and methods Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. Results ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24–55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7–11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. Conclusion We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged

  5. Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study.

    Science.gov (United States)

    Schock, Helena; Fortner, Renée T; Surcel, Heljä-Marja; Grankvist, Kjell; Pukkala, Eero; Lehtinen, Matti; Lundin, Eva

    2015-07-15

    Insulin-like growth factor-I (IGF-I) signaling may promote ovarian tumor development by exerting mitotic, antiapoptotic and proangiogenic effects. During pregnancy, maternal production of IGF-I is regulated by placental growth hormone (GH). Parity is an established protective factor for ovarian cancer, however, no prior study has evaluated placental GH and IGF-I in pregnancy and epithelial ovarian cancer (EOC). Prior prospective studies on the association between IGF-I and EOC in nonpregnant populations were inconclusive and did not address associations in subtypes of EOC. Among members of the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort, we identified 1,045 EOC cases, diagnosed after recruitment (1975-2008) and before March 2011 and 2,658 individually matched controls. Placental GH and IGF-I were measured in serum from the last pregnancy before EOC diagnosis or selection as control. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles and a doubling of hormone concentrations. Higher IGF-I was associated with a nonsignificant decrease in risk for invasive [ORT3 vs. T1 : 0.79 (0.62-1.02); ptrend  = 0.07] and endometrioid tumors [ORT3 vs. T1 : 0.55 (0.28-1.07); ptrend  = 0.07]. The protective association between higher IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged study provides the first data on placental GH and IGF-I in pregnancy and EOC risk overall and by subtype. Our data suggest higher IGF-I levels in pregnancy may be associated with lower risk of invasive and endometrioid EOC. PMID:25516257

  6. Antagonists of IGF:Vitronectin Interactions Inhibit IGF-I-Induced Breast Cancer Cell Functions.

    Science.gov (United States)

    Kashyap, Abhishek S; Shooter, Gary K; Shokoohmand, Ali; McGovern, Jacqui; Sivaramakrishnan, Manaswini; Croll, Tristan I; Cane, Gaëlle; Leavesley, David I; Söderberg, Ola; Upton, Zee; Hollier, Brett G

    2016-07-01

    We provide proof-of-concept evidence for a new class of therapeutics that target growth factor:extracellular matrix (GF:ECM) interactions for the management of breast cancer. Insulin-like growth factor-I (IGF-I) forms multiprotein complexes with IGF-binding proteins (IGFBP) and the ECM protein vitronectin (VN), and stimulates the survival, migration and invasion of breast cancer cells. For the first time we provide physical evidence for IGFBP-3:VN interactions in breast cancer patient tissues; these interactions were predominantly localized to tumor cell clusters and in stroma surrounding tumor cells. We show that disruption of IGF-I:IGFBP:VN complexes with L(27)-IGF-II inhibits IGF-I:IGFBP:VN-stimulated breast cancer cell migration and proliferation in two- and three-dimensional assay systems. Peptide arrays screened to identify regions critical for the IGFBP-3/-5:VN and IGF-II:VN interactions demonstrated IGFBP-3/-5 and IGF-II binds VN through the hemopexin-2 domain, and VN binds IGFBP-3 at residues not involved in the binding of IGF-I to IGFBP-3. IGFBP-interacting VN peptides identified from these peptide arrays disrupted the IGF-I:IGFBP:VN complex, impeded the growth of primary tumor-like spheroids and, more importantly, inhibited the invasion of metastatic breast cancer cells in 3D assay systems. These studies provide first-in-field evidence for the utility of small peptides in antagonizing GF:ECM-mediated biologic functions and present data demonstrating the potential of these peptide antagonists as novel therapeutics. Mol Cancer Ther; 15(7); 1602-13. ©2016 AACR. PMID:27196774

  7. Serum insulin-like growth factor-binding protein-2 levels and metabolic and cardiovascular risk factors in young adults and children born small for gestational age

    OpenAIRE

    Kort, Sandra; Doorn, Jaap van; Sande, Ad; Leunissen, Ralph; Hokken-Koelega, Anita

    2010-01-01

    textabstractBackground: IGF binding protein (IGFBP)-2 might protect against cardiovascular disease. Small for gestational age (SGA) birth could be associated with a higher risk for type 2 diabetes mellitus and cardiovascular disease in later life. No data are available on the relationship between serum IGFBP-2 levels and cardiovascular risk factors in young adults and children born SGA. Objective: The aim of the study was to determine circulating IGFBP-2 levels in subjects born SGA and to inv...

  8. Data regarding association between serum osteoprotegerin level, numerous of circulating endothelial-derived and mononuclear-derived progenitor cells in patients with metabolic syndrome.

