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

    International Nuclear Information System (INIS)

    Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Using the first transgenic animal model to

  5. A Fasting Insulin–Raising Allele at IGF1 Locus Is Associated with Circulating Levels of IGF-1 and Insulin Sensitivity

    Science.gov (United States)

    Mannino, Gaia Chiara; Greco, Annalisa; De Lorenzo, Carlo; Andreozzi, Francesco; Marini, Maria A.; Perticone, Francesco; Sesti, Giorgio

    2013-01-01

    Background A meta-analysis of genome-wide data reported the discovery of the rs35767 polymorphism near IGF1 with genome-wide significant association with fasting insulin levels. However, it is unclear whether the effects of this polymorphism on fasting insulin are mediated by a reduced insulin sensitivity or impaired insulin clearance. We investigated the effects of the rs35767 polymorphism on circulating IGF-1 levels, insulin sensitivity, and insulin clearance. Methodology/Principal Findings Two samples of adult nondiabetic white Europeans were studied. In sample 1 (n=569), IGF-1 levels were lower in GG genotype carriers compared with A allele carriers (190±77 vs. 218±97 ng/ml, respectively; P=0.007 after adjusting for age, gender, and BMI). Insulin sensitivity assessed by euglycaemic-hyperinsulinemic clamp was lower in GG genotype carriers compared with A allele carriers (8.9±4.1 vs. 10.1±5.1 mg x Kg-1 free fat mass x min-1, respectively; P=0.03 after adjusting for age, gender, and BMI). The rs35767 polymorphism did not show significant association with insulin clearance. In sample 2 (n=859), IGF-1 levels were lower in GG genotype carriers compared with A allele carriers (155±60 vs. 164±63 ng/ml, respectively; P=0.02 after adjusting for age, gender, and BMI). Insulin sensitivity, as estimated by the HOMA index, was lower in GG genotype carriers compared with A allele carriers (2.8±2.2 vs. 2.5±1.3, respectively; P=0.03 after adjusting for age, gender, and BMI). Conclusion/Significance The rs35767 polymorphism near IGF1 was associated with circulating IGF-1 levels, and insulin sensitivity with carriers of the GG genotype exhibiting lower IGF-1 concentrations and insulin sensitivity as compared with subjects carrying the A allele. PMID:24392014

  6. A fasting insulin-raising allele at IGF1 locus is associated with circulating levels of IGF-1 and insulin sensitivity.

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    Gaia Chiara Mannino

    Full Text Available BACKGROUND: A meta-analysis of genome-wide data reported the discovery of the rs35767 polymorphism near IGF1 with genome-wide significant association with fasting insulin levels. However, it is unclear whether the effects of this polymorphism on fasting insulin are mediated by a reduced insulin sensitivity or impaired insulin clearance. We investigated the effects of the rs35767 polymorphism on circulating IGF-1 levels, insulin sensitivity, and insulin clearance. METHODOLOGY/PRINCIPAL FINDINGS: Two samples of adult nondiabetic white Europeans were studied. In sample 1 (n=569, IGF-1 levels were lower in GG genotype carriers compared with A allele carriers (190±77 vs. 218±97 ng/ml, respectively; P=0.007 after adjusting for age, gender, and BMI. Insulin sensitivity assessed by euglycaemic-hyperinsulinemic clamp was lower in GG genotype carriers compared with A allele carriers (8.9±4.1 vs. 10.1±5.1 mg x Kg(-1 free fat mass x min(-1, respectively; P=0.03 after adjusting for age, gender, and BMI. The rs35767 polymorphism did not show significant association with insulin clearance. In sample 2 (n=859, IGF-1 levels were lower in GG genotype carriers compared with A allele carriers (155±60 vs. 164±63 ng/ml, respectively; P=0.02 after adjusting for age, gender, and BMI. Insulin sensitivity, as estimated by the HOMA index, was lower in GG genotype carriers compared with A allele carriers (2.8±2.2 vs. 2.5±1.3, respectively; P=0.03 after adjusting for age, gender, and BMI. CONCLUSION/SIGNIFICANCE: The rs35767 polymorphism near IGF1 was associated with circulating IGF-1 levels, and insulin sensitivity with carriers of the GG genotype exhibiting lower IGF-1 concentrations and insulin sensitivity as compared with subjects carrying the A allele.

  7. 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

  8. 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.

  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. 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; Jeansson, Stig; Jenum, Pål A; Eskild, Anne

    2008-01-01

    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...... interval, 1.1-21.8). Low concentrations of IGFBP-1, both in the first and in the second trimesters, were related to higher risk of term preeclampsia (OR 4.0, 95% confidence interval, 1.9-8.4) and moderately increased risk of preterm preeclampsia (OR 2.3, 95% confidence interval, 1.2-4.4). CONCLUSION: The...

  11. 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...

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

    International Nuclear Information System (INIS)

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

  13. 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...

  14. 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

  15. 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

    free fatty acids (P = .028) and β-hydroxybutyrate (P = .014), increased accumulation of IMCLs in tibialis anterior muscle (P = .008), and a tendency for elevated fat oxidation rates (P = .058); however, glycerol Ra values were similar. Gene expression of the fatty acid metabolism pathway (P = .0014......) was upregulated, whereas the GLUT1 gene was downregulated (P = .005) in the skeletal muscle in low-IGF subjects. CONCLUSIONS: These data suggest that serum IGF-1 levels could be an important marker of β-cell function and glucose as well as lipid metabolic responses during fasting....

  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. 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

  19. 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.

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

    OpenAIRE

    Wang Z; Lei L; Cai X; Chen LY; Yuan M; Yang G; Huang P; Wang X

    2016-01-01

    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 angi...

  1. 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

  2. Influence of Intramuscular Application of Autologous Conditioned Plasma on Systemic Circulating IGF-1

    OpenAIRE

    2011-01-01

    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...

  3. 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.

  4. 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...

  5. Circulating epidermal growth factor (EGF) and insulin - like growth factor - I (IGF-I) in patients with epithelial ovarian carcinoma

    International Nuclear Information System (INIS)

    Circulating epidermal growth factor (EGF) and insulin - like growth factor - I (EGF-I) were estimated in 58 patients with epithelial ovarian cancer and were correlated with clinically and biochemically important prognosticators. EGF-I levels were significantly low in patients as compared to controls. The relation of growth factors with clinically important prognosticators was non - significant. Moreover, the levels of EGF and IGF - I in ER+/PR+ and ER-/PR- groups and in the low and high EGFR + tumors did not differ significantly. Patients with EGF1.0 ng/ml. (author)

  6. 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 cancer....... Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2......). Significant sex interactions, which were characterized by different genotype-phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between...

  7. A prospective study on circulating insulin-like growth factor I (IGF-I), IGF-binding proteins, and cognitive function in the elderly

    OpenAIRE

    Kalmijn, Sandra; Pols, Huib; Lamberts, Steven; Breteler, Monique; Janssen, Joop

    2000-01-01

    textabstractThe objective of this study was to investigate the longitudinal relation between the insulin-like growth factor I (IGF-I)/IGF-binding protein (IGFBP) system and cognitive function. The study population consisted of a sample of 186 healthy participants from the population-based Rotterdam Study, aged 55-80 yr. At baseline, we determined fasting blood levels of free and total IGF-I, IGFBP-1, and IGFBP-3. The 30-point Mini-Mental State Examination (MMSE) was used to assess cognitive i...

  8. 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

    -I. However, the diagnostic value of IGFBP-3 is still controversial, perhaps because the quality of the available normative data for IGFBP-3 varies. It has recently been shown that a large number of individuals is required to establish reference ranges for IGF-I that take into account age, sex, body mass...... index (BMI), and pubertal stage. Therefore, we measured IGFBP-3, IGF-I, IGF-II, IGFBP-1, and IGFBP-2 levels by RIA in 907 healthy children to establish well characterized normative data on IGFBP-3 according to age, sex, and pubertal stage and to study the complex relationship between IGFs and their BPs...... 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...

  9. 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

  10. 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...

  11. 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...

  12. 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; Müller, J; Skakkebaek, N E

    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...

  13. 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...

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

    OpenAIRE

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

    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 (...

  15. 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.

  16. 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)....

  17. 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....

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. 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....

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Relationship between serum levels of IGF-II and HA, P III P in patients with hepatic cirrhosis

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical significance of changes of serum IGF-II, HA and P III P levels in patients with hepatic cirrhosis. Methods: Serum IGF-II, HA and P III P levels were measured with RIA in 65 patients with hepatic cirrhosis and 30 controls. Results: Serum IGF-II levels were significantly higher than those in controls (P<0.01), and were significantly positively correlated to the serum levels of HA, P III P. Conclusion: Determination of serum IGF-II levels in patients with hepatic cirrhosis is of help for assessment of the severity of diseases as well as outcome prediction. (authors)

  3. 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...

  4. 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

  5. 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

    , 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...... cyproterone acetate (Androcur; n = 23) or with long acting GnRH analog (Decapeptyl Depot; n = 17). We found that serum IGF-I levels were increased before treatment in both groups (mean +/- SE, 446 +/- 35 and 391 +/- 35 micrograms/L; P <0.0001, respectively) compared to those in normal age-matched prepubertal...... levels after 2 yr of treatment (P <0.0001). Serum IGF-I levels remained unchanged during monthly im treatment with long acting GnRH analog, whereas IGFBP-3 levels significantly increased during the first year of this treatment despite unmeasurable estradiol levels. Thus, in both groups, the molar ratio...

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

    Directory of Open Access Journals (Sweden)

    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

  7. Reducing Igf-1r levels leads to paradoxical and sexually dimorphic effects in HD mice.

    Directory of Open Access Journals (Sweden)

    Silvia Corrochano

    Full Text Available Many of the neurodegenerative diseases that afflict people in later life are associated with the formation of protein aggregates. These so-called "proteinopathies" include Alzheimer's disease (AD and Huntington's disease (HD. The insulin/insulin-like growth factor signalling (IIS pathway has been proposed to modulate such diseases in model organisms, as well as the general ageing process. In this pathway, insulin-like growth factor binds to insulin-like growth factor receptors, such as the insulin-like growth factor 1 receptor (IGF-1R. Heterozygous deletion of Igf-1r has been shown to lead to increased lifespan in mice. Reducing the activity of this pathway had benefits in a HD C. elegans model, and some of these may be attributed to the expected inhibition of mTOR activity resulting in an increase in autophagy, which would enhance mutant huntingtin clearance. Thus, we tested if heterozygous deletion of Igf-1r would lead to benefits in HD related phenotypes in the mouse. Surprisingly, reducing Igf-1r levels led to some beneficial effects in HD females, but also led to some detrimental effects in HD males. Interestingly, Igf-1r deficiency had no discernible effects on downstream mTOR signalling in HD mice. These results do not support a broad beneficial effect of diminishing the IIS pathway in HD pathology in a mammalian system.

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

    International Nuclear Information System (INIS)

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

  9. 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)....

  10. 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

  11. 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

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

    International Nuclear Information System (INIS)

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

  13. 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.

  14. 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

  15. 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...... treatment with GnRH in combination with an antiandrogen (cyproterone acetate) to block the possible effect of adrenal androgens has not previously been evaluated. We, therefore, studied 40 patients with idiopathic CPP that were treated for 24 months with either GnRH analog (Buserelin) in combination with...

  16. 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....

  17. Levels of circulating peptide and steroid hormones in men with lung cancer

    International Nuclear Information System (INIS)

    Levels of circulating peptide (FSH, LH, prolactin, ACTH, calcitonin, gastrin and insulin-like growth factor-1 [IGF-1]) and steroid (estradiol, progesterone, DHEA-S and testosterone)hormones were estimated by radioimmunoassay (RIA) and immunoradiometric assay (IRMA) in male patients with lung cancer (n=37) pre-therapeutically and compared with 25 age matched healthy controls. In this retrospective study, FSH, LH, prolactin, ACTH, calcitonin, gastrin and IGF-1 were significantly higher with concomitant lower levels of DHEA-S and testosterone, while the difference was statistically non-significant for estradiol and progesterone in patients with lung cancer when compared with controls. Early stage patients (Stage II) exhibited higher levels of gastrin as compared to advanced stage patients (Stages III and IV). It is suggested that hormonal imbalance might play an important role in the development and progression in male patients with lung cancer. (author)

  18. 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...

  19. 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

  20. 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

    this study, we elucidate the association of adiposity and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), testosterone, oestrogen, IGF-I and IGFBP-3 with the presence of pubertal gynaecomastia in a large cohort of healthy boys. PATIENTS: A...... total of 501 healthy Danish school boys (aged 6·1-19·8 year) from the COPENHAGEN Puberty Study. MEASUREMENTS: Anthropometry and pubertal stages (PH1-6 and G1-5) were evaluated, and the presence of gynaecomastia was assessed. Body fat percentage was calculated by means of four skin folds and impedance....... Nonfasting blood samples were analysed for FSH, LH, testosterone, SHBG, oestradiol, IGF-I, IGFBP-3 and prolactin. RESULTS: We found that 23% (31/133) of all pubertal boys had gynaecomastia. More specifically, 63% (10/16) of boys in genital stage 4 had gynaecomastia. Boys with gynaecomastia had significantly...

  1. 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.

  2. 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...

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

    Science.gov (United States)

    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 to determine the association between tertiles of IGF-1 and IL-6 and the MetS and its components. RESULTS—After adjusting for age and sex, both IGF-1 and IL-6 were correlated with insulin resistance and individual components of MetS, but in opposite directions. In the logistic regression model adjusted for age and sex, higher IL-6 and lower IGF-1 levels confer increased risk of having MetS and its two underlying pathophysiological abnormalities, i.e., visceral obesity and insulin resistance. CONCLUSIONS—The present results raise the possibility that lowered protection against inflammation, i.e., lower IGF-1 levels, may have a role in the development of MetS and its features, resulting in an imbalance between proinflammatory and anti-inflammatory proteins. PMID:18535190

  4. 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...

  5. Clinical significance of changes of serum Hcy and IGF-I levels after treatment in patients with acute cerebral infarction

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical significance of serum Hcy and IGF-I levels in patients with acute cerebral infarction. Methods: Serum IGF-I (with RIA), Hcy (with ELISA)levels were measured in 32 patients with acute cerebral infarction both before and after treatment as well as in 35 normal controls. Results: Before treatment, the serum Hcy level was remarkably higher than that in controls (P0.05). Conclusion: The level of Hcy increased and IGF-I decreased in the patients with acute cerebral infarction which closely to the severity of acute cerebral infarction and may be taken as a sensitive biochemical indicator for predicting pathogenesis and progress of ACI. (authors)

  6. 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

  7. 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.

  8. Diagnostic value of measurement of serum levels of insulin-like growth factor (IGF-1) and IGF binding protein 3(IGFBP-3) for children with growth hormone deficiency (GHD)

    International Nuclear Information System (INIS)

    Objective: To appraise the feasibility of establishment of diagnosis of GHD with determination of serum IGF-1 and IGFBP-3 levels. Methods: Serum IGF-1 and IGFBP-3 levels were measured with IRMA in 38 children with GHD and 42 controls. GH releasing stimulation test was also performed in these subjects with GH amount measured by chemiluminescence immunoassay (CLIA) for contrast study and verification of the diagnosis. Results: In children with GHD, the serum IGF-1 and IGFBP-3 levels were significantly lower than those in the controls (p<0.01). The amount of GH increased in the test was also significantly less. Conclusion: Determination of serum levels of IGF-1 and IGFBP-3 can be used for the diagnosis of GHD in children, which may replace the traditional GH releasing stimulation test saving the children from repeated blood withdrawal

  9. 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

  10. 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

  11. 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

  12. 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...

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

    International Nuclear Information System (INIS)

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

  14. 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...

  15. 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.

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

    Science.gov (United States)

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

    2016-02-01

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

  17. 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

  18. 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

  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. Disposition of radiolabelled insulin-like growth factor I (IGF-I), IGF-II and their N-terminal truncated variants in rats

    International Nuclear Information System (INIS)

    Serum half life, tissue uptake and urinary excretion of N-terminal truncated IGF variants and their intact precursors were compared to see whether the variants regulate the bioavailability of those growth factors. IGF-I, des(1-3) IGF-I, IGF-II and des(1-6) IGF-II were labeled with 125I and intravenously administered to SD rats. Blood from femoral artery and urine from implanted bladder catheter were collected at appropriate intervals until sacrifice of animals at 2 hr after administration. Tissues were dissected out and all of these samples were measured for their radioactivity with a gamma counter. The half lives of des(1-3) IGF-I, IGF-I, des(1-6) IGF-II and IGF-II were 20.5, 228.3, 21.3 and 181.7 min, respectively. Maximal accumulation of all peptides was found in the kidney. 125I-IGF-I and -II showed the following distribution pattern; levels were higher in the kidney>pancreas>small intestine>liver>duodenum>stomach>lung>spleen>heart>large intestine>testis>brain>skeletal muscle. Skeletal muscle, kidney and testis showed a preferential uptake of the variants. Urinary excretion of the variants were much greater. Thus the variants were more rapidly cleared from circulation. The physiological significance of tissue distribution of 4 peptides remains to be further investigated. (K.H.)

  1. 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.

  2. Evaluation of insulin like growth factor-1 (IGF-1) level and its impact on muscle and bone mineral density in frail elderly male.

    Science.gov (United States)

    Mohamad, Magda I; Khater, Mohamed S

    2015-01-01

    Decrease in IGF-1 level is a major endocrine dysregulation that has been implicated in frailty, disability, and mortality in older adults. Our aim was to clarify the effect of IGF-1 on muscle and bone mineral density (BMD) in frail males. One hundred elderly males were included and divided into frail group (n=50) and robust group (n=50) based on the study of osteoporotic fractures (SOF) frailty index. Anthropometric measures, femoral BMD, and serum IGF-1 level were measured. Our results showed that the IGF-1 level was significantly lower in the frail males in comparison to the robust with mean value 37.1±24.2 versus 68.5±18.4ng/ml (PReceiver operating curve (ROC) analysis of the IGF-1 level revealed that sensitivity was 88.5%, specificity was 100%, cutoff value was 46.5ng/ml and area under the curve (AUC) was 0.897 (Pdiseases adjustment. Male subjects with a low IGF-1 level may be at risk of being frail and having abnormal BMD. 16.8% and 15% of variability in MCC and BMD may be attributed to IGF-1 level respectively. PMID:25240725

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

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

    International Nuclear Information System (INIS)

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

  9. 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

  10. 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

  11. Alteration in pancreatic immunoreactivity of insulin-like growth factor (IGF)-binding protein (IGFBP)-6 and in intracellular degradation of IGFBP-3 in fibroblasts of IGF-II receptor/IGF-II-deficient mice.

    Science.gov (United States)

    Braulke, T; Dittmer, F; Götz, W; von Figura, K

    1999-01-01

    The Type-2 insulin-like growth factor receptor (IGF2R) mediates the transport of lysosomal hydrolases to lysosomes and the clearance of insulin-like growth factor II (IGF-II). Mutant mice lacking IGF2R usually die perinatally, but are completely rescued from lethality in the absence of IGF-II. IGF2R/IGF-II-deficient mice have elevated levels of circulating IGF binding protein (IGFBP)-3 and show a strong IGFBP-6 immunoreactivity in all pancreatic islet cells and in secretory granules of different size in acinar cells and interlobular connective tissue of exocrine pancreas. Fibroblasts derived from double mutant mice missort the lysosomal protease cathepsin D, and are able to degrade endocytosed (125I)IGFBP-3 intracellularly, however, with lower efficiency than in control cells. These results show that the deficiency of IGF2R and IGF-II affects the expression and metabolism of IGFBPs in a tissue- and cell type-specific manner. PMID:10226807

  12. 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

  13. 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.

  14. Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia

    International Nuclear Information System (INIS)

    Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 (with RIA) and hs-CRP (with immunoturbidity method) levels were determined in 36 pediatric patients with bronchopneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and hs-CRP levels in the patients were significantly higher than those in the controls (P0.05). Conclusion: Determination of serum IGF-II, IL-6, IL-8 and hs-CRP levels in pediatric patients with bronchopneumonia was important for diagnosis and outcome prediction. (authors)

  15. Clinical significance of determination of serum IGF-I, TNF-α and SS levels in patients with chronic viral hepatitis

    International Nuclear Information System (INIS)

    Objective: To study the clinical significance of changes of serum IGF-I, TNF-α and somatostatin(SS) levels in patients with chronic viral hepatitis. Methods: Serum IGF-I, TNF-α and SS levels were determined with RIA in 30 patients with chronic viral hepatitis (B hepatitis, n=24,C hepatitis, n=6) and 30 controls.Results The serum IGF-I, TNF-α and SS levels in the patients were all significantly higher than those in controls (P<0.01). Conclusion: Serum IGF-I, TNF-α and SS levels were markedly increased in patients with chronic viral hepatitis, the exact mechanism and consequence of the changes required further study. (authors)

  16. 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)

  17. 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

  18. 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.

