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Sample records for igf-i levels increased

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

  2. 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...

  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. Low serum insulin-like growth factor-I (IGF-I) level is associated with increased risk of vascular dementia.

    Science.gov (United States)

    Quinlan, Patrick; Horvath, Alexandra; Nordlund, Arto; Wallin, Anders; Svensson, Johan

    2017-12-01

    Insulin-like growth factor-I (IGF-I) is important for the adult brain, but little is known of the role of IGF-I in Alzheimeŕs disease (AD) or vascular dementia (VaD). A prospective study of 342 patients with subjective or objective mild cognitive impairment recruited at a single memory clinic. We determined whether serum IGF-I concentrations at baseline were associated with the risk of all-cause dementia, AD, or VaD. Patients developing mixed forms of AD and VaD were defined as suffering from VaD. The statistical analyses included Cox proportional hazards regression analysis. During the follow-up (mean 3.6 years), 95 (28%) of the patients developed all-cause dementia [AD, n=37 (11%) and VaD, n=42 (12%)]. Low as well as high serum IGF-I (quartile 1 or 4 vs. quartiles 2-3) did not associate with all-cause dementia [crude hazard ratio (HR) 1.30, 95% confidence interval (CI): 0.81-2.08 and crude HR 1.05, 95% CI: 0.63-1.75, respectively] or AD (crude HR 0.79, 95% CI: 0.35-1.79 and crude HR 0.94, 95% CI: 0.43-2.06, respectively]. In contrast, low serum IGF-I concentrations were associated with increased risk of VaD (quartile 1 vs. quartiles 2-3, crude HR 2.22, 95% CI: 1.13-4.36). The latter association remained significant also after adjustment for multiple covariates. In a memory clinic population, low serum IGF-I was a risk marker for subsequent VaD whereas low IGF-I did not associate with the risk of AD. High serum IGF-I was not related to the risk of conversion to dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Liver-derived IGF-I contributes to GH-dependent increases in lean mass and bone mineral density in mice with comparable levels of circulating GH.

    Science.gov (United States)

    Nordstrom, Sarah M; Tran, Jennifer L; Sos, Brandon C; Wagner, Kay-Uwe; Weiss, Ethan J

    2011-07-01

    The relative contributions of circulating and locally produced IGF-I in growth remain controversial. The majority of circulating IGF-I is produced by the liver, and numerous mouse models have been developed to study the endocrine actions of IGF-I. A common drawback to these models is that the elimination of circulating IGF-I disrupts a negative feedback pathway, resulting in unregulated GH secretion. We generated a mouse with near total abrogation of circulating IGF-I by disrupting the GH signaling mediator, Janus kinase (JAK)2, in hepatocytes. We then crossed these mice, termed JAK2L, to GH-deficient little mice (Lit). Compound mutant (Lit-JAK2L) and control (Lit-Con) mice were treated with equal amounts of GH such that the only difference between the two groups was hepatic GH signaling. Both groups gained weight in response to GH but there was a reduction in the final weight of GH-treated Lit-JAK2L vs. Lit-Con mice. Similarly, lean mass increased in both groups, but there was a reduction in the final lean mass of Lit-JAK2L vs. Lit-Con mice. There was an equivalent increase in skeletal length in response to GH in Lit-Con and Lit-JAK2L mice. There was an increase in bone mineral density (BMD) in both groups, but Lit-JAK2L had lower BMD than Lit-Con mice. In addition, GH-mediated increases in spleen and kidney mass were absent in Lit-JAK2L mice. Taken together, hepatic GH-dependent production of IGF-I had a significant and nonredundant role in GH-mediated acquisition of lean mass, BMD, spleen mass, and kidney mass; however, skeletal length was dependent upon or compensated for by locally produced IGF-I.

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

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

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    Science.gov (United States)

    Laron, Z; Klinger, B; Silbergeld, A

    1999-01-01

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

  11. 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, C.; 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...... animal PI can stimulate growth. During protein deprivation IGF-I decrease, but it is unknown whether a high PI can increase s-IGF-I in well-nourished children....

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

    Science.gov (United States)

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

    2016-09-01

    Sleep deprivation is known to suppress circulating trophic factors such as insulin-like growth factor (IGF)-I and brain-derived neurotrophic factor (BDNF). This experiment examined the effect of an intervention involving 6 nights of extended sleep before total sleep deprivation on this catabolic profile. In a randomized crossover design, 14 young men (age range: 26-37 years) were either in an extended (EXT; time in bed: 2100-0700 h) or habitual (HAB: 2230-0700 h) sleep condition, followed by 3 days in the laboratory with blood sampling at baseline (B), after 24 h of sleep deprivation (24h-SD), and after 1 night of recovery sleep (R). In the EXT condition compared with the HAB condition, free IGF-I levels were significantly higher at B, 24h-SD, and R (P sleep deprivation was for insulin levels, which were significantly higher after R compared with B. In a healthy adult, additional sleep over 1 week increased blood concentrations of the anabolic factor IGF-I before and during 24 h of sleep deprivation and after the subsequent recovery night without effects on BDNF. With further research, these findings may prove to be important in guiding effective lifestyle modifications to limit physical or cognitive deficits associated with IGF-I decrease with age.

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

    Directory of Open Access Journals (Sweden)

    Seyyed Mahmoud Hejazi

    2017-04-01

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

  14. 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....

  15. 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; Clemmensen, Christoffer; Andersen, Jesper L

    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...... and 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

    2004-01-01

    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....

  18. Long-term IGF-I treatment of children with Laron syndrome increases adiposity.

    Science.gov (United States)

    Laron, Zvi; Ginsberg, Shira; Lilos, Pnina; Arbiv, Mira; Vaisman, Nahum

    2006-02-01

    Laron syndrome (LS) is an autosomal recessive disease caused by deletions or mutations in the GH receptor gene leading to an inability of insulin-like growth factor I (IGF-I) generation. Among the major resulting body changes are dwarfism and obesity. The only effective treatment is daily administration of biosynthetic IGF-I. Body composition determination by DEXA (dual energy X-ray absorptiometry) of three girls with LS treated by IGF-I for 1, 3 and 11 1/2 years, respectively, revealed that concomitantly with the increase in growth there was a significant increase in body adipose tissue to double or triple the normal values. Due to the underdevelopment of the muscular and skeletal systems body mass index (BMI) did not accurately reflect the degree of obesity. In conclusion, IGF-I similar to insulin, exerts an adipogenic effect.

  19. Positive associations between serum levels of IGF-I and subcutaneous fat depots in young men. The Odense Androgen Study

    DEFF Research Database (Denmark)

    Andersen, M; Brixen, K; Hagen, C

    2012-01-01

    Serum levels of IGF-I are of growing interest due to the associations with morbidity and mortality. Despite markedly suppressed GH secretion, total IGF-I levels are often within normal range in obese adults.......Serum levels of IGF-I are of growing interest due to the associations with morbidity and mortality. Despite markedly suppressed GH secretion, total IGF-I levels are often within normal range in obese adults....

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

    International Nuclear Information System (INIS)

    Deng Weiqun; Zhao Yushan

    2007-01-01

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

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

    International Nuclear Information System (INIS)

    Wang Yuezhou

    2011-01-01

    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 (P 0.05). 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)

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

    International Nuclear Information System (INIS)

    Zhang Zaigao; Lv Yuliang; Li Jiacheng

    2006-01-01

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

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

    International Nuclear Information System (INIS)

    Li Yong; Sun Yefu; Xia Aiping

    2008-01-01

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

  4. Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states.

    Science.gov (United States)

    Chan, Jean L; Williams, Catherine J; Raciti, Patricia; Blakeman, Jennifer; Kelesidis, Theodore; Kelesidis, Iosif; Johnson, Michael L; Thorner, Michael O; Mantzoros, Christos S

    2008-07-01

    States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels. The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit. We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2-3 months of r-metHuLeptin treatment. GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured. During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month. The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.

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

    International Nuclear Information System (INIS)

    Yu Suqing; Chu Kaiqiu; Chen Shengjie

    2008-01-01

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

  6. Low Circulating IGF-I Bioactivity in Elderly Men is associated with Increased Mortality

    NARCIS (Netherlands)

    M.P. Brugts (Michael); A.W. van den Beld (Annewieke); L.J. Hofland (Leo); K. van der Wansem (Katy); P.M. van Koetsveld (Peter); J. Frystyk (Jan); S.W.J. Lamberts (Steven); J.A.M.J.L. Janssen (Joseph)

    2008-01-01

    textabstractContext: Low IGF-I signaling activity prolongs lifespan in certain animal models, but the precise role of IGF-I in human survival remains controversial. The IGF-I kinase receptor activation assay (IGF-I KIRA) is a novel method for measuring IGF-I bioactivity in human serum. We

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

    International Nuclear Information System (INIS)

    Zhu Peiming

    2009-01-01

    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)

  8. IGF-I and IGFBP-3 levels and their correlations with ...

    African Journals Online (AJOL)

    Background: Colorectal cancer is one of the most frequently seen cancers worldwide. Currently, CEA is the most commonly used tumor marker in colorectal cancer. The changes in IGF/IGFBP equilibrium is also known to cause carcinogenesis. In this study, we aimed to monitor IGF-I/IGFBP-3 levels, the changes in ...

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

    Science.gov (United States)

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

    2010-01-01

    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 IGF-I and IGFBP-3 among 984 premenopausal African American and Caucasian women. In both races, IGFBP-3 rs2854746 (Ala32Gly) was positively associated with plasma IGFBP-3 (CC versus GG mean difference among Caucasians = 631 ng/ml, 95% confidence interval: 398, 864; African Americans = 897 ng/ml, 95% confidence interval: 656, 1138), and IGFBP-3 diplotypes with the rs2854746 GG genotype had lower mean IGFBP-3 levels than referent diplotypes with the CG genotype, while IGFBP-3 diplotypes with the CC genotype had higher mean IGFBP-3 levels. IGFBP-3 rs2854744 (−202 A/C) was in strong linkage disequilibrium with rs2854746 in Caucasians only, but was associated with plasma IGFBP-3 in both races. Eight additional IGFBP-3 SNPs were associated with 5% or greater differences in mean IGFBP-3 levels, with generally consistent associations between races. Twelve IGF-I SNPs were associated with 10% or greater differences in mean IGF-I levels, but associations were generally discordant between races. Diplotype associations with plasma IGF-I did not parallel IGF-I SNP associations. Our study supports that common IGFBP-3 SNPs, especially rs2854746, influence plasma IGFBP-3 levels among African Americans and Caucasians, but provides less evidence that IGF-I SNPs affect plasma IGF-I levels. PMID:19240240

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

    International Nuclear Information System (INIS)

    Sun Zihan; Luo Nanping; Niu Aijun; Qi Falian

    2006-01-01

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

  11. Gene expression profiling of preovulatory follicle in the buffalo cow: effects of increased IGF-I concentration on periovulatory events.

    Directory of Open Access Journals (Sweden)

    Jyotsna U Rao

    Full Text Available The preovulatory follicle in response to gonadotropin surge undergoes dramatic biochemical, and morphological changes orchestrated by expression changes in hundreds of genes. Employing well characterized bovine preovulatory follicle model, granulosa cells (GCs and follicle wall were collected from the preovulatory follicle before, 1, 10 and 22 h post peak LH surge. Microarray analysis performed on GCs revealed that 450 and 111 genes were differentially expressed at 1 and 22 h post peak LH surge, respectively. For validation, qPCR and immunocytochemistry analyses were carried out for some of the differentially expressed genes. Expression analysis of many of these genes showed distinct expression patterns in GCs and the follicle wall. To study molecular functions and genetic networks, microarray data was analyzed using Ingenuity Pathway Analysis which revealed majority of the differentially expressed genes to cluster within processes like steroidogenesis, cell survival and cell differentiation. In the ovarian follicle, IGF-I is established to be an important regulator of the above mentioned molecular functions. Thus, further experiments were conducted to verify the effects of increased intrafollicular IGF-I levels on the expression of genes associated with the above mentioned processes. For this purpose, buffalo cows were administered with exogenous bGH to transiently increase circulating and intrafollicular concentrations of IGF-I. The results indicated that increased intrafollicular concentrations of IGF-I caused changes in expression of genes associated with steroidogenesis (StAR, SRF and apoptosis (BCL-2, FKHR, PAWR. These results taken together suggest that onset of gonadotropin surge triggers activation of various biological pathways and that the effects of growth factors and peptides on gonadotropin actions could be examined during preovulatory follicle development.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  13. Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study.

    NARCIS (Netherlands)

    Canzian, F; McKay, J D; Cleveland, R J; Dossus, Laure; Biessy, Carine; Rinaldi, Sabina; Landi, S; Boillot, C; Monnier, S; Chajès, V; Clavel-Chapelon, Françoise; Téhard, B; Chang-Claude, J; Linseisen, Jakob; Lahmann, Petra H; Pischon, Tobias; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Zilis, D; Palli, Domenico; Tumino, Rosario; Vineis, Paolo; Berrino, Franco; Bueno-de-Mesquita, H Bas; Gils, C H van; Peeters, Petra H M; Pera, Guillem; Ardanaz, Eva; Chirlaque, María-Dolores; Quirós, José Ramón; Larrañaga, Nerea; Martínez-García, Carmen; Allen, Naomi E; Key, Timothy J; Bingham, Sheila A; Khaw, Kay-Tee; Slimani, N; Norat, Teresa; Riboli, Elio; Kaaks, Rudolf

    2006-01-01

    Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of

  14. FOXO1 Content Is Reduced in Cystic Fibrosis and Increases with IGF-I Treatment

    Directory of Open Access Journals (Sweden)

    Arianna Smerieri

    2014-10-01

    Full Text Available Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF. The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-, whereas winged helix forkhead (FOXO1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced β2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I increased FOXO1 content in vitro and in vivo in muscle and adipose tissue. In conclusion; we present the first description of reduced FOXO1 content in CF, which is compatible with reduced gluconeogenesis and increased adipogenesis, both features of insulin insensitivity. IGF-I treatment was effective in increasing FOXO1, thereby suggesting that it could be considered as a potential treatment in CF patients possibly to prevent and treat cystic fibrosis-related diabetes.

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

    Science.gov (United States)

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

    2016-07-01

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

  16. Is further evaluation for growth hormone (GH) deficiency necessary in fibromyalgia patients with low serum insulin-like growth factor (IGF)-I levels?