    Science.gov (United States)

    Berezin, Alexander E; Kremzer, Alexander A; Berezina, Tatyana A; Martovitskaya, Yulia V; Gronenko, Elena A

    2016-09-01

    Metabolic syndrome (MetS) is defined as cluster of multiple metabolic and cardiovascular (CV) abnormalities included abdominal obesity, high-normal blood pressure, dyslipidaemia, and impaired fasting glucose tolerance that exhibits has a growing prevalence worldwide. We investigated whether an elevated level of osteoprotegerin (OPG) predicts imbalance between different phenotypes of circulating endothelial (EPCs) and mononuclear (MPCs) progenitor cells in MetS patients. We have analyzed data regarding dysmetabolic disorder subjects without known CV disease), as well as with known type two diabetes mellitus. All patients have given their informed written consent for participation in the study. This article contains data on the independent predictors of depletion in numerous of circulating EPCs and MPCs in MetS patients. The data are supplemental to our original research article describing detailed associations of elevated OPG level in MetS patients with numerous of EPCs and MPCs beyond traditional CV risk factors. PMID:27508223

  9. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes

    DEFF Research Database (Denmark)

    Pedersen, Maria; Bruunsgaard, Helle; Hendel, Helle W;

    2003-01-01

    The purpose of the current study was to test the hypothesis that an altered fat distribution in elderly healthy subjects and in patients with type-2 diabetes contributes to high circulating levels of interleukin (IL)-6 and tumor necrotic factor (TNF)-alpha, which secondly is related to lower musc...... cytokines are partly derived from this adipose tissue bed. Furthermore, TNF-alpha was related to lower ASM and BCM, suggesting that TNF-alpha contributes to sarcopenia in ageing....

  10. Circulating levels of reactive oxygen species in patients with nonproliferative diabetic retinopathy and the influence of antioxidant supplementation: 6-month follow-up

    OpenAIRE

    Daniela Domanico; Serena Fragiotta; Alessandro Cutini; Carmela Carnevale; Luigi Zompatori; Enzo Maria Vingolo

    2015-01-01

    Aims: The aim was to evaluate circulating levels of reactive oxygen species (ROS) and changes in central macular thickness (CMT) in patients with nonproliferative diabetic retinopathy (NPDR) after antioxidant supplementation. Materials and Methods: A total of 68 patients (68 eyes) with NPDR were enrolled. Patients were randomly divided into two groups: Treated with antioxidant supplement (Group A) and untreated control group (Group B). Each tablet, for oral administration, containing pycnogen...

  11. Circulating High-Molecular-Weight (HMW) Adiponectin Level Is Related with Breast Cancer Risk Better than Total Adiponectin: A Case-Control Study

    OpenAIRE

    Ming-ming Guo; Xue-ning Duan; Shu-de Cui; Fu-guo Tian; Xu-chen Cao; Cui-zhi Geng; Zhi-min Fan; Xiang Wang; Shu Wang; Hong-chuan Jiang; Jian-guo Zhang; Feng Jin; Jin-hai Tang; Hong Liang; Zhen-lin Yang

    2015-01-01

    The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family...

  12. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes

    DEFF Research Database (Denmark)

    Pedersen, Maria; Bruunsgaard, Helle; Weis, Nina;

    2003-01-01

    The purpose of the current study was to test the hypothesis that an altered fat distribution in elderly healthy subjects and in patients with type-2 diabetes contributes to high circulating levels of interleukin (IL)-6 and tumor necrotic factor (TNF)-alpha, which secondly is related to lower musc...... that cytokines are partly derived from this adipose tissue bed. Furthermore, TNF-alpha was related to lower ASM and BCM, suggesting that TNF-alpha contributes to sarcopenia in ageing....

  13. 早孕妇女血清IGF-Ⅰ、IGFBP-3检测临床意义分析%Significance analysis of maternal serum IGF-Ⅰ,IGFBP-3 content

    Institute of Scientific and Technical Information of China (English)

    陈载融; 李菡; 徐佩

    2012-01-01

    目的 探讨早孕妇女血清胰岛素样生长因子Ⅰ(IGF-Ⅰ)、胰岛素样生长因子结合蛋白3 (IGFBP-3)含量检测的临床意义.方法 选择体外受精与胚胎移植术(IVT-ET)患者,以术后第14天人绒毛膜促性腺激素β亚基(β-HCG)阴性者为试验组A (30例),β-HCG>650.00 mIU/mL为试验组B (30例).以健康孕6周妇女为试验组C( 30例).测定各组IGF-Ⅰ、IGFBP-3.结果 试验组B血清IGF-Ⅰ、IGFBP-3含量低于试验组A(P650. 00 mlU/mL into group B for 30 cases. Normal 6 weeks pregnant women were enrolled into group C for 30 cases. Serum IGF- Ⅰ and IGFBP-3 were detected. Results Serum content of IGF- Ⅰ and IGFBP-3 in group B were significantly lower than those in group A(P<0. 05). IGF- Ⅰ level in group C was higher than that in group A and B(P<0. 05). Group C and A were with no difference for IGFBP-3 , but IGFBP-3 content was significantly higher in group B(P<0. 05). IGF - I and IGFBP-3 were related(r = 0. 766 7). Conclusion On the 14th day post IVT-ET,maternal serum IGF- Ⅰ and IGFBP-3 content might be low, but could increase with the prolonged pregnant and placenta formation. Maternal serum IGF- Ⅰ and IGFBP-3 could be used to predict the development of embryos and fetal growth status.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Increases Circulating Zinc-Α2-Glycoprotein Levels in Patients with Type 2 Diabetes.