  19. Genetic architecture of circulating lipid levels

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...

  20. 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.

  1. Clinical singnificance of determination of changes of serum and peritoneal fluid TGF-β, IGF-I, TNF-α and IL-8 levels in patients with endometriosis

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical significance of the changes of serum and peritioneal fluid TGF-β, IGF - I , TNF-α and IL-8 levels in patients with endometriosis. Methods: Serum and peritoneal fluid levels of TGF-β, IGF-I, TNF-α and IL-8 were measured with RIA in 30 patients with endometriosis and 30 controls. Results: The levels of TGF-β, IGF-I, TNF-α and IL-8 in serum and peritoneal fluid in endometriosis group were significantly higher than those in the controls (P<0.05), moreover, the levels of the markers in peritoneal fluid were significantly higher than those in serum (P<0.05). Conclusion: It is likely that elevation of serum and peritoneal fluid levels of the markers may play a role in the pathogenesis of endometriosis. (authors)

  2. 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.

  3. 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.

  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. Dynamic sea level changes following changes in the thermohaline circulation

    Energy Technology Data Exchange (ETDEWEB)

    Levermann, Anders; Griesel, Alexa; Hofmann, Matthias; Rahmstorf, Stefan [Potsdam Institute for Climate Impact Research, Potsdam (Germany); Montoya, Marisa [Universidad Complutense de Madrid, Facultad de Ciencias Fisicas, Madrid (Spain)

    2005-03-01

    Using the coupled climate model CLIMBER-3{alpha}, 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 {proportional_to}1 m, 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. (orig.)

  6. 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.

  7. 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

  8. 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)

  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. Dynamic sea level changes following changes in the thermohaline circulation

    OpenAIRE

    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 chang...

  11. Relationship of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) gene polymorphism with the susceptibility to development of prostate cancer and influence on serum levels of IGF-I, and IGFBP-3.

    Science.gov (United States)

    Safarinejad, Mohammad Reza; Shafiei, Nayyer; Safarinejad, Shiva

    2011-06-01

    The bioavailability of IGF-I is controlled by the binding protein, IGF binding protein-3 (IGFBP-3). In addition, IGFBP-3 is a strong anti-proliferative protein that provokes apoptosis and inhibits cell proliferation in prostate cancer. We conducted this study to investigate the association between IGFBP-3 gene polymorphism and serum levels of IGF-I and IGFBP-3 and the incidence of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). DNA isolation was performed in peripheral blood samples obtained from all participants. Required areas were amplified with polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique by using proper primers belonging to this gene area. We also measured serum IGF-I and IGFBP-3 levels. The IGFBP-3 -202 A/C polymorphism genotype frequencies showed a significant difference between PCa patients and controls (χ(2)=6.27, df=2.0, P=0.026), as well as between BPH patients and controls (χ(2)=11.57, df=4.0, P=0.014). The AA genotype frequency was significantly decreased in PCa and BPH patients compared to control group and the risk of PCa and BPH occurrence of this genotype was decreased accordingly (PCa; OR=0.28, 95% CI=0.17-0.44, P=0.0001; BPH: OR=0.48, 95% CI=0.29-0.77, P=0.001). Age-adjusted mean serum IGFBP-3 concentrations were highest in the individuals with the AA genotype and diminished significantly in a stepwise manner in the presence of 1 or 2 copies of the C allele (4577 ng/ml, 3929 ng/ml and 3349 ng/ml, respectively). Patients with PCa and BPH had lower serum IGF-1 (P=0.001, and P=0.01, respectively) and IGFBP-3 levels (P=0.001, and P=0.01, respectively) compared with controls. The AA genotype at IGFBP-3 gene polymorphism is associated with reduced risks of PCa and BPH. Both IGF-I and IGFBP-3 concentrations, are associated with modified risks of PCa and BPH. PMID:21536469

  12. 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

  13. Upper-level circulation in the South Atlantic Ocean

    Science.gov (United States)

    Peterson, Ray G.; Stramma, Lothar

    In this paper we present a literature survey of the South Atlantic's climate and its oceanic upper-layer circulation and meridional heat transport. The opening section deals with climate and is focused upon those elements having greatest oceanic relevance, i.e., distributions of atmospheric sea level pressure, the wind fields they produce, and the net surface energy fluxes. The various geostrophic currents comprising the upper-level general circulation are then reviewed in a manner organized around the subtropical gyre, beginning off southern Africa with the Agulhas Current Retroflection and then progressing to the Benguela Current, the equatorial current system and circulation in the Angola Basin, the large-scale variability adn interannual warmings at low latitudes, the Brazil Current, the South Atlantic Current, and finally to the Antarctic Circumpolar Current system in which the Falkland (Malvinas) Current is included. A summary of estimates of the meridional heat transport at various latitudes in the South Atlantic ends the survey.

  14. 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

  15. 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...

  16. Effect of oral alpha-tocopherol and zinc on plasma status, IGF-I levels, weight gain and immune response in young calves

    DEFF Research Database (Denmark)

    Sehested, J.; Jørgensen, C.; Mortensen, S.B.; Jensen, S.K.; Vestergaard, M.; Koch, P.; Jungersen, Gregers; Eriksen, Lizzie

    Thirty newborn calves were supplemented with a-tocopherol (vit. E) (n = 10), zinc (Zn) (n = 10) or nothing (control) (n = 10) for 8 weeks. All calves were vaccinated against tetanus at week 5. Plasma Zn and cc-tocopherol were significantly increased in the Zn and vit. E groups, respectively. Plasma...... IGF-I levels generally increased from birth to week 8, but were not affected by Zn or vit. E. Daily weight gain was highest in the Zn group, but this was not related to an increased IGF-I level. The vit. E group responded earlier than the Zn and control groups to the tetanus vaccination....

  17. 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.

  18. 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)

  19. Clinical significance of determination of serum NSE and plasma ET, IGF-II, CNP levels in patients with acute brain injury

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical significance of changes of plasma ET, IGF-II, CNP and serum NSE contents in patients with acute brain injury. Methods: Serum contents of neuron specific enolase (NSE) were measured with chemiluminescence immunoassay and plasma endothelin (ET), insulin-like growth factor-II (IGF-II) and C-type natriuretic peptide (CNP) were measured with radioimmunoassay in 30 patients with acute brain injury and 35 controls. Results: Serum contents of NSE and plasma IGF-II, CNP were not much different in patients with mild brain injury from those in controls (P >0.05), but plasma contents of ET were already significantly higher in patients with mild brain injury than those in controls(P < 0.01). The serum NSE and plasma ET levels in patients with moderate and severe brain injury were significantly higher than those in patients with mild brain injury and controls (P < 0.01). Decrease of plasma levels of IGF-II and CNP was not significant in patients with mild brain injury (vs controls). However, the plasma levels of IGF-II and CNP were significantly lower in patients with moderate and severe brain injury than those in patients with mild brain injury and controls (P <0.01). As a whole, the magnitude of changes of these parameters was proportional to the severity of the injury. Conclusion: Changes of serum NSE and plasma IGF-II, ET and CNP levels were closely related to the pathological process of brain injury. Determination of these parameters was of clinical importance for evaluation of the severity of injury and outcome prediction. (authors)

  20. 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

  1. 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....

  2. 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.

  3. 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

  4. 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

  5. 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...

  6. 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

  7. 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

  8. 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

  9. 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...

  10. 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

  11. 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)

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Elevated GH/IGF-I promotes mammary tumors in high-fat, but not low-fat, fed mice.

    Science.gov (United States)

    Gahete, Manuel D; Córdoba-Chacón, José; Lantvit, Daniel D; Ortega-Salas, Rosa; Sanchez-Sanchez, Rafael; Pérez-Jiménez, Francisco; López-Miranda, José; Swanson, Steven M; Castaño, Justo P; Luque, Raúl M; Kineman, Rhonda D

    2014-11-01

    Growth hormone (GH) and/or insulin-like growth factor I (IGF-I) are thought to promote breast cancer based on reports showing circulating IGF-I levels correlate, in epidemiological studies, with breast cancer risk. Also, mouse models with developmental GH/IGF-I deficiency/resistance are less susceptible to genetic- or chemical-induced mammary tumorigenesis. However, given the metabolic properties of GH, medical strategies have been considered to raise GH to improve body composition and metabolic function in elderly and obese patients. Since hyperlipidemia, inflammation, insulin resistance and obesity increase breast cancer risk, elevating GH may serve to exacerbate cancer progression. To better understand the role GH/IGF-I plays in tumor formation, this study used unique mouse models to determine if reducing GH/IGF-I in adults protects against 7,12-dimethylbenz[α]anthracene (DMBA)-induced mammary tumor development, and if moderate elevations in endogenous GH/IGF-I alter DMBA-induced tumorigenesis in mice fed a standard-chow diet or in mice with altered metabolic function due to high-fat feeding. We observed that adult-onset isolated GH-deficient mice, which also have reduced IGF-I levels, were less susceptible to DMBA-treatment. Specifically, fewer adult-onset isolated GH-deficient mice developed mammary tumors compared with GH-replete controls. In contrast, chow-fed mice with elevated endogenous GH/IGF-I (HiGH mice) were not more susceptible to DMBA-treatment. However, high-fat-fed, HiGH mice showed reduced tumor latency and increased tumor incidence compared with diet-matched controls. These results further support a role of GH/IGF-I in regulating mammary tumorigenesis but suggest the ultimate consequences of GH/IGF-I on breast tumor development are dependent on the diet and/or metabolic status. PMID:25085903

  17. 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。

  18. 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...

  19. 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...

  20. Dietary methionine level affects growth performance and hepatic gene expression of GH-IGF system and protein turnover regulators in rainbow trout (Oncorhynchus mykiss) fed plant protein-based diets

    DEFF Research Database (Denmark)

    Rolland, Marine; Dalsgaard, Anne Johanne Tang; Holm, Jorgen;

    2015-01-01

    ), cathepsin L, calpains 1 and 2 (Capn 1 and Capn 2, respectively), and calpastatin long and short isoforms (CAST-L and CAST-S, respectively) were measured for each dietary treatment. The transcript levels of GHR-I and IGF-I increased linearly with the increase of dietary Met content (P <0.01), reflecting...... somatotropic axis: including the growth hormone receptor I (GHR-I), insulin-like growth hormones land II (IGF-I and IGF-II, respectively), and insulin-like growth hormone binding protein-1b (IGFBP-1b); and ii) protein turnover: including the target of rapamycin protein (TOR), proteasome 20 delta (Prot 20D...... or indirectly, the expression of genes involved in the GH/IGF axis response and protein turnover, which are centrally involved in the regulation of growth. (C) 2014 Elsevier Inc. All rights reserved....

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

    OpenAIRE

    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

    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

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

    OpenAIRE

    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

    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 i...

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

    OpenAIRE

    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

    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 ident...

  4. Differential effects of IGF-1 deficiency during the life span on structural and biomechanical properties in the tibia of aged mice.

    Science.gov (United States)

    Ashpole, Nicole M; Herron, Jacquelyn C; Estep, Patrick N; Logan, Sreemathi; Hodges, Erik L; Yabluchanskiy, Andriy; Humphrey, Mary Beth; Sonntag, William E

    2016-04-01

    Advanced aging is associated with the loss of structural and biomechanical properties in bones, which increases the risk for bone fracture. Aging is also associated with reductions in circulating levels of the anabolic signaling hormone, insulin-like growth factor (IGF)-1. While the role of IGF-1 in bone development has been well characterized, the impact of the age-related loss of IGF-1 on bone aging remains controversial. Here, we describe the effects of reducing IGF-1 at multiple time points in the mouse life span--early in postnatal development, early adulthood, or late adulthood on tibia bone aging in both male and female igf (f/f) mice. Bone structure was analyzed at 27 months of age using microCT. We find that age-related reductions in cortical bone fraction, cortical thickness, and tissue mineral density were more pronounced when IGF-1 was reduced early in life and not in late adulthood. Three-point bone bending assays revealed that IGF-1 deficiency early in life resulted in reduced maximum force, maximum bending moment, and bone stiffness in aged males and females. The effects of IGF-1 on bone aging are microenvironment specific, as early-life loss of IGF-1 resulted in decreased cortical bone structure and strength along the diaphysis while significantly increasing trabecular bone fraction and trabecular number at the proximal metaphysis. The increases in trabecular bone were limited to males, as early-life loss of IGF-1 did not alter bone fraction or number in females. Together, our data suggest that the age-related loss of IGF-1 influences tibia bone aging in a sex-specific, microenvironment-specific, and time-dependent manner. PMID:26968399

  5. Hyperoxia exposure induced hormesis decreases mitochondrial superoxide radical levels via Ins/IGF-1 signaling pathway in a long-lived age-1 mutant of Caenorhabditis elegans

    International Nuclear Information System (INIS)

    The hormetic effect, which extends the lifespan by various stressors, has been confirmed in Caenorhabditis elegans (C. elegans). We have previously reported that oxidative stress resistance in a long-lived mutant age-1 is associated with the hormesis. In the age-1 allele, which activates an insulin/insulin-like growth factor-1 (Ins/IGF-1) signaling pathway, the superoxide dismutase (SOD) and catalase activities increased during normal aging. We now demonstrate changes in the mitochondrial superoxide radical (O2-) levels of the hormetic conditioned age-related strains. The O2- levels in age-1 strain significantly decreased after intermittent hyperoxia exposure. On the other hand, this phenomenon was not observed in a daf-16 null mutant. This hormesis-dependent reduction of the O2- levels was observed even if the mitochondrial Mn-SOD was experimentally reduced. Therefore, it is indicated that the hormesis is mediated by events that suppress the mitochondrial O2- production. Moreover, some SOD gene expressions in the hormetic conditioned age-1 mutant were induced over steady state messenger ribonucleic acid (mRNA) levels. These data suggest that oxidative stress-inducible hormesis is associated with a reduction of the mitochondrial O2- production by activation of the antioxidant system via the Ins/IGF-1 signaling pathway. (author)

  6. The nutritional quality of an infant food from quinoa and its effect on the plasma level of insulin-like growth factor-1 (IGF-1) in undernourished children.

    Science.gov (United States)

    Ruales, Jenny; de Grijalva, Yolanda; Lopez-Jaramillo, Patricio; Nair, Baboo M

    2002-03-01

    An infant food product was manufactured by drum drying a pre-cooked slurry of quinoa (Chenopodium quinoa, Willd) flour. The chemical composition shows that the product is a potential source of valuable nutrients, like protein (16%), vitamin E (19 mg/kg), thiamine (0.7 mg/100 g), iron (70 mg/kg), zinc (48 mg/kg) and magnesium (1.8 g/kg), all the values expressed on dry basis, to pre-school children (of 5 years of age). The animal feeding experiments with rats showed a net protein utilisation (NPU) of 68, digestibility (TD) 95 and biological value (BV) 71. The level of insulin-like growth factor-1 (IGF-1) in the plasma of the children who consumed a supplementary portion of 2 x 100 g of the above infant food product showed an increase after a period of 15 days, while the plasma level of IGF-1 in the children of the control group as well as the reference group did not show any significant increase. PMID:11939108

  7. IGF and IGF-binding protein expression in the growth plate of normal, dexamethasone-treated and human IGF-II transgenic mice.

    Science.gov (United States)

    Smink, J J; Koster, J G; Gresnigt, M G; Rooman, R; Koedam, J A; Van Buul-Offers, S C

    2002-10-01

    Glucocorticoid (GC) treatment in childhood can lead to suppression of longitudinal growth as a side effect. The actions of GCs are thought to be mediated in part by impaired action of the insulin-like growth factors (IGF-I and IGF-II) and their binding proteins (IGFBP-1 to -6). We have studied the effects of GCs on IGF and IGFBP expression at the local level of the growth plate, using non-radioactive in situ hybridization. We treated 3-week-old normal mice for 4 weeks with dexamethasone (DXM). We also treated human IGF-II (hIGF-II) transgenic mice in order to investigate whether IGF-II could protect against the growth retarding effect of this GC. DXM treatment resulted in general growth retardation in both mice strains, however, only in normal mice was tibial length decreased. In both normal and hIGF-II trangenic mice, the total width of the growth plate was not affected, whereas the width of the proliferative zone decreased as a result of the DXM treatment. Additionally, only in normal mice, the width of the hypertrophic zone thickened. Only expression of IGF-I, IGF-II and IGFBP-2 could be detected in the growth plates of 7-week-old normal mice. IGFBP-1, -3, -4, -5 and -6 mRNAs were not detected. DXM treatment of normal mice induced a significant 2.4-fold increase in the number of cells expressing IGF-I mRNA, whereas IGF-II and IGFBP-2 mRNA levels were not affected. In hIGF-II transgenic mice, IGF-I mRNA levels were significantly increased, while endogenous IGF-II and IGFBP-2 mRNAs were unaffected, compared to normal animals. DXM treatment of the hIGF-II transgenic mice induced a further increase of IGF-I mRNA expression, to a similar extent as in DXM-treated normal mice. The increase of IGF-I due to DXM treatment in normal mice might be a reaction in order to minimize the GC-induced growth retardation. Another possibility could be that the increase of IGF-I would contribute to the GC-induced growth retardation by accelerating the differentiation of chondrocytes

  8. 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

  9. 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...... of OCT on the IGF system could have therapeutical implications in diabetes mellitus, cardiovascular disease, and certain malignancies in which IGF-I might be involved. The aim of this study was to examine possible GH-independent effects of OCT on IGF components in humans. Six GH-deficient (GHD......) patients were studied for 24 h after each of the following treatment regimens (each of 1 weeks duration): (a) daily s.c. GH injection (2 IU/m(2)); (b) as (a) + continuous s.c. infusion of OCT (200 microg/24 h) by means of a portable pump (Nordic Infuser); (c) no treatment. Serum GH binding protein (GHBP...

  10. Pituitary and hypothalamic insulin-like growth factor-I (IGF-I) and IGF-I receptor expression in food-deprived rats.

    Science.gov (United States)

    Olchovsky, D; Song, J; Gelato, M C; Sherwood, J; Spatola, E; Bruno, J F; Berelowitz, M

    1993-06-01

    The present study was designed to evaluate a possible role for the insulin-like growth factor-I (IGF-I) system in mediating the suppression of growth hormone (GH) secretion observed in food-deprived rats by measuring IGF-I mRNA, receptor concentration and receptor mRNA in neuroendocrine tissues (hypothalamus and pituitary). Rats were deprived of food (food-deprived) for 72 h or had free access to food (fed). Tissues were processed for measurement of steady-state levels of: (a) IGF-I and IGF-I receptor mRNA (by solution hybridization/RNase protection assay); (b) IGF-I in serum and tissue extracts (by RIA) and (c) IGF-I displaceable [125I]IGF-I binding to plasma membrane preparations. Food deprivation resulted in decreased serum and liver levels of IGF-I. Kidney IGF-I mRNA levels were reduced 80% in food-deprived rats with a concomitant increase in IGF-I receptor concentration and mRNA levels. Refeeding of food-deprived rats fully normalized these perturbations. Pituitary IGF-I content was reduced 50% in food-deprived rats while IGF-I mRNA levels were unaffected. A modest increase was seen in pituitary IGF-I receptor concentration; however, IGF-I receptor mRNA levels were not changed. Hypothalamic IGF-I mRNA content was reduced in 72 h food-deprived rats while IGF-I receptor binding capacity and mRNA were unaffected. In conclusion, IGF-I mRNA levels are decreased in liver, kidney and hypothalamus together with a reduction in plasma IGF-I in food-deprived rats but is unaffected in anterior pituitary. IGF-I receptor gene expression and binding capacity are coordinately regulated in kidney and hypothalamus, but not in the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8349028

  11. 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; Laursen, Torben; Møller, Jens; Weeke, Jørgen; Jørgensen, Jens Otto Lunde; Christiansen, Jens Sandahl; Ørskov, Hans

    2000-01-01

    Abstract OBJECTIVE: It is generally accepted that there is no clinically significant circadian variation in total insulin-like growth factor (IGF)-I or total IGF-II in healthy subjects. In contrast there is a significant nocturnal decrease in free IGF-I in healthy subjects, corresponding 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 with...... a slow-release formulation of octreotide. Seven GH-deficient patients were studied without GH replacement. In addition 5 of the GH-deficient patients were studied during GH replacement. DESIGN: Serum samples were obtained every hour for 24 h. Free IGF-I and IGF-II were measured every 2nd hour. Total...