    Science.gov (United States)

    Yuen, Kevin C J; Bennett, Robert M; Hryciw, Cheryl A; Cook, Marie B; Rhoads, Sharon A; Cook, David M

    2007-02-01

    Fibromyalgia (FM) is characterized by diffuse pain, fatigue, and sleep disturbances; symptoms that resemble the adult growth hormone (GH) deficiency syndrome. Many FM patients have low serum GH levels, with a hypothesized aetiology of dysregulated GH/insulin-like growth factor (IGF)-I axis. The aim of this study was to assess the GH reserve in FM patients with low serum IGF-I levels using the GH-releasing hormone (GHRH)-arginine test. We retrospectively reviewed the GHRH-arginine data of 77 FM patients with low serum IGF-I levels referred to our tertiary unit over a 4-year period. Of the 77 FM patients, 13 patients (17%) failed the GHRH-arginine test. Further evaluation with pituitary imaging revealed normal pituitary glands (n=7), coincident microadenomas (n=4), empty sella (n=1) and pituitary cyst (n=1), and relevant medical histories such as previous head injury (n=4), Sheehan's syndrome (n=1), and whiplash injury (n=1). In contrast, the remaining 64 patients (83%) that responded to the GHRH-arginine test demonstrated higher peak GH levels compared to age and BMI-matched controls (n=24). Our data shows that a subpopulation of FM patients with low serum IGF-I levels will fail the GHRH-arginine test. We, thus, recommend that the GH reserve of these patients should be evaluated further, as GH replacement may potentially improve the symptomatology of those with true GH deficiency. Additionally, the increased GH response rates to GHRH-arginine stimulation in the majority of FM patients with low serum IGF-I levels further supports the hypothesis of a dysregulated GH/IGF-I axis in the pathophysiology of FM.

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

    OpenAIRE

    Seyyed Mahmoud Hejazi

    2017-01-01

    Introduction: It is well-recognized that exercise has a significant impact on the GH/IGF system but less is known about the effects of HIIT on this axis. Aim of the present study was to evaluate the effect of ten weeks of HIIT on plasma levels of GH and IGF-I in healthy men. Methods: Twenty young men (age 23.34 ± 2.56 weight 72.47 ± 12.01 height 174.10 ± 5.75) recruited and randomly assigned into control (n=10) and HIIT (n=12) groups. HIIT protocol was started with 4 cycles. Then,...

  18. Postpartum IGF-I and IGFBP-2 levels are prospectively associated with the development of type 2 diabetes in women with previous gestational diabetes mellitus.

    Science.gov (United States)

    Lappas, M; Jinks, D; Shub, A; Willcox, J C; Georgiou, H M; Permezel, M

    2016-12-01

    Women with previous gestational diabetes mellitus (GDM) are at greater risk of developing type 2 diabetes. In the general population, the insulin-like growth factor (IGF) system has been implicated in the development of type 2 diabetes. The aim of this study was to determine if circulating IGF-I, IGF-II, IGFBP-1 and IGFBP-2 levels 12weeks following a GDM pregnancy are associated with an increased risk of developing type 2 diabetes. IGF-I, IGF-II, IGFBP-1 and IGFBP-2 levels were measured in 98 normal glucose tolerant women, 12weeks following an index GDM pregnancy using enzyme immunoassay. Women were assessed for up to 10years for the development of overt type 2 diabetes. Among the 98 women with previous GDM, 21 (21%) developed diabetes during the median follow-up period of 8.5years. After adjusting for age and BMI, IGF-I and IGFBP-2 were significantly associated with the development of type 2 diabetes. In a clinical model of prediction of type 2 diabetes that included age, BMI, pregnancy fasting glucose and postnatal fasting glucose, the addition of IGF-I and IGFBP-2 resulted in an improvement in the net reclassification index of 17.8%. High postpartum IGF-I and low postpartum IGFBP-2 levels are a significant risk factor for the development of type 2 diabetes in women with a previous history of GDM. This is the first report that identifies IGF-I and IGFBP-2 as a potential biomarker for the prediction of type 2 diabetes in women with a history of GDM. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. IGF-I levels reflect hypopituitarism severity in adults with pituitary dysfunction.

    Science.gov (United States)

    Tirosh, Amit; Toledano, Yoel; Masri-Iraqi, Hiba; Eizenberg, Yoav; Tzvetov, Gloria; Hirsch, Dania; Benbassat, Carlos; Robenshtok, Eyal; Shimon, Ilan

    2016-08-01

    To evaluate the utility of Insulin-like growth factor I (IGF-I) standard deviation score (SDS) as a surrogate marker of severity of hypopituitarism in adults with pituitary pathology. We performed a retrospective data analysis, including 269 consecutive patients with pituitary disease attending a tertiary endocrine clinic in 1990-2015. The medical files were reviewed for the complete pituitary hormone profile, including IGF-I, and clinical data. Age-adjusted assay reference ranges of IGF-I were used to calculate IGF-I SDS for each patient. The main outcome measures were positive and negative predictive values of low and high IGF-I SDS, respectively, for the various pituitary hormone deficiencies. IGF-I SDS correlated negatively with the number of altered pituitary axes (p hypopituitarism in adults with pituitary disease, and thus can serve as a marker of hypopituitarism severity.

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

    Directory of Open Access Journals (Sweden)

    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

  1. Effects of dietary carbohydrate sources on plasma glucose, insulin and IGF-I levels in multiparous sows

    NARCIS (Netherlands)

    Wientjes, J.G.M.; Soede, N.M.; Aarsse, F.; Laurenssen, B.F.A.; Koopmanschap, R.E.; Brand, van den H.; Kemp, B.

    2012-01-01

    Effects of different carbohydrate sources on plasma glucose, insulin and insulin-like growth factor-I (IGF-I) levels were compared to subsequently be able to study effects of insulin-stimulating diets on follicle development in sows. The following feed components were tested in 12 sows during six

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

    DEFF Research Database (Denmark)

    Ringholm Nielsen, L; Juul, A; Pedersen-Bjergaard, U

    2008-01-01

    Severe hypoglycaemia is a significant problem in pregnant women with Type 1 diabetes. We explored whether frequent severe hypoglycaemia during pregnancy in women with Type 1 diabetes is related to placental growth hormone (GH) and insulin-like growth factor I (IGF-I) levels....

  3. Administration route-dependent effects of estrogens on IGF-I levels during fixed GH replacement in women with hypopituitarism

    NARCIS (Netherlands)

    van der Klaauw, Agatha A.; Biermasz, Nienke R.; Zelissen, Pierre M. J.; Pereira, Alberto M.; Lentjes, Eef G. W. M.; Smit, Johannes W. A.; van Thiel, Sjoerd W.; Romijn, Johannes A.; Roelfsema, Ferdinand

    2007-01-01

    GH-deficient women using oral estradiol treatment require higher doses of recombinant human GH (rhGH) to achieve similar IGF-I levels when compared with men and women on transdermal estradiol replacement. The aim of this study was to evaluate the effects of oral versus transdermal estrogen

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

    International Nuclear Information System (INIS)

    Li Yuqiang; Niu Guoping

    2006-01-01

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

  5. 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

    by centrifugation. In addition, GH, GH-binding protein, total IGFs, IGFBP-1 to -4, and IGFBP-3 proteolytic activity were measured. The IGFBPs were measured by both immunoassays and Western ligand blotting. Twelve of the patients were restudied 3 months after a minor increase in body mass index. In AN, the levels...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  7. 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...

  8. IGF-I abuse in sport.

    Science.gov (United States)

    Guha, Nishan; Dashwood, Alexander; Thomas, Nicholas J; Skingle, Alexander J; Sönksen, Peter H; Holt, Richard I G

    2009-09-01

    It is widely believed that growth hormone (GH) is abused by athletes for its anabolic and lipolytic effects. Many of the physiological effects of GH are mediated by the production of insulin-like growth factor-I (IGF-I). Both GH and IGF-I appear on the World Anti-Doping Agency list of prohibited substances. Little is known, however, about the prevalence of abuse with exogenous IGF-I. IGF-I has effects on carbohydrate, lipid and protein metabolism and some of these actions could prove beneficial to competitive athletes. No studies have demonstrated a positive effect of IGF-I on physical performance in healthy individuals but this has not yet been studied in appropriately designed trials. Two pharmaceutical preparations of IGF-I have recently become available for the treatment of growth disorders in children. This availability is likely to increase the prevalence of IGF-I abuse. Combining IGF-I with its binding protein IGFBP-3 in one preparation has the potential to reduce the side-effect profile but the adverse effects of long term IGF-I abuse are currently unknown. Detection of abuse with IGF-I is a major challenge for anti-doping authorities. It is extremely difficult to distinguish the exogenous recombinant form of the hormone from endogenously-produced IGF-I. One approach currently being investigated is based on measuring markers of GH and IGF-I action. This has already proved successful in the fight against GH abuse and, it is hoped, will subsequently lead to a similar test for detection of IGF-I abuse.

  9. 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.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  11. 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)

    Zao Yuhua; Zhang Juhong; Ma Yunbao

    2006-01-01

    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)

  12. Clinical diagnostic value of combined determination of serum tPSA, cPSA and IGF-I levels in patients with prostatic disorders

    International Nuclear Information System (INIS)

    Zhang Bashan; Zhang Zigang; Lai Fudi

    2008-01-01

    Objective: To investigate the diagnostic value of combined determination of serum total prostatic specific antigen (tPSA), complex prostatic specific antigen (cPSA) and IGF-I levels in patients with prostatic disorders. Methods: Serum tPSA, cPSA (with CLIA) and IGF-I (with IRMA) levels were determined in 41 patients with prostatic carcinoma, 60 patients with benign prosta- tic hypertrophy (BPH) and 55 controls. Results: The serum tPSA, cPSA and IGF-I levels in patients with prostatic cancer were significantly higher than those in patients with BPH and controls (P<0.01). Taking the cut-off values of 4ng/ml, 3.6ng/ml and 150 for tPSA, cPSA and IGF-I respectively, the combined determination of these three items would yield a sensitivity of 88.6%, specificity of 84.9%, positive predicative value of 83% and negative predicative value of 90.0% for diagnosis of prostatic cancer. Conclusion: Combined determination of tPSA, cPSA and IGF-I would yield better sensitive and accurate diagnostic rate in patients with prostatic cancer, especially in those with laboratory values within the 'grey zone'. (authors)

  13. 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...

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

    Directory of Open Access Journals (Sweden)

    Min Sun Kim

    2015-06-01

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

  15. 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)

    Zhu Conggang

    2009-01-01

    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)

  16. Bone Growth Mechanical Stimulus and IGF-I

    National Research Council Canada - National Science Library

    Gilsanz, Vicente

    2003-01-01

    .... This study also examines the possible relations between the cross-sectional properties of bone and circulating levels of IGF-I, IGF-binding protein-3, and IGF-I genotypes in teenagers ages 15 to 20...

  17. Bone Growth, Mechanical Stimulus and IGF-I

    National Research Council Canada - National Science Library

    Gilsanz, Vicente

    2002-01-01

    ... exercise intervention or no intervention. This study also examines the possible relations between the cross-sectional properties of bone and circulating levels of IGF-I, JGF-binding protein-3, and IGF-I genotypes in teenagers...

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

    Science.gov (United States)

    2012-01-01

    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. PMID:23148873

  19. 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.

  20. 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

  1. High-intensity interval training (HIIT) increases insulin-like growth factor-I (IGF-I) in sedentary aging men but not masters' athletes: an observational study.

    Science.gov (United States)

    Herbert, Peter; Hayes, Lawrence D; Sculthorpe, Nicholas; Grace, Fergal M

    2017-03-01

    The aim of this investigation was to examine the impact high-intensity interval training (HIIT) on serum insulin-like growth factor-I (IGF-I) in active compared with sedentary aging men. 22 lifetime sedentary (SED; 62 ± 2 years) and 17 masters' athletes (LEX; 60 ± 5 years) were recruited to the study. As HIIT requires preconditioning exercise in sedentary cohorts, the study required three assessment phases; enrollment (phase A), following preconditioning exercise (phase B), and post-HIIT (phase C). Serum IGF-I was determined by electrochemiluminescent immunoassay. IGF-I was higher in LEX compared to SED at baseline (p = 0.007, Cohen's d = 0.91), and phase B (p = 0.083, Cohen's d = 0.59), with only a small difference at C (p = 0.291, Cohen's d = 0.35). SED experienced a small increase in IGF-I following preconditioning from 13.1 ± 4.7 to 14.2 ± 6.0 μg·dl -1 (p = 0.376, Cohen's d = 0.22), followed by a larger increase post-HIIT (16.9 ± 4.4 μg·dl -1 ), which was significantly elevated compared with baseline (p = 0.002, Cohen's d = 0.85), and post-preconditioning (p = 0.005, Cohen's d = 0.51). LEX experienced a trivial changes in IGF-I from A to B (18.2 ± 6.4 to 17.2 ± 3.7 μg·dl -1 [p = 0.538, Cohen's d = 0.19]), and a small change post-HIIT (18.4 ± 4.1 μg·dl -1 [p = 0.283, Cohen's d = 0.31]). Small increases were observed in fat-free mass in both groups following HIIT (p HIIT with preconditioning exercise abrogates the age associated difference in IGF-I between SED and LEX, and induces small improvements in fat-free mass in both SED and LEX.

  2. The DNA methylation status of MyoD and IGF-I genes are correlated with muscle growth during different developmental stages of Japanese flounder (Paralichthys olivaceus).