    Science.gov (United States)

    Liao, Xin; Wang, Xuemei; Li, Haopeng; Li, Ling; Zhang, Guohao; Yang, Mengliu; Yuan, Lei; Liu, Hua; Yang, Gangyi; Gao, Lin

    2016-01-01

    ZAG has recently been characterized as a potent metabolic regulator, but the effect of anti-diabetic agents on ZAG in humans remains unknown. Our aim was to study the effects of SGLT2 inhibitor on circulating ZAG and ADI in nT2DM. 162 subjects with nT2DM were treated by a placebo or DAPA. After 3-months of DAPA therapy, HbA1c, FBG, 2h-PBG, FFA, TG, blood pressure, BMI, WHR, body weight, FAT%, FINS, and HOMA-IR in T2DM patients decreased significantly, whereas HDL-C was significantly increased. Importantly, circulating ZAG and ADI levels in these patients were also significantly increased after DAPA therapy. Basal ZAG levels were associated with changes in BMI, FAT%, TC, HbA1c, HDL-C and ADI at post-treatment, whereas basal ADI levels were associated with changes in FAT%, TC, HbA1c, FFA and HDL-c. In vitro, DAPA treatment showed increased ZAG expression and secretion in HepG2 cells. When combined with a PPAR-γinhibitor GW9662, the effect of DAPA on ZAG was abrogated. These findings suggest that circulating ZAG can be regulated by DAPA, and DAPA promotes the expression and secretion of ZAG in the liver via the activation of PPAR-γ. The changes in ZAG induced by DAPA may play a physiologic role in enhancing insulin sensitivity. PMID:27611858

  16. Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Increases Circulating Zinc-Α2-Glycoprotein Levels in Patients with Type 2 Diabetes

    Science.gov (United States)

    Liao, Xin; Wang, Xuemei; Li, Haopeng; Li, Ling; Zhang, Guohao; Yang, Mengliu; Yuan, Lei; Liu, Hua; Yang, Gangyi; Gao, Lin

    2016-01-01

    ZAG has recently been characterized as a potent metabolic regulator, but the effect of anti-diabetic agents on ZAG in humans remains unknown. Our aim was to study the effects of SGLT2 inhibitor on circulating ZAG and ADI in nT2DM. 162 subjects with nT2DM were treated by a placebo or DAPA. After 3-months of DAPA therapy, HbA1c, FBG, 2h-PBG, FFA, TG, blood pressure, BMI, WHR, body weight, FAT%, FINS, and HOMA-IR in T2DM patients decreased significantly, whereas HDL-C was significantly increased. Importantly, circulating ZAG and ADI levels in these patients were also significantly increased after DAPA therapy. Basal ZAG levels were associated with changes in BMI, FAT%, TC, HbA1c, HDL-C and ADI at post-treatment, whereas basal ADI levels were associated with changes in FAT%, TC, HbA1c, FFA and HDL-c. In vitro, DAPA treatment showed increased ZAG expression and secretion in HepG2 cells. When combined with a PPAR-γinhibitor GW9662, the effect of DAPA on ZAG was abrogated. These findings suggest that circulating ZAG can be regulated by DAPA, and DAPA promotes the expression and secretion of ZAG in the liver via the activation of PPAR-γ. The changes in ZAG induced by DAPA may play a physiologic role in enhancing insulin sensitivity. PMID:27611858

  17. RNA microarray analysis in prenatal mouse cochlea reveals novel IGF-I target genes: implication of MEF2 and FOXM1 transcription factors.

    Directory of Open Access Journals (Sweden)

    Hortensia Sanchez-Calderon

    Full Text Available BACKGROUND: Insulin-like growth factor-I (IGF-I provides pivotal cell survival and differentiation signals during inner ear development throughout evolution. Homozygous mutations of human IGF1 cause syndromic sensorineural deafness, decreased intrauterine and postnatal growth rates, and mental retardation. In the mouse, deficits in IGF-I result in profound hearing loss associated with reduced survival, differentiation and maturation of auditory neurons. Nevertheless, little is known about the molecular basis of IGF-I activity in hearing and deafness. METHODOLOGY/PRINCIPAL FINDINGS: A combination of quantitative RT-PCR, subcellular fractionation and Western blotting, along with in situ hybridization studies show IGF-I and its high affinity receptor to be strongly expressed in the embryonic and postnatal mouse cochlea. The expression of both proteins decreases after birth and in the cochlea of E18.5 embryonic Igf1(-/- null mice, the balance of the main IGF related signalling pathways is altered, with lower activation of Akt and ERK1/2 and stronger activation of p38 kinase. By comparing the Igf1(-/- and Igf1(+/+ transcriptomes in E18.5 mouse cochleae using RNA microchips and validating their results, we demonstrate the up-regulation of the FoxM1 transcription factor and the misexpression of the neural progenitor transcription factors Six6 and Mash1 associated with the loss of IGF-I. Parallel, in silico promoter analysis of the genes modulated in conjunction with the loss of IGF-I revealed the possible involvement of MEF2 in cochlear development. E18.5 Igf1(+/+ mouse auditory ganglion neurons showed intense MEF2A and MEF2D nuclear staining and MEF2A was also evident in the organ of Corti. At P15, MEF2A and MEF2D expression were shown in neurons and sensory cells. In the absence of IGF-I, nuclear levels of MEF2 were diminished, indicating less transcriptional MEF2 activity. By contrast, there was an increase in the nuclear accumulation of FoxM1 and a