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. Circulating Irisin Levels Are Positively Associated with Metabolic Risk Factors in Sedentary Subjects

    OpenAIRE

    Moreno, María; Moreno-Navarrete, José María; Serrano, Marta; Ortega, Francisco; Delgado, Elías; Sanchez-Ragnarsson, Cecilia; Valdés, Sergio; Botas, Patricia; Ricart, Wifredo; Fernández-Real, José Manuel

    2015-01-01

    Introduction A physically active life-style plays an independent role in the protection against type 2 diabetes and cardiovascular diseases. Irisin, a novel exercise-induced myokine, activates thermogenesis in rodents through increasing beige fat cells abundance within white fat. We aimed to investigate circulating irisin levels in association with the degree of physical activity and various metabolic parameters in humans. Methods Circulating irisin levels (ELISA) and metabolic parameters wer...

  2. A Human Variant of Glucose-Regulated Protein 94 That Inefficiently Supports IGF Production.

    Science.gov (United States)

    Marzec, Michal; Hawkes, Colin P; Eletto, Davide; Boyle, Sarah; Rosenfeld, Ron; Hwa, Vivian; Wit, Jan M; van Duyvenvoorde, Hermine A; Oostdijk, Wilma; Losekoot, Monique; Pedersen, Oluf; Yeap, Bu Beng; Flicker, Leon; Barzilai, Nir; Atzmon, Gil; Grimberg, Adda; Argon, Yair

    2016-05-01

    IGFs are critical for normal intrauterine and childhood growth and sustaining health throughout life. We showed previously that the production of IGF-1 and IGF-2 requires interaction with the chaperone glucose-regulated protein 94 (GRP94) and that the amount of secreted IGFs is proportional to the GRP94 activity. Therefore, we tested the hypothesis that functional polymorphisms of human GRP94 affect IGF production and thereby human health. We describe a hypomorphic variant of human GRP94, P300L, whose heterozygous carriers have 9% lower circulating IGF-1 concentration. P300L was found first in a child with primary IGF deficiency and was later shown to be a noncommon single-nucleotide polymorphism with frequencies of 1%-4% in various populations. When tested in the grp94(-/-) cell-based complementation assay, P300L supported only approximately 58% of IGF secretion relative to wild-type GRP94. Furthermore, recombinant P300L showed impaired nucleotide binding activity. These in vitro data strongly support a causal relationship between the GRP94 variant and the decreased concentration of circulating IGF-1, as observed in human carriers of P300L. Thus, mutations in GRP94 that affect its IGF chaperone activity represent a novel causal genetic mechanism that limits IGF biosynthesis, quite a distinct mechanism from the known genes in the GH/IGF signaling network. PMID:26982636

  3. 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

  4. 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

    sitting height, serum levels of reproductive hormones, IGF-I, and IGFBP-3 were measured. RESULTS: In boys with 47,XXY and 47,XYY karyotypes, growth was accelerated already in childhood, compared with healthy boys. 46,XX-males were significantly shorter than healthy boys but matched the stature of healthy...... girls. In 47,XXY sitting height to height ratios were lower than expected, whereas body proportions in 46,XX-males and 47,XYY were normal. In all subjects serum levels of IGF-I and IGFBP-3 were within normal limits. The boys with 46,XX and 47,XXY karyotypes presented with low normal testosterone and...... elevated LH levels after puberty, whereas the sex hormone secretion of the 47,XYY boys remained normal. CONCLUSION: We found accelerated growth in early childhood in boys with 47,XXY and 47,XYY karyotypes, whereas 46,XX-males were shorter than controls. These abnormal growth patterns were not reflected in...

  5. Circulating MKRN3 levels decline during puberty in healthy boys

    DEFF Research Database (Denmark)

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

    2016-01-01

    .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...

  6. Venus: cloud level circulation during 1982 as determined from Pioneer cloud photopolarimeter images. 11. Solar longitude dependent circulation

    International Nuclear Information System (INIS)

    Pioneer Venus Orbiter images obtained in 1982 indicate a marked solar-locked dependence of cloud level circulation in both averaged cloud motions and cloud layer UV reflectivity. An apparent relationship is noted between horizontal divergence and UV reflectivity: the highest reflectivities are associated with regions of convergence at high latitudes, while lower values are associated with equatorial latitude regions where the motions are divergent. In solar-locked coordinates, the rms deviation of normalized UV brightness is higher at 45-deg latitudes than in equatorial regions. 37 references

  7. 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. PMID:26628272

  8. 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...

  9. 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

  10. 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.

  11. 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....... 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...

  12. 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

  13. 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.

  14. 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

  15. 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 ...

  16. 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

  17. Circulating soluble Fas levels and risk of ovarian cancer

    International Nuclear Information System (INIS)

    Dysregulation of apoptosis, specifically overexpression of soluble Fas (sFas), has been proposed to play a role in the development of ovarian cancer. The main objective of the present study was to evaluate serum sFas as a potential biomarker of ovarian cancer risk. The association between serum sFas levels and the risk of ovarian cancer was examined in a case-control study nested within three prospective cohorts in New York (USA), Umeå (Sweden), and Milan (Italy). Case subjects were 138 women with primary invasive epithelial ovarian cancer diagnosed between 2 months and 13.2 years after the initial blood donation. Control subjects were 263 women who were free of cancer, and matched the case on cohort, menopausal status, age, and enrollment date. Serum sFas levels were determined using a quantitative sandwich enzyme immunoassay. Serum sFas levels were similar in women subsequently diagnosed with ovarian cancer (median, 6.5 ng/mL; range, 4.4 – 10.2) and in controls (median, 6.8 ng/mL; range, 4.5 – 10.1). Statistically significant trends of increasing serum sFas with age were observed among cases (r = 0.39, p < 0.0001) and controls (r = 0.42, p < 0.0001). Compared to women in the lowest third, women in the highest third of serum sFas were not at increased risk of ovarian cancer after adjustment for potential confounders (odd ratio (OR), 0.87; 95% confidence interval (CI), 0.42 – 1.82). The results suggest that serum sFas may not be a suitable marker for identification of women at increased risk of ovarian cancer

  18. 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

  19. 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.

  20. 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

  1. 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...

  2. Effects of space flight and IGF-1 on immune function

    Science.gov (United States)

    1999-01-01

    We tested the hypothesis that insulin-like growth factor-1 (IGF-1) would ameliorate space flight-induced effects on the immune system. Twelve male, Sprague-Dawley rats, surgically implanted with mini osmotic pumps, were subjected to space flight for 10 days on STS-77. Six rats received 10 mg/kg/day of IGF-1 and 6 rats received saline. Flight animals had a lymphocytopenia and granulocytosis which were reversed by IGF-1. Flight animals had significantly higher corticosterone levels than ground controls but IGF-1 did not impact this stress hormone. Therefore, the reversed granulocytosis did not correlate with serum corticosterone. Space flight and IGF-1 also combined to induce a monocytopenia that was not evident in ground control animals treated with IGF-1 or in animals subjected to space flight but given physiological saline. There was a significant increase in spleen weights in vivarium animals treated with IGF-1, however, this change did not occur in flight animals. We observed reduced agonist-induced lymph node cell proliferation by cells from flight animals compared to ground controls. The reduced proliferation was not augmented by IGF-1 treatment. There was enhanced secretion of TNF, IL-6 and NO by flight-animal peritoneal macrophages compared to vivarium controls, however, O2- secretion was not affected. These data suggest that IGF-1 can ameliorate some of the effects of space flight but that space flight can also impact the normal response to IGF-1.

  3. Prolonged Fasting reduces IGF-1/PKA to promote hematopoietic stem cell-based regeneration and reverse immunosuppression

    OpenAIRE

    Cheng, Chia-Wei; Adams, Gregor B.; Perin, Laura; Wei, Min; Zhou, Xiaoying; Lam, Ben S.; Da Sacco, Stefano; Mirisola, Mario; Quinn, David I.; Dorff, Tanya B.; Kopchick, John J.; Longo, Valter D.

    2014-01-01

    Immune system defects are at the center of aging and a range of diseases. Here we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSC) and niche cells that promote stress resistance, self-renewal and lineage-balanced regeneration. Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy, and reversed age-dependent myelo...

  4. 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

  5. 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...

  6. Decreased circulating endothelial progenitor cell levels and function in patients with nonalcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Chia-Hung Chiang

    Full Text Available OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD is associated with advanced atherosclerosis and a higher risk of cardiovascular disease. Increasing evidence suggests that injured endothelial monolayer is regenerated by circulating bone marrow derived-endothelial progenitor cells (EPCs, and levels of circulating EPCs reflect vascular repair capacity. However, the relation between NAFLD and EPC remains unclear. Here, we tested the hypothesis that patients with nonalcoholic fatty liver disease (NAFLD might have decreased endothelial progenitor cell (EPC levels and attenuated EPC function. METHODS AND RESULTS: A total of 312 consecutive patients undergoing elective coronary angiography because of suspected coronary artery disease were screened and received examinations of abdominal ultrasonography between July 2009 and November 2010. Finally, 34 patients with an ultrasonographic diagnosis of NAFLD, and 68 age- and sex-matched controls without NAFLD were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34(+, CD34(+KDR(+, and CD34(+KDR(+CD133(+ in peripheral blood samples was used to assess circulating EPC numbers. The adhesive function, and migration, and tube formation capacities of EPCs were also determined in NAFLD patients and controls. Patients with NAFLD had a significantly higher incidence of metabolic syndrome, previous myocardial infarction, hyperuricemia, and higher waist circumference, body mass index, fasting glucose and triglyceride levels. In addition, patients with NAFLD had significantly decreased circulating EPC levels (all P<0.05, attenuated EPC functions, and enhanced systemic inflammation compared to controls. Multivariate logistic regression analysis showed that circulating EPC level (CD34(+KDR(+ [cells/10(5 events] was an independent reverse predictor of NAFLD (Odds ratio: 0.78; 95% confidence interval: 0.69-0.89, P<0.001. CONCLUSIONS: NAFLD patients have decreased circulating EPC numbers and

  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

    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).

  8. Early programming of the IGF-I axis

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  9. Rubella-associated arthritis. II. Relationship between circulating immune complex levels and joint manifestations.

    OpenAIRE

    Singh, V. K.; Tingle, A J; Schulzer, M

    1986-01-01

    The role played by raised circulating immune complex (CIC) levels in the pathogenesis of rubella-associated joint reactions has been assessed during the course of RA 27/3 rubella immunisation and epidemic wild rubella infection. CIC levels were evaluated by C1q microplate enzyme-linked immunosorbent assay (ELISA) and Raji cell ELISA techniques. Mean CIC levels were generally higher both before and after immunisation among individuals developing vaccine-associated arthritis than among those de...

  10. Variability in Solomon Sea circulation derived from altimeter sea level data

    OpenAIRE

    A. Melet; Gourdeau, Lionel; J. Verron

    2010-01-01

    The Solomon Sea is a key region in the Pacific Ocean where equatorial and subtropical circulations are connected. The region exhibits the highest levels in sea level variability in the entire south tropical Pacific Ocean. Altimeter data was utilized to explore sea level and western boundary currents in this poorly understood portion of the ocean. Since the geography of the region is extremely intricate, with numerous islands and complex bathymetry, specifically reprocessed along-track data in...

  11. 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.

  12. Serum IGF-1 Concentrations Change With Soy and Seaweed Supplements in Healthy Postmenopausal American Women

    OpenAIRE

    Teas, Jane; Irhimeh, Mohammad R; Druker, Susan; Hurley, Thomas G.; Hébert, James R.; Savarese, Todd M.; Kurzer, Mindy S

    2011-01-01

    Insulin-like growth factor 1 (IGF-1) is an anabolic hormone important for growth and development. However, high-circulating serum concentrations in adults are associated with increased risk of postmenopausal breast cancer. Nutritional status and specific foods influence serum IGF-1 concentrations. Breast cancer incidence is typically low in Asian countries where soy is commonly consumed. Paradoxically, soy supplement trials in American women have reported significant increases in IGF-1. Seawe...

  13. 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.

  14. 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.

  15. 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.

  16. The Dependence of the Low-Level Equatorial Easterly Jet on Hadley and Walker Circulations.

    Science.gov (United States)

    Battisti, David S.; Ovens, David D.

    1995-11-01

    How the time-mean Hadley and Walker circulations affect the formation of a low-level equatorial easterly jet is investigated. Experiments are conducted for equinoctial conditions using a general circulation model, the Community Climate Model (CCM1), that includes a Kuo convective scheme and a lower boundary that is specified to be water at a fixed sea surface temperature (SST). Several zonally symmetric SST forcings are used to determine how various Hadley circulations affect the tropical zonal wind field. A zonal wavenumber one equatorial SST anomaly superimposed on a zonally symmetric SST distribution forces a wind field that includes both Hadley and Walker circulations.The Hadley circulation experiments produce equatorial easterlies and low-level jets on the poleward sides of the intertropical convergence zone (ITCZ) 10° to 15° from the equator. In an experiment with a single, dominant off-equatorial ITCZ in the Northern Hemisphere, the Southern Hemisphere jet moves to within 7.5° of the equator; yet none of the Hadley circulation cases produce a low-level easterly jet on the equator because they lack a mechanism to vertically confine the flow.The experiment that includes a zonally overturning cell on the equator produces a low-level equatorial easterly jet in the cold tongue region that is similar to the observed jet over the central to eastern Pacific. That case shows that east of the equatorial warm pool the Walker circulation and its induced Kelvin wave response provide the necessary upper-level westerly flow and subsidence to vertically confine the low-level easterlies into a jet. Spring and fall climatological runs of the CCMI with land surfaces, seasonally varying SSTs and insolation, and a moist convective adjustment scheme support the hypothesis that the Walker circulation provides the vertical confinement necessary to form a low-level equatorial easterly jet in the region east of the equatorial convective center, regardless of the Hadley circulation

  17. Analysis of circulating hem-endothelial marker RNA levels in preterm infants

    Directory of Open Access Journals (Sweden)

    Kuint Jacob

    2009-06-01

    Full Text Available Abstract Background Circulating endothelial cells may serve as novel markers of angiogenesis. These include a subset of hem-endothelial progenitor cells that play a vital role in vascular growth and repair. The presence and clinical implications of circulating RNA levels as an expression for hematopoietic and endothelial-specific markers have not been previously evaluated in preterm infants. This study aims to determine circulating RNA levels of hem-endothelial marker genes in peripheral blood of preterm infants and begin to correlate these findings with prenatal complications. Methods Peripheral blood samples from seventeen preterm neonates were analyzed at three consecutive post-delivery time points (day 3–5, 10–15 and 30. Using quantitative reverse transcription-polymerase chain reaction we studied the expression patterns of previously established hem-endothelial-specific progenitor-associated genes (AC133, Tie-2, Flk-1 (VEGFR2 and Scl/Tal1 in association with characteristics of prematurity and preterm morbidity. Results Circulating Tie-2 and SCL/Tal1 RNA levels displayed an inverse correlation to gestational age (GA. We observed significantly elevated Tie-2 levels in preterm infants born to mothers with amnionitis, and in infants with sustained brain echogenicity on brain sonography. Other markers showed similar expression patterns yet we could not demonstrate statistically significant correlations. Conclusion These preliminary findings suggest that circulating RNA levels especially Tie2 and SCL decline with maturation and might relate to some preterm complication. Further prospective follow up of larger cohorts are required to establish this association.

  18. 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

  19. 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

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

    Directory of Open Access Journals (Sweden)

    HenrykUrbanski

    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.

  1. 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.

  2. Effect of the sea breeze circulation on surface ozone levels at Wallops Island, Virginia

    International Nuclear Information System (INIS)

    Surface measurements of windspeed, direction, and ozone concentration collected at Walloops Island, Virginia, during the summers of 1977 and 1978 are analyzed to study the effects of the dominant mesoscale sea breeze circulation on th local photochemical oxidant levels. A bimodality in the atmospheric dynamics is linked to systematic variations in ozone concentration. It is concluded that during certain phases of the two circulation modes, increased wind speed reduces the resistance of the earth's surface to the deposition of ozone, and decreased ozone concentration levels result. For other phases, light wind occur, signifying high resistance to deposition and high ozone levels. This modulation by the local dynamics is a major impediment for pollutant studies in coastal environments, especially those centering on transport, because it tends to mask other processes that may be occurring

  3. The effect of the sea breeze circulation on surface ozone levels at Wallops Island, Virginia

    Science.gov (United States)

    Parsons, C. L.; Williams, M. E.

    1979-01-01

    Surface measurements of windspeed, direction, and ozone concentration collected at Wallops Island, Virginia, during the summers of 1977 and 1978 are analyzed to study the effects of the dominant mesoscale sea breeze circulation on the local photochemical oxidant levels. A bimodality in the atmospheric dynamics is linked to systematic variations in ozone concentration. It is concluded that during certain phases of the two circulation modes, increased wind speed reduces the resistance of the earth's surface to the deposition of ozone, and decreased ozone concentration levels result. For other phases, light winds occur, signifying high resistance to deposition and high ozone levels. This modulation by the local dynamics is a major impediment for pollutant studies in coastal environments, especially those centering on transport, because it tends to mask other processes that may be occurring.

  4. 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....

  5. 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...

  6. 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...... 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 <0.05). Circulating adrenaline was independently associated with 30...

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

    OpenAIRE

    Akahori, Yoichiro; Takamoto, Norio; Masumoto,Akio; Inoue,Seiji; Nakatsukasa, Hideki; MASUYAMA, HISASHI; Hiramatsu,Yuji

    2010-01-01

    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 w...

  8. 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...

  9. 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...

  10. 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.

  11. 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

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

    Science.gov (United States)

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

    1999-12-01

    A three-dimensional, fully non-linear semi-diagnostic (adaptation) model is described. This model is used to compute the climatological mean circulation and to understand the role of local, steady forcing of the wind and thermohaline forcing on the observed circulation in the western tropical Indian Ocean. The model consists of equations of motion and continuity, sea surface topography, equations of state and temperature, and salinity diffusion equations. While the sea surface topography equation is solved by a successive overrelaxation technique, the other model equations are solved by a leap-frog numerical scheme. Two versions of the model, having 18 and 33 levels in the vertical direction, were prepared to study climatological mean circulation in the western tropical Indian Ocean. The first numerical experiment is carried out with the 18-level adaptation model to study the sensitivity of the solution to different values of eddy coefficients. The main scientific rationale behind these numerical experiments was to obtain the most appropriate values of the eddy coefficients for the realistic computation of climatological circulation in the western tropical Indian Ocean. Three numerical experiments were conducted for the month of February to understand the sensitivity of the model solution to different eddy coefficients. The model reproduced the circulation features during February, even with low values of horizontal and vertical eddy coefficients. In the second experiment, the adaptation model, with 33 levels in the vertical direction, is applied to study the seasonal mean climatological circulation at selected depths during Spring in the western tropical Indian Ocean. Adapted (steady state) results of currents, sea surface topography, temperature and salinity anomaly fields are presented. Reasonable agreement is obtained between the model results on currents and the observational data. The computed anomaly fields for temperature and salinity at selected depths

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. 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.

  16. High levels of circulating extracellular vesicles with altered expression and function during pregnancy.

    Science.gov (United States)

    Nardi, Fabiola da Silva; Michelon, Tatiana Ferreira; Neumann, Jorge; Manvailer, Luis Felipe Santos; Wagner, Bettina; Horn, Peter A; Bicalho, Maria da Graça; Rebmann, Vera

    2016-07-01

    Extracellular vesicles (EVs) are widely considered important modulators of cell-cell communication and may interact with target cells locally and on a systemic level. Several studies had shown that circulating EVs' levels are increased during pregnancy. However, EVs characteristics, composition and biological functions in pregnancy still need to be clarified. This study aims to determine if circulating EVs during pregnancy are modified regarding levels, markers and cytokine profile as well as their reactivity towards peripheral blood cells. 26 pregnant women (PW) being in the second gestational trimester and 59 non-pregnant women (NPW) were investigated. EVs enrichment was performed by ExoQuick™ or ultracentrifugation; nanoparticle tracking analysis, SDS-PAGE followed by Western Blotting and densitometry, and IFN-γ, IL-10 and TGF-β1 ELISA for EVs characterization; imaging flow cytometry to analyze EVs' uptake by peripheral blood cells and flow cytometry were performed to analyze EVs function regarding induction of caspase-3 activity. Circulating EVs' levels were increased during pregnancy [26.9×10(6)EVs/ml (range: 6.4-46.3); p=0.003] vs NPW [18.9×10(6)EVs/ml (range: 2.5-61.3)]. Importantly, the immunosuppressive TGF-β1 and IL-10 cytokine cargo were increased in EVs of PW even after normalization to 1 million EVs [TGF-β1: 0.25pg/10(6)EVs (range: 0.0-2.0); p<0.0001] and [IL-10: 0.21pg/10(6)EVs (range: 0.0-16.8); p=0.006] vs NPW. Although EVs derived from non-pregnant and pregnant women were taken up by NK cells, the latter exclusively enhanced the caspase-3 activity in CD56(dim) NK cells (8.2±0.9; p=0.02). The qualitative and quantitative pregnancy-related alterations of circulating EVs provide first hints for an immune modulating role of circulating EVs during pregnancy. PMID:27005781

  17. 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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    INTRODUCTION: GH activity may be involved in male reproductive function. A common genetic polymorphism in the gene encoding the GH receptor (GHR) results in deletion of the entire exon 3 sequence (GHRd3 isoform). The short GHRd3/d3 isoform seems more sensitive compared with full-length receptors...... (GHRfl/fl). AIM: TO INVESTIGATE THE ASSOCIATIONS BETWEEN GH ACTIVITY, EVALUATED BY EXON 3 GHR POLYMORPHISM, AND SERUM IGF1 VS REPRODUCTIVE HORMONES, SEMEN QUALITY, AND PRE- AND POSTNATAL GROWTH IN HEALTHY YOUNG MALES (N=838, MEAN AGE: 19.4 years). RESULTS: Compared with GHRfl/fl homozygous individuals (n...... genotype and serum IGF1 were not associated with size at birth or final height. CONCLUSIONS: GHRd3 polymorphism seemed only to have a weak influence on male reproductive function of borderline significance. The sensitive GHRd3/d3 genotype may slightly increase testicular function, as evaluated by semen...