    Science.gov (United States)

    Huang, Yajuan; Wen, Haishen; Zhang, Meizhao; Hu, Nan; Si, Yufeng; Li, Siping; He, Feng

    2018-05-01

    Many genes related to muscle growth modulate myoblast proliferation and differentiation and promote muscle hypertrophy. MyoD is a myogenic determinant that contributes to myoblast determination, and insulin-like growth factor 1 (IGF-I) interacts with MyoD to regulate muscle hypertrophy and muscle mass. In this study, we aimed to assess DNA methylation and mRNA expression patterns of MyoD and IGF-I during different developmental stages of Japanese flounder, and to examine the relationship between MyoD and IGF-I gene. DNA and RNA were extracted from muscles, and DNA methylation of MyoD and IGF-I promoter and exons was detected by bisulfite sequencing. The relative expression of MyoD and IGF-I was measured by quantitative polymerase chain reaction. IGF-I was measured by radioimmunoassay. Interestingly, the lowest expression of MyoD and IGF-I emerged at larva stage, and the mRNA expression was negatively associated with methylation. We hypothesized that many skeletal muscle were required to complete metamorphosis; thus, the expression levels of MyoD and IGF-I genes increased from larva stage and then decreased. The relative expression levels of MyoD and IGF-I exhibited similar patterns, suggesting that MyoD and IGF-I regulated muscle growth through combined effects. Changes in the concentrations of IGF-I hormone were similar to those of IGF-I gene expression. Our results the mechanism through which MyoD and IGF-I regulate muscle development and demonstrated that MyoD interacted with IGF-I to regulate muscle growth during different developmental stages. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Lv Kuan; Liu Chunyu; Lu Yingju

    2006-01-01

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

  4. Igf-I regulates pheochromocytoma cell proliferation and survival in vitro and in vivo.

    Science.gov (United States)

    Fernández, María Celia; Venara, Marcela; Nowicki, Susana; Chemes, Héctor E; Barontini, Marta; Pennisi, Patricia A

    2012-08-01

    IGFs are involved in malignant transformation and growth of several tissues, including the adrenal medulla. The present study was designed to evaluate the impact of IGF-I on pheochromocytoma development. We used a murine pheochromocytoma (MPC) cell line (MPC4/30) and an animal model with a reduction of 75% in circulating IGF-I levels [liver-IGF-I-deficient (LID) mice] to perform studies in vitro and in vivo. We found that, in culture, IGF-I stimulation increases proliferation, migration, and anchorage-independent growth, whereas it inhibits apoptosis of MPC cells. When injected to control and to LID mice, MPC cells grow and form tumors with features of pheochromocytoma. Six weeks after cell inoculation, all control mice developed sc tumors. In contrast, in 73% of LID mice, tumor development was delayed to 7-12 wk, and the remaining 27% did not develop tumors up to 12 wk after inoculation. LID mice harboring MPC cells and treated with recombinant human IGF-I (LID+) developed tumors as controls. Tumors developed in control, LID, and LID+ mice had similar histology and were similarly positive for IGF-I receptor expression. The apoptotic index was higher in tumors from LID mice compared with those from control mice, whereas vascular density was decreased. In summary, our work demonstrates that IGF-I has a critical role in maintaining tumor phenotype and survival of already transformed pheochromocytoma cells and is required for the initial establishment of these tumors, providing encouragement to carry on research studies to address the IGF-I/IGF-I receptor system as a target of therapeutic strategies for pheochromocytoma treatment in the future.

  5. Systemic administration of IGF-I enhances healing in collagenous extracellular matrices: evaluation of loaded and unloaded ligaments

    Science.gov (United States)

    Provenzano, Paolo P; Alejandro-Osorio, Adriana L; Grorud, Kelley W; Martinez, Daniel A; Vailas, Arthur C; Grindeland, Richard E; Vanderby, Ray

    2007-01-01

    Background Insulin-like growth factor-I (IGF-I) plays a crucial role in wound healing and tissue repair. We tested the hypotheses that systemic administration of IGF-I, or growth hormone (GH), or both (GH+IGF-I) would improve healing in collagenous connective tissue, such as ligament. These hypotheses were examined in rats that were allowed unrestricted activity after injury and in animals that were subjected to hindlimb disuse. Male rats were assigned to three groups: ambulatory sham-control, ambulatory-healing, and hindlimb unloaded-healing. Ambulatory and hindlimb unloaded animals underwent surgical disruption of their knee medial collateral ligaments (MCLs), while sham surgeries were performed on control animals. Healing animals subcutaneously received systemic doses of either saline, GH, IGF-I, or GH+IGF-I. After 3 weeks, mechanical properties, cell and matrix morphology, and biochemical composition were examined in control and healing ligaments. Results Tissues from ambulatory animals receiving only saline had significantly greater strength than tissue from saline receiving hindlimb unloaded animals. Addition of IGF-I significantly improved maximum force and ultimate stress in tissues from both ambulatory and hindlimb unloaded animals with significant increases in matrix organization and type-I collagen expression. Addition of GH alone did not have a significant effect on either group, while addition of GH+IGF-I significantly improved force, stress, and modulus values in MCLs from hindlimb unloaded animals. Force, stress, and modulus values in tissues from hindlimb unloaded animals receiving IGF-I or GH+IGF-I exceeded (or were equivalent to) values in tissues from ambulatory animals receiving only saline with greatly improved structural organization and significantly increased type-I collagen expression. Furthermore, levels of IGF-receptor were significantly increased in tissues from hindlimb unloaded animals treated with IGF-I. Conclusion These results

  6. Systemic administration of IGF-I enhances healing in collagenous extracellular matrices: evaluation of loaded and unloaded ligaments

    Directory of Open Access Journals (Sweden)

    Martinez Daniel A

    2007-03-01

    Full Text Available Abstract Background Insulin-like growth factor-I (IGF-I plays a crucial role in wound healing and tissue repair. We tested the hypotheses that systemic administration of IGF-I, or growth hormone (GH, or both (GH+IGF-I would improve healing in collagenous connective tissue, such as ligament. These hypotheses were examined in rats that were allowed unrestricted activity after injury and in animals that were subjected to hindlimb disuse. Male rats were assigned to three groups: ambulatory sham-control, ambulatory-healing, and hindlimb unloaded-healing. Ambulatory and hindlimb unloaded animals underwent surgical disruption of their knee medial collateral ligaments (MCLs, while sham surgeries were performed on control animals. Healing animals subcutaneously received systemic doses of either saline, GH, IGF-I, or GH+IGF-I. After 3 weeks, mechanical properties, cell and matrix morphology, and biochemical composition were examined in control and healing ligaments. Results Tissues from ambulatory animals receiving only saline had significantly greater strength than tissue from saline receiving hindlimb unloaded animals. Addition of IGF-I significantly improved maximum force and ultimate stress in tissues from both ambulatory and hindlimb unloaded animals with significant increases in matrix organization and type-I collagen expression. Addition of GH alone did not have a significant effect on either group, while addition of GH+IGF-I significantly improved force, stress, and modulus values in MCLs from hindlimb unloaded animals. Force, stress, and modulus values in tissues from hindlimb unloaded animals receiving IGF-I or GH+IGF-I exceeded (or were equivalent to values in tissues from ambulatory animals receiving only saline with greatly improved structural organization and significantly increased type-I collagen expression. Furthermore, levels of IGF-receptor were significantly increased in tissues from hindlimb unloaded animals treated with IGF-I

  7. A low-fat, whole-food vegan diet, as well as other strategies that down-regulate IGF-I activity, may slow the human aging process.

    Science.gov (United States)

    McCarty, Mark F

    2003-06-01

    A considerable amount of evidence is consistent with the proposition that systemic IGF-I activity acts as pacesetter in the aging process. A reduction in IGF-I activity is the common characteristic of rodents whose maximal lifespan has been increased by a wide range of genetic or dietary measures, including caloric restriction. The lifespans of breeds of dogs and strains of rats tend to be inversely proportional to their mature weight and IGF-I levels. The link between IGF-I and aging appears to be evolutionarily conserved; in worms and flies, lifespan is increased by reduction-of-function mutations in signaling intermediates homologous to those which mediate insulin/IGF-I activity in mammals. The fact that an increase in IGF-I activity plays a key role in the induction of sexual maturity, is consistent with a broader role for-IGF-I in aging regulation. If down-regulation of IGF-I activity could indeed slow aging in humans, a range of practical measures for achieving this may be at hand. These include a low-fat, whole-food, vegan diet, exercise training, soluble fiber, insulin sensitizers, appetite suppressants, and agents such as flax lignans, oral estrogen, or tamoxifen that decrease hepatic synthesis of IGF-I. Many of these measures would also be expected to decrease risk for common age-related diseases. Regimens combining several of these approaches might have a sufficient impact on IGF-I activity to achieve a useful retardation of the aging process. However, in light of the fact that IGF-I promotes endothelial production of nitric oxide and may be of especial importance to cerebrovascular health, additional measures for stroke prevention-most notably salt restriction-may be advisable when attempting to down-regulate IGF-I activity as a pro-longevity strategy.

  8. Burn-induced increase in atrogin-1 and MuRF-1 in skeletal muscle is glucocorticoid independent but downregulated by IGF-I.

    Science.gov (United States)

    Lang, Charles H; Huber, Danuta; Frost, Robert A

    2007-01-01

    The present study determined whether thermal injury increases the expression of the ubiquitin (Ub) E3 ligases referred to as muscle ring finger (MuRF)-1 and muscle atrophy F-box (MAFbx; aka atrogin-1), which are muscle specific and responsible for the increased protein breakdown observed in other catabolic conditions. After 48 h of burn injury (40% total body surface area full-thickness scald burn) gastrocnemius weight was reduced, and this change was associated with an increased mRNA abundance for atrogin-1 and MuRF-1 (3.1- to 8-fold, respectively). Similarly, burn increased polyUb mRNA content in the gastrocnemius twofold. In contrast, there was no burn-induced atrophy of the soleus and no significant change in atrogin-1, MuRF-1, or polyUb mRNA. Burns also did not alter E3 ligase expression in heart. Four hours after administration of the anabolic agent insulin-like growth factor (IGF)-I to burned rats, the mRNA content of atrogin-1 and polyUb in gastrocnemius had returned to control values and the elevation in MuRF-1 was reduced 50%. In contrast, leucine did not alter E3 ligase expression. In a separate study, in vivo administration of the proteasome inhibitor Velcade prevented burn-induced loss of muscle mass determined at 48 h. Finally, administration of the glucocorticoid receptor antagonist RU-486 did not prevent burn-induced atrophy of the gastrocnemius or the associated elevation in atrogin-1, MuRF-1, or polyUb. In summary, the acute muscle wasting accompanying thermal injury is associated with a glucocorticoid-independent increase in the expression of several Ub E3 ligases that can be downregulated by IGF-I.

  9. The IGF-I/IGFBP-3 system in gingival crevicular fluid and dependence on application of fixed force.

    Science.gov (United States)

    Toia, M; Galazzo, R; Maioli, C; Granata, R; Scarlatti, F

    2005-12-01

    During application of orthodontic force on the tooth, various molecular parameters associated with tissue remodeling are changed. IGF-I is a regulatory protein produced during periodontal regeneration. IGF binding proteins-3 (IGFBP-3), a specific IGF-I binding protein, is the major regulatory factor of IGF-I activity. We tested the hypothesis that changes in the IGF-I/ IGFBP-3 system occur during fixed force application to the tooth and that these changes are detectable in the gingival crevicular fluid (GCF). IGFBP-3 and IGF-I secretion into gingival crevicular fluid (GCF) was analyzed by Western blotting and immunoradiometric assay (IRMA), respectively, in GCF of 6 healthy subjects just prior to and during orthodontics treatment using fixed appliances. We observed a significant time-dependent decrease of IGFBP-3 content in GCF during orthodontic treatment (4 h and 10 days). Reduction in levels of intact, glycosylated 47 kDa form of IGFBP-3 was associated with its degradation and the appearance of intermediate breakdown products. IGF-I levels were significantly increased 4 h after application of orthodontic force, while they were significantly reduced 10 days after the start of treatment. IGFBP-3 secretion into GCF and its molecular structure are modified by the fixed force of orthodontic treatment. Alterations in IGFBP-3 appear to be unrelated to the binding to IGF-I, suggesting an IGF-independent role of this binding protein in tooth movement.

  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

    2008-01-01

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

  11. 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; Vestgaard, Marianne; Laugesen, Caroline S

    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....

  12. Early programming of the IGF-I axis

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  13. Gender and age influence the relationship between serum GH and IGF-I in patients with acromegaly.

    Science.gov (United States)

    Parkinson, C; Renehan, A G; Ryder, W D J; O'Dwyer, S T; Shalet, S M; Trainer, P J

    2002-07-01

    In patients with acromegaly serum IGF-I is increasingly used as a marker of disease activity. As a result, the relationship between serum GH and IGF-I is of profound interest. Healthy females secrete three times more GH than males but have broadly similar serum IGF-I levels, and women with GH deficiency require 30-50% more exogenous GH to maintain the same serum IGF-I as GH-deficient men. In a selected cohort of patients with active acromegaly, studied off medical therapy using a single fasting serum GH and IGF-I measurement, we have reported previously that, for a given GH level, women have significantly lower circulating IGF-I. To evaluate the influence of age and gender on the relationship between serum GH and IGF-I in an unselected cohort of patients with acromegaly independent of disease control and medical therapy. Sixty (34 male) unselected patients with acromegaly (median age 51 years (range 24-81 years) attending a colonoscopy screening programme were studied. Forty-five had previously received pituitary radiotherapy. Patients had varying degrees of disease control and received medical therapy where appropriate. Mean serum GH was calculated from an eight-point day profile (n = 45) and values obtained during a 75-g oral glucose tolerance test (n = 15). Serum IGF-I, IGFBP-3 and acid-labile subunit were measured and the dependency of these factors on covariates such as log10 mean serum GH, sex, age and prior radiotherapy was assessed using regression techniques. The median calculated GH value was 4.7 mU/l (range 1-104). A significant linear association was observed between serum IGF-I and log10 mean serum GH for the cohort (R = 0.5, P fall by 0.37 nmol/l per year (P = 0.04, 95% CI 0.015-0.72). In keeping with previous observations of relative GH resistance in normal and GH-deficient females we have observed lower serum IGF-I levels for equivalent mean serum GH levels in females patients with acromegaly. This gender-dependent difference is independent of

  14. 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......-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several...