  18. Circulating vitamin D binding protein levels are not associated with relapses or with vitamin D status in multiple sclerosis

    OpenAIRE

    Smolders, Joost; Peelen, Evelyn; Thewissen, Marielle; Menheere, Paul; Damoiseaux, Jan; Hupperts, Raymond

    2014-01-01

    Background: A low vitamin D status has been associated with multiple sclerosis (MS). Most circulating vitamin D metabolites are bound to vitamin D binding protein (DBP). Objectives: The purpose of this study was to explore whether there is an association between MS and DBP. Methods: We compared DBP concentrations in blood samples of controls (n = 30) and subjects with relapsing-remitting MS (RRMS) during remission (n = 29) and relapse (n = 15). Furthermore, we explored correlations of DBP wit...

  19. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer

    OpenAIRE

    Pailler, E.; Auger, N.; Lindsay, C. R.; Vielh, P; Islas-Morris-Hernandez, A.; Borget, I; Ngo-Camus, M.; Planchard, D.; Soria, J.-C.; Besse, B.; Farace, F.

    2015-01-01

    Background Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Patients and methods Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluoresce...

  20. Multi-level evidence that circulating CK18 is a biomarker of tumour burden in colorectal cancer

    OpenAIRE

    Greystoke, A; Dean, E; Saunders, M P; Cummings, J; Hughes, A; Ranson, M; Dive, C; Renehan, A G

    2012-01-01

    Background: Circulating total cytokeratin 18 (tCK18) and/or caspase cleaved cytokeratin 18 (cCK18) (measured by M65 and M30 enzyme-linked immunosorbent assays (ELISAs), respectively) are used as pharmacodynamic (PD) biomarkers of epithelial cell death in clinical trials. Having validated these ELISAs, we assessed their utility in colorectal cancer (CRC). Methods: We applied the assays in several settings: 53 controls; 97 patients undergoing surgery and 74 patients with metastatic CRC undergoi...

  1. Intrauterine growth restriction perturbs nucleosome depletion at a growth hormone-responsive element in the mouse IGF-1 gene.

    Science.gov (United States)

    McKnight, Robert A; Yost, Christian C; Yu, Xing; Wiedmeier, Julia E; Callaway, Christopher W; Brown, Ashley S; Lane, Robert H; Fung, Camille M

    2015-12-01

    Intrauterine growth restriction (IUGR) is a common human pregnancy complication. IUGR offspring carry significant postnatal risk for early-onset metabolic syndrome, which is associated with persistent reduction in IGF-1 protein expression. We have previously shown that preadolescent IUGR male mice have decreased hepatic IGF-1 mRNA and circulating IGF-1 protein at postnatal day 21, the age when growth hormone (GH) normally upregulates hepatic IGF-1 expression. Here we studied nucleosome occupancy and CpG methylation at a putative growth hormone-responsive element in intron 2 (in2GHRE) of the hepatic IGF-1 gene in normal, sham-operated, and IUGR mice. Nucleosome occupancy and CpG methylation were determined in embryonic stem cells (ESCs) and in liver at postnatal days 14, 21, and 42. For CpG methylation, additional time points out to 2 yr were analyzed. We confirmed the putative mouse in2GHRE was GH-responsive, and in normal mice, a single nucleosome was displaced from the hepatic in2GHRE by postnatal day 21, which exposed two STAT5b DNA binding sites. Nucleosome displacement correlated with developmentally programmed CpG demethylation. Finally, IUGR significantly altered the nucleosome-depleted region (NDR) at the in2GHRE of IGF-1 on postnatal day 21, with either complete absence of the NDR or with a shifted NDR exposing only one of two STAT5b DNA binding sites. An NDR shift was also seen in offspring of sham-operated mothers. We conclude that prenatal insult such as IUGR or anesthesia/surgery could perturb the proper formation of a well-positioned NDR at the mouse hepatic IGF-1 in2GHRE necessary for transitioning to an open chromatin state.