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

    2016-06-01

    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

  3. 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

  4. 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.

  5. 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...

  6. Circulating endothelin-1 levels in obese patients with the metabolic syndrome.

    Science.gov (United States)

    Ferri, C; Bellini, C; Desideri, G; Baldoncini, R; Properzi, G; Santucci, A; De Mattia, G

    1997-01-01

    We evaluated venous plasma ET-1 concentrations in 18 never-treated obese men (body mass index 31.0 +/- 0.5 kg/m2; age 45.4 +/- 4.3 years) showing the whole features of the above syndrome and 12 control men (age 44.1 +/- 3.6 years). Circulating ET-1 levels were significantly higher in patients than in controls (p < 0.05), and were directly correlated with fasting insulin levels (r = 0.564, p = 0.015) and erythrocyte Na+/Li+ counter-transport activity (r = 0.504, p = 0.033). In conclusion, venous plasma ET-1 levels are elevated in obese men manifesting the whole features of the metabolic syndrome. Due to the biological properties of ET-1, our findings suggest the peptide as a further component of the cluster of cardiovascular risk factors which characterizes this syndrome. PMID:9288542

  7. 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).

  8. Sensitivity of Red Sea circulation to sea level and insolation forcing during the last interglacial

    Directory of Open Access Journals (Sweden)

    G. Trommer

    2011-04-01

    Full Text Available This study investigates the response of Red Sea circulation to sea level and insolation changes during termination II and across the last interglacial, in comparison with termination I and the Holocene. Sediment cores from the central and northern part of the Red Sea were investigated by micropaleontological and geochemical proxies. The recovery of the planktonic foraminiferal fauna following high salinities during MIS 6 took place at similar sea-level stand (~50 m below present day, and with a similar species succession, as during termination I. This indicates a consistent sensitivity of the basin oceanography and the plankton ecology to sea-level forcing. Based on planktonic foraminifera, we find that increased water exchange with the Gulf of Aden especially occurred during the sea-level highstand of interglacial MIS 5e. From MIS 6 to the peak of MIS 5e, northern Red Sea SST increased from 21 °C to 25 °C, with about 3 °C of this increase taking place during termination II. Changes in planktonic foraminiferal assemblages indicate that the development of the Red Sea oceanography during MIS 5 was strongly determined by insolation and monsoon strength. The SW Monsoon summer circulation mode was enhanced during the termination, causing low productivity in northern central Red Sea core KL9, marked by high abundance of G. sacculifer, which – as in the Holocene – followed summer insolation. Core KL11 records the northern tip of the intruding intermediate water layer from the Gulf of Aden and its planktonic foraminifera fauna shows evidence for elevated productivity during the sea-level highstand in the southern central Red Sea. By the time of MIS 5 sea-level regression, elevated organic biomarker BIT values suggest denudation of soil organic matter into the Red Sea and high abundances of G. glutinata, and high reconstructed chlorophyll-a values, indicate an intensified NE Monsoon winter circulation mode. Our results imply

  9. Sensitivity of Red Sea circulation to sea level and insolation forcing during the last interglacial

    Directory of Open Access Journals (Sweden)

    G. Trommer

    2011-08-01

    Full Text Available This study investigates the response of Red Sea circulation to sea level and insolation changes during termination II and across the last interglacial, in comparison with termination I and the Holocene. Sediment cores from the central and northern part of the Red Sea were investigated by micropaleontological and geochemical proxies. The recovery of the planktic foraminiferal fauna following high salinities during marine isotopic stage (MIS 6 took place at similar sea-level stand (~50 m below present day, and with a similar species succession, as during termination I. This indicates a consistent sensitivity of the basin oceanography and the plankton ecology to sea-level forcing. Based on planktic foraminifera, we find that increased water exchange with the Gulf of Aden especially occurred during the sea-level highstand of interglacial MIS 5e. From MIS 6 to the peak of MIS 5e, northern Red Sea sea surface temperature (SST increased from 21 °C to 25 °C, with about 3 °C of this increase taking place during termination II. Changes in planktic foraminiferal assemblages indicate that the development of the Red Sea oceanography during MIS 5 was strongly determined by insolation and monsoon strength. The SW Monsoon summer circulation mode was enhanced during the termination, causing low productivity in northern central Red Sea core KL9, marked by high abundance of G. sacculifer, which – as in the Holocene – followed summer insolation. Core KL11 records the northern tip of the intruding intermediate water layer from the Gulf of Aden and its planktic foraminifera fauna shows evidence for elevated productivity during the sea-level highstand in the southern central Red Sea. By the time of MIS 5 sea-level regression, elevated organic biomarker BIT values suggest denudation of soil organic matter into the Red Sea and high abundances of G. glutinata, and high reconstructed chlorophyll-a values, indicate an intensified NE Monsoon

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

    Directory of Open Access Journals (Sweden)

    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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. Alterations in hepatic production and peripheral clearance of IGF-I after endotoxin.

    Science.gov (United States)

    Fan, J; Char, D; Kolasa, A J; Pan, W; Maitra, S R; Patlak, C S; Spolarics, Z; Gelato, M C; Lang, C H

    1995-07-01

    Lipopolysaccharide (LPS) produces a rapid and sustained reduction in the circulating concentration of insulin-like growth factor I (IGF-I), which may be responsible, in part, for the alterations in protein metabolism observed in these animals. The purpose of the present study was to determine whether this drop was due to a decreased hepatic production of IGF-I and/or an increased clearance of the peptide from the blood. Four hours after intravenous injection of LPS the plasma IGF-I concentration was decreased 50%. IGF-I release by in situ perfused livers from control rats was constant throughout the 60-min perfusion period and averaged 111 +/- 3 ng/min. In contrast, hepatic IGF-I output was decreased 46% by in vivo LPS. In contrast, livers from LPS-injected rats released more IGF binding proteins-1, -2 and -4 than did control livers. Hepatic cell isolation indicated that LPS decreased the IGF-I content in Kupffer and parenchymal cells, but not endothelial cells, by approximately 45%. Pharmacokinetic analysis of blood 125I-IGF-I decay curves indicated that the half-life for whole body clearance of 125I-IGF-I from the circulation was not altered by LPS. However, LPS increased 125I-IGF-I uptake by spleen, liver, lung, and kidney while decreasing uptake by the pancreas and gastrointestinal tract. These results indicate that the LPS-induced decrease in blood IGF-I concentration is primarily due to a reduction in hepatic production, not a change in whole body peptide clearance, and that a decreased production by both parenchymal and Kupffer cells contributes to this alteration. PMID:7543247

  17. 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.

  18. IGF-I and IGFBP2 in peripheral artery disease

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND AND OBJECTIVES: The search for novel risk factors of cardiovascular disease (CVD) has provided valuable clinical data concerning underlying mechanism of disease. Increasing evidence indicates a possible involvement of insulin-like growth factor-I (IGF-I) and its binding protein 2 (IGFBP......-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...... levels were obtained in 440 patients (257 males) with symptomatic PAD. Patients were followed for a median of 6.1 (IQ 5.1-7.2) years. The relationship between times to lethal outcome and baseline serum IGF-I and IFGBP-2 levels were examined by Cox proportional hazard analysis. The role of IFGBP-2 for...

  19. 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. PMID:27221117

  20. Exercise-induced changes in circulating levels of transforming growth factor-beta-1 in humans

    DEFF Research Database (Denmark)

    Heinemeier, Katja; Langberg, Henning; Kjaer, Michael

    resting subjects (reported values range from 500 to 18,300 pg ml(-1)) and also the extent of intra-individual variation is unknown. As a basis for detecting exercise-induced changes in transforming growth factor-beta-1, we measured its concentration, by enzyme-linked immunosorbent assay, in plasma from...... eight healthy resting subjects. Plasma was sampled from each subject on five successive days according to a procedure designed to minimize activation of platelets, as platelet alpha-granules contain large amounts of transforming growth factor-beta-1. The mean plasma level was relatively low [1155 (30......Mechanical loading of cells induces the expression of transforming growth factor-beta-1, and acute exercise, which involves mechanical loading of several tissues, could thus increase its circulating level in humans. However, no consensus exists regarding the plasma concentration of this cytokine in...

  1. 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...

  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. 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

  4. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    OpenAIRE

    Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

    2013-01-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation f...

  5. 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.

  6. 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; Hansen, Tine W; Olsen, Michael H; Linneberg, Allan; Madsbad, Sten; Fenger, Mogens; Berg, Nikolaj D

    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......-h ambulatory BP measurements (ABPMs) will influence the effect of NP gene variations on BP levels.MethodsWe used rs632793 at the NPPB (NP precursor B) locus to investigate the relationship between genetically determined serum N-terminal pro-brain NP (NT-proBNP) concentrations and BP levels...... participants with the G:G genotype (geometric mean (95% confidence interval (CI)): 34.8 (31.5-38.4) pg/ml vs. 48.1 (41.9-55.3) pg/ml, P = 0.0002), but higher 24-h ambulatory BP levels (mean difference (95% CI): 2.0 (0.1-4.1) mm Hg, P = 0.043, for systolic BP and 1.7 (0.4-3.1) mm Hg, P = 0.011, for diastolic BP...

  7. 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.

  8. Hubungan Antara Kadar Insulin-Like Growth Factor-1 (IGF-1) Dalam Serum Dan Derajat Keparahan Akne Vulgaris

    OpenAIRE

    Panjaitan, Joice Sonya

    2011-01-01

    Background Acne vulgaris is a skin disease that is commonly found in the community. Acne vulgaris has been known had a complex pathogenesis and IGF-1 was allegedly had a role in the pathogenesis of acne vulgaris. IGF-1 can enhance keratinocyte cell proliferation and increase sebum production. However, the role of IGF-1 in the various degree of acne vulgaris severity remains unclear. Objective To determine the correlation between the serum IGF-1 level and the severity degree of acne ...

  9. 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

  10. Levels and values of circulating endothelial progenitor cells, soluble angiogenic factors, and mononuclear cell apoptosis in liver cirrhosis patients

    Directory of Open Access Journals (Sweden)

    Chen Chih-Hung

    2012-07-01

    Full Text Available Abstract Background The roles of circulating endothelial progenitor cell (EPC and mononuclear cell apoptosis (MCA in liver cirrhosis (LC patients are unknown. Moreover, vascular endothelial growth factor (VEGF and stromal cell-derived factor (SDF-1α are powerful endogenous substances enhancing EPC migration into circulation. We assessed the level and function of EPCs [CD31/CD34 (E1, KDR/CD34 (E2, CXCR4/CD34 (E3], levels of MCA, VEGF and SDF-1α in circulation of LC patients. Methods Blood sample was prospectively collected once for assessing EPC level and function, MCA, and plasma levels of VEGF and SDF-1α using flow cytometry and enzyme-linked immunosorbent assay (ELISA, respectively, in 78 LC patients and 25 age- and gender-matched healthy controls. Results Number of EPCs (E1, E2, E3 was lower (all p 2, E3 was higher but MCA was lower (all p  Conclusion The results of this study demonstrated that level, angiogenic capacity, and function of circulating EPCs were significantly reduced, whereas plasma levels of SDF-1α and circulating MCA were substantially enhanced in cirrhotic patients.

  11. The Role of Insulin-like Growth Factor-I and IGF-binding Proteins in Mammary Gland Development

    OpenAIRE

    Weber, Miriam S

    1998-01-01

    Development of the mammary gland is likely mediated by locally produced growth factors acting in concert with circulating mitogens. To investigate the importance of mammary synthesis of insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGFBP), the initial objective was to evaluate the physiological effects of recombinant IGF-I synthesis in the mouse mammary gland. Expression of recombinant IGF-I was targeted by the mouse mammary tumor virus - long terminal repeat (MMTV-LTR) to ...

  12. 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

  13. Lead-bismuth cooled reactor with a high level of natural circulation (RBEC-M)

    International Nuclear Information System (INIS)

    The RBEC-M is a lead-bismuth cooled fast reactor with a high level of primary coolant natural circulation and a gas lift system in the primary circuit to ensure a supply of inert gas (argon) in the coolant under the core. The name reflects the basic technology of the concept: a fast neutron spectrum, heavy metal lead-bismuth coolant, a high level of natural circulation with a nominal operation of inert gas blowers and safe cooldown of the core after the trip of gas supply blowers. The RBEC-M reactor is a conceptual development based on the preliminary design of the RBEC reactor, hereafter referred to as a 'basic project'. The direct predecessor of the RBEC-M is the design named RBEC, one of the Russian-developed designs of fast reactors with heavy metal coolants. The preliminary design of the RBEC reactor of 900 MW(th) and 340 MW(e) was completed in the 1990s by Russian design and scientific institutions: OKB 'Gidropress', Russian Research Centre (RRC) 'Kurchatov Institute' and IPPE, with the participation of VNIINM and RIAR. The main objective of the development of the RBEC lead-bismuth cooled fast reactor was to provide a reliable solution for nuclear fuel breeding, while using an approach alternative to sodium cooled fast reactors. It was assumed that design development of a nuclear power plant (NPP) with such reactor could be completed in a rather short period, with modest expenditures for additional testing and qualification of separate equipment units

  14. Increased levels of circulating Annexin A5 in Familial Mediterranean fever

    Directory of Open Access Journals (Sweden)

    Hovhannisyan Lilit P

    2010-11-01

    Full Text Available Abstract Background Familial Mediterranean fever is a genetic autoinflammatory disease most commonly affecting the ethnic groups originating from around the Mediterranean Sea. Apoptosis plays an important role in down-regulation of the inflammatory response by reducing the lifespan of activated immunocompetent cells. Thus, increased apoptosis may be associated with pathogenesis of familial Mediterranean fever. Methods In the present study we determined the serum levels of apoptotic marker, Annexin A5, in familial Mediterranean fever patients, within an attack and attack-free, in comparison to healthy subjects and assessed the influence of colchicine treatment on this parameter. In addition, in all study subjects serum levels of C-reactive protein and interleukine-1β, and the total leukocyte count were also determined. Results Our results demonstrated that pathogenesis of familial Mediterranean fever is characterized by the increased levels of circulating Annexin A5, which is higher in patients within the attack and which associate with the increased levels of C-reactive protein and interleukine-1β and total leukocyte count. Conclusions The results obtained indicate elevated rates of apoptosis of subpopulations of leukocytes involved in autoinflammation and recurrent episodes of fever in familial Mediterranean fever. It was also revealed that regular colchicine treatment sufficiently decreases the rate of apoptosis in familial Mediterranean fever patients by affecting the intensity of autoinflammatory reactions.

  15. 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...

  16. 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

  17. Estimation of glucose utilization in a type 2 diabetes mellitus patient on insulin analogs with tumor hypoglycemia induced by IGF-II.

    Science.gov (United States)

    Chode, Suresh; Albert, Stewart G; Shoemaker, James D; Green, Aileen L

    2016-02-01

    We present a 38-year-old male patient with insulin requiring type 2 diabetes mellitus (DM) who had fasting hypoglycemia caused by a non-pancreatic-islet-cell mesenchymal tumor producing IGF-II. The evaluation was confounded in that there was pre-existing DM being treated with insulin analogs. Insulin levels were assessed with an immunoassay with cross reactivity with the insulin analogs. An 18-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) scan localized the 19.7×18.0×17.8cm retroperitoneal mass. A 3.25kg tumor was resected. Post-operatively insulin treatment was resumed and circulating IGF-II levels returned to normal. The maximum standardized uptake values of FDG (SUVmax) along with a steady state glucose infusion of 17.5g/h were used to determine the components of glucose utilization due to IGF-II induced muscle glucose uptake (utilization, 62%) whereas the tumor itself was responsible for approximately 22% of measurable glucose uptake. Whereas tumor induced hypoglycemia has been ascribed to preferential glucose utilization by the tumor, the predominant hypoglycemic effect was due to hormonal IGF-II induced total body glucose uptake. PMID:26774399

  18. 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

    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...... in the striped bass. Transfer from freshwater (FW) to seawater (SW) induced an overall increase in gill IGF-1R mRNA expression (P<0.01). Plasma IGF-1 concentration decreased significantly after SW transfer (1 and 4 days).  Transfer from SW to FW had no overall effect on gill IGF-1R expression, while...... regulation of gill ion transport in striped bass. The plasma IGF-1 responses indicate, in accordance with previous data showing a rapid negative effect of IGF-1 on SW acclimation, that IGF-1 has a role in hyperosmoregulation in this species. The increased level of IGFBP-3 in SW-acclimated fish may buffer the...

  19. 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.

  20. Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding proteins by tumor necrosis factor.

    Science.gov (United States)

    Fan, J; Char, D; Bagby, G J; Gelato, M C; Lang, C H

    1995-11-01

    The purpose of the present study was to determine 1) whether exogenous administration of tumor necrosis factor-alpha (TNF-alpha) alters insulin-like growth factor-I (IGF-I) and IGF-binding proteins (BPs) and 2) whether the enhanced endogenous production of TNF mediates the lipopolysaccharide (LPS)-induced changes in the IGF system. The overnight infusion of murine TNF-alpha reduced circulating concentrations of both growth hormone (GH) and IGF-I in fasted rats. Furthermore, TNF-alpha decreased IGF-I content in liver, gastrocnemius muscle, and pituitary. In contrast, TNF-alpha increased IGF-I content in kidney and brain. IGFBP-1 was increased in plasma, liver, and muscle in response to TNF-alpha. In a second study, rats were injected with LPS after treatment with a neutralizing anti-TNF antibody (Ab), and blood and tissues were collected 4 h later. In LPS-treated rats, plasma concentrations of GH and IGF-I were reduced. LPS also decreased the IGF-I content in liver and skeletal muscle and increased plasma, liver, and muscle concentrations of IGFBP-1. Pretreatment with anti-TNF Ab attenuated the LPS-induced reduction in IGF-I and the increased IGFBP-1 in plasma and liver and completely prevented the decrease in IGF-I observed in muscle. In contrast, the LPS-induced decrease in plasma GH and the increased IGFBP-1 observed in muscle were unaltered by the anti-TNF Ab.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7503312

  1. 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.

  2. Elevated Circulating Levels of Inflammatory Markers in Patients with Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Hamad Al Shahi

    2015-01-01

    Full Text Available Objective. We evaluated inflammatory cytokines and chemokine in peripheral blood mononuclear cells (PBMCs in patients with either acute coronary syndrome (ACS or stable coronary artery disease (CAD. Methods. We enrolled 20 ACS patients and 50 stable CAD patients without previous history of ACS who underwent cardiac catheterization. Patients with an estimated glomerular filtration rate of ≤30 mL/min/1.73 m2 and C-reactive protein of ≥1.0 mg/dL were excluded. Blood samples were collected from the patients just before catheterization, and PBMCs were isolated from the whole blood. The levels of inflammatory cytokines and chemokine were measured by using real-time quantitative polymerase chain reaction and immunoassays. Results. The expression of tumor necrosis factor alpha (TNF-α, interleukin- (IL- 6, IL-10, IL-23A, IL-27, and IL-37 was significantly higher in the ACS group than in the CAD group (P<0.05. In contrast, the expression of IL-33 was significantly lower in the ACS group than in the CAD group (P<0.05. The ACS patients had higher plasma levels of TNF-α, IL-6, and IL-10 in the ACS group than in the CAD group. Conclusion. Circulating levels of pro-/anti-inflammatory cytokines, including IL-23A, IL-27, IL-33, and IL-37, may be associated with the pathogenesis of atherosclerosis in ACS patients.

  3. 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.