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

    International Nuclear Information System (INIS)

    Li Liren; Liu Jiumin; Lu Bailing

    2001-01-01

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

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

    International Nuclear Information System (INIS)

    Haffner, Michael C; Petridou, Barbara; Peyrat, Jean Phillipe; Révillion, Françoise; Müller-Holzner, Elisabeth; Daxenbichler, Günter; Marth, Christian; Doppler, Wolfgang

    2007-01-01

    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

  17. 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-I

  18. Forkhead box A1 (FOXA1) is a key mediator of insulin-like growth factor I (IGF-I) activity.

    Science.gov (United States)

    Potter, Adam S; Casa, Angelo J; Lee, Adrian V

    2012-01-01

    The insulin-like growth factor receptor (IGF-IR) has been implicated in a number of human tumors, including breast cancer. Data from human breast tumors has demonstrated that IGF-IR is over-expressed and hyper-phosphorylated. Additionally, microarray analysis has shown that IGF-I treatment of MCF7 cells leads to a gene signature comprised of induced and repressed genes, which correlated with luminal B tumors. FOXA1, a forkhead family transcription factor, has been shown to be crucial for mammary ductal morphogenesis, similar to IGF-IR, and expressed at high levels in luminal subtype B breast tumors. Here, we investigated the relationship between FOXA1 and IGF-I action in breast cancer cells. We show that genes regulated by IGF-I are enriched for FOXA1 binding sites, and knock down of FOXA1 blocked the ability of IGF-I to regulate gene expression. IGF-I treatment of MCF7 cells increased the half-life of FOXA1 protein and this increase in half-life appeared to be dependent on canonical IGF-I signal transduction through both MAPK and AKT pathways. Finally, knock down of FOXA1 led to a decreased ability of IGF-I to induce proliferation and protect against apoptosis. Together, these results demonstrate that IGF-I can increase the stability of FOXA1 protein expression and place it as a critical mediator of IGF-I regulation of gene expression and IGF-I-mediated biological responses. Copyright © 2011 Wiley Periodicals, Inc.

  19. [Differences in dynamics of insulin and insulin-like growth I (IGF-I) receptors internalization in isolated rat hepatocytes].

    Science.gov (United States)

    Kolychev, A P; Ternovskaya, E E; Arsenieva, A V; Shapkina, E V

    2013-01-01

    Insulin and IGF-I are two related peptides performing in the mammalian body functionally different roles of the metabolic and growth hormones, respectively. Internalization of the insulin-receptor complex (IRC) is the most important chain of mechanism of the action of hormone. To elucidate differences in the main stages of internalization of the two related hormones, the internalization dynamics of 125I-insulin and 125I-IGF-I was traced in isolated rat hepatocytes at 37 and 12 degrees C. There were established marked differences in the process of internalization of labeled hormones, which is stimulated by insulin and IGF-I. At 37 degrees C the insulin-stimulated internalization, unlike the process initiated by IGF-I, did not reach the maximal level for 1 h of incubation. However, essential differences in the internalization course of these two related peptide were obvious at the temperature of 12 degrees C. The internalization level of insulin receptors at 12 degrees C decreased by one third in spite of a significant increase of the insulin receptor binding on the hepatocytes plasma membrane. At 12 degrees C a slight decrease of the proportion of intracellular 125I-IGF-I correlated with a decrease in the 125I-IGF-I binding to receptors on the cell membrane. Internalization of IGF-I receptors was not affected by low temperature, as neither its level, nor the rate changed at 12 degrees C. The paradoxical decrease of the insulin-stimulated internalization at low temperature seems to represent a peculiar "inhibition mechanism" of immersion of IRC into the cell, which leads to accumulation of the complexes on the cell surface and possibly to a readjustment of the insulin biological activity. The resistance of internalization of the IGF-I receptor to cold seems to be related to the more ancient origin of this mechanism in the poikilothermal vertebrates.

  20. The Association Between IGF-I and Insulin Resistance

    DEFF Research Database (Denmark)

    Friedrich, Nele; Thuesen, Betina; Jørgensen, Torben

    2012-01-01

    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...... 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...

  1. Endurance training-induced changes in the GH-IGF-I axis influence maximal muscle strength in previously untrained men.

    Science.gov (United States)

    Grandys, Marcin; Majerczak, Joanna; Kuczek, Piotr; Sztefko, Krystyna; Duda, Krzysztof; Zoladz, Jerzy A

    2017-02-01

    In this study we have determined the effects of 20weeks of endurance running training on the GH-IGF-I axis changes in the context of the skeletal muscle performance and physical capacity level. Before and after the endurance training program a maximal incremental exercise tests, a 1500m race and a muscle strength measurements were performed and the blood samples were taken to determine both resting as well as end-exercise serum growth hormone (GH), insulin-like growth hormone-I (IGF-I), insulin-like growth hormone binding protein-3 (IGFBP-3) and plasma interleukin-6 (IL-6) concentrations. 20weeks of endurance running training improved power output generated at the end of the maximal incremental test by 24% (P<0.012), 1500m running time by 13% (P<0.012) and maximal muscle strength by 9% (P<0.02). End-exercise IGF-I/IGFBP-3 ratio was decreased by 22% after the training (P<0.04) and the magnitude of IGF-I/IGFBP-3 ratio decrease (ΔIGF-I/IGFBP-3 ex ) was 2.3 times higher after the training (P<0.04). The magnitude of the exercise-induced changes in IGFBP-3 concentration was also significantly higher (P<0.04) and there was a trend toward lower end-exercise IGF-I concentration (P=0.08) after the training. These changes were accompanied by a significantly higher (30%) end-exercise IL-6 concentration (P<0.01) as well as by a 3.4 times higher magnitude of IL-6 increase (P<0.02) after the training. Moreover, there were strong positive correlations between changes in resting serum IGF-I concentration (ΔIGF-I res ) and IGF-I/IGFBP-3 ratio (ΔIGF-I/IGFBP-3 res ) and changes in muscle strength (ΔMVC) (r=0.95, P=0.0003 and r=0.90, P=0.002, respectively). The training-induced changes in the components of the GH-IGF-I axis may have additive effects on skeletal muscle performance and physical capacity improvement. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  3. IGF-I and GH: potential use in gene doping.

    Science.gov (United States)

    Harridge, Stephen D R; Velloso, Cristiana P

    2009-08-01

    Gene doping is the term given to the potential misuse of gene therapy for the purposes of enhancing athletic performance. Insulin like growth factor-I (IGF-I), the prime target of growth hormone action, is one candidate gene for improving performance. In recent years a number of transgenic and somatic gene transfer studies on animals have shown that upregulation of IGF-I stimulates muscle growth and improves function. This increase in muscle IGF-I is not reflected in measurable increases in circulating IGF-I. Whilst the responses obtained in the animal studies would appear to give clear benefits for performance, the transfer of such techniques to humans still presents many technical challenges. Further challenges will also be faced by the anti doping authorities in detecting the endogenously produced products of enhanced gene expression.

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

    Science.gov (United States)

    Bielohuby, Maximilian; Zarkesh-Esfahani, Sayyed Hamid; Manolopoulou, Jenny; Wirthgen, Elisa; Walpurgis, Katja; Toghiany Khorasgani, Mohaddeseh; Aghili, Zahra Sadat; Wilkinson, Ian Robert; Hoeflich, Andreas; Thevis, Mario; Ross, Richard J.; Bidlingmaier, Martin

    2014-01-01

    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; PIGF-I levels from the fourth injection onwards (PIGF-I immunoassay can be used in rabbits. Similar to rodents, rabbits display variations in IGF-I depending on sex, age and genetic background. Unlike in rodents, the IGF-I response to treatment with recombinant human GH or a GHA closely mimics the

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

    Science.gov (United States)

    Chennaoui, Mounir; Arnal, Pierrick J; Dorey, Rodolphe; Sauvet, Fabien; Ciret, Sylvain; Gallopin, Thierry; Leger, Damien; Drogou, Catherine; Gomez-Merino, Danielle

    2017-11-17

    Extended sleep improves sustained attention and reduces sleep pressure in humans. Downregulation of adenosine A₁ receptor (A₁R) and modulation of the neurotrophic factor insulin growth factor-1 (IGF-I) in brain structures controlling attentional capacities could be involved. In the frontal cortex and hippocampus of rats, we measured adenosine A₁R and IGF-I protein concentrations after photoperiod-induced sleep extension. Two groups of twelve rats were adapted over 14 days to a habitual (CON) 12:12 light-dark (LD) schedule and an extended (EXT) 16:8 LD schedule. IGF-I content was also measured in plasma, liver, and skeletal muscle. In EXT, compared to CON rats, A₁R content in the frontal cortex was significantly lower ( p IGF-I content was higher ( p IGF-I content in plasma and muscle was higher ( p IGF-I levels. This photoperiod induced an anabolic profile with increased weight gain and circulating and muscular IGF-I levels. An extension of sleep duration might favor cerebral and peripheral anabolism, which may help attentional and physical capacities.

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

    NARCIS (Netherlands)

    A. Teumer (Alexander); Q. Qi; M. Nethander (Maria); H. Aschard (Hugues); S. Bandinelli (Stefania); M. Beekman (Marian); S.I. Berndt (Sonja); M. Bidlingmaier (Martin); L. Broer (Linda); A.R. Cappola (Anne); Ceda, G.P. (Gian Paolo); S.J. Chanock (Stephen); M.-H. Chen (Ming-Huei); Chen, T.C. (Tai C.); Y.D. Chen (Y.); Chung, J. (Jonathan); Del Greco Miglianico, F. (Fabiola); J. Eriksson (Joel); L. Ferrucci (Luigi); N. Friedrich (Nele); C. Gnewuch (Carsten); M. Goodarzi (Mark); N. Grarup (Niels); Guo, T. (Tingwei); Hammer, E. (Elke); R.B. Hayes (Richard); A.A. Hicks (Andrew); A. Hofman (Albert); J.J. Houwing-Duistermaat (Jeanine); Hu, F. (Frank); D. Hunter (David); L.L.N. Husemoen (Lise Lotte); A.J. Isaacs (Aaron); K.B. Jacobs (Kevin); J.A.M.J.L. Janssen (Joseph); J.-O. Jansson (John-Olov); Jehmlich, N. (Nico); Johnson, S. (Simon); A. Juul (Anders); M. Karlsson (Magnus); T.O. Kilpeläinen (Tuomas); P. Kovacs (Peter); P. Kraft (Peter); Li, C. (Chao); A. Linneberg (Allan); Y. Liu (YongMei); R.J.F. Loos (Ruth); M. Lorentzon (Mattias); Y. Lu (Yingchang); M. Maggio (Marcello); R. Mägi (Reedik); J.B. Meigs (James); D. Mellström (Dan); M. Nauck (Matthias); A.B. Newman (Anne B.); M.N. Pollak (Michael); P.P. Pramstaller (Peter Paul); I. Prokopenko (Inga); B.M. Psaty (Bruce); M. Reincke (Martin); E.B. Rimm (Eric B.); Rotter, J.I. (Jerome I.); Saint Pierre, A. (Aude); C. Schurmann (Claudia); S. Seshadri (Sudha); Sjögren, K. (Klara); P.E. Slagboom (Eline); Strickler, H.D. (Howard D.); M. Stumvoll (Michael); Y. Suh (Yousin); Q. Sun (Qi); Zhang, C. (Cuilin); Svensson, J. (Johan); T. Tanaka (Toshiko); Tare, A. (Archana); A. Tönjes (Anke); H.-W. Uh (Hae-Won); C.M. van Duijn (Cornelia); D. van Heemst (Diana); L. Vandenput (Liesbeth); R.S. Vasan (Ramachandran Srini); U. Völker (Uwe); S.M. Willems (Sara); C. Ohlsson (Claes); H. Wallaschofski (Henri); R.C. Kaplan (Robert)

    2016-01-01

    textabstractThe 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,

  7. Circulating IGF-I and IGFBP3 levels control human colonic stem cell function and are disrupted in diabetic enteropathy

    Science.gov (United States)

    Maestroni, Anna; Jung, Peter; Orsenigo, Elena; Nasr, Moufida Ben; Tezza, Sara; Bassi, Roberto; Finzi, Giovanna; Marando, Alessandro; Vergani, Andrea; Frego, Roberto; Albarello, Luca; Andolfo, Annapaola; Manuguerra, Roberta; Viale, Edi; Staudacher, Carlo; Corradi, Domenico; Batlle, Eduard; Breault, David; Secchi, Antonio; Folli, Franco; Fiorina, Paolo

    2016-01-01

    Summary The role of circulating factors in regulating colonic stem cells (CoSCs) and colonic epithelial homeostasis is unclear. Individuals with long-standing type 1 diabetes (T1D) frequently have intestinal symptoms, termed diabetic enteropathy (DE), though its etiology is unknown. Here, we report T1D patients with DE exhibit abnormalities in their intestinal mucosa and CoSCs, which fail to generate in vitro mini-guts. Proteomic profiling of T1D+DE patient serum revealed altered levels of insulin-like growth factor 1 (IGF-1) and its binding protein-3 (IGFBP3). IGFBP3 prevented in vitro growth of patient-derived organoids via binding its receptor TMEM219, in an IGF-1-independent manner, and disrupted in vivo CoSC function in a preclinical DE model. Restoration of normoglycemia in patients with long-standing T1D via kidney-pancreas transplantation or in diabetic mice by treatment with an ecto-TMEM219 recombinant protein normalized circulating IGF-1/IGFBP3 levels and reestablished CoSC homeostasis. These findings demonstrate that peripheral IGF-1/IGFBP3 control CoSCs and their dysfunction in DE. PMID:26431183

  8. 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 (PIGF1Ea and IGF1Ec...

  9. Polymorphisms of genes coding for ghrelin and its receptor in relation to anthropometry, circulating levels of IGF-I and IGFBP-3, and breast cancer risk: a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC).

    Science.gov (United States)

    Dossus, Laure; McKay, James D; Canzian, Federico; Wilkening, Stefan; Rinaldi, Sabina; Biessy, Carine; Olsen, Anja; Tjønneland, Anne; Jakobsen, Marianne U; Overvad, Kim; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Fournier, Agnes; Linseisen, Jakob; Lukanova, Annekatrin; Boeing, Heiner; Fisher, Eva; Trichopoulou, Antonia; Georgila, Christina; Trichopoulos, Dimitrios; Palli, Domenico; Krogh, Vittorio; Tumino, Rosario; Vineis, Paolo; Quirós, José Ramon; Sala, Núria; Martínez-García, Carmen; Dorronsoro, Miren; Chirlaque, Maria-Dolores; Barricarte, Aurelio; van Duijnhoven, Fränzel J B; Bueno-de-Mesquita, H B; van Gils, Carla H; Peeters, Petra H M; Hallmans, Göran; Lenner, Per; Bingham, Sheila; Khaw, Kay Tee; Key, Tim J; Travis, Ruth C; Ferrari, Pietro; Jenab, Mazda; Riboli, Elio; Kaaks, Rudolf

    2008-07-01

    Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also suggests a role of ghrelin in cancer development. We conducted a case-control study on 1359 breast cancer cases and 2389 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition, to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with anthropometric measures, circulating insulin growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 and breast cancer risk. Pair-wise tagging was used to select the 15 polymorphisms that represent the majority of common genetic variants across the GHRL and GHSR genes. A significant increase in breast cancer risk was observed in carriers of the GHRL rs171407-G allele (odds ratio: 1.2; 95% confidence interval: 1.0-1.4; P = 0.02). The GHRL single-nucleotide polymorphism rs375577 was associated with a 5% increase in IGF-I levels (P = 0.01). A number of GHRL and GHSR polymorphisms were associated with body mass index (BMI) and height (P between GHRL variations are associated with BMI. Furthermore, we have observed evidence for association of GHRL polymorphisms with circulating IGF-I levels and with breast cancer risk. These associations, however, might also be due to chance findings and further large studies are needed to confirm our results.