  2. Do IGF-I concentrations better reflect growth hormone (GH action in children with short stature than the results of GH stimulating tests? Evidence from the simultaneous assessment of thyroid function

    Directory of Open Access Journals (Sweden)

    Smyczyńska Joanna

    2011-01-01

    Full Text Available Abstract Background The diagnosis of growth hormone (GH deficiency (GHD in short children seems unquestionable when both GH peak in stimulating tests (GHST and IGF-I concentration are decreased. However, the discrepancies between the results of GHST and IGF-I secretion are observed. It seems purposeful to determine the significance of GHST and IGF-I assessment in diagnosing GHD. The relationship between GH secretion and thyroid function, as well as GH influence on the peripheral thyroxine (T4 to triiodothyronine (T3 deiodination, mediated by IGF-I, were identified. Thus, clear differences in thyroid function between GH-deficient and non-GH-deficient subjects should exist. Methods Analysis comprised 800 children (541 boys, age 11.6 ± 3.1 years (mean ± SD, with short stature, in whom two (2 standard GHST (with clonidine and with glucagon were performed and IGF-I, free T4 (FT4, free T3 (FT3 and TSH serum concentrations were assessed. The patients were qualified to the following groups: GHD - decreased GH peak in GHST and IGF-I SDS (n = 81, ISS - normal GH peak and IGF-I SDS (n = 347, low GH - normal IGF-I SDS, and decreased GH peak (n = 212, low IGF - decreased IGF-I SDS, and normal GH peak (n = 160. The relationships among the results of particular tests were evaluated. Results In the groups with decreased IGF-I concentrations (GHD Group and low IGF Group, the more severe deficit of height was observed, together with higher TSH and FT4 but lower FT3 levels than in groups with normal IGF-I concentrations (ISS Group and low GH Group, independently of the results of GHST. TSH, FT4 and FT3 concentrations were - respectively - similar in two groups with decreased IGF-I secretion, as well as in two groups with normal IGF-I levels. Significant correlations were found between patients' height SDS and IGF-I SDS, between FT3 and IGF-I SDS (positive, and between FT4 and IGF-I SDS (negative, with no correlation between GH peak and any of the parameters

  3. Activation of IGF-1 and insulin signaling pathways ameliorate mitochondrial function and energy metabolism in Huntington's Disease human lymphoblasts.

    Science.gov (United States)

    Naia, Luana; Ferreira, I Luísa; Cunha-Oliveira, Teresa; Duarte, Ana I; Ribeiro, Márcio; Rosenstock, Tatiana R; Laço, Mário N; Ribeiro, Maria J; Oliveira, Catarina R; Saudou, Frédéric; Humbert, Sandrine; Rego, A Cristina

    2015-02-01

    Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Mitochondrial dysfunction associated with energy failure plays an important role in this untreated pathology. In the present work, we used lymphoblasts obtained from HD patients or unaffected parentally related individuals to study the protective role of insulin-like growth factor 1 (IGF-1) versus insulin (at low nM) on signaling and metabolic and mitochondrial functions. Deregulation of intracellular signaling pathways linked to activation of insulin and IGF-1 receptors (IR,IGF-1R), Akt, and ERK was largely restored by IGF-1 and, at a less extent, by insulin in HD human lymphoblasts. Importantly, both neurotrophic factors stimulated huntingtin phosphorylation at Ser421 in HD cells. IGF-1 and insulin also rescued energy levels in HD peripheral cells, as evaluated by increased ATP and phosphocreatine, and decreased lactate levels. Moreover, IGF-1 effectively ameliorated O2 consumption and mitochondrial membrane potential (Δψm) in HD lymphoblasts, which occurred concomitantly with increased levels of cytochrome c. Indeed, constitutive phosphorylation of huntingtin was able to restore the Δψm in lymphoblasts expressing an abnormal expansion of polyglutamines. HD lymphoblasts further exhibited increased intracellular Ca(2+) levels before and after exposure to hydrogen peroxide (H2O2), and decreased mitochondrial Ca(2+) accumulation, being the later recovered by IGF-1 and insulin in HD lymphoblasts pre-exposed to H2O2. In summary, the data support an important role for IR/IGF-1R mediated activation of signaling pathways and improved mitochondrial and metabolic function in HD human lymphoblasts.

  4. Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: Direct correlation with clinical retinopathy of prematurity

    OpenAIRE

    Hellstrom, Ann; Perruzzi, Carole; Ju, Meihua; Engström, Eva; Hård, Anna-Lena; Liu, Jun-Li; Albertsson-Wikland, Kerstin; Carlsson, Björn; Niklasson, Aimon; Sjödell, Lena; LeRoith, Derek; Senger, Donald R.; Smith, Lois E. H.

    2001-01-01

    Retinopathy of prematurity is a blinding disease, initiated by lack of retinal vascular growth after premature birth. We show that lack of insulin-like growth factor I (IGF-I) in knockout mice prevents normal retinal vascular growth, despite the presence of vascular endothelial growth factor, important to vessel development. In vitro, low levels of IGF-I prevent vascular endothelial growth factor-induced activation of protein kinase B (Akt), a kinase critical for e...