  4. Circulating endothelin-1 levels in lean non-insulin-dependent diabetic patients. Influence of ACE inhibition.

    Science.gov (United States)

    Ferri, C; Laurenti, O; Bellini, C; Faldetta, M R; Properzi, G; Santucci, A; De Mattia, G

    1995-01-01

    To evaluate the effect of captopril on plasma endothelin-1 (ET-1) levels and insulin sensitivity, 15 lean normotensive men (51.6 +/- 3.8 years) affected by non-insulin-dependent diabetes mellitus (NIDDM) underwent 2-h euglycemic hyperinsulinemic clamp. Each patient was then assigned to receive either captopril (25 mg twice daily for 1 week) or placebo, in a double-blind randomized fashion, before repeating clamp. At baseline, plasma ET-1 levels were 0.77 +/- 0.25 pg/mL in captopril (n = 10) and 0.83 +/- 0.3 pg/mL in placebo patients (n = 5). A twofold increase in plasma ET-1 levels occurred during the 2-h insulin infusion in both groups (P < .05 after 60 and 120 min), with a rapid return to baseline after 30 min from insulin withdrawal. After 1 week of therapy, total glucose uptake significantly increased in captopril (from 3.71 +/- 1.70 mg/kg/min to 4.24 +/- 1.72 mg/kg/min, P < .03) but not in placebo patients. Plasma ET-1 levels significantly decreased after captopril therapy (0.48 +/- 0.25 pg/mL at time 0, P < .03 v pretreatment levels), but were unaffected by placebo. Moreover, captopril slightly reduced the magnitude of ET-1 increment during insulin infusion (0.65 +/- 0.28 pg/mL and 0.88 +/- 0.48 pg/mL at 60 and 120 min, respectively, P < .05 v time 0). As a consequence, during the second insulin infusion circulating ET-1 levels were significantly lower in captopril- than in placebo-treated patients at time 0 (P < .02), 60 (P < .002), 120 (P < .004), and 150 min (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7734095

  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. 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.

    without small Copyright © 1999 John Wiley & Sons, Ltd. Int. J. Numer. Meth. Fluids 31: 1221–1264 (1999) CIRCULATION OF WESTERN INDIAN OCEAN 1223 scale ‘noises’. Semi-diagnostic circulation models are effective tools for obtaining mutually adjusted... field and bottom relief of the ocean and that the observed data were found to be fully smoothed during the adaptation stage. Copyright © 1999 John Wiley & Sons, Ltd. KEY WORDS: adaptation model; climatic circulation; sea surface topography; thermohaline...

  7. 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

  8. 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.…

  9. Prognostic value of circulating microRNA-210 levels in patients with moderate to severe aortic stenosis.

    Directory of Open Access Journals (Sweden)

    Helge Røsjø

    Full Text Available Circulating micro-RNAs have been proposed as a novel class of cardiovascular (CV biomarkers, but whether they meet analytical requirements and provide additional information to establish risk indices have not been established. miR-210 levels are increased in subjects with low VO2 max, which is a recognized risk factor in patients with aortic stenosis (AS, and we hypothesized that circulating miR-210 levels may be increased in patients with AS and associated with a poor prognosis.We measured circulating miR-210 levels by real-time PCR in 57 patients with moderate to severe AS and in 10 age- and gender-matched healthy controls. The merit of miR-210 as a biomarker was assessed according to established criteria, including by comparing miR-210 levels with NT-proBNP and miR-22 levels, which is another miRNA biomarker candidate.All patients and control subjects had miR-210 levels within the range of detection (Cq<35 and the analytical variability was low. Circulating miR-210 levels were 2.0±0.2 [mean±SEM] fold increased in AS patients compared to controls (p = 0.002, whereas miR-22 levels were not differently expressed in the AS patients (0.12±0.06 fold increase, p = 0.45. The increase in miR-210 levels in AS patients was comparable to the increment in NT-proBNP levels: [AUC] 0.82 (95% CI 0.70-0.90 vs. 0.85 (0.75-0.93, respectively, p = 0.71. During a median follow-up of 1287 days, 15 patients (26% died. There was a significant association between higher circulating levels of miR-210 and increased mortality during follow-up: hazard ratio [supra- vs. inframedian levels] 3.3 (95% CI 1.1-10.5, p = 0.039. Adjusting for other risk indices in multivariate analysis did not attenuate the prognostic merit of circulating miR-210 levels.Circulating miR-210 levels are increased in patients with AS and provide independent prognostic information to established risk indices. Analytical characteristics were also excellent supporting the potential of

  10. Variability in Solomon Sea circulation derived from altimeter sea level data

    Science.gov (United States)

    Melet, Angélique; Gourdeau, Lionel; Verron, Jacques

    2010-08-01

    The Solomon Sea is a key region in the Pacific Ocean where equatorial and subtropical circulations are connected. The region exhibits the highest levels in sea level variability in the entire south tropical Pacific Ocean. Altimeter data was utilized to explore sea level and western boundary currents in this poorly understood portion of the ocean. Since the geography of the region is extremely intricate, with numerous islands and complex bathymetry, specifically reprocessed along-track data in addition to standard gridded data were utilized in this study. Sea level anomalies (SLA) in the Solomon Sea principally evolve at seasonal and interannual time scales. The annual cycle is phased by Rossby waves arriving in the Solomon Strait, whereas the interannual signature corresponds to the basin-scale ENSO mode. The highest SLA variability are concentrated in the eastern Solomon Sea, particularly at the mouth of the Solomon Strait, where they are associated with a high eddy kinetic energy signal that was particularly active during the phase transition during the 1997-1998 ENSO event. Track data appear especially helpful for documenting the fine structure of surface coastal currents. The annual variability of the boundary currents that emerged from altimetry compared quite well with the variability seen at the thermocline level, as based on numerical simulations. At interannual time scales, western boundary current transport anomalies counterbalance changes in western equatorial Pacific warm water volume, confirming the phasing of South Pacific western boundary currents to ENSO. Altimetry appears to be a valuable source of information for variability in low latitude western boundary currents and their associated transport in the South Pacific.

  11. The effects of prednisone and azathioprine on circulating immunoglobulin levels and lymphocyte subpopulations in normal dogs.

    Science.gov (United States)

    Rinkardt, N E; Kruth, S A; Kaushik, A

    1999-01-01

    This study investigates serum immunoglobulin (SIg) levels and lymphocyte subpopulations in normal dogs in response to putative immunosuppressive doses of prednisone and/or azathioprine. The objectives were to quantify SIg levels and lymphocyte subpopulations, including Thy-1+, CD4+, CD8+ and B cells, in normal dogs both before and after the administration of prednisone and/or azathioprine at 2 mg/kg, PO, each. Eighteen beagles were divided into 3 groups of 6 dogs each. Blood samples for radial immunodiffusion assay of IgG, IgM and IgA, complete blood count (CBC)and flow cytometry were collected prior to the administration of any drugs and again after 14 d of azathioprine, prednisone or azathioprine and prednisone. Peripheral blood mononuclear cells were isolated using density centrifugation and were incubated with monoclonal antibodies reacting with CD4+, CD8+, Thy-1+ and membrane immunoglobulin. Lymphocyte subsets were quantified using flow cytometry. Azathioprine-treated dogs had no significant changes in SIg levels or lymphocyte subpopulations. Prednisone-treated dogs had significant (P azathioprine-treated dogs had significant (P dogs also had a significant decrease in erythrocyte number and a significant increase in the monocyte count. These findings suggest that azathioprine and prednisone in combination or prednisone alone may be useful for the treatment of T cell-mediated diseases since decreased circulating T cell levels were demonstrated following treatment. The combination of drugs or azathioprine alone may not be appropriate for treatment of acute or autoantibody-mediated immune disease, because SIg levels were minimally affected by treatment. PMID:9918329

  12. 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.

  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

    OpenAIRE

    WANG, ZENG

    2016-01-01

    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 circulat...

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

    International Nuclear Information System (INIS)

    Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 μl 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

  15. 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.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.)

  19. 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...

  20. 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

  1. 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

  2. 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...

  3. Circulating heat shock protein 60 levels are elevated in HIV patients and are reduced by anti-retroviral therapy.

    Directory of Open Access Journals (Sweden)

    Itaru Anraku

    Full Text Available Circulating heat shock protein 60 (Hsp60 and heat shock protein 10 (Hsp10 have been associated with pro- and anti-inflammatory activity, respectively. To determine whether these heat shock proteins might be associated with the immune activation seen in HIV-infected patients, the plasma levels of Hsp60 and Hsp10 were determined in a cohort of 20 HIV-infected patients before and after effective combination anti-retroviral therapy (cART. We show for the first time that circulating Hsp60 levels are elevated in HIV-infected patients, with levels significantly reduced after cART, but still higher than those in HIV-negative individuals. Hsp60 levels correlated significantly with viral load, CD4 counts, and circulating soluble CD14 and lipopolysaccharide levels. No differences or correlations were seen for Hsp10 levels. Elevated circulating Hsp60 may contribute to the immune dysfunction and non-AIDS clinical events seen in HIV-infected patients.

  4. 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.

  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. PMID:7649082

  6. 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.

  7. 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

  8. [GH/IGF-1 and cancer: what's new in this association].

    Science.gov (United States)

    Castro, Angela M Spinola e; Guerra-Júnior, Gil

    2005-10-01

    Evidence from in vitro and animal studies suggests that members of the insulin-like growth factors (IGFs) system, including IGF-I, IGF-II, the IGF-I receptor (IGF-IR), and the IGF-binding proteins (IGFBPs) play a central role in the development and progression of cancer. More specifically, IGFs may promote cell cycle progression and inhibition of apoptosis either by directly associating with other growth factors or indirectly by interacting with other molecular systems, which have an established role in carcinogenesis and cancer promotion. In addition, a growing number of epidemiologic studies suggest that increased serum levels of IGFs and/or altered levels of their binding proteins are associated with increased risk for developing several malignancies. This review aims to summarize and to show the role of IGF system in tumor regulation, a revision of epidemiologic studies and the risk of neoplasia in patients (with or without personal history of previous neoplasia) who received growth hormone (rhGH). It is important to emphasize that the clinical use of rhGH, in the indications internationally approved, is secure, and there are not evidences, at this moment, of the association with neoplasias development. PMID:16444368

  9. 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...

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

    Science.gov (United States)

    Chen, Dong; Wang, Wei; Ru, Shaoguo

    2016-01-01

    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, igf-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.

  11. 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.

  12. 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.

  13. 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...

  14. Polymorphisms in the CRP gene moderate an association between depressive symptoms and circulating levels of C Reactive Protein

    OpenAIRE

    Halder, Indrani; Marsland, Anna L; Cheong, JeeWon; Muldoon, Matthew F.; Ferrell, Robert E.; Manuck, Stephen B.

    2009-01-01

    Although many studies have found psychological depression associated with higher circulating levels of C-reactive protein (CRP), not all findings are consistent. Since DNA sequence variation in the CRP gene has also been shown to predict plasma CRP levels, we hypothesized that plasma CRP may covary with depressive symptomatology as a function of allelic variation in the CRP gene. We tested this hypothesis in 868 healthy community volunteers of European ancestry. Depressive symptomatology was ...

  15. The mean seasonal cycle in sea level estimated from a data-constrained general circulation model

    Science.gov (United States)

    Vinogradov, Sergey V.; Ponte, Rui M.; Heimbach, Patrick; Wunsch, Carl

    2008-03-01

    A near-global ocean state estimate over the period 1992-2004 is used to study the mean seasonal cycle in sea level ζ. The state estimate combines most available observations, including all the altimetric missions, with a general circulation model in an optimization procedure. The annual cycle tends to be larger than the semi-annual one, except in tropical regions. For global mean ζ, annual thermosteric and freshwater terms are nearly out-of-phase and lead to an annual cycle of only a few mm in amplitude. Regionally, surface wind stress and heat flux are the primary drivers for seasonal ζ variations in the tropics and midlatitudes, respectively, with both mechanisms playing a role at high latitudes. A substantial part of the annual ζ variability can be assigned to changes in thermosteric height in the upper 100 m in midlatitudes and 200 m in the tropics. Bottom pressure variability is larger at high latitudes, and also in some regions in the Southern Ocean and North Pacific. Apparent nonlinear rectification processes lead to a noticeable impact of submonthly forcing on the annual cycle in the western North Atlantic and North Pacific. Other features include the substantial ζ gradients associated with strong spatial variability in seasonal surface heat flux in some western boundary regions, the damping effects of surface heat flux on the seasonal cycle in the tropics, and the importance of wind driving and bottom pressure in shallow regions, which can cause differences in the seasonal cycle in some coastal and contiguous deep-ocean regions.

  16. 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.

  17. Altered Methylation of IGF2 Locus 20 Years after Preterm Birth at Very Low Birth Weight.

    Directory of Open Access Journals (Sweden)

    Karoliina Wehkalampi

    Full Text Available People born preterm at very low birth weight (VLBW, ≤1500g have higher rates of risk factors for adult-onset diseases, including cardiovascular diseases and type 2 diabetes. These risks may be mediated through epigenetic modification of genes that are critical to normal growth and development.We measured the methylation level of an imprinted insulin-like-growth-factor 2 (IGF2 locus (IGF2/H19 in young adults born preterm at VLBW and in their peers born at term. We studied 158 VLBW and 161 control subjects aged 18 to 27 years from the Helsinki Study of Very Low Birth Weight Adults. Methylation fraction at two IGF2 differentially methylated regions (DMRs - IGF2 antisense transcript (IGF2AS, also known as IGF2 DMR0 and last exon of IGF2 (IGF2_05, also known as IGF2 DMR2 - were measured with Sequenom Epityper. We used linear regression and adjustment for covariates to compare methylation fractions at these DMRs between VLBW and control subjects.At one IGF2AS CpG site, methylation was significantly lower in VLBW than in control subjects, mean difference -0.017 (95% CI; -0.028, -0.005, P = 0.004. Methylation at IGF2_05 was not different between the groups.Methylation of IGF2AS is altered 20 years after preterm birth at VLBW. Altered methylation may be a mechanism of later increased disease risk but more data are needed to indicate causality.

  18. 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.

  19. 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.

  20. Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor.

    Science.gov (United States)

    De Santis, S; Pace, A; Bove, L; Cognetti, F; Properzi, F; Fiore, M; Triaca, V; Savarese, A; Simone, M D; Jandolo, B; Manzione, L; Aloe, L

    2000-01-01

    The aim of our study was to explore whether nerve growth factor (NGF) plays any role in the development of peripheral neuropathy induced by anticancer treatment. We measured the circulating NGF levels in 23 cancer patients before and after chemotherapy. We evaluated whether the development of peripheral neurotoxicity was associated with changes in basal NGF concentrations in patients studied with a comprehensive neurological and neurophysiological examination. The results of these studies showed that the circulating levels of NGF, which are about 20 pg/ml in plasma of controls, decrease during chemotherapy and in some cases completely disappeared after prolonged treatment with antitumor agents. The decrease in NGF levels seems to be correlated with the severity of neurotoxicity. These results clearly suggest that NGF might become a useful agent to prevent neuropathies induced by antineoplastic drugs and restore peripheral nerve dysfunction induced by these pharmacological compounds. PMID:10656436

  1. 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) as...

  2. In vivo oocyte developmental competence is reduced in lean but not in obese superovulated dairy cows after intraovarian administration of IGF1.

    Science.gov (United States)

    Velazquez, Miguel A; Hadeler, Klaus-Gerd; Herrmann, Doris; Kues, Wilfried A; Ulbrich, Susanne E; Ulbrich, Susanne; Meyer, Heinrich H D; Rémy, Benoît; Beckers, Jean-François; Sauerwein, Helga; Niemann, Heiner

    2011-07-01

    The present study investigated the role of IGF1 in lactating lean and non-lactating obese dairy cows by injecting 1 μg IGF1 into the ovaries prior to superovulation. This amount of IGF1 has been linked with pregnancy loss in women with the polycystic ovary syndrome (PCOS) and was associated with impaired bovine oocyte competence in vitro. Transcript abundance and protein expression of selected genes involved in apoptosis, glucose metabolism, and the IGF system were analyzed. Plasma concentrations of IGF1 and leptin, and IGF1 in uterine luminal fluid (ULF), were also measured. IGF1 treatment decreased embryo viability in lean cows to the levels observed in obese cows. Obese cows were not affected by IGF1 treatment and showed elevated levels of IGF1 (in both plasma and ULF) and leptin. Blastocysts from lean cows treated with IGF1 showed a higher abundance of SLC2A1 and IGFBP3 transcripts. IGF1 treatment reduced protein expression of tumor protein 53 in blastocysts of lean cows, whereas the opposite was observed in obese cows. IGF1 in plasma and ULF was correlated only in the control groups. Blastocyst transcript abundance of IGF1 receptor and IGFBP3 correlated positively with IGF1 concentrations in both plasma and ULF in lean cows. The detrimental microenvironment created by IGF1 injection in lean cows and the lack of effect in obese cows resemble to a certain extent the situation observed in PCOS patients, where IGF1 bioavailability is increased in normal-weight women but reduced in obese women, suggesting that this bovine model could be useful for studying IGF1 involvement in PCOS. PMID:21543511

  3. 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

  4. 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; Borski, Russell John

    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,...... first time in teleosts that IGF-IR and Na+-K+-ATPase are localized in putative chloride cells at the base of the lamellae, identifying these cells in the gill as a target for IGF-I and IGF-II. Overall the data suggest a hyperosmoregulatory role of IGF-I in this species....

  5. 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.

  6. Increased circulating heat shock protein 70 (HSPA1A) levels in gestational diabetes mellitus: a pilot study.

    Science.gov (United States)

    Garamvölgyi, Zoltán; Prohászka, Zoltán; Rigó, János; Kecskeméti, András; Molvarec, Attila

    2015-07-01

    Recent data indicate that serum Hsp70 (HSPA1A) levels are increased in type 1 and 2 diabetes mellitus. However, there is no report in the literature on circulating Hsp70 levels in gestational diabetes mellitus. In this pilot study, we measured serum Hsp70 levels in 11 pregnant women with pregestational diabetes, 38 women with gestational diabetes, and 40 healthy pregnant women with ELISA. Plasma glucose levels, serum insulin concentrations, HbA1c values, and the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index were also determined. According to our results, serum Hsp70 concentrations were significantly higher in women with pregestational and gestational diabetes mellitus than in healthy pregnant women. In addition, pregestational diabetic women had significantly higher Hsp70 levels than those with gestational diabetes. Furthermore, in the group of women with gestational diabetes mellitus, serum Hsp70 levels showed a significant positive correlation with HbA1c values. However, there was no other relationship between clinical features and metabolic parameters of the study subjects and their serum Hsp70 levels in either study group. In conclusion, we demonstrated for the first time in the literature that serum Hsp70 levels are increased and correlate with HbA1c values in women with gestational diabetes mellitus. Nevertheless, further studies are needed to determine whether circulating Hsp70 plays a causative role in the pathogenesis of gestational diabetes or elevated serum Hsp70 levels are only consequences of the disease. PMID:25720752

  7. 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.

  8. Prognostic significance of IGF-1R expression in patients treated with breast-conserving surgery and radiation therapy

    International Nuclear Information System (INIS)

    Background: Insulin-like growth factor (IGF) receptor is a key receptor in apoptotic protection, cell adhesion, longevity, and transformation into a cancerous cell and can induce malignant changes in the presence of the IGF ligand. Over-expression of IGF-1R has been associated with resistance to radiation. Inhibitors of IGF-1R have been shown to enhance tumor radiation sensitivity and amplify radiation therapy-induced apoptosis. The purpose of this study is to evaluate the prognostic significance of IGF-1R expression in patients with breast cancer treated with breast conserving therapy. Materials and methods: Paraffin specimens from 345 women with early stage breast cancer treated with BCT were constructed into tissue microarrays and stained for IGF-1R, COX-2 and p53. The molecular profiles were correlated with clinical-pathologic factors, overall, local, and distant relapse-free survival. The association between IGF-1R, other co-variables, and outcome was assessed. Results: IGF-1R over-expression was identified in 197 cases (57%). IGF-1R over-expression was found to be correlated with African-American race (p = 0.0233), p53 status (p = 0.0082) and COX-2 expression (p < 0.0001). While IGF-1R over-expression was associated with lower overall survival (p = 0.0224) in node-negative patients, there was no impact of IGF-1R expression on local control. Conclusions: In node-negative patients, patients with high levels of IGF-1R were found to have a significant reduction in overall survival, but no apparent effect on local control. Given the limited published data on IGF-1R in early stage, conservatively treated patients, further studies investigating IGF-1R expression in this cohort are necessary.

  9. 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

  10. 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.

  11. 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.