  10. SERUM IGF-I AND HORMONAL RESPONSES TO INCREMENTAL EXERCISE IN ATHLETES WITH AND WITHOUT LEFT VENTRICULAR HYPERTROPHY

    Directory of Open Access Journals (Sweden)

    Aleksandra Zebrowska

    2009-03-01

    Full Text Available We investigated the response of insulin-like growth factor (IGF- I, insulin-like growth factor binding protein-3 (IGFBP-3 and some hormones, i.e., testosterone (T, growth hormone (GH, cortisol (C, and insulin (I, to maximal exercise in road cyclists with and without diagnosed left ventricular hypertrophy. M-mode and two-dimensional Doppler echocardiography was performed in 30 professional male endurance athletes and a group of 14 healthy untrained subjects using a Hewlett-Packard Image Point HX ultrasound system with standard imaging transducers. Echocardiography and an incremental physical exercise test were performed during the competitive season. Venous blood samples were drawn before and immediately after the maximal cycling exercise test for determination of somatomedin and hormonal concentrations. The basal concentration of IGF-I was statistically higher (p < 0.05 in athletes with left ventricular muscle hypertrophy (LVH when compared to athletes with a normal upper limit of the left ventricular wall (LVN (p < 0.05 and to the control group (CG (p < 0.01. The IGF-I level increased significantly at maximal intensity of incremental exercise in CG (p < 0.01, LVN (p < 0.05 and LVH (p < 0.05 compared to respective values at rest. Long-term endurance training induced an increase in resting (p < 0.01 and post-exercise (p < 0.05 IGF-I/IGFBP-3 ratio in athletes with LVH compared to LVN. The testosterone (T level was lower in LVH at rest compared to LVN and CG groups (p < 0.05. These results indicate that resting serum IGF-I concentration were higher in trained subjects with LVH compared to athletes without LVH. Serum IGF- I/IGFBP-3 elevation at rest and after exercise might suggest that IGF-I act as a potent stimulant of left ventricular hypertrophy in chronically trained endurance athletes

  11. 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)

    Thordarson, Gudmundur; Slusher, Nicole; Leong, Harriet; Ochoa, Dafne; Rajkumar, Lakshmanaswamy; Guzman, Raphael; Nandi, Satyabrata; Talamantes, Frank

    2004-01-01

    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 D 1 and transforming growth factor-β 3 in the mammary gland were lower in the age-matched virgin rats than in the untreated parous and IGF-I-treated parous

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

    Science.gov (United States)

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

    1996-12-17

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

  13. High protein diets do not attenuate decrements in testosterone and IGF-I during energy deficit.

    Science.gov (United States)

    Henning, Paul C; Margolis, Lee M; McClung, James P; Young, Andrew J; Pasiakos, Stefan M

    2014-05-01

    Energy deficit (ED) diminishes fat-free mass (FFM) with concomitant reductions in anabolic hormone secretion. A modest increase in protein to recommended dietary allowance (RDA) levels during ED minimally attenuates decrements in insulin-like growth factor-I (IGF-I). The impact of dietary protein above the RDA on circulating anabolic hormones and their relationships with FFM in response to ED are not well described. Thirty-three adults were assigned diets providing protein at 0.8 (RDA), 1.6 (2×-RDA), and 2.4 (3×-RDA) g/kg/d for 31days. Testosterone, sex-hormone binding globulin (SHBG) and IGF-I system components were assessed after a 10-day period of weight-maintenance (WM) and after a 21-day period of ED (40%) achieved by an increase in energy expenditure and decreased energy intake. Associations between the change in FFM and anabolic hormone levels were determined. As compared to WM and regardless of dietary protein intake, total and free testosterone, total IGF-I, and acid-labile subunit decreased (Phormones or IGF-I system components measured. Changes in FFM in response to ED were negatively associated with acid-labile subunit (ALS) (r=-0.62, Phormone concentrations. Published by Elsevier Inc.

  14. IGF-I AND FGF-2 RESPONSES TO WINGATE ANAEROBIC TEST IN OLDER MEN

    Directory of Open Access Journals (Sweden)

    Ruthie Amir

    2007-06-01

    Full Text Available Reduced activity of the potent anabolic effectors: insulin-like growth factor-I (IGF-I and fibroblast growth factor-2 (FGF-2, play a role in aging associated muscle loss. The effect of fitness level on IGF-I and FGF-2 responses to all-out anaerobic exercise in older men was studied. Twenty four healthy older males: 12 higher fit (58 ± 1y and 12 lower fit (59 ± 1y underwent the Wingate anaerobic test. Serum levels of IGF-I and FGF-2 were measured before, immediately after exercise, and 50 min into recovery. Immediately post exercise, the average peak power output and serum lactate were higher (p < 0.05 in the higher fit (446.0 ± 14. 9 kgm·min-1 for mean (± SD peak power and 12.6 ± 1.1 mml·l-1 for lactate compared with the lower fit individuals (284.0 ± 6.5 kgm·min-1 and 8.5 ± 0.7 mml·l-1, respectively. Pre-exercise IGF-I was lower and FGF-2 was higher in the higher fit (335.0 ± 54.0 ng·ml-1 and 1.6 ± 0.1 ng·ml-1, respectively compared with lower fit individuals (402.0 ± 50.0 ng·ml-1 and 1.4 ± 0.2 ng·ml-1, respectively. Following the anaerobic exercise, in both groups, FGF-2 decreased dramatically (p < 0.05; in the higher fit individuals FGF-2 level was 0.4 ± 0.1 pg·ml-1 compared to 0.1 ± 0.02 pg·ml-1 in the lower fit individuals. In contrast to FGF-2, IGF-I increased transiently to levels of 405.0 ± 62.0 ng·ml-1 in the higher fit individuals and to levels of 436 ± 57.0 ng·ml-1 in the lower fit individuals. However, the IGF-I elevation was significant (p < 0. 05 only in the higher fit individuals. In conclusion, the present study demonstrates that during aging, fitness level can alter circulating levels of IGF-I and FGF-2. Furthermore, fitness level can affect the response of both mediators to all-out anaerobic exercise.

  15. A polymorphism in the gene for IGF-I: functional properties and risk for type 2 diabetes and myocardial infarction

    NARCIS (Netherlands)

    N. Vaessen (Norbert); J.C.M. Witteman (Jacqueline); L. Testers; S.W.J. Lamberts (Steven); B.A. Oostra (Ben); H.A.P. Pols (Huib); C.M. van Duijn (Cornelia); J.A.M.J.L. Janssen (Joseph); P. Heutink (Peter); A. Hofman (Albert)

    2001-01-01

    textabstractEvidence is accumulating that low levels of IGF-I play a role in the pathogenesis of type 2 diabetes and cardiovascular diseases. We examined the role of a genetic polymorphism in the promoter region of the IGF-I gene in relation to circulating IGF-I levels and growth measured as body

  16. Determination of LongR3-IGF-I, R3-IGF-I, Des1-3 IGF-I and their metabolites in human plasma samples by means of LC-MS.

    Science.gov (United States)

    Thomas, Andreas; Walpurgis, Katja; Delahaut, Philippe; Fichant, Eric; Schänzer, Wilhelm; Thevis, Mario

    2017-08-01

    According to the regulations of the World Anti-Doping Agency (WADA), growth promoting peptides such as the insulin-like growth factor-I (IGF-I) and its synthetic analogues belong to the class of prohibited compounds. While several assays to quantify endogenous IGF-I have been established, the potential misuse of synthetic analogues such as LongR 3 -IGF-I, R 3 -IGF-I and Des1-3-IGF-I remains a challenge and superior pharmacokinetic properties have been described for these analogues. Within the present study, it was demonstrated that the target peptides can be successfully detected in plasma samples by means of magnetic beads-based immunoaffinity purification and subsequent nanoscale liquid chromatographic separation with high resolution mass spectrometric detection. Noteworthy, the usage of a specific antibody for LongR 3 -IGF-I enables the determination in low ng/mL levels despite the presence of an enormous excess of endogenous human IGF-I. In addition, different metabolism studies (in-vitro and in-vivo) were performed using sophisticated strategies such as incubation with skin tissue microsomes, degradation in biological fluids (for all analogues), and administration to rats (for LongR 3 -IGF-I). Herewith, several C-and N-terminally truncated metabolites were identified and their relevancy was additionally confirmed by in-vivo experiments with rodents. Especially for LongR 3 -IGF-I, a metabolite ((Des1-11)-LongR 3 -IGF-I) was identified that prolonged the detectability in-vivo by a factor of approximately 2. The method was validated for qualitative interpretation considering the parameters specificity, identification capability, recovery (26-60%), limit of detection (0.5ng/mL), imprecision (IGF-I was used as internal standard to control all sample preparation steps. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Impact of IGF-I release kinetics on bone healing: a preliminary study in sheep.

    Science.gov (United States)

    Luginbuehl, Vera; Zoidis, Evangelos; Meinel, Lorenz; von Rechenberg, Brigitte; Gander, Bruno; Merkle, Hans P

    2013-09-01

    Spatiotemporal release of growth factors from a delivery device can profoundly affect the efficacy of bone growth induction. Here, we report on a delivery platform based on the encapsulation of insulin-like growth factor I (IGF-I) in different poly(D,L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) microsphere (MS) formulations to control IGF-I release kinetics. In vitro IGF-I release profiles generally exhibited an initial burst (14-36% of total IGF-I content), which was followed by a more or less pronounced dormant phase with little release (2 to 34 days), and finally, a third phase of re-increased IGF-I release. The osteoinductive potential of these different IGF-I PL(G)A MS formulations was tested in studies using 8-mm metaphyseal drill hole bone defects in sheep. Histomorphometric analysis at 3 and 6 weeks after surgery showed that new bone formation was improved in the defects locally treated with IGF-I PL(G)A MS (n=5) as compared to defects filled with IGF-I-free PL(G)A MS (n=4). The extent of new bone formation was affected by the particular release kinetics, although a definitive relationship was not evident. Local administration of IGF-I resulted in down-regulation of inflammatory marker genes in all IGF-I treated defects. The over-expression of growth factor genes in response to IGF-I delivery was restricted to formulations that produced osteogenic responses. These experiments demonstrate the osteoinductive potential of sustained IGF-I delivery and show the importance of delivery kinetics for successful IGF-I-based therapies. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. 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)

    Quirion, R.; Rowe, W.; Kar, S.; Dore, S.

    1997-01-01

    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, [ 125 I]IGF-I receptors are concentrated primarily in the dentate gyrus (DG) and the CA3 sub-field while high amounts of [ 125 I]IGF-II binding sites are localized to the pyramidal cell layer, and the granular cell layer of the DG. [ 125 I]insulin binding sites are mostly found in the molecular layer of the DG and the CA1 sub-field. No significant differences were found in [ 125 I]IGF-I, [ 125 I]IGF-II or [ 125 I]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

  19. IGFBP-1 and IGF-I as markers for advanced fibrosis in NAFLD - a pilot study.

    Science.gov (United States)

    Hagström, Hannes; Stål, Per; Hultcrantz, Rolf; Brismar, Kerstin; Ansurudeen, Ishrath

    2017-12-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. Advanced fibrosis (stage 3-4) is the most robust marker for future mortality, but diagnosis requires liver biopsy. Current non-invasive scoring systems aimed to identify advanced fibrosis are imperfect. Insulin-like growth factor I (IGF-I) and its binding protein IGFBP-1 are liver derived proteins, that are involved in various liver disorders. The aim of this study was to examine the possible association between advanced fibrosis and IGF-I and IGFBP-1 in NAFLD. Fasting blood samples were obtained from 52 patients diagnosed with NAFLD by liver biopsy. Total IGF-I and IGFBP-1 concentrations were determined in serum by in-house radio-immuno-assays. IGF-I levels were age-standardized (IGF-SD). A logistic regression model was used to investigate the association of IGF-SD and IGFBP-1 with advanced fibrosis (stage 3-4). Patients with advanced fibrosis (stage 3-4 vs. 0-2) had lower IGF-SD (-1.17 vs. 0.11, p = .01) and higher mean levels of IGFBP-1 (29.9 vs. 18.8 µg/l, p = .02). IGFBP-1 was associated with presence of advanced fibrosis (OR 1.04 per unit increase, 95%CI 1.0-1.07, p = .05), while IGF-1 was negatively associated with advanced fibrosis (OR 0.63 per standard deviation, 95%CI 0.44-0.92, p = .02). This pilot study suggests an association between serum IGFBP-1 and IGF-I levels with advanced fibrosis in NAFLD patients. IGFBP1 and IGF-1 could be of interest as future biomarkers. Similar studies in larger cohorts are needed.