  5. Bioactive insulin-like growth factor (IGF) I and IGF-binding protein-1 in anorexia nervosa

    DEFF Research Database (Denmark)

    Støving, René; Chen, Jian-Wen; Glintborg, Dorte;

    2007-01-01

    CONTEXT: Regulation of IGF-I activity appears crucial in anorexia nervosa (AN) during adaptation to chronic starvation as well as during the regenerative processes on nutritional restoration. OBJECTIVE: The objective of this study was to examine the relationship between IGF-I bioactivity and IGF...

  6. Monoclonal antibodies directed to human insulin-like growth factor I (IGF I). Use for radioimmunoassay and immunopurification of IGF

    Energy Technology Data Exchange (ETDEWEB)

    Laubli, U.K. (Zurich Univ. (Switzerland). Biochemisches Inst.); Baier, W.; Celio, M.R. (Zurich Univ. (Switzerland). Anatomisches Inst.); Binz, H.; Humbel, R.E. (Zurich Univ. (Switzerland). Inst. fuer Immunologie und Virologie)

    1982-11-22

    Mouse hybridomas secreting antibodies to human insulin-like growth factor I (IGF I) were produced by fusion of spleen cells of hyperimmunised mice with FO mouse-myeloma cells. Eight clones producing antibodies against human IGF I have been isolated, two of which have been characterised. One was used in a radioimmunoassay, the other for immunopurification of IGF.

  7. Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy

    Directory of Open Access Journals (Sweden)

    Elizabeth Silbermann

    2012-08-01

    Full Text Available Alcohol-related myopathy (Alc-M is highly prevalent among heavy drinkers, although its pathogenesis is not well understood. We hypothesize that Alc-M is mediated by combined effects of insulin/IGF resistance and oxidative stress, similar to the effects of ethanol on liver and brain. We tested this hypothesis using an established model in which adult rats were pair-fed for 8 weeks with isocaloric diets containing 0% (N = 8 or 35.5% (N = 13 ethanol by caloric content. Gastrocnemius muscles were examined by histology, morphometrics, qRT-PCR analysis, and ELISAs. Chronic ethanol feeding reduced myofiber size and mRNA expression of IGF-1 polypeptide, insulin, IGF-1, and IGF-2 receptors, IRS-1, and IRS-2. Multiplex ELISAs demonstrated ethanol-associated inhibition of insulin, IRS-1, Akt, and p70S6K signaling, and increased activation of GSK-3β. In addition, ethanol-exposed muscles had increased 4-hydroxy-2-nonenal immunoreactivity, reflecting lipid peroxidation, and reduced levels of mitochondrial Complex IV, Complex V, and acetylcholinesterase. These results demonstrate that experimental Alc-M is associated with inhibition of insulin/IGF/IRS and downstream signaling that mediates metabolism and cell survival, similar to findings in alcoholic liver and brain degeneration. Moreover, the increased oxidative stress, which could be mediated by mitochondrial dysfunction, may have led to inhibition of acetylcholinesterase, which itself is sufficient to cause myofiber atrophy and degeneration.

  8. Anabolic effects of IGF-1 signaling on the skeleton

    Directory of Open Access Journals (Sweden)

    Candice G. T Tahimic

    2013-02-01

    Full Text Available This review focuses on the anabolic effects of IGF-1 signaling on the skeleton, emphasizing the requirement for IGF-1 signaling in normal bone formation and remodeling. We first discuss the genomic context, splicing variants and species conservation of the IGF-1 locus. The modulation of IGF-1 action by growth hormone (GH is then reviewed while also discussing the current model which takes into account the GH-independent actions of IGF-1. Next, the skeletal phenotypes of IGF-1-deficient animals are described in both embryonic and postnatal stages of development, which include severe dwarfism and an undermineralized skeleton. We then highlight two mechanisms by which IGF-1 exerts its anabolic action on the skeleton. Firstly, the role of IGF-1 signaling in the modulation of anabolic effects of parathyroid hormone (PTH on bone will be discussed, presenting in vitro and in vivo studies that establish this concept and the proposed underlying molecular mechanisms involving Indian hedgehog (Ihh and the ephrins. Secondly, the crosstalk of IGF-1 signaling with mechanosensing pathways will be discussed, beginning with the observation that animals subjected to skeletal unloading by hindlimb elevation are unable to mitigate cessation of bone growth despite infusion with IGF-1 and the failure of IGF-1 to activate its receptor in bone marrow stromal cell cultures from unloaded bone. Disrupted crosstalk between IGF-1 signaling and the integrin mechanotransduction pathways is discussed as one of the potential mechanisms for this IGF-1 resistance. Next, emerging paradigms on bone-muscle crosstalk are examined, focusing on the potential role of IGF-1 signaling in modulating such interactions. Finally, we present a future outlook on IGF research.