  12. Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection

    Directory of Open Access Journals (Sweden)

    Hao Chuanming

    2004-08-01

    Full Text Available Abstract Background Viruses are obligate intracellular parasites and rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virus infection and/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. Results A gene entrapment approach was used to identify candidate cellular genes that affect reovirus infection or virus induced cell lysis. Four of the 111 genes disrupted in clones selected for resistance to infection by reovirus type 1 involved the insulin growth factor-2 (IGF-II pathway, including: the mannose-6-phosphate/IGF2 receptor (Igf2r, a protease associated with insulin growth factor binding protein 5 (Prss11, and the CTCF transcriptional regulator (Ctcf. The disruption of Ctcf, which encodes a repressor of Igf2, was associated with enhanced Igf2 gene expression. Plasmids expressing either the IGF-II pro-hormone or IGF-II without the carboxy terminal extension (E-peptide sequence independently conferred high levels of cellular resistance to reovirus infection. Forced IGF-II expression results in a block in virus disassembly. In addition, Ctcf disruption and forced Igf2 expression both enabled cells to proliferate in soft agar, a phenotype associated with malignant growth in vivo. Conclusion These results indicate that IGF-II, and by inference other components of the IGF-II signalling pathway, can confer resistance to lytic reovirus infection. This report represents the first use of gene entrapment to identify host factors affecting virus infection. Concomitant transformation observed in some virus resistant cells illustrates a potential mechanism of carcinogenesis associated with chronic virus infection.

  13. 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

    2014-05-01

    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. Their group models, which were represented by discourse and blood circulation diagrams, were analyzed for the development of the framework that informed the model evaluation levels and epistemological features. The model evaluation levels were categorized into levels one to four based on the following evaluation criteria: no evaluation, authoritative sources, superficial criteria, and more comprehensive criteria. The qualities of group models varied with the criteria of model evaluation. While students who used authoritative sources for evaluating the group model appeared to have an absolutist epistemology, students who evaluated according to the superficial criteria and more comprehensive criteria appeared to have an evaluative epistemology. Furthermore, groups with Level four showed a chain reaction of cognitive reasoning during the modeling practice concerning practical epistemology. The findings have implications for science teachers and education researchers who want to understand the context for developing students' practical epistemologies.

  14. 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

  15. 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 , ...

  16. 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.

  17. 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.

  18. Cardiovascular complications and increased levels of circulating modified low density lipoprotein in HIV patients and patients with lipodystrophy

    Directory of Open Access Journals (Sweden)

    K.R.O.M. Ronchini

    2004-01-01

    Full Text Available The introduction of highly active antiretroviral therapy (HAART for patients infected with HIV has significantly prolonged the life expectancy and to some extent has restored a functional immune response. However, the premature introduction of HAART has led to a significant and alarming increase in cardiovascular complications, including myocardial infarction and the appearance of abnormal distribution of body fat seen as lipodystrophy. One key element in the development of ischemic coronary artery disease is the presence of circulating and tissue-fixed modified low density lipoprotein (mLDL that contributes to the initiation and progression of arterial lesions and to the formation of foam cells. Even though not completely elucidated, the most likely mechanism involves mLDL in the inflammatory response and the induction of a specific immune response against mLDL. Circulating antibodies against mLDL can serve as an indirect marker of the presence of circulating and vessel-fixed mLDL. In the present study, we measured antibodies to mLDL and correlated them with immune status (i.e., number of CD4+ T cells in 59 HIV patients and with the clinical manifestation of lipodystrophy in 10 patients. We observed a significant reduction in anti-mLDL antibody levels related both to lipodystrophy and to an immunocompromised state in HIV patients. We speculate that these antibodies may explain in part the rapid development of ischemic coronary artery disease in some patients.

  19. 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.

  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. Follicular fluid insulin like growth factor-1 (FF IGF-1) is a biochemical marker of embryo quality and implantation rates in in vitro fertilization cycles

    OpenAIRE

    Mehta, Bindu N.; Chimote, Natachandra M.; Chimote, Meena N; Chimote, Nishad N; Nirmalendu M Nath

    2013-01-01

    CONTEXT: Insulin-like growth factor-1 (IGF-1) has been reported to play a role in human follicular and embryonic development. However, earlier studies carried out mostly in animal models or in culture mediums supplemented with IGF-1 have been unable to directly link IGF-1 with embryo quality. Results correlating IGF-1 with pregnancy outcome have also been ambiguous so far. AIM: The aim of this study is to find if in situ follicular-fluid level of IGF-1 is predictive of embryo quality and impl...

  2. 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...

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

    Science.gov (United States)

    Mester, Tünde; Wei, Yi-Hsuan; Douglas, Raymond S.

    2015-01-01

    Purpose 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. Aim To characterize the molecular mechanisms underlying TSH-induced TNFα production by FCs, and the role of IGF-1R blockade by TMB. Design 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. Results 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). Conclusion 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

  4. 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

  5. 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

  6. High circulating irisin levels are associated with insulin resistance and vascular atherosclerosis in a cohort of nondiabetic adult subjects.

    Science.gov (United States)

    Sesti, G; Andreozzi, F; Fiorentino, T V; Mannino, G C; Sciacqua, A; Marini, M A; Perticone, F

    2014-10-01

    Irisin, a novel myokine, was proposed to be able to regulate glucose homeostasis and obesity in mice. Whether irisin levels are associated with cardio-metabolic variables, insulin sensitivity, and vascular atherosclerosis in humans remain unsettled. To determine the associations between circulating irisin levels, cardio-metabolic variables, insulin sensitivity, and common carotid intima-media thickness (IMT), an indicator of vascular atherosclerosis, a cross-sectional evaluation of circulating irisin levels and cardio-metabolic variables in 192 White adults was conducted. Insulin sensitivity and insulin clearance were assessed by euglycemic-hyperinsulinemic clamp. Common carotid IMT was measured by ultrasound. After adjusting for age and gender, irisin levels were positively correlated with body fat mass (r = 0.12, P < 0.05), fasting (r = 0.17, P < 0.01), 2 h post-load insulin (r = 0.15, P < 0.02) levels, and IMT (r = 0.29, P < 0.0001) and were negatively correlated with insulin-stimulated glucose disposal (r = -0.18, P = 0.007), Matsuda index (r = -0.13, P < 0.04), disposition index (r = -0.278, P < 0.0001), and insulin clearance (r = -0.26, P < 0.0001). After adjusting for age, gender, and BMI, individuals in the highest tertile of irisin levels exhibited higher body fat mass (P < 0.01), fasting (P < 0.05), 2 h post-load (P < 0.01) insulin levels, carotid IMT (P < 0.001), lower insulin-stimulated glucose disposal (P < 0.001), Matsuda index (P < 0.01), disposition index (P < 0.01), and insulin clearance (P < 0.001) as compared with subjects in the lowest tertile of circulating irisin levels. Irisin is inversely associated with insulin sensitivity and positively associated with carotid IMT in humans, suggesting either increased release by adipose/muscle tissue in response to deterioration of insulin sensitivity or a compensatory increase in irisin to overcome an underlying irisin resistance. PMID:24619655

  7. 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

  8. 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

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    PriyaBalsubramanian

    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

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

    International Nuclear Information System (INIS)

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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Coordinated increase in skeletal muscle fiber area and expression of IGF-I with resistance exercise in elderly post-operative patients

    DEFF Research Database (Denmark)

    Suetta, Charlotte; Suetta, Charlotte Arneboe; Clemmensen, Christoffer;

    2010-01-01

    Hypertrophy of developing skeletal muscle involves stimulation by insulin-like growth factor-I (IGF-I), however, the role of IGF-I in adult muscle is less clarified. In the present study, the mRNA splice variants of IGF-I (IGF-IEa and MGF) and the changes in muscle fiber cross sectional area after...... in addition induces marked increases in the expression of IGF-I splice variants, supporting the idea that IGF-I is involved in regulating muscle hypertrophy.......-operated-side served as a within subject control. Muscle biopsies were obtained from the vastus lateralis of both limbs at +2d post-operative (baseline), at 5weeks and 12weeks post-surgery to analyze for changes in type 1 and type 2 muscle fiber area. Changes in expression levels of IGF-I mRNA isoforms were determined...

  18. Effects of rhIGF-1 administration on surrogate markers of bone turnover in adolescents with anorexia nervosa☆

    Science.gov (United States)

    Misra, Madhusmita; McGrane, Jacob; Miller, Karen K.; Goldstein, Mark A.; Ebrahimi, Seda; Weigel, Thomas; Klibanski, Anne

    2013-01-01

    Background Adolescents with anorexia nervosa (AN) have low bone density and low levels of surrogate markers of bone formation. Low bone density is a consequence of hormonal alterations that include hypogonadism and decreases in IGF-1, a bone trophic factor. Although IGF-1 is key to pubertal bone accretion, and effects have been demonstrated in adults, there are no data regarding the effect of recombinant human (rh) IGF-1 administration in adolescents with AN. Objectives We hypothesized that rhIGF-1 would cause an increase in PINP, a bone formation marker, in girls with AN, without any effect on CTX, a bone resorption marker. Subjects and methods RhIGF-1 was administered at a dose of 30–40 mcg/k twice daily to 10 consecutive girls with AN 12–18 years old for 7–9 days. Ten age-matched girls with AN were followed without rhIGF-1 for a similar period. IGF-1, PINP and CTX levels were measured. Results RhIGF-1 administration caused an increase in IGF-1 from day-1 to day-4/5 (p < 0.0001) and day-1 to day-8/9 (p < 0.0001). Simultaneously, PINP increased from day-1 to day-4/5 (p=0.004) and day-1 to day-8/9 (p=0.004), with a smaller increase from day-4/5 to day-8/9 (p=0.048). CTX levels did not change with rhIGF-1 administration. No changes occurred in IGF-1 or PINP levels in girls not receiving rhIGF-1; however, CTX levels increased significantly (p=0.01). Percent change in PINP was significantly higher (p=0.02) and percent change in CTX was significantly lower (p=0.006) in girls who received rhIGF-1 compared to those who did not receive any intervention. RhIGF-1 was well tolerated without hypoglycemia. Conclusion Short-term administration of rhIGF-1 causes an increase in a surrogate bone formation markers in girls with AN without significant side effects. PMID:19523548

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS.

    Science.gov (United States)

    Allodi, Ilary; Comley, Laura; Nichterwitz, Susanne; Nizzardo, Monica; Simone, Chiara; Benitez, Julio Aguila; Cao, Ming; Corti, Stefania; Hedlund, Eva

    2016-01-01

    The fatal disease amyotrophic lateral sclerosis (ALS) is characterized by the loss of somatic motor neurons leading to muscle wasting and paralysis. However, motor neurons in the oculomotor nucleus, controlling eye movement, are for unknown reasons spared. We found that insulin-like growth factor 2 (IGF-2) was maintained in oculomotor neurons in ALS and thus could play a role in oculomotor resistance in this disease. We also showed that IGF-1 receptor (IGF-1R), which mediates survival pathways upon IGF binding, was highly expressed in oculomotor neurons and on extraocular muscle endplate. The addition of IGF-2 induced Akt phosphorylation, glycogen synthase kinase-3β phosphorylation and β-catenin levels while protecting ALS patient motor neurons. IGF-2 also rescued motor neurons derived from spinal muscular atrophy (SMA) patients from degeneration. Finally, AAV9::IGF-2 delivery to muscles of SOD1(G93A) ALS mice extended life-span by 10%, while preserving motor neurons and inducing motor axon regeneration. Thus, our studies demonstrate that oculomotor-specific expression can be utilized to identify candidates that protect vulnerable motor neurons from degeneration. PMID:27180807

  5. 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

  6. 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

  7. 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

  8. 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...

  9. The effects of prednisone and azathioprine on circulating immunoglobulin levels and lymphocyte subpopulations in normal dogs.

    OpenAIRE

    Rinkardt, N E; Kruth, S.A.; A Kaushik

    1999-01-01

    This study investigates serum immunoglobulin (SIg) levels and lymphocyte subpopulations in normal dogs in response to putative immunosuppressive doses of prednisone and/or azathioprine. The objectives were to quantify SIg levels and lymphocyte subpopulations, including Thy-1+, CD4+, CD8+ and B cells, in normal dogs both before and after the administration of prednisone and/or azathioprine at 2 mg/kg, PO, each. Eighteen beagles were divided into 3 groups of 6 dogs each. Blood samples for radia...

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Barry Bogin

    2015-05-01

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

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

    Science.gov (United States)

    Bogin, Barry; Hermanussen, Michael; Blum, Werner F; Aßmann, Christian

    2015-05-01

    We test the hypothesis that differences in social status between groups of people within a population may induce variation in insulin-like growth factor-1(IGF-1) levels and, by extension, growth in height. This is called the community effect in height hypothesis. The relationship between IGF-1, assessed via finger-prick dried blood spot, and elite level sport competition outcomes were analysed for a sample of 116 undergraduate men and women. There was a statistically significant difference between winners and losers of a competition. Winners, as a group, had higher average pre-game and post-game IGF-1 levels than losers. We proposed this type of difference as a proxy for social dominance. We found no evidence that winners increased in IGF-1 levels over losers or that members of the same team were more similar in IGF-1 levels than they were to players from other teams. These findings provide limited support toward the community effect in height hypothesis. The findings are discussed in relation to the action of the growth hormone/IGF-1 axis as a transducer of multiple bio-social influences into a coherent signal which allows the growing human to adjust and adapt to local ecological conditions. PMID:25946190

  13. 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

  14. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    Science.gov (United States)

    Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

    2013-06-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

  15. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    International Nuclear Information System (INIS)

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis. (paper)

  16. 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...

  17. 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...

  18. 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.

  19. 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...

  20. 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

  1. 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

    Directory of Open Access Journals (Sweden)

    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

  2. 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

    International Nuclear Information System (INIS)

    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. 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. 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. 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 activation of p53, suggesting its potential role as a

  3. Circulating MKRN3 levels decline prior to pubertal onset and through puberty

    DEFF Research Database (Denmark)

    Hagen, Casper P; Sørensen, Kaspar; Mieritz, Mikkel G;

    2015-01-01

    MKRN3 (rs12148769) affects age at menarche in healthy girls. OBJECTIVE: The purpose of this study was to evaluate whether serum levels of MKRN3 declined before pubertal onset in healthy girls. DESIGN: This was a population-based longitudinal study of healthy Danish girls and a cohort study of early...

  4. 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

    OBJECTIVE AND DESIGN: To elucidate whether platelets differentiate cytokine release following trauma, we prospectively measured three major platelet-derived cytokines in 213 trauma patients on hospital arrival. METHODS: We measured plasma levels of the anti-inflammatory β-thromboglobulins (β...

  5. 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

  6. IGF-1 attenuates LPS induced pro-inflammatory cytokines expression in buffalo (Bubalus bubalis) granulosa cells.

    Science.gov (United States)

    Onnureddy, K; Ravinder; Onteru, Suneel Kumar; Singh, Dheer

    2015-03-01

    Interaction between immune and endocrine system is a diverse process influencing cellular function and homeostasis in animals. Negative energy balance (NEB) during postpartum period in dairy animals usually suppresses these systems resulting in reproductive tract infection and infertility. These negative effects could be due to competition among endocrine and immune signaling pathways for common signaling molecules. The present work studied the effect of IGF-1 (50 ng/ml) on LPS (1 μg/ml) mediated pro-inflammatory cytokine expression (IL-1β, TNF-α, IL-6) and aromatase (CYP19A1) genes' expressions as well as proliferation of buffalo granulosa cells. The crosstalk between LPS and IGF-1 was also demonstrated through studying the activities of downstream signaling molecules (ERK1/2, Akt, NF-κB) by western blot and immunostaining. Gene expression analysis showed that IGF-1 significantly reduced the LPS induced expression of IL-1β, TNF-α and IL-6. LPS alone inhibited the CYP19A1 expression. However, co-treatment with IGF-1 reversed the inhibitory effect of LPS on CYP19A1 expression. LPS alone did not affect granulosa cell proliferation, but co-treatment with IGF-1, and IGF-1 alone enhanced the proliferation. Western blot results demonstrated that LPS caused the nuclear translocation of the NF-κB and increased the phosphorylation of ERK1/2 and Akt maximum at 15 min and 60 min, respectively. Nonetheless, co-treatment with IGF-1 delayed LPS induced phosphorylation of ERK1/2 (peak at 120 min), while promoting early Akt phosphorylation (peak at 5 min) with no effect on NF-κB translocation. Overall, IGF-1 delayed and reversed the effects of LPS, suggesting that high IGF-1 levels may combat infection during critical periods like NEB in postpartum dairy animals. PMID:25433435

  7. IGF-II receptors and IGF-II-stimulated glucose transport in human fat cells

    International Nuclear Information System (INIS)

    Insulin-like growth factor II (IGF-II) receptors have been described in rat but not in human adipocytes. In both species, IGF-II has been reported to stimulate glucose transport by interacting with the insulin receptor. In this study, we have unequivocally demonstrated the presence of IGF-II receptors in human adipocytes. 125I-labeled IGF-II specifically binds to intact adipocytes, membranes, and lectin-purified detergent solubilized extracts. Through the use of 0.5 mM disuccinimidyl suberate, 125I-IGF-II is cross-linked to a 260-kDa protein that is identified as the IGF-II receptor by displacement experiments with unlabeled IGF-II, IGF-I, and insulin and either by immunoprecipitation or by Western blot analysis with mannose 6-phosphate receptor antibodies. The concentrations of IGF-II required for half-maximal and maximal stimulation of glucose transport in human adipocytes are 35 and 100 times more than that of insulin. The possibility of IGF-II stimulating glucose transport by interacting predominantly with the insulin receptor is suggested by the following: (1) the concentration of IGF-II that inhibits half of insulin binding is only 20 times more than that of insulin; (2) the lack of an additive effect of IGF-II and insulin for maximal stimulation of glucose transport; (3) the ability of monoclonal insulin receptor antibodies to decrease glucose transport stimulated by submaximal concentrations of both IGF-II and insulin; and (4) the ability of IGF-II to stimulate insulin receptor autophosphorylation albeit at a reduced potency when compared with insulin

  8. Skin fibrosis correlates with circulating thyrotropin levels in systemic sclerosis: translational association with Hashimoto's thyroiditis.

    Science.gov (United States)

    Bagnato, Gian Luca; Roberts, William Neal; Fiorenza, Alessia; Arcuri, Chiara; Certo, Rosaria; Trimarchi, Francesco; Ruggeri, Rosaria Maddalena; Bagnato, Gian Filippo

    2016-02-01

    Systemic sclerosis (SSc) is a connective tissue disease, characterized by cutaneous and multi-organ fibrosis, and vascular abnormalities. Skin thickening is a characteristic feature of SSc and resembles myxedematous skin. Our aim was to correlate the degree of skin involvement in SSc patients with serum TSH levels, since TSH receptors are widely expressed in human tissues, including the skin. In this cross-sectional study, we enrolled 70 SSc patients, all females with a mean age of 47 ± 11 year. Thirty-five age- and sex-matched HT patients were recruited, as controls. Subjects under L-thyroxine therapy and/or with positive anti-TSH receptor antibodies were excluded. In all subjects, we measured serum TSH, FT4, and free tri-iodothyronine (FT3) levels. Skin thickness was evaluated using the modified Rodnan total skin score (mRSS). mRSS averaged 14 ± 9 for SSc and 4 ± 6 for HT patients. TSH levels positively correlated with skin scores in both SSc and HT patients groups. In SSc patients, FT3 and FT4 showed an inverse correlation with mRSS, while in HT only FT4 levels showed this inverse significance. When divided by cutaneous extent, SSc patients with diffuse disease form had higher TSH serum levels compared to those with the limited form; additionally, the correlations between TSH, FT4, and mRSS reached statistical significance. Our preliminary data clearly indicate that serum TSH is higher in SSc patients with more severe skin disease, and significantly correlate with the mRSS. Therefore, TSH could play a role in the development of cutaneous changes in SSc patients. PMID:25994300

  9. 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)

  10. SiRNA-mediated IGF-1R inhibition sensitizes human colon cancer SW480 cells to radiation

    International Nuclear Information System (INIS)

    Purpose. Insulin like growth factor receptor 1 (IGF-1R) is well-documented to play a key role in radiation response and tumor radiosensitivity, thus offering an attractive clinic drug target to enhance tumor sensitivity to anti-cancer radiotherapy. Material and methods. Human colon carcinoma SW480 cells were transfected with the specific small interference RNA (siRNA) expression vector (pkD-shRNA-IGF-1R-V2) designed to target IGF-1R mRNA. The expression of IGF-1R mRNA and its protein among the transfected and untransfected cells were detected by semi-quantitative RT-PCR and ELISA assay. The changes in cell radiosensitivity were examined by MTT assay. Results. Transfection of mammalian expression vector pkD containing IGF-1R siRNA was shown to reduce IGF-1R mRNA levels by up to 95%. ELISA assay detected a similar inhibition of IGF-1R protein levels in cells transfected with IGF-1R siRNA. SW480 cells transfected with the expression vector for siRNA significantly rendered cells more sensitive to radiation and the highest radiation enhancement ratio was 2.02 ± 0.08. Conclusion. These data provide the first evidence that specific siRNA fragment (pkD-shRNA-IGF-1R-V2) targeting human IGF-1R mRNA is able to enhance colon cancer radiosensitivity. Also results indicated that, combining IGF-1R siRNA and radiation significantly enhances antitumor efficacy compared with either modality alone

  11. Impact of obesity control on circulating level of endothelial progenitor cells and angiogenesis in response to ischemic stimulation

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

  13. 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...