  20. Changes of blood and myocardial tissue contents of IGF-I after development of acute myocardial infarction in rat models

    International Nuclear Information System (INIS)

    Cao Heng; Wei Youquan

    2006-01-01

    Objective: To study the changes of IGF-I contents in blood and myocardium after experimental acute myocardial infarction in rat models. Methods: Rat models of acute myocardial infarction were prepared with intraperitoneal injection of isoproterenol. Eight models were sacrificed 48h later and another 8 models were sacrificed 14 days after preparation. Serum and myocardium homogenate contents of IGF-I were measured with RIA in these models as well as 8 control rats. Results: The serum and myocardial contents of IGF-I increased in the models sacrificed at 48h, but were not significantly higher than those in the controls (P>0.05). At 14 th day, the levels were significantly higher than those in controls and at 48h (both P<0.05). The serum and myocardial contents of IGF-I were mutually correlated in the controls and 14 day models (r=0.9987, r=0.9992; P<0.01). Conclusion After myocardial infarction, the serum and myocardial IGF-I contents increased along with the course of disease in the rat models. (authors)

  1. The IGF-I/JAK2-STAT3/miR-21 signaling pathway may be associated with human renal cell carcinoma cell growth.

    Science.gov (United States)

    Su, Ying; Zhao, An; Cheng, Guoping; Xu, Jingjing; Ji, Enming; Sun, Wenyong

    2017-07-04

    Renal cell carcinoma (RCC) is the highest mortality rate of the genitourinary cancers, and the treatment options are very limited. Thus, identification of molecular mechanisms underlying RCC tumorigenesis, is critical for identifying biomarkers for RCC diagnosis and prognosis. To validate whether the IGF-I/JAK2-STAT3/miR-21 signaling pathway is associated with human RCC cell growth. qRT-PCR and Western blotting were used to detect the mRNA and protein expression levels, respectively. The MTT assay was performed to determine cell survival rate. The Annexin V-FITC/PI apoptosis detection kit was used to detect cell apoptosis. We employed RCC tissues and cell lines (A498; ACHN; Caki-1; Caki-2 and 786-O) in the study. IGF-I, and its inhibitor (NT-157) were administrated to detect the effects of IGF-I on the expression of miR-21 and p-JAK2. JAK2 inhibitor (AG490), and si-STAT3 were used to detect the effects of JAK2/STAT3 signaling pathway on the expression of miR-21. In our study, we firstly showed that the expression levels of IGF-I and miR-21 were up-regulated in RCC tissues and cell lines. After exogenous IGF-I treatment, the expression levels of miR-21, p-IGF-IR and p-JAK2 were significantly increased, whereas NT-157 treatment showed the reversed results. Further study indicated that JAK2 inhibitor or si-STAT3 significantly reversed the IGF-I-induced miR-21 expression level. Finally, we found that IGF-I treatment significantly prompted human RCC cell survival and inhibited cell apoptosis, and NT-157 treatment showed the reversed results. The IGF-I/JAK2-STAT3/miR-21 signaling pathway may be associated with human RCC cell growth.

  2. Role of IGF-I in follistatin-induced skeletal muscle hypertrophy.

    Science.gov (United States)

    Barbé, Caroline; Kalista, Stéphanie; Loumaye, Audrey; Ritvos, Olli; Lause, Pascale; Ferracin, Benjamin; Thissen, Jean-Paul

    2015-09-15

    Follistatin, a physiological inhibitor of myostatin, induces a dramatic increase in skeletal muscle mass, requiring the type 1 IGF-I receptor/Akt/mTOR pathway. The aim of the present study was to investigate the role of IGF-I and insulin, two ligands of the IGF-I receptor, in the follistatin hypertrophic action on skeletal muscle. In a first step, we showed that follistatin increases muscle mass while being associated with a downregulation of muscle IGF-I expression. In addition, follistatin retained its full hypertrophic effect toward muscle in hypophysectomized animals despite very low concentrations of circulating and muscle IGF-I. Furthermore, follistatin did not increase muscle sensitivity to IGF-I in stimulating phosphorylation of Akt but, surprisingly, decreased it once hypertrophy was present. Taken together, these observations indicate that increased muscle IGF-I production or sensitivity does not contribute to the muscle hypertrophy caused by follistatin. Unlike low IGF-I, low insulin, as obtained by streptozotocin injection, attenuated the hypertrophic action of follistatin on skeletal muscle. Moreover, the full anabolic response to follistatin was restored in this condition by insulin but also by IGF-I infusion. Therefore, follistatin-induced muscle hypertrophy requires the activation of the insulin/IGF-I pathway by either insulin or IGF-I. When insulin or IGF-I alone is missing, follistatin retains its full anabolic effect, but when both are deficient, as in streptozotocin-treated animals, follistatin fails to stimulate muscle growth. Copyright © 2015 the American Physiological Society.

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

    Science.gov (United States)

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

    2016-08-01

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

  4. 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.

  5. Overexpression of IGF-I in skeletal muscle of transgenic mice does not prevent unloading-induced atrophy

    Science.gov (United States)

    Criswell, D. S.; Booth, F. W.; DeMayo, F.; Schwartz, R. J.; Gordon, S. E.; Fiorotto, M. L.

    1998-01-01

    This study examined the association between local insulin-like growth factor I (IGF-I) overexpression and atrophy in skeletal muscle. We hypothesized that endogenous skeletal muscle IGF-I mRNA expression would decrease with hindlimb unloading (HU) in mice, and that transgenic mice overexpressing human IGF-I (hIGF-I) specifically in skeletal muscle would exhibit less atrophy after HU. Male transgenic mice and nontransgenic mice from the parent strain (FVB) were divided into four groups (n = 10/group): 1) transgenic, weight-bearing (IGF-I/WB); 2) transgenic, hindlimb unloaded (IGF-I/HU); 3) nontransgenic, weight-bearing (FVB/WB); and 4) nontransgenic, hindlimb unloaded (FVB/HU). HU groups were hindlimb unloaded for 14 days. Body mass was reduced (P < 0.05) after HU in both IGF-I (-9%) and FVB mice (-13%). Contrary to our hypothesis, we found that the relative abundance of mRNA for the endogenous rodent IGF-I (rIGF-I) was unaltered by HU in the gastrocnemius (GAST) muscle of wild-type FVB mice. High-level expression of hIGF-I peptide and mRNA was confirmed in the GAST and tibialis anterior (TA) muscles of the transgenic mice. Nevertheless, masses of the GAST and TA muscles were reduced (P < 0.05) in both FVB/HU and IGF-I/HU groups compared with FVB/WB and IGF-I/WB groups, respectively, and the percent atrophy in mass of these muscles did not differ between FVB and IGF-I mice. Therefore, skeletal muscle atrophy may not be associated with a reduction of endogenous rIGF-I mRNA level in 14-day HU mice. We conclude that high local expression of hIGF-I mRNA and peptide in skeletal muscle alone cannot attenuate unloading-induced atrophy of fast-twitch muscle in mice.

  6. IGF-I at 9 and 36 months of age — relations with body composition and diet at 3 years — the SKOT cohort

    DEFF Research Database (Denmark)

    Ejlerskov, Katrine Tschentscher; Larnkjær, A.; Pedersen, D.

    2014-01-01

    Objective High infancy levels of insulin-like growth factor-I (IGF-I) have been associated with increased linear growth and fat-free mass (FFM) but also with risk of obesity. This paper examines how IGF-I at 9 and 36 months relates to diet and body composition. Design Healthy term infants from...... and values were considerably higher in girls (43%). Children breastfed at 9 months had lower IGF-I concentrations at 9 months but reached the same IGF-I concentrations at 36 months as infants not breastfed at 9 months. IGF-I at 36 months was positively associated with height, weight, BMI, predicted FFM...... and FFM index (FFM/height (kg/m2)). Although there also was a positive association with predicted fat mass (FM) there was no association with FM index (FM/height (kg/m2)). Further, a negative association with skin fold thickness was observed. A change in IGF-I from 9–36 months was positively related...

  7. IGF-I and NEFA concentrations in fetal fluids of term pregnancy dogs.

    Science.gov (United States)

    Meloni, Tea; Comin, Antonella; Rota, Alessandro; Peric, Tanja; Contri, Alberto; Veronesi, Maria Cristina

    2014-06-01

    Insulin-like growth factor-I (IGF-I) and non-esterified fatty acids (NEFA) play an essential role in fetal growth and development. To date, fetal fluids IGF-I and NEFA levels at term canine pregnancy are unknown and could be related to the neonatal development and breed size. For these reasons, the aims of the present study were as follows: (1) to evaluate IGF-I and NEFA concentrations in fetal fluids collected from normally developed and viable newborn puppies born at term of normal pregnancies; (2) to assess possible differences between IGF-I and NEFA levels in amniotic compared with allantoic fluid; (3) to detect possible relationship between breed body size and IGF-I and NEFA amniotic and allantoic concentrations; (4) to evaluate possible differences in IGF-I fetal fluids levels between male and female puppies; and (5) to assess possible correlations between the two hormones in each type of fluid. The study enrolled 25 pure breed bitches submitted to elective Cesarean section at term because of the high risk of dystocia or previous troubles at parturition. At surgery, amniotic and allantoic fluids were collected and assayed for IGF-I and NEFA. IGF-I and NEFA amounts in both amniotic and allantoic fluids of different breed size bitches (small: ≤10 kg; medium: 11-25 kg; large: 26-40 kg) were detected, as well as the effect of gender on IGF-I levels. On a total of 73 amniotic and 76 allantoic samples collected by normal, viable, and mature newborns, the mean IGF-I concentration was significantly higher in amniotic than in allantoic fluid in all three groups, but the amniotic IGF-I levels were significantly lower in small and medium size bitches when compared with large ones. No significant differences were found in allantoic IGF-I concentrations among size groups. A significant effect of the puppy gender on IGF-I content in both fetal fluids was not reported. Regarding NEFA, in all the three groups, the mean NEFA concentration did not significantly differ

  8. Deficiency of liver-derived insulin-like growth factor-I (IGF-I) does not interfere with the skin wound healing rate

    Science.gov (United States)

    Narayanan, Sampath; Grünler, Jacob; Sunkari, Vivekananda Gupta; Calissendorff, Freja S.; Ansurudeen, Ishrath; Illies, Christopher; Svensson, Johan; Jansson, John-Olov; Ohlsson, Claes; Brismar, Kerstin; Catrina, Sergiu-Bogdan

    2018-01-01

    Objective IGF-I is a growth factor, which is expressed in virtually all tissues. The circulating IGF-I is however derived mainly from the liver. IGF-I promotes wound healing and its levels are decreased in wounds with low regenerative potential such as diabetic wounds. However, the contribution of circulating IGF-I to wound healing is unknown. Here we investigated the role of systemic IGF-I on wound healing rate in mice with deficiency of liver-derived IGF-I (LI-IGF-I-/- mice) during normal (normoglycemic) and impaired wound healing (diabetes). Methods LI-IGF-I-/- mice with complete inactivation of the IGF-I gene in the hepatocytes were generated using the Cre/loxP recombination system. This resulted in a 75% reduction of circulating IGF-I. Diabetes was induced with streptozocin in both LI-IGF-I-/- and control mice. Wounds were made on the dorsum of the mice, and the wound healing rate and histology were evaluated. Serum IGF-I and GH were measured by RIA and ELISA respectively. The expression of IGF-I, IGF-II and the IGF-I receptor in the skin were evaluated by qRT-PCR. The local IGF-I protein expression in different cell types of the wounds during wound healing process was analyzed using immunohistochemistry. Results The wound healing rate was similar in LI-IGF-I-/- mice to that in controls. Diabetes significantly delayed the wound healing rate in both LI-IGF-I-/- and control mice. However, no significant difference was observed between diabetic animals with normal or reduced hepatic IGF-I production. The gene expression of IGF-I, IGF-II and IGF-I receptor in skin was not different between any group of animals tested. Local IGF-I levels in the wounds were similar between of LI-IGF-I-/- and WT mice although a transient reduction of IGF-I expression in leukocytes in the wounds of LI-IGF-I-/- was observed seven days post wounding. Conclusion Deficiency in the liver-derived IGF-I does not affect wound healing in mice, neither in normoglycemic conditions nor in

  9. Binding of IGF I and IGF I-stimulated phosphorylation in canine renal basolateral membranes

    International Nuclear Information System (INIS)

    Hammerman, M.R.; Gavin, J.R. III.

    1986-01-01

    To characterize the interaction of the renal proximal tubular cell with insulin like growth factor I (IGF I), we measured binding of 125 I-IGF I to proximal tubular basolateral membranes from dog kidney and induced IGF I-stimulated phosphorylation of basolateral membranes. Specific binding of 125 I-IGF I to basolateral membranes was observed that was half-maximal at between 10(-9) and 10(-8) M IGF I. 125 I-IGF I was affinity cross-linked to a 135,000 Mr protein in basolateral membranes that was distinct from the alpha-subunit of the insulin receptor and from the IGF II receptor. IGF I-stimulated phosphorylation of a 92,000 Mr protein was effected in detergent-solubilized membranes incubated with 100 microM [gamma- 32 P]ATP. The 32 P-labeled protein was distinct from the beta-subunit of the insulin receptor, the 32 P phosphorylation of which was stimulated by insulin. We conclude that specific receptors for IGF I are present in the basolateral membrane of the renal proximal tubular cell. Physiological actions of IGF I at this nephron site may occur through the binding of this peptide circulating in plasma, to specific basolateral membrane receptors, followed by IGF I stimulated phosphorylation

  10. Differential binding of 125I-IGF-I preparations to human fibroblast monolayers

    International Nuclear Information System (INIS)

    Conover, C.A.; Misra, P.; Hintz, R.L.; Rosenfeld, R.G.

    1988-01-01

    Specific, high affinity binding of 125 I-IGF-I to the type IIGF receptor on human fibroblast monolyaers was not altered by varying feeding schedules, serum lots, washing procedures, or incubation times and temperatures. However, markedly different competitive binding curves were obtained when different iodinated IGF-I preparations were used. Five of six radioligands bound preferentially to the type IIGF receptor on human fibroblast monolayers, with 50% displacement at 4-8 μg/l unlabelled IGF-I; with one radioligand a paradoxical 20-200% increase in 125 I-IGF-I binding was observed at low concentrations of unlabelled IGF-I, while concentrations as high as 100 μg/l IGF-I failed to displace this radioligand. The latter binding pattern cannot be accounted for by 125 -I-IGF-I binding to the type II IGF receptor. These data indicate that various radioligands may have preferential affinities for different IGF-I binding sites on human fibroblast monolayers. (author)

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

    Directory of Open Access Journals (Sweden)

    Mounir Chennaoui

    2017-11-01

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

  12. Nutritional regulation of IGF-II, but not IGF-I, is age dependent in sheep.

    Science.gov (United States)

    Oldham, J M; Martyn, J A; Hua, K M; MacDonald, N A; Hodgkinson, S C; Bass, J J

    1999-12-01

    In post-natal animals, plasma concentrations of IGF-I are tightly regulated by nutritional status. The current study reports that plasma levels of IGF-II in sheep are also regulated by nutrition, but whether plasma IGF-II is increased, decreased or remains the same, depends on the age of the animal. Ewe lambs, ranging in age from 2 days to 2 years, were fed or fasted for lengths of time between 24 and 72 h. Blood samples were taken at intervals of 24 h throughout the treatment period and immediately before slaughter. Plasma concentrations of IGF-I increased with advancing age in fed animals (Panimals matured (Pnutrition (Panimals (Panimals (Pnutritional sensitivity of serum IGF-binding proteins (BPs) also changed with age. The 29 kDa BP, which we presume to be BP1, was elevated by fasting in young animals and reduced slightly in older animals. BP2 was increased to a similar magnitude by fasting at all ages. BP3 was depressed by fasting in young animals and showed little change in adults. In contrast, a 24 kDa BP, which is probably BP4, showed little change in young animals and was reduced substantially in older sheep. In conclusion, the response of plasma IGF-II to fasting suggests that this peptide has functions in mediating nutritional stress which depend on the age of the animal, and also that the role of IGF-II may differ from that of IGF-I in adults.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  14. 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)....