  9. Serine 204 phosphorylation and O-β-GlcNAC interplay of IGFBP-6 as therapeutic indicator to regulate IGF-II functions in viral mediated hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Sarwar Muhammad T

    2011-05-01

    Full Text Available Abstract Hepatocellular carcinoma is mainly associated with viral hepatitis B and C. Activation of cell growth stimulator IGF-II gene is observed in tumor formation especially in viral associated hepatocellular carcinoma. Elevated IGF-II levels are indicator of increased risk for cholangiocellular and hepatocellular carcinomas through over saturation of IGF-II binding capacities with IGF receptors leading to cellular dedifferentiation. In HCV, core protein is believed to trans-activate host IGF-II receptor through PKC pathway and the inhibition of tumor cell growth can be achieved by blocking IGF-II pathway either at transcriptional level or increasing its binding with IGFBPs (Insulin like growth factor proteins at C-terminal, so that it is not available in free form. IGFBP-6 is a specific inhibitor of IGF-II actions. Affinity of IGFBPs with IGFs is controlled by post-translational modifications. Phosphorylation of IGFBPs inhibits IGFs action on target cells while O-glycosylation prevents binding of IGFBP-6 to glycosaminoglycans and cell membranes and resulting in a 10-fold higher affinity for IGF-II. O-glycosylation and phosphorylation operate the functional expression of cellular proteins, this switching on and off the protein expression is difficult to monitor in vivo. By using neural network based prediction methods, we propose that alternate O-β-GlcNAc modification and phosphorylation on Ser 204 control the binding of IGFBP-6 with IGF-II. This information may be used for developing new therapies by regulating IGFBP-6 assembly with IGF-II to minimize the risk of viral associated hepatocellular carcinoma. We can conclude that during HCV/HBV infection, O-β-GlcNAc of IGFBP-6 at Ser 204 diminish their binding with IGF-II, increase IGF-II cellular expression and promote cancer progression which can lead to hepatocellular carcinoma. Furthermore, this site can be used for developing new therapies to control the IGF-II actions during viral

  10. Circulating Vascular Endothelial Growth Factor (VEGF Levels in Advanced Stage Cancer Patients Compared to Normal Controls and Diabetes Mellitus Patients with Critical Ischemia

    Directory of Open Access Journals (Sweden)

    Yoka H. Kusumanto

    2007-01-01

    Full Text Available Anti-angiogenic therapy is emerging as a valuable tool in the treatment of patients with cancer. As VEGF is a central target in anti-angiogenic therapy, its levels in the circulation might be relevant in selecting tumor types or patients likely to respond to this treatment. Additional VEGF has been recognized as a key factor in the pathogenesis of diabetic retinopathy. Recently anti-angiogenic therapy has been advocated in this situation. We measured VEGF levels in whole blood in 42 patients with high grade (n = 26 and low grade (n = 16 end stage cancer, and in 28 healthy controls and 37 patients with diabetes related vascular disease. Only 2/26 patients in the group of high grade cancer had signifi cantly elevated VEGF levels, 1/16 in the low grade group and 1/28 in the healthy control group. In contrast, in 10/37 diabetic patients the mean VEGF levels were significantly elevated compared to the other groups. The mean level in these diabetic patients was significantly elevated compared to the other groups. These data indicate the limitation of the use of circulating VEGF levels as a potential selection criterion for anti-angiogenic therapy in cancer patients and suggest further studies into its application in the management of diabetic complications.

  11. Maternal deprivation induces a rapid decline in circulating leptin levels and sexually dimorphic modifications in hypothalamic trophic factors and cell turnover.

    Science.gov (United States)

    Viveros, María-Paz; Díaz, Francisca; Mateos, Beatriz; Rodríguez, Noé; Chowen, Julie A

    2010-04-01

    Pathological outcomes, including metabolic and endocrine disturbances, of maternal deprivation (MD) in Wistar rats depend on gender and the timing of deprivation during development. We analyzed the effect of MD between postnatal days 9 and 10, a critical period in hypothalamic development, on circulating hormones and local production of trophic factors involved in this process, as well as on markers of cell turnover and maturation. Males and females were studied 12 and 24 h after MD and 12 h (MD36) after returning the dam to her pups. Circulating corticosterone levels were increased and glucose and leptin levels decreased throughout the study in both sexes. Hypothalamic mRNA levels of leptin receptor increased significantly at MD24 in both sexes, normalizing in females at MD36, but not in males. In male rats insulin-like growth factor mRNA levels were significantly decreased at MD24 and brain derived neurotrophic factor mRNA levels decreased at MD12 and MD24, with both trophic factors unaffected in females. In males cell proliferation was significantly decreased at MD36, as were the glial structural proteins, glial fibrillary acidic protein and vimentin. In females, nestin levels decreased significantly at MD24. These results indicate that MD differently affects trophic factors and cell-turnover in the hypothalamus of males and females, which may underlie the sex differences seen in the endocrine and metabolic outcome.