  14. 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...... ±12 ng/mL, P<0.05), 23.8% in F1 (348 ±12 ng/mL, P<0.05) and 28.8% in F2 (362 ±25 P<0.05). CONCLUSION: We demonstrated increased serological levels of citrullinated and MMP degraded vimentin in an animal model of liver fibrosis and in early fibrosis associated with HCV and NAFLD patients. These data...

  15. Role of IGF-1 pathway in the pathogenesis of Graves’ orbitopathy

    OpenAIRE

    Smith, Terry J.; Huetwell, Frederick G.L.; Hegedüs, Laszlo; Douglas, Raymond S.

    2012-01-01

    The etiology of Graves’ orbitopathy (GO) remains enigmatic and thus controversy surrounds its pathogenesis. The role of the TSH receptor (TSHR) and the activating antibodies directed against it in the hyperthyroidism of Graves’ disease (GD) is firmly established. Less well elucidated is what part the TSHR pathway might play in the development of GO. Also uncertain is the participation of other cell surface receptors in the disease. Elevated levels of IGF-1 receptor (IGF-1R) have been found in...

  16. Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo.

    Science.gov (United States)

    Ferri, C; Pittoni, V; Piccoli, A; Laurenti, O; Cassone, M R; Bellini, C; Properzi, G; Valesini, G; De Mattia, G; Santucci, A

    1995-03-01

    Endothelin-1 (ET-1) is a potent vasoactive and mitogenic peptide produced by the vascular endothelium. In this study, we evaluated whether insulin stimulates ET-1 secretion by human endothelial cells derived from umbilical cord veins and by human permanent endothelial hybrid cells Ea.hy 926. Moreover, to provide evidence that insulin may stimulate ET-1 secretion in vivo, plasma ET-1 levels were evaluated in 7 type II diabetic normotensive males (mean age, 54.3 +/- 4.0 yr) during 2-h hyperinsulinemic euglycemic clamps (287 pmol insulin/m2.min-1) as well as in 12 obese hypertensive males (mean age, 44.2 +/- 4.6 yr) before and after a 12-week period of caloric restriction. Our results showed that insulin stimulated ET-1 release from cultured endothelial cells in a dose-dependent fashion. ET-1 release persisted for 24 h and was also observed at physiological insulin concentrations (10(-9) mol/L). The insulin-induced ET-1 secretion was inhibited by genistein, a tyrosine kinase inhibitor, and by cycloheximide, a protein synthesis inhibitor, suggesting that it requires de novo protein synthesis rather than ET-1 release from intracellular stores. In the in vivo experiments, plasma ET-1 levels rapidly increased during euglycemic hyperinsulinemic clamps (from 0.76 +/- 0.18 pg/mL at time zero to 1.65 +/- 0.21 pg/mL at 60 min; P < 0.05) and persisted elevated until the end of insulin infusion (1.37 +/- 0.37 pg/mL at 120 min; P < 0.05 vs. time zero). In obese hypertensives, plasma ET-1 levels significantly decreased after 12 weeks of caloric restriction (from 0.85 +/- 0.51 to 0.48 +/- 0.28 pg/mL; P < 0.04). The decrease in body weight induced by caloric restriction was accompanied by a significant reduction in fasting insulin levels (from 167.2 +/- 94.0 to 98.9 +/- 44.9 pmol/L; P < 0.05) which correlated with the reduction in plasma ET-1 levels (r = 0.78; P < 0.003). In conclusion, our data show that insulin stimulates both in vitro and in vivo ET-1 secretion. Such interaction

  17. Circulating Glutamate and Taurine Levels Are Associated with the Generation of Reactive Oxygen Species in Paroxysmal Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. Baseline IGF-I Levels Determine Insulin Secretion and Insulin Sensitivity during the First Year on Growth Hormone Therapy in Children Born Small for Gestational Age. Results from a North European Multicentre Study (NESGAS)

    DEFF Research Database (Denmark)

    Jensen, Rikke Beck; Thankamony, Ajay; O'Connell, Susan M; Salgin, Burak; Kirk, Jeremy; Donaldson, Malcolm; Ivarsson, Sten-A; Söder, Olle; Roche, Edna; Hoey, Hilary; Dunger, David B; Holm, Kirsten; Juul, Anders

    2013-01-01

    ), 110 short SGA children received GH at 67 µg/kg/day for 1 year. Insulin secretion was assessed by acute insulin response (AIR), insulin sensitivity (IS) by HOMA and disposition index (DI) by insulin secretion adjusted for IS. Results: First-year GH therapy led to increases in height and IGF-I standard......Objective: Developmental programming alters growth and metabolic outcome in children born small for gestational age (SGA). We explored insulin and glucose metabolism in SGA children treated with a fixed GH dose over 1 year. Methods: In the North European Small for Gestational Age Study (NESGAS...... deviation score (SDS), and reductions in IS (p <0.0001). Compensatory increases in AIR (p <0.0001) were insufficient and resulted in reduced DI (p = 0.032). Children in the highest IGF-I SDS tertile at baseline were the least insulin sensitive at baseline (p = 0.024) and 1 year (p = 0.006). IGF-I responses...

  20. Tailored antihypertensive drug therapy prescribed to older women attenuates circulating levels of interleukin-6 and tumor necrosis factor-α

    Directory of Open Access Journals (Sweden)

    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

  1. 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

  2. Association of High Vitamin D Status with Low Circulating Thyroid-Stimulating Hormone Independent of Thyroid Hormone Levels in Middle-Aged and Elderly Males

    Directory of Open Access Journals (Sweden)

    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.

  3. The Role of Type I Insulin Like Growth Factor Receptor (IGF-IR) in Adult and Childhood Acute Lymphoblastic Leukemia

    International Nuclear Information System (INIS)

    Background: Type 1 insulin like growth factor receptor (IGF-IR) is over expressed in many tumors including hematological cancers. It is a critical signaling molecule for tumor cell proliferation and survival. Data suggest that IGF-IR antibodies can effectively and specifically inhibit cancer cell growth in vitro and in vivo. Blockage of IGF-IR expression could be a promising therapeutic approach for the management of cancer patients. Aim of Work: To characterize the expression pattern of IGF-IR gene in malignant lymphoblasts of children and adults suffering from ALL in relation to clinical features at diagnosis. Patients and Methods: The expression of IGF-IR was analyzed in 60 patients with ALL, 30 childhood ALL (16 newly diagnosed and 14 in complete remission) and 30 adulthood ALL (15 newly diagnosed and 15 in complete remission) together with 20 normal age and sex matched healthy controls using a Real-Time Quantitative Reverse- Transcriptase Polymerase Chain Reaction (RTQ-PCR) to assess the possible relation, association or correlation between IGF-IR expression and ALL clinical and laboratory features at diagnosis. Results: IGF-IR was expressed in all 60 patients with ALL; the expression levels of IGF-IR were significantly higher in newly diagnosed patients than in patients in complete remission (CR) and controls (p<0.001). There were no statistically significant differences in the expression of IGF-IR between patients with different clinical and laboratory features. Conclusion: IGF-1R seems to play a crucial role in patients with ALL since it is expressed in all ALL cases (adulthood and childhood). Therefore, new therapeutic agents targeting IGF-1R may provide a better chance for those patients

  4. 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

  5. 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; Skakkebaek, N E

    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 some...... controversy still exists. In adults, the diagnostic value of IGF-I and IGFBP-3 suspected of GHD has been reported in only a few studies. We performed a GH provocative test, using oral clonidine, in 108 patients who had previously been treated with GH during childhood (73 men and 35 women). Basal IGF-I and...... 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...

  6. 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.

  7. Circulating levels of monocyte chemoattractant protein-1 and interleukin-7 in women who have undergone bilateral salpingo-oophorectomy

    Directory of Open Access Journals (Sweden)

    Tani A

    2013-12-01

    Full Text Available Anna Tani,1 Toshiyuki Yasui,2 Sumika Matsui,1 Takeshi Kato,1 Naoko Tsuchiya,3 Mitsutoshi Yuzurihara,3 Yoshio Kase,3 Minoru Irahara11Department of Obstetrics and Gynecology, 2Department of Reproductive Technology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan; 3Pharmacology Research Department, Tsumura Central Research Institute, Ibaraki, JapanPurpose: The aim of the study reported here was to determine the effect of surgical menopause by bilateral salpingo-oophorectomy (BSO on circulating levels of cytokines and chemokines related to the pathogenesis of atherosclerosis.Patients and methods: A total of 110 women were recruited for this study from the outpatient clinic of our facility. We divided the women into three groups: 1 women with a regular menstrual cycle, 2 women in whom less than 5 years had passed since their BSO, and 3 women in whom 5 years or more had passed since their BSO. Concentrations of nine cytokines and chemokines in serum were measured.Results: The serum monocyte chemoattractant protein-1 (MCP-1 level in women in whom less than 5 years had passed since their BSO was significantly higher than in women with a regular menstrual cycle (P<0.05. There were significant differences in serum interleukin (IL-7 among the three groups (P=0.035. MCP-1 showed a significant positive correlation (r=0.320, P=0.008 with follicle-stimulating hormone in women with a regular menstrual cycle and in women in whom less than 5 years had passed since their BSO.Conclusion: A hypoestrogenic state due to BSO induced changes in MCP-1 and IL-7 levels. MCP-1 level showed a significant increase in the early period after BSO, while IL-7 level showed a significant decrease in the late period after BSO.Keywords: follicle-stimulating hormone, cytokines, chemokines, hypoestrogenism, surgical menopause

  8. 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 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.

  9. Pioglitazone treatment increases spontaneous growth hormone (GH) secretion and stimulated GH levels in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Støving, René Klinkby; Hagen, Claus;

    2005-01-01

    treatment. Before and after intervention, levels of fasting insulin, GH, total IGF-I, free IGF-I, IGF binding protein-1, IGF-II, free fatty acids, testosterone, and SHBG were measured. Patients underwent whole-body dual x-ray absorptiometry scans, pyridostigmine-GHRH tests, and 24-h 20-min integrated blood......, approximate entropy levels, or basal GH release. Levels of IGF binding protein-1 significantly increased, whereas no significant differences were measured in total IGF-I and free IGF-I. Pioglitazone treatment significantly decreased fasting insulin and homeostasis model assessment levels. No significant...

  10. 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

  11. 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

  12. 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. 

  13. 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.

  14. 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

  15. 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.

  16. β2-Adrenergic receptor agonist ameliorates phenotypes and corrects microRNA-mediated IGF1 deficits in a mouse model of Rett syndrome

    OpenAIRE

    Mellios, Nikolaos; Woodson, Jonathan; Garcia, Rodrigo I.; Crawford, Benjamin; Sharma, Jitendra; Sheridan, Steven D.; Haggarty, Stephen J.; Sur, Mriganka

    2014-01-01

    Rett syndrome is a devastating neurodevelopmental disorder with diverse symptoms and no available treatment. Previous work from our laboratory has identified deficits in insulin-like growth factor 1 (IGF1) levels in Mecp2 mutant mice, and demonstrated correction of symptoms and molecular-signaling alterations with IGF1 treatment. Here, we show that treatment with the adrenergic receptor agonist clenbuterol rescues a microRNA pathway that underlies IGF1 expression, improves survival, and ameli...

  17. Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS

    OpenAIRE

    Lepore, Angelo C.; Haenggeli, Christine; Gasmi, Mehdi; Bishop, Kathie M.; Bartus, Raymond T.; Maragakis, Nicholas J.; Rothstein, Jeffrey D.

    2007-01-01

    The potent neuroprotective activities of neurotrophic factors, including insulin-like growth factor 1 (IGF-1), make them promising candidates for treatment of amyotrophic lateral sclerosis (ALS). In an effort to maximize rate of motor neuron transduction, achieve high levels of spinal IGF-1, and thus enhance therapeutic benefit, we injected an adeno-associated virus 2 (AAV2)-based vector encoding human IGF-1 (CERE-130) into lumbar spinal cord parenchyma of SOD1G93A mice. We observed robust an...

  18. 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

  19. 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.

  20. 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.

  1. Overexpression of IGF-I receptor in HeLa cells enhances in vivo radioresponse

    International Nuclear Information System (INIS)

    Insulin-like growth factor I receptor (IGF-IR) is a transmembrane receptor tyrosine kinase whose activation strongly promotes cell growth and survival. We previously reported that IGF-IR activity confers intrinsic radioresistance in mouse embryo fibroblasts in vitro. However, it is still unclear whether tumor cells overexpressing IGF-IR exhibit radioresistance in vivo. For this purpose, we established HeLa cells that overexpress IGF-IR (HeLa-R), subcutaneously transplanted these cells into nude mice, and examined radioresponse in the resulting solid tumors. HeLa-R cells exhibited typical in vitro phenotypes generally observed in IGF-IR-overexpressing cells, as well as significant intrinsic radioresistance in vitro compared with parent cells. As expected, the transplanted HeLa-R tumors grew at a remarkably higher rate than parent tumors. Histological analysis revealed that HeLa-R tumors expressed more VEGF and had a higher density of tumor vessels. Unexpectedly, a marked growth delay was observed in HeLa-R tumors following 10 Gy of X-irradiation. Immunostaining of HeLa-R tumors for the hypoxia marker pimonidazole revealed a significantly lower level of hypoxic cells. Moreover, clamp hypoxia significantly increased radioresistance in HeLa-R tumors. Tumor microenvironments in vivo generated by the IGF-IR expression thus could be a major factor in determining the tumor radioresponse in vivo

  2. Effects of IGFS on blood lipid metabolism in experimental hyperlipidemia rats

    International Nuclear Information System (INIS)

    Objective: To observe the effects of injection of ginseng fruit saponins (IGFS) on total cholesterol (TC), lipoprotein cholesterol metabolism and antioxidative activity in experimental hyperlipidemia rats. Methods: The TC, lipoprotein cholesterol and lipidperoxidation (LPO) contents, prostacycline (PGI2) and thromboxane (TXA2) levels, superoxidedismutase (SOD) activity and blood viscosity were measured respectively in hyperlipidemia rats which had been given IGFS 10, 20 and 40 mg·kg-1·d-'1 ip, respectively, for fifteen days. In addition, fat accumulation in liver was observed. Results: The triglyceride (TG), TC, low density lipoprotein cholesterol (LDL-c) in serum, TXA2 in plasma, LPO in serum and liver and blood viscosity were decreased significantly, and PGI2 in plasma and SOD in serum and liver were significantly increased after administration with IGFS (20 and 40 mg·kg-1·d-1) in experimental hyperlipidemia rats. Moreover, IGFS decreased ratios of TC/HDL-c and LDL-c/HDL-c, increased the ratio of PGI2/TXA2 and inhibit fat accumulation in liver. The content of high density lipoprotein cholesterol (HDL-c) in serum were significantly increased after administration IGFS (40 mg·kg-1·-1) in experimental hyperlipidemia rats. Conclusions: IGFS can inhibit arterioscleros by improving cholesterol and lipoprotein cholesterol metabolism, suppressing LPO and increasing antioxidation. (authors)

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. Luteolin decreases IGF-II production and downregulates insulin-like growth factor-I receptor signaling in HT-29 human colon cancer cells

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    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.

  11. 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

  12. 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...

  13. 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.

  14. HIF2A and IGF2 Expression Correlates in Human Neuroblastoma Cells and Normal Immature Sympathetic Neuroblasts

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    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.

  15. 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...

  16. 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....

  17. 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

  18. 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.

  19. 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; Nielsen, C T; Halberg, P; Karlsmark, T; Heegaard, Niels Henrik Helweg; Jacobsen, Søren

    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...

  20. Cross-sectional and longitudinal study of association between circulating thiobarbituric acid-reacting substance levels and clinicobiochemical parameters in 1,178 middle-aged Japanese men - the Amagasaki Visceral Fat Study

    OpenAIRE

    Okauchi Yukiyoshi; Kishida Ken; Funahashi Tohru; Noguchi Midori; Ogawa Tomoko; Okita Kohei; Iwahashi Hiromi; Ohira Tetsuya; Imagawa Akihisa; Nakamura Tadashi; Shimomura Iichiro

    2011-01-01

    Abstract Background Circulating thiobarbituric acid-reacting substance (TBARS) levels, a marker of systemic oxidative stress, are predictive of cardiovascular events. However, they has not been evaluated in Japanese, especially with regard to the factors that contribute to the changes in circulating TBARS levels. We investigated the cross-sectional and longitudinal relationships between circulating TBARS levels and various clinicobiochemical parameters in middle-aged men. Methods In this popu...

  1. 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

  2. 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

  3. Deep circulation in the Indian and Pacific Oceans and its implication for the dumping of low-level radioactive waste

    International Nuclear Information System (INIS)

    The complexity of ocean transport processes has meant that the limits for the dumping of low-activity radioactive wastes have had to be based on very simplified models of the oceans. This report discusses the models used to determine dumping limits and contrasts them with the known ocean circulation patterns. The deep circulations of the Indian and Pacific Oceans are reviewed to provide a basis for estimating the possible destinations and likely transit times for dissolved material released at the ocean floor

  4. 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

  5. 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...

  6. Appearance of insulin and insulin-like growth factor-I (IGF-I) receptors throughout the ontogeny of brown trout (Salmo trutta fario).

    Science.gov (United States)

    Maestro, M A; Méndez, E; Bayraktaroglu, E; Baños, N; Gutiérrez, J

    1998-06-01

    Insulin and IGF-I receptors were characterized in glycoprotein fractions prepared by affinity chromatography from different developmental stages of brown trout. The specificity of insulin and IGF-I binding was demonstrated by crossed-competition assays: unlabelled insulin displaced bound radiolabelled insulin at concentrations 45-fold lower than unlabelled IGF-I, whilst unlabelled IGF-I displaced bound radiolabelled IGF-I at concentrations 2,000-fold lower than unlabelled insulin. The affinity of these receptors did not change significantly during trout development. Insulin-specific binding was detectable 3 weeks after spawning, after which it increased to a maximum in fry weighing 0.4 g, and decreased progressively to adult levels. IGF-I specific binding was detectable in newly laid eggs and increased to a maximum during organogenesis in eyed eggs. It then decreased progressively during subsequent stages of development to adult levels. The apparent molecular weight (Mr) of the alpha-subunit of brown trout insulin and IGF-I receptors was smaller than that of the alpha-subunit of the rat insulin receptor. Receptor tyrosine kinase activity was stimulated in a dose-dependent manner by insulin and IGF-I. Insulin and IGF-I stimulated tyrosine kinase activity and reached a maximum of 201 +/- 17.6 and 240 +/- 29.6% of basal phosphorylation, respectively. PMID:10984307

  7. Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance

    Science.gov (United States)

    Sayers, Sophie R.; Reimann, Frank; Gribble, Fiona M.; Parker, Helen; Zac-Varghese, Sagen; Bloom, Stephen R.; Foretz, Marc; Viollet, Benoit; Rutter, Guy A.

    2016-01-01

    Background 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. Method 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. Results 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). Conclusion 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. PMID:27010458

  8. 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.

  9. 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.

  10. 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. PMID:25808997

  11. Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3

    OpenAIRE

    Wang, Wei; Yan ZHANG; Lv, Ming; Feng, Jiannan; Peng, Hui; Geng, Jing; Lin, Zhou; Zhou, Tingting; Li, Xinying; Shen, Beifen; Ma, Yuanfang; Qiao, Chunxia

    2014-01-01

    Background Antibody resistance, not only de novo but also acquired cases, usually exists and is related with lower survival rate and high risk of recurrence. Reversing the resistance often results in better clinical therapeutic effect. Previously, we established a trastuzumab-resistant ovarian cancer cell line, named as SKOV3-T, with lower HER2 and induced higher IGF-1R expression level to keep cell survival. Methods IGF-1R was identified important for SKOV3-T growth. Then, a novel anti-IGF-1...

  12. Validation of serum IGF-I as a biomarker to monitor the bioactivity of exogenous growth hormone agonists and antagonists in rabbits

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    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

  13. 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

  14. 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...

  15. 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

  16. Common genetic variation in the SERPINF1 locus determines overall adiposity, obesity-related insulin resistance, and circulating leptin levels.

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    Anja Böhm

    , obesity-related insulin resistance, and circulating leptin levels.