  15. Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence.

    Science.gov (United States)

    Matsumoto, Ryusaku; Fukuoka, Hidenori; Iguchi, Genzo; Odake, Yukiko; Yoshida, Kenichi; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Yamada, Shozo; Ogawa, Wataru; Takahashi, Yutaka

    2015-01-01

    Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases. We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts. Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047). In addition, telomere length in acromegaly was negatively correlated with the disease duration (R2 = 0.210, P = 0.003). In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence. Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I.

  16. Postprandial hyperglycemia corrected by IGF-I (Increlex®) in Laron syndrome.

    Science.gov (United States)

    Latrech, Hanane; Simon, Albane; Beltrand, Jacques; Souberbielle, Jean-Claude; Belmejdoub, Ghizlane; Polak, Michel

    2012-01-01

    Laron syndrome is caused by a mutation in the growth hormone (GH) receptor and manifests as insulin-like growth factor-I (IGF-I) deficiency, severe short stature, and early hypoglycemia. We report a case with postprandial hyperglycemia, an abnormality not reported previously. Postprandial hyperglycemia was due to chronic IGF-I deficiency, and was reversed by IGF-I replacement therapy. A Moroccan girl referred for short stature at 7 years and 8 months of age had dwarfism [height, 78 cm (-9 SDs); weight, 10 kg (-4 SDs)], hypoglycemia, and truncal obesity. Her serum IGF-I level was very low, and her baseline serum GH level was elevated to 47 mIU/l. Molecular analysis showed a homozygous mutation in the GH receptor gene. Continuous glucose monitoring before treatment showed asymptomatic hypoglycemia with postprandial hyperglycemia (2.5 g/l, 13.75 mmol/l). Treatment with recombinant human IGF-I (mecasermin, Increlex®) was started. The blood glucose profile improved with 0.04 µg/kg/day and returned to normal with 0.12 µg/kg/day. Postprandial hyperglycemia is a metabolic consequence of chronic IGF-I deficiency. The beneficial effect of IGF-I replacement therapy may be ascribable to improved postprandial transfer of glucose. Copyright © 2012 S. Karger AG, Basel.

  17. Chronic alcohol consumption, type 2 diabetes mellitus, insulin-like growth factor-I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats.

    Science.gov (United States)

    Kim, Soo-Jeong; Ju, Anes; Lim, Seul-Gi; Kim, Dai-Jin

    2013-11-13

    Alcohol has deleterious influences on glucose metabolism which may contribute to the development of type 2 diabetes mellitus (T2DM). Insulin-like growth factor I (IGF-I) and growth hormone (GH), which interact with insulin to modulate metabolic control, have been shown to be related to impaired glucose tolerance. This study was conducted to assess the possibility that altered circulating IGF-I and GH levels contribute to the exacerbation of T2DM by alcohol use in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats. OLETF rats were pair-fed a Lieber-DeCarli Regular Ethanol diet and LETO rats were pair-fed a control diet for 6 weeks. At 6 weeks, an Intraperitoneal Glucose Tolerance Test (IP-GTT) was performed and IGF-I and GH levels were evaluated. Prior to an IP-GTT, OLETF-Ethanol (O-E) group had significantly a decrease in the mean glucose levels compared to OLETF-Control (O-C) group. At 120 min post IP-GTT, the O-E group had significantly an increase in the mean glucose levels compared to O-C group. The serum IGF-I levels were significantly lower and the serum GH levels were significantly higher in the O-E group than in L-C group. These results suggest that IGF-I and GH are prominent in defining the risk and development of T2DM, and may be adversely affected by heavy alcohol use, possibly mediating its diabetogenic effects. Thus, the overall glucose intolerance in the setting of alcoholism may be attributable to inappropriate alteration of IGF-I and GH levels. © 2013. Published by Elsevier Inc. All rights reserved.

  18. DHT and testosterone, but not DHEA or E2, differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells.

    Science.gov (United States)

    Le, Hanh; Arnold, Julia T; McFann, Kimberly K; Blackman, Marc R

    2006-05-01

    Prostate cancer is one of the four most common cancers in the United States, affecting one of six men. Increased serum levels of androgens and IGF-I are associated with an augmented risk of prostate cancer. Dihydrotestosterone (DHT) and testosterone (T) stimulate prostate cancer cell growth, development, and function, whereas the effects of DHT and T in prostate stromal cells, and of dehydroepiandrosterone (DHEA) in prostate cancer or stromal cells, are uncertain. We investigated the actions of DHT, T, DHEA, and estradiol (E2) on insulin-like growth factor (IGF)-I, IGF-II, IGF-I receptor (R), IGF-binding protein (IGFBP)-2, IGFBP-3, and IGFBP-5 in primary cultures of human prostatic stromal cells by assessing cell proliferation, mRNA expression, and protein secretion by MTT growth assay, quantitative real-time PCR, and ELISA, respectively. DHT and T each increased IGF-I (7-fold) and decreased IGFBP-3 (2-fold) mRNA expression and protein secretion in a dose- and time-dependent manner and increased IGFBP-2 (2-fold) mRNA in a dose- and time-dependent manner. DHEA and E2 did not significantly alter these measures. Flutamide abolished the DHT-modulated increases in IGF-I and IGFBP-2, suggesting that the influences of DHT and T on these measures were androgen receptor mediated. None of the four steroids significantly affected IGF-IR, IGF-II, or IGFBP-5 mRNA levels or stromal cell proliferation. The effects of DHT on IGF-I, IGFBP-2, and IGFBP-3 were more pronounced in stromal cultures that did not express desmin. These data suggest that DHT and T promote prostate growth partly via modulation of the stromal cell IGF axis, with potential paracrine effects on prostate epithelial cells.

  19. GH/IGF-I Transgene Expression on Muscle Homeostasis

    Science.gov (United States)

    Schwartz, Robert J.

    1999-01-01

    We propose to test the hypothesis that the growth hormone/ insulin like growth factor-I axis through autocrine/paracrine mechanisms may provide long term muscle homeostasis under conditions of prolonged weightlessness. As a key alternative to hormone replacement therapy, ectopic production of hGH, growth hormone releasing hormone (GHRH), and IGF-I will be studied for its potential on muscle mass impact in transgenic mice under simulated microgravity. Expression of either hGH or IGF-I would provide a chronic source of a growth-promoting protein whose biosynthesis or secretion is shut down in space. Muscle expression of the IGF-I transgene has demonstrated about a 20% increase in hind limb muscle mass over control nontransgenic litter mates. These recent experiments, also establish the utility of hind-limb suspension in mice as a workable model to study atrophy in weight bearing muscles. Thus, transgenic mice will be used in hind-limb suspension models to determine the role of GH/IGF-I on maintenance of muscle mass and whether concentric exercises might act in synergy with hormone treatment. As a means to engineer and ensure long-term protein production that would be workable in humans, gene therapy technology will be used by to monitor muscle mass preservation during hind-limb suspension, after direct intramuscular injection of a genetically engineered muscle-specific vector expressing GHRH. Effects of this gene-based therapy will be assessed in both fast twitch (medial gastrocnemius) and slow twitch muscle (soleus). End-points include muscle size, ultrastructure, fiber type, and contractile function, in normal animals, hind limb suspension, and reambutation.

  20. Loss of neutrophil polarization in colon carcinoma liver metastases of mice with an inducible, liver-specific IGF-I deficiency.

    Science.gov (United States)

    Rayes, Roni F; Milette, Simon; Fernandez, Maria Celia; Ham, Boram; Wang, Ni; Bourdeau, France; Perrino, Stephanie; Yakar, Shoshana; Brodt, Pnina

    2018-03-20

    The growth of cancer metastases in the liver depends on a permissive interaction with the hepatic microenvironment and neutrophils can contribute to this interaction, either positively or negatively, depending on their phenotype. Here we investigated the role of IGF-I in the control of the tumor microenvironment in the liver, using mice with a conditional, liver-specific, IGF-I deficiency (iLID) induced by a single tamoxifen injection. In mice that had a sustained (3 weeks) IGF-I deficiency prior to the intrasplenic/portal inoculation of colon carcinoma MC-38 cells, we observed an increase in neutrophil accumulation in the liver relative to controls. However, unlike controls, these neutrophils did not acquire the (anti-inflammatory) tumor-promoting phenotype, as evidenced by retention of high ICAM-1 expression and nitric oxide production and low CXCR4, CCL5, and VEGF expression and arginase production, all characteristic of the (pro-inflammatory) phenotype. This coincided with an increase in apoptotic tumor cells and reduced metastasis. Neutrophils isolated from these mice also had reduced IGF-IR expression levels. These changes were not observed in iLID mice with a short-term (2 days) IGF-I depletion, despite a 70% reduction in their circulating IGF-I levels, indicating that a sustained IGF-I deficiency was necessary to alter the neutrophil phenotype. Similar results were obtained with the highly metastatic Lewis lung carcinoma subline H-59 cells and in mice injected with an IGF-Trap that blocks IGF-IR signaling by reducing ligand bioavailability. Our results implicate the IGF axis in neutrophil polarization and the induction of a pro-metastatic microenvironment in the liver.

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

    Science.gov (United States)

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

    2001-01-01

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

  2. Compensatory growth assessment by plasma IGF-I hormone ...

    African Journals Online (AJOL)

    USER

    2010-06-21

    Jun 21, 2010 ... feeding diets and regimes will be evaluated in future studies. Key words: Compensatory growth, food coefficient ratio, food intake, IGF-I, rainbow trout, special growth .... Blood was sampled for IGF-I hormone concentration.

  3. Effect of Modified and accumulated decoction on serum ER, PR, sex hormone, IGF-I and IGF-I in patients with uterine fibroids

    Directory of Open Access Journals (Sweden)

    Yi-Sha Li

    2017-11-01

    Full Text Available Objective: To study the effect of Modified and accumulated Decoction on serum ER, PR, sex hormone, IGF-I and IGF-I in patients with uterine fibroids. Method: A total of 90 patients with uterine fibroids in our hospital from January 2015 to January 2017 were enrolled in this study. The subjects were divided into the control group (n=45 and the treatment group (n=45 randomly. The control group was treated with mifepristone, the treatment group was treated with Modified and accumulated Decoction combined with mifepristone, and both the two groups were treated for 3 months. The uterine fibroid volume and uterine volume of the two groups before and after treatment were compared. The serum ER, PR, P, E 2 , LH, FSH, IGF-I and IGF-IR of the two groups before and after treatment were compared. Result: There were no significantly differences of the uterine fibroid volume and uterine volume of the two groups before treatment. The uterine fibroid volume and uterine volume of the two groups after treatment were significantly less than before treatment, and that of the treatment group after treatment were significantly less than the control group. There were no significantly differences among the serum ER, PR, P, E 2 , LH, FSH, IGF-I and IGF-IR of the two groups before treatment. The serum ER, PR, P, E 2 , LH, FSH, IGF-I and IGF-IR of the two groups after treatment were significantly lower than before treatment, and that of the treatment group after treatment were significantly lower than the control group. Conclusion: Modified and accumulated Decoction combined with mifepristonecan significantly reduce the uterine fibroid volume, improve the serum ER, PR, sex hormone, IGF-I and IGF-I levels of the patients with uterine fibroids, and it was worthy clinical application.

  4. Systemic administration of insulin-like growth factor I (IGF-I) causes growth of the rat prostate

    DEFF Research Database (Denmark)

    Tørring, N; Vinter-Jensen, L; Pedersen, S B

    1997-01-01

    -I after 3 days of treatment, and administration of IGF-I concomitantly with DFMO significantly inhibited ODC activity and the weight increase of the prostate. Stereological examination of the prostate in the IGF-I-treated animals showed growth of the epithelial component of the gland. Systemic treatment...

  5. Insulin and insulin-like growth factor-I (IGF-I) receptor phosphorylation in µ-calpain knockout mice

    Science.gov (United States)

    Numerous cellular processes are controlled by insulin and IGF-I signaling pathways. Due to previous work in our laboratories, we hypothesized that insulin (IR) and type 1 IGF-I (IGF-IR) receptor signaling is decreased due to increased protein tyrosine phosphatase 1B (PTP1B) activity. C57BL/6J mice...

  6. Increased cardiac alpha-myosin heavy chain in left atria and decreased myocardial insulin-like growth factor (Igf-I) expression accompany low heart rate in hibernating grizzly bears.