  12. Data on the circulating levels of endothelial microparticles are elevated in patients with bicuspid aortic valve and are related to aortic dilation

    Directory of Open Access Journals (Sweden)

    Josep M. Alegret

    2016-09-01

    Full Text Available The data included here support the research article “Circulating endothelial microparticles are elevated in bicuspid aortic valve (BAV disease and related to aortic dilation” (Alegret et al., 2016 [1] where circulating levels of platelet endothelial cell adhesion molecule (PECAM+ endothelial microparticles (EMPs were identified as a biological variable related to aortic dilation in patients with BAV disease. The data presented in this article are composed by four tables and one figure containing the clinical and echocardiographic characteristics of the patients (Alegret et al., 2016 [1] included in this study, and summarize the results of multivariate linear analyses. Furthermore, is also included a figure showing a representative flow cytometry dot plots and histograms used in PECAM+ EMPs quantification is also included.

  13. Longitudinal Changes in Circulating Testosterone Levels Determined by LC-MS/MS and by a Commercially Available Radioimmunoassay in Healthy Girls and Boys during the Pubertal Transition

    DEFF Research Database (Denmark)

    Mouritsen, Annette; Søeborg, Tue; Johannsen, Trine Holm;

    2014-01-01

    (detection limit 0.23 nmol/l). RESULTS: Serum concentrations of testosterone increased gradually with age by both methods. However, serum testosterone was quantifiable in 9/10 girls prior to pubic hair development measured with LC-MS/MS, and in 2/10 girls measured with immunoassay. In boys, testosterone was...... quantifiable in 10/10 boys 1 year prior to pubic hair development measured with LC-MS/MS, and only in 1/10 boys measured with immunoassay. Serum testosterone levels were quantifiable 1.5 years (range 0.5-2.5) earlier using LC-MS/MS. CONCLUSION: Assessment of longitudinal circulating levels of serum...

  14. Increased intragenic IGF2 methylation is associated with repression of insulator activity and elevated expression in serous ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Zhiqing eHuang

    2013-05-01

    Full Text Available Overexpression of insulin-like growth factor-II (IGF2 is a prominent characteristic of many epithelial ovarian malignancies. IGF2 imprinting and transcription are regulated in part through DNA methylation, which in turn regulates binding of the insulator protein, CTCF, within the IGF2/H19 imprint center. We have shown that IGF2 overexpression in ovarian cancer is associated with hypermethylation of CTCF binding sites within the IGF2/H19 imprint center. The aim of this study was to investigate the methylation and binding capacity of a novel putative CTCF binding motif located intragenic to IGF2 and determine how this relates to IGF2 expression. In 35 primary serous epithelial ovarian cancer specimens, methylation of two CpGs, including one within the core binding motif and another adjacent to this motif, was higher in the 18 cancers with elevated IGF2 expression versus 10 with low expression (avg. 68.2% vs. 38.5%; p<0.0001. We also found that the CpG site within the CTCF binding motif is hypermethylated in male gametes (>92%; avg. 93.2%; N=16. We confirmed binding of CTCF to this region in ovarian cancer cells, as well as the paralog of CTCF, BORIS, which is frequently overexpressed in cancers. The unmethylated CTCF binding motif has insulator activity in cells that express CTCF or BORIS, but not in cells that express both CTCF and BORIS. These intragenic CpG dinucleotides comprise a novel paternal germline imprint mark and are located in a binding motif for the insulator protein CTCF. Methylation of the CpG dinucleotides is positively correlated with IGF2 transcription, supporting that increased methylation represses insulator function. These combined results suggest that methylation and CTCF binding at this region play important roles in regulating the level of IGF2 transcription. Our data have revealed a novel epigenetic regulatory element within the IGF2/H19 imprinted domain that is highly relevant to aberrant IGF2 expression in ovarian

  15. Assessment of Cord Blood Vascular Endothelial Growth Factor Levels and Circulating CD34+ Cells in Preterm Infants with Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    Azza Tawfeek Moawed, Nihad Ahmed El Nashar

    2012-04-01

    Full Text Available Respiratory distress syndrome (RDS secondary to surfactant deficiency is a common cause of mobility and mortality in premature infants. Vascular endothelial growth factor (VEGF is a major angiogenic factor and prime regulator of endothelial cells proliferation. So, VEGF may contribute to surfactant secretion and pulmonary maturation. Additionally, circulating CD34+ stem – progenitor cells are elevated along with its mobilizing cytokines in neonatal RDS. Aim of work: This study aimed to elucidate the role of cord blood VEGF and the circulating CD34+ cells in preterm infants with and without RDS. Patients & method: This study was conducted on 55 preterm neonates divided into 25 preterm (15 males/ 10 females without RDS with mean age of 31.60 ± 1.56 weeks and 30 preterm neonates with RDS (18 males/ 12 females with mean age of 29.95 ± 1.09 weeks . Twenty healthy neonates (14 males/ 6 females served as controls with mean age of 38.20 ± 3.57 weeks. All neonates were subjected to full history taking; thorough clinical examination and laboratory investigations including determination of VEGF levels in cord blood samples using ELISA and circulating CD34+ cells in peripheral blood by flowcytometery. Results:The results of this study revealed that cord blood VEGF levels were significantly decreased in preterms with RDS versus pret