  17. Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease

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    Masuda Takashi

    2010-05-01

    Full Text Available Abstract Background Glucagon-like peptide-1 (GLP-1 is an incretin hormone that has a wide range of effects on glucose metabolism and cardiovascular function (e.g., improving insulin sensitivity, reduction in appetite, modulation of heart rate, blood pressure and myocardial contractility. Metabolic syndrome (MetS is associated with an increased risk of developing atherosclerotic cardiovascular diseases. Novel glycemic control drugs, the dipeptidyl-peptidase-4 (DPP-4 inhibitors, work by inhibiting the inactivation of incretin hormones, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP. In spite of good effects of these drugs in diabetic patients, circulating levels of incretins and their role in MetS are largely unknown. Methods To examine relationships between incretin hormones and MetS risk factors, we measured circulating levels of incretins in obese high-risk patients for cardiovascular disease. Fasting serum GLP-1 and GIP levels were measured by ELISA. We performed a cross-sectional analysis of metabolic variables in the fasting state in two subject groups: with MetS (n = 60 and pre-MetS (n = 37. Results Fasting levels of Serum GLP -1 in the peripheral circulation were significantly increased correlated with the accumulation of MetS risk factors components (r = 0. 470, P Conclusion Circulating levels of GLP-1 in relation to the accumulation in MetS factors suggested that MetS patients with elevated levels of GLP-1 are high-risk patients for cardiovascular disease, independent with the presence of diabetes.

  18. 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.

  19. RNA microarray analysis in prenatal mouse cochlea reveals novel IGF-I target genes: implication of MEF2 and FOXM1 transcription factors.

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    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

  20. 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 ...

  1. Lower Circulating C1q/TNF-Related Protein-3 (CTRP3 Levels Are Associated with Obesity: A Cross-Sectional Study.

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    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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. Elevated circulating insulin-like growth factor binding protein-1 is sufficient to cause fetal growth restriction.

    Science.gov (United States)

    Watson, Carole S; Bialek, Peter; Anzo, Makoto; Khosravi, Javad; Yee, Siu-Pok; Han, Victor K M

    2006-03-01

    IGF binding protein-1 (IGFBP-1) inhibits the mitogenic actions of the IGFs. Circulating IGFBP-1 is elevated in newborns and experimental animals with fetal growth restriction (FGR). To establish a causal relationship between high circulating IGFBP-1 and FGR, we have generated transgenic mice using the mouse alpha-fetoprotein gene promoter to target overexpression of human IGFBP-1 (hIGFBP-1) in the fetal liver. These transgenic mice (AFP-BP1) expressed hIGFBP-1 mainly in the fetal hepatocytes, starting at embryonic d 14.5 (E14.5), with lower levels in the gut. The expression peaked at 1 wk postnatally (plasma concentration, 474 +/- 34 ng/ml). At birth, AFP-BP1 pups were 18% smaller [weighed 1.34 +/- 0.02 g compared with 1.62 +/- 0.04 g for wild type (WT); P catch-up growth. The placentas of the AFP-BP1 mice were larger than WT from E16.5 onwards (150 +/- 12 for AFP-BP1 vs. 100 +/- 5 mg for WT at E16.5; P catch-up growth. Overall, these data clearly demonstrate that high concentrations of circulating IGFBP-1 are sufficient to cause FGR. PMID:16293667

  9. 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

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

    International Nuclear Information System (INIS)

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

  11. Biological variation in circulating levels of mannan-binding lectin (MBL) and MBL-associated serine protease-2 and the influence of age, gender and physical exercise

    DEFF Research Database (Denmark)

    Ytting, H; Christensen, IJ; Thiel, Steffen; Jensenius, Jens Christian; Svendsen, MN; Nielsen, L; Lottenburger, T; Nielsen, HJ

    2007-01-01

    needed. We here investigate variations of MBL and MASP-2 in healthy persons over time and in relation to gender, age and physical activity. MBL and MASP-2 concentrations were determined in serum from healthy adults over a 3-week period and this was repeated 6 months later (n = 32); during a 24-h period...... affect the levels (P > 0.8). Serum and plasma levels were only marginally different, and were independent of age and gender. Circulating levels of MBL and MASP-2 are stable over time in healthy individuals, which is advantageous for their potential application as biomarkers....

  12. Biological Variation in Circulating Levels of Mannan-Binding Lectin (MBL) and MBL-Associated Serine Protease-2 and the Influence of Age, Gender and Physical Exercise

    DEFF Research Database (Denmark)

    Ytting, Henriette; Christensen, Ib Jarle; Thiel, S.; Jensenius, J. C.; Nordahl Svendsen, Mads; Nielsen, L.; Lottenburger, T; Nielsen, Hans Jørgen

    2007-01-01

    needed. We here investigate variations of MBL and MASP-2 in healthy persons over time and in relation to gender, age and physical activity. MBL and MASP-2 concentrations were determined in serum from healthy adults over a 3-week period and this was repeated 6 months later (n = 32); during a 24-h period...... affect the levels (P > 0.8). Serum and plasma levels were only marginally different, and were independent of age and gender. Circulating levels of MBL and MASP-2 are stable over time in healthy individuals, which is advantageous for their potential application as biomarkers....

  13. 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...

  14. Anticipatory and consummatory effects of (hedonic) chocolate intake are associated with increased circulating levels of the orexigenic peptide ghrelin and endocannabinoids in obese adults

    OpenAIRE

    Rigamonti, Antonello E.; Piscitelli, Fabiana; Aveta, Teresa; Agosti, Fiorenza; De Col, Alessandra; Bini, Silvia; Cella, Silvano G.; Di Marzo, Vincenzo; Sartorio, Alessandro

    2015-01-01

    Background: Hedonic hunger refers to consumption of food just for pleasure and not to maintain energy homeostasis. Recently, consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and the endocannabinoid 2-arachidonoyl-glycerol (2-AG) in normal-weight subjects. To date, the effects of hedonic hunger, and in particular of chocolate craving, on these mediators in obese subjects are still unknown.Methods: To explore...

  15. 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....

  16. 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...

  17. 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...

  18. 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...... 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 the...... development of lupus nephritis at an early stage....

  19. 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

  20. 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

  1. Insulin-like growth factor 1 (IGF-1) therapy: Mitochondrial dysfunction and diseases.

    Science.gov (United States)

    Sádaba, M C; Martín-Estal, I; Puche, J E; Castilla-Cortázar, I

    2016-07-01

    This review resumes the association between mitochondrial function and diseases, especially neurodegenerative diseases. Additionally, it summarizes the major role of IGF-1 as a mitochondrial protector, as studied in several experimental models (cirrhosis, aging …). The contribution of mitochondrial dysfunction to impairments in insulin metabolic signaling is also suggested by gene array analysis showing that reductions in gene expression, that regulates mitochondrial ATP production, are associated with insulin resistance and type 2 diabetes mellitus. Moreover, reductions in oxidative capacity of mitochondrial electron transport chain are manifested in obese, insulin-resistant and diabetic patients. Genetic and environmental factors, oxidative stress, and alterations in mitochondrial biogenesis can adversely affect mitochondrial function, leading to insulin resistance and several pathological conditions, such as type 2 diabetes. Finally, it remains essential to know the exact mechanisms involved in mitochondrial generation and metabolism, mitophagy, apoptosis, and oxidative stress to establish new targets in order to develop potentially effective therapies. One of the newest targets to recover mitochondrial dysfunction could be the administration of IGF-1 at low doses. In the last years, it has been observed that IGF-1 therapy has several beneficial effects: restores physiological IGF-1 levels; improves insulin resistance and lipid metabolism; exerts mitochondrial protection; and has hepatoprotective, neuroprotective, antioxidant and antifibrogenic effects. In consequence, treatment of mitochondrial dysfunctions with low doses of IGF-1 could be a powerful and useful effective therapy to restore normal mitochondrial functions. PMID:27020404

  2. 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.

  3. 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...

  4. 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...

  5. 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...

  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. 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...

  8. 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

  9. Circulating interferon-α2 levels are increased in the majority of patients with systemic lupus erythematosus and are associated with disease activity and multiple cytokine activation.

    Science.gov (United States)

    Becker-Merok, A; Østli-Eilersten, G; Lester, S; Nossent, Jc

    2013-02-01

    Mutations in interferon (IFN) regulatory factor genes and the biological activity of type I IFN on expression of specific genes that are induced by IFN have been associated with various aspects of systemic lupus erythematosus (SLE). Circulating levels of IFN-α in SLE has not been extensively studied because of limited sensitivity of available ELISA assays. We performed a cross-sectional case-control study where circulating levels of IFN-α2 were measured by a highly sensitive, solution phase multiplex magnetized bead assay and investigated the relation of IFN-α2 with autoantibody profiles, clinical disease activity and levels of inflammatory cytokines in SLE patients (n = 87). Cytokine levels were determined on stored sera aliquots with cut-off levels determined by the geometric mean + 2SD in healthy controls (n = 27). IFN-α2 levels were increased in 64% of SLE patients, who displayed more renal disease and higher disease activity (p = 0.06) and had a significantly higher sum of activated cytokines (median 4.5, range 7) compared to patients with normal IFN-α2 (median one, range 3; p phase micro-bead assay thus identified increased IFN-α2 levels in two-thirds of SLE patients with longstanding disease. The association with clinical disease and activation of multiple inflammatory cytokines supports a role for IFN-α2 in disease perpetuation in a large subset of SLE patients. PMID:23213068

  10. The somatotropic axis in neonatal calves can be modulated by nutrition, growth hormone, and Long-R3-IGF-I.

    Science.gov (United States)

    Hammon, H; Blum, J W

    1997-07-01

    Effects on the somatotropic axis [plasma levels of insulin-like growth factors (IGFs) I and II, IGF-binding proteins (IGFBPs), and growth hormone (GH)] of feeding different amounts of colostrum or milk replacer, of Long-R3-IGF-I (administered subcutaneously or orally; 50 micrograms.kg body wt-1.day-1 for 7 days), and of subcutaneously injected recombinant bovine GH (rbGH; 1 mg.kg body wt-1.day-1 for 7 days) were evaluated in calves during the 1st wk of life. Plasma Long-R3-IGF-I increased after subcutaneous application but not with the oral dose. Endogenous IGF-I was higher in calves fed colostrum six times compared with those fed only milk replacer. Native IGF-I was highest in rbGH-injected calves but was lowered by the subcutaneous injection of Long-R3-IGF-I. IGF-II concentrations were not modified by any of the treatments. IGFBP-2 increased in calves fed only milk replacer and those receiving subcutaneous Long-R3-IGF-I. GH was not modulated by differences in nutrition but increased after rbGH administration and similarly in all groups after intravenous injection of GH-releasing factor analog GRF-(1-29). Parenteral administration of Long-R3-IGF-I decreased GH concentration but did not affect the secretory pattern. The data demonstrate that the somatotrophic axis is basically functioning in neonatal calves and is influenced by nutrition, GH, and Long-R3-IGF-I. PMID:9252489

  11. The cAMP Response Element Binding protein (CREB) is activated by Insulin-like Growth Factor-1 (IGF-1) and regulates myostatin gene expression in skeletal myoblast

    International Nuclear Information System (INIS)

    Highlights: •IGF-1 induces the activation of CREB via IGF-1R/PI3K/PLC signaling pathway. •Calcium dependent signaling pathways regulate myostatin gene expression. •IGF-1 regulates myostatin gene expression via CREB transcription in skeletal myoblast. -- Abstract: Myostatin, a member of the Transforming Growth Factor beta (TGF-β) superfamily, plays an important role as a negative regulator of skeletal muscle growth and differentiation. We have previously reported that IGF-1 induces a transient myostatin mRNA expression, through the activation of the Nuclear Factor of Activated T cells (NFAT) in an IP3/calcium-dependent manner. Here we examined the activation of CREB transcription factor as downstream targets of IGF-1 during myoblast differentiation and its role as a regulator of myostatin gene expression. In cultured skeletal myoblast, IGF-1 induced the phosphorylation and transcriptional activation of CREB via IGF-1 Receptor/Phosphatidylinositol 3-Kinase (PI3K)/Phospholipase C gamma (PLC γ), signaling pathways. Also, IGF-1 induced calcium-dependent molecules such as Calmodulin Kinase II (CaMK II), Extracellular signal-regulated Kinases (ERK), Protein Kinase C (PKC). Additionally, we examined myostatin mRNA levels and myostatin promoter activity in differentiated myoblasts stimulated with IGF-1. We found a significant increase in mRNA contents of myostatin and its reporter activity after treatment with IGF-1. The expression of myostatin in differentiated myoblast was downregulated by the transfection of siRNA–CREB and by pharmacological inhibitors of the signaling pathways involved in CREB activation. By using pharmacological and genetic approaches together these data demonstrate that IGF-1 regulates the myostatin gene expression via CREB transcription factor during muscle cell differentiation

  12. The cAMP Response Element Binding protein (CREB) is activated by Insulin-like Growth Factor-1 (IGF-1) and regulates myostatin gene expression in skeletal myoblast

    Energy Technology Data Exchange (ETDEWEB)

    Zuloaga, R. [Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago (Chile); Fuentes, E.N.; Molina, A. [Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago (Chile); Interdisciplinary Center for Aquaculture Research (INCAR), Víctor Lamas 1290, PO Box 160-C, Concepción (Chile); Valdés, J.A., E-mail: jvaldes@unab.cl [Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago (Chile); Interdisciplinary Center for Aquaculture Research (INCAR), Víctor Lamas 1290, PO Box 160-C, Concepción (Chile)

    2013-10-18

    Highlights: •IGF-1 induces the activation of CREB via IGF-1R/PI3K/PLC signaling pathway. •Calcium dependent signaling pathways regulate myostatin gene expression. •IGF-1 regulates myostatin gene expression via CREB transcription in skeletal myoblast. -- Abstract: Myostatin, a member of the Transforming Growth Factor beta (TGF-β) superfamily, plays an important role as a negative regulator of skeletal muscle growth and differentiation. We have previously reported that IGF-1 induces a transient myostatin mRNA expression, through the activation of the Nuclear Factor of Activated T cells (NFAT) in an IP{sub 3}/calcium-dependent manner. Here we examined the activation of CREB transcription factor as downstream targets of IGF-1 during myoblast differentiation and its role as a regulator of myostatin gene expression. In cultured skeletal myoblast, IGF-1 induced the phosphorylation and transcriptional activation of CREB via IGF-1 Receptor/Phosphatidylinositol 3-Kinase (PI3K)/Phospholipase C gamma (PLC γ), signaling pathways. Also, IGF-1 induced calcium-dependent molecules such as Calmodulin Kinase II (CaMK II), Extracellular signal-regulated Kinases (ERK), Protein Kinase C (PKC). Additionally, we examined myostatin mRNA levels and myostatin promoter activity in differentiated myoblasts stimulated with IGF-1. We found a significant increase in mRNA contents of myostatin and its reporter activity after treatment with IGF-1. The expression of myostatin in differentiated myoblast was downregulated by the transfection of siRNA–CREB and by pharmacological inhibitors of the signaling pathways involved in CREB activation. By using pharmacological and genetic approaches together these data demonstrate that IGF-1 regulates the myostatin gene expression via CREB transcription factor during muscle cell differentiation.

  13. Growth Hormone Ameliorates the Radiotherapy-Induced Ovarian Follicular Loss in Rats: Impact on Oxidative Stress, Apoptosis and IGF-1/IGF-1R Axis.

    Directory of Open Access Journals (Sweden)

    Yasmen F Mahran

    Full Text Available Radiotherapy is one of the standard cytotoxic therapies for cancer. However, it has a profound impact on ovarian function leading to premature ovarian failure and infertility. Since none of the currently available methods for fertility preservation guarantees future fertility, the need for an effective radioprotective agent is highly intensified. The present study investigated the mechanisms of the potential radioprotective effect of growth hormone (GH on γ irradiation-induced ovarian failure and the impact of the insulin like growth factor 1 (IGF-1 in the underlying protection. Immature female Sprague-Dawley rats were either exposed to single whole body irradiation (3.2 Gy and/or treated with GH (1 mg/kg s.c. Experimental γ-irradiation produced an array of ovarian dysfunction that was evident by assessment of hormonal changes, follicular development, proliferation marker (PCNA, oxidative stress as well as apoptotic markers. In addition, IGF-1/IGF-1R axis expression was assessed using real-time PCR and immunolocalization techniques. Furthermore, after full maturity, fertility assessment was performed. GH significantly enhanced follicular development and restored anti-Mullerian hormone serum level as compared with the irradiated group. In addition, GH significantly ameliorated the deleterious effects of irradiation on oxidative status, PCNA and apoptosis. Interestingly, GH was shown to enhance the ovarian IGF-1 at transcription and translation levels, a property that contributes significantly to its radioprotective effect. Finally, GH regained the fertility that was lost following irradiation. In conclusion, GH showed a radioprotective effect and rescued the ovarian reserve through increasing local IGF-1 level and counteracting the oxidative stress-mediated apoptosis.

  14. VISFATIN (NAMPT) Improves In Vitro IGF1-Induced Steroidogenesis and IGF1 Receptor Signaling Through SIRT1 in Bovine Granulosa Cells.

    Science.gov (United States)

    Reverchon, Maxime; Rame, Christelle; Bunel, Audrey; Chen, Wenyong; Froment, Pascal; Dupont, Joëlle

    2016-03-01

    VISFATIN is a novel adipokine, also known as a nicotinamide phosphorybosyltransferase (NAMPT), that is able to modulate different processes, including lipid and glucose metabolism, oxidative stress, inflammation, and insulin resistance. Recent data suggest that it also plays a role in reproductive function in rats, humans, and chickens. Here we identified VISFATIN in the bovine ovary and investigated the in vitro effects of this hormone on granulosa cell steroidogenesis and proliferation and oocyte maturation. By RT-PCR, immunoblotting, and immunohistochemistry, we found VISFATIN in various ovarian cells, including granulosa and theca cells, corpus luteum, and oocytes. In cultured bovine granulosa cells, we showed that IGF1 (10(-8) M) and VISFATIN (10 and 100 ng/ml) but not FSH (10(-8) M) increased mRNA expression levels of NAMPT after 48 h of stimulation. Moreover, we observed that human recombinant VISFATIN (hVisf, 10 ng/ml, 48 h) increased the release of progesterone and estradiol secretion, and this was associated with an increase in the protein level of STAR, the HSD3B activity, and the phosphorylation levels of IGF1R and MAPK ERK1/2 in the presence or absence of IGF1 (10(-8) M). All these effects were abolished when NAMPT was knocked down and when the sirtuin pharmacological inhibitors CHIC-35 (60 nM) and EX-527 (0.5 μM) were preincubated in bovine granulosa cells. Thus, in cultured bovine granulosa cells, VISFATIN improves basal and IGF1-induced steroidogenesis and IGF1 receptor signaling through SIRT1. PMID:26792944

  15. Altered Methylation of IGF2 Locus 20 Years after Preterm Birth at Very Low Birth Weight

    OpenAIRE

    Wehkalampi, Karoliina; Muurinen, Mari; Wirta, Sara Bruce; Hannula-Jouppi, Katariina; Hovi, Petteri; Järvenpää, Anna-Liisa; Eriksson, Johan G.; Andersson, Sture; Kere, Juha; Kajantie, Eero

    2013-01-01

    Introduction People born preterm at very low birth weight (VLBW, ≤1500g) have higher rates of risk factors for adult-onset diseases, including cardiovascular diseases and type 2 diabetes. These risks may be mediated through epigenetic modification of genes that are critical to normal growth and development. Methods We measured the methylation level of an imprinted insulin-like-growth-factor 2 (IGF2) locus (IGF2/H19) in young adults born preterm at VLBW and in their peers born at term. We stud...

  16. THE RICHNESS OF THE ENVIRONMENT AFFECTS VISUAL SYSTEM DEVELOPMENT: A ROLE FOR IGF-1

    OpenAIRE

    Roberta Narducci

    2014-01-01

    A pre-weaning enriched experience is sufficient to affect maturation of the visual system, suggesting that factors influenced by the environment during the first days of life might prime visual circuits towards a faster development. Here, we showed that IGF-1 levels are increased in the visual cortex of EE rats as early as P6 and this is a crucial event for setting in motion the developmental program induced by EE. Early intracerebroventricular (i.c.v.) infusion of IGF-1 in standard rats was ...

  17. PAPP-A proteolytic activity enhances IGF bioactivity in ascites from women with ovarian carcinoma

    DEFF Research Database (Denmark)

    Thomsen, Jacob; Hjortebjerg, Rikke; Espelund, Ulrick;

    2015-01-01

    serum and ascites from 22 women with ovarian carcinoma. We found that ascites contained 46-fold higher PAPP-A levels as compared to serum (P < 0.001). The majority (80%) of PAPP-A was enzymatically active. This is supported by the finding that ascites contained more cleaved than intact IGFBP-4 (P < 0......Pregnancy-associated plasma protein-A (PAPP-A) stimulates insulin-like growth factor (IGF) action through proteolysis of IGF-binding protein (IGFBP)-4. In experimental animals, PAPP-A accelerates ovarian tumor growth by this mechanism. To investigate the effect of PAPP-A in humans, we compared...

  18. 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