    Science.gov (United States)

    Barrows, N D; Nelson, O L; Robbins, C T; Rourke, B C

    2011-01-01

    Grizzly bears (Ursus arctos horribilis) tolerate extended periods of extremely low heart rate during hibernation without developing congestive heart failure or cardiac chamber dilation. Left ventricular atrophy and decreased left ventricular compliance have been reported in this species during hibernation. We evaluated the myocardial response to significantly reduced heart rate during hibernation by measuring relative myosin heavy-chain (MyHC) isoform expression and expression of a set of genes important to muscle plasticity and mass regulation in the left atria and left ventricles of active and hibernating bears. We supplemented these data with measurements of systolic and diastolic function via echocardiography in unanesthetized grizzly bears. Atrial strain imaging revealed decreased atrial contractility, decreased expansion/reservoir function (increased atrial stiffness), and decreased passive-filling function (increased ventricular stiffness) in hibernating bears. Relative MyHC-α protein expression increased significantly in the atrium during hibernation. The left ventricle expressed 100% MyHC-β protein in both groups. Insulin-like growth factor (IGF-I) mRNA expression was reduced by ∼50% in both chambers during hibernation, consistent with the ventricular atrophy observed in these bears. Interestingly, mRNA expression of the atrophy-related ubiquitin ligases Muscle Atrophy F-box (MAFBx) and Muscle Ring Finger 1 did not increase, nor did expression of myostatin or hypoxia-inducible factor 1α (HIF-1α). We report atrium-specific decreases of 40% and 50%, respectively, in MAFBx and creatine kinase mRNA expression during hibernation. Decreased creatine kinase expression is consistent with lowered energy requirements and could relate to reduced atrial emptying function during hibernation. Taken together with our hemodynamic assessment, these data suggest a potential downregulation of atrial chamber function during hibernation to prevent fatigue and dilation

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

    Directory of Open Access Journals (Sweden)

    Marc U Baumann

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

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

    Science.gov (United States)

    Chen, Dong; Wang, Wei; Ru, Shaoguo

    2016-09-01

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

  9. Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence

    Science.gov (United States)

    Matsumoto, Ryusaku; Fukuoka, Hidenori; Iguchi, Genzo; Odake, Yukiko; Yoshida, Kenichi; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Yamada, Shozo; Ogawa, Wataru; Takahashi, Yutaka

    2015-01-01

    Objective Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases. Methods We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts. Results Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047). In addition, telomere length in acromegaly was negatively correlated with the disease duration (R 2 = 0.210, P = 0.003). In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence. Conclusion Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I. PMID:26448623

  10. Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence.

    Directory of Open Access Journals (Sweden)

    Ryusaku Matsumoto

    Full Text Available Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases.We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts.Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047. In addition, telomere length in acromegaly was negatively correlated with the disease duration (R2 = 0.210, P = 0.003. In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence.Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I.

  11. IGF-I Stimulates Cooperative Interaction between the IGF-I Receptor and CSK Homologous Kinase that Regulates SHPS-1 Phosphorylation in Vascular Smooth Muscle Cells

    Science.gov (United States)

    Radhakrishnan, Yashwanth; Shen, Xinchun; Maile, Laura A.; Xi, Gang

    2011-01-01

    IGF-I plays an important role in smooth muscle cell proliferation and migration. In vascular smooth muscle cells cultured in 25 mm glucose, IGF-I stimulated a significant increase in Src homology 2 domain containing protein tyrosine phosphatase substrate-1 (SHPS-1) phosphorylation compared with 5 mm glucose and this increase was required for smooth muscle cell proliferation. A proteome-wide screen revealed that carboxyl-terminal SRC kinase homologous kinase (CTK) bound directly to phosphotyrosines in the SHPS-1 cytoplasmic domain. Because the kinase(s) that phosphorylates these tyrosines in response to IGF-I is unknown, we determined the roles of IGF-I receptor (IGF-IR) and CTK in mediating SHPS-1 phosphorylation. After IGF-I stimulation, CTK was recruited to IGF-IR and subsequently to phospho-SHPS-1. Expression of an IGF-IR mutant that eliminated CTK binding reduced CTK transfer to SHPS-1, SHPS-1 phosphorylation, and cell proliferation. IGF-IR phosphorylated SHPS-1, which provided a binding site for CTK. CTK recruitment to SHPS-1 resulted in a further enhancement of SHPS-1 phosphorylation. CTK knockdown also impaired IGF-I-stimulated SHPS-1 phosphorylation and downstream signaling. Analysis of specific tyrosines showed that mutation of tyrosines 428/452 in SHPS-1 to phenylalanine reduced SHPS-1 phosphorylation but allowed CTK binding. In contrast, the mutation of tyrosines 469/495 inhibited IGF-IR-mediated the phosphorylation of SHPS-1 and CTK binding, suggesting that IGF-IR phosphorylated Y469/495, allowing CTK binding, and that CTK subsequently phosphorylated Y428/452. Based on the above findings, we conclude that after IGF-I stimulation, CTK is recruited to IGF-IR and its recruitment facilitates CTK's subsequent association with phospho-SHPS-1. This results in the enhanced CTK transfer to SHPS-1, and the two kinases then fully phosphorylate SHPS-1, which is necessary for IGF-I stimulated cellular proliferation. PMID:21799000

  12. Free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and their relationships to the presence of diabetic retinopathy and glomerular hyperfiltration in insulin-dependent diabetes mellitus

    NARCIS (Netherlands)

    J.A.M.J.L. Janssen (Joseph); M.L. Jacobs (Marloes); F.H.M. Derkx (Frans); R.F.A. Weber (Rob); A-J. van der Lely (Aart-Jan); S.W.J. Lamberts (Steven)

    1997-01-01

    textabstractThe existing literature on serum insulin-like growth factor I (IGF-I) levels in insulin-dependent diabetes mellitus (IDDM) is conflicting. Free IGF-I may have greater physiological and clinical relevance than total IGF- I. Recently, a validated method has been developed to measure free

  13. Free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and their relationships to the presence of diabetic retinopathy and glomerular hyperfiltration in insulin-dependent diabetes mellitus

    NARCIS (Netherlands)

    J.A.M.J.L. Janssen (Joseph); M.L. Jacobs (Marloes); F.H.M. Derkx (Frans); R.F.A. Weber (Robert); A-J. van der Lely (Aart-Jan); S.W.J. Lamberts (Steven)

    1997-01-01

    textabstractThe existing literature on serum insulin-like growth factor I (IGF-I) levels in insulin-dependent diabetes mellitus (IDDM) is conflicting. Free IGF-I may have greater physiological and clinical relevance than total IGF-I. Recently, a validated method has

  14. Clinical significance of changes of serum expression of IGF-I in patients with astrocytoma

    International Nuclear Information System (INIS)

    Liu Jianbo; Ding Dongmei; Yang Fubing

    2005-01-01

    Objective: To investigate the serum expression of IGF-I in patients with astrocytoma of different degrees of malignancy as well as the changes of levels after operative removal of the tumor. Methods: Serum IGF-I contents were measured with IRMA in 16 patients with Grade I-II astrocytoma and 14 patients with Grade III-IV astrocytoma both before and after operation as well as in 30 controls. Results: The serum contents of IGF-I in both groups of patients were significantly higher than those in controls (P<0.05). The levels in Grade III-IV patients were significantly higher than those in Grade I-II patients (P < 0.05 ). After operation, the levels dropped significantly (vs before operation, P<0.05). Conclusion: The serum contents of IGF - I in patients with astrocytoma were positively correlated with the degree of malignancy. Post-operative decrease of IGF-I contents was related to the decrease of tumor burden. (authors)

  15. IGF-I treatment improves the functional properties of fast- and slow-twitch skeletal muscles from dystrophic mice.

    Science.gov (United States)

    Lynch, G S; Cuffe, S A; Plant, D R; Gregorevic, P

    2001-04-01

    Although insulin-like growth factor-I (IGF-I) has been proposed for use by patients suffering from muscle wasting conditions, few studies have investigated the functional properties of dystrophic skeletal muscle following IGF-I treatment. 129P1 ReJ-Lama2(dy) (129 ReJ dy/dy) dystrophic mice suffer from a deficiency in the structural protein, laminin, and exhibit severe muscle wasting and weakness. We tested the hypothesis that 4 weeks of IGF-I treatment ( approximately 2 mg/kg body mass, 50 g/h via mini-osmotic pump, subcutaneously) would increase the mass and force producing capacity of skeletal muscles from dystrophic mice. IGF-I treatment increased the mass of the extensor digitorum longus (EDL) and soleus muscles of dystrophic mice by 20 and 29%, respectively, compared with untreated dystrophic mice (administered saline-vehicle only). Absolute maximum force (P(o)) of the EDL and soleus muscle was increased by 40 and 32%, respectively, following IGF-I treatment. Specific P(o) (sP(o)) was increased by 23% in the EDL muscles of treated compared with untreated mice, but in the soleus muscle sP(o) was unchanged. IGF-I treatment increased the proportion of type IIB and type IIA fibres and decreased the proportion of type I fibres in the EDL muscles of dystrophic mice. In the soleus muscles of dystrophic mice, IGF-I treatment increased the proportion of type IIA fibres and decreased the proportion of type I fibres. Average fibre cross-sectional area was increased in the EDL and soleus muscles of treated compared with untreated mice. We conclude that IGF-I treatment ameliorates muscle wasting and improves the functional properties of skeletal muscles of dystrophic mice. The findings have important implications for the role of IGF-I in ameliorating muscle wasting associated with the muscular dystrophies.

  16. CLINICAL AND HORMONAL MILIEU OF 9 PATIENTS WITH PRIMARY GROWTH HORMONE INSENSITIVITY SYNDROME AND THEIR RESPONSE TO IGF-I GENERATION TEST

    Directory of Open Access Journals (Sweden)

    M. Razzaghy-Azar

    2006-05-01

    Full Text Available Primary growth hormone insensitivity syndrome (GHIS is a rare entity which can be due to defects in growth hormone (GH receptor that is called type 1 Laron syndrome (T1LS or post receptor defects (type 2 Laron syndrome . The aim of study was determining the clinical and hormonal milieu of the patients with primary GHIS and their response to IGF-I (insulin like growth factor-I generation test (IGT. GH, IGF-I, IGF-II, IGF binding protein 1 and 3 (BP-1 and BP-3, GH binding protein (GHBP and anti-GH antibody were detected by ELISA and RIA methods. IGF-I and BP-3 were measured before and after IGT. Nine patients (8 males, 1 female (mean age ± SD, 6.4 ± 5 years with severe short stature and high GH level were studied. Height SDS was - 8.5 ± 2.6. In 7 patients GHBP was zero, IGF-I and BP-3 were low and did not increase after IGT, so they had T1LS. Two brothers did not show the hormonal milieu of GH receptor defect, and were called non Laron syndrome (NLS. Birth weight in patients with T1LS and NLS was 3.65 ± 0.2 Kg and 1.65 ± 0.2 Kg, respectively (P = 0.001. All of the patients had typical clinical feature of GH-deficiency, but nasal bridge depression and microphallus were not seen in NLS. GH treatment of NLS, normalized their growth velocity, but without catch up growth. In conclusion IGT can differentiate Laron syndrome from other types of short stature. GH and IGF-I of fetus have no role in intrauterine growth.

  17. Altered expression of IGF-I system in neurons of the inflamed spinal cord during acute experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Parvaneh Tafreshi, Azita; Talebi, Farideh; Ghorbani, Samira; Bernard, Claude; Noorbakhsh, Farshid

    2017-10-01

    There is growing evidence that the impaired IGF-I system contributes to neurodegeneration. In this study, we examined the spinal cords of the EAE, the animal model of multiple sclerosis, to see if the expression of the IGF-I system is altered. To induce EAE, C57/BL6 mice were immunized with the Hooke lab MOG kit, sacrificed at the peak of the disease and their spinal cords were examined for the immunoreactivities (ir) of the IGF-I, IGF binding protein-1 (IGFBP-1) and glycogen synthase kinase 3β (GSK3β), as one major downstream molecule in the IGF-I signaling. Although neurons in the non EAE spinal cords did not show the IGF-I immunoreactivity, they were numerously positive for the IGFBP-1. In the inflamed EAE spinal cord however, the patterns of expressions were reversed, that is, a significant increased number of IGF-I expressing neurons versus a reduced number of IGFBP-1 positive neurons. Moreover, while nearly all IGF-I-ir neurons expressed GSK3β, some expressed it more intensely. Considering our previous finding where we showed a significant reduced number of the inactive (phosphorylated) but not that of the total GSK3β expressing neurons in the EAE spinal cord, it is conceivable that the intense total GSK3β expression in the IGF-I-ir neurons belongs to the active form of GSK3β known to exert neuroinflammatory effects. We therefore suggest that the altered expression of the IGF-I system including GSK3β in spinal cord neurons might involve in pathophysiological events during the EAE. © 2017 Wiley Periodicals, Inc.

  18. Role of IGF-I Signaling in Muscle Bone Interactions

    Science.gov (United States)

    Bikle, Daniel D; Tahimic, Candice; Chang, Wenhan; Wang, Yongmei; Philippou, Anastassios; Barton, Elisabeth R.

    2015-01-01

    Skeletal muscle and bone rely on a number of growth factors to undergo development, modulate growth, and maintain physiological strength. A major player in these actions is insulin-like growth factor I (IGF-I). However, because this growth factor can directly enhance muscle mass and bone density, it alters the state of the musculoskeletal system indirectly through mechanical crosstalk between these two organ systems. Thus, there are clearly synergistic actions of IGF-I that extend beyond the direct activity through its receptor. This review will cover the production and signaling of IGF-I as it pertains to muscle and bone, the chemical and mechanical influences that arise from IGF-I activity, and the potential for therapeutic strategies based on IGF-I. PMID:26453498

  19. The effect of epidermal growth factor and IGF-I infusion on hepatic and renal expression of the IGF-system in adult female rats

    NARCIS (Netherlands)

    J.W. van Neck (Han); E.M. Berghout; L. Vinter-Jensen; C.A.H. Groffen; V. Cingel-Ristic; N.F. Dits (Natasja); S.L.S. Drop (Stenvert); A. Flyvbjerg (Allan)

    2000-01-01

    textabstractSystemic administration of epidermal growth factor (EGF) in neonatal rats results in reduced body weight gain and decreased circulating levels of IGF-I, suggesting its involvement in EGF-induced growth retardation. We investigated the effect of EGF and/or IGF-I

  20. Changes in calcitropic hormones, bone markers and insulin-like growth factor I (IGF-I) during pregnancy and postpartum: a controlled cohort study.

    Science.gov (United States)

    Møller, U K; Streym, S; Mosekilde, L; Heickendorff, L; Flyvbjerg, A; Frystyk, J; Jensen, L T; Rejnmark, L

    2013-04-01

    Pregnancy and lactation cause major changes in calcium homeostasis and bone metabolism. This population-based cohort study presents the physiological changes in biochemical indices of calcium homeostasis and bone metabolism during pregnancy and lactation We describe physiological changes in calcium homeostasis, calcitropic hormones and bone metabolism during pregnancy and lactation. We studied 153 women planning pregnancy (n=92 conceived) and 52 non-pregnant, age-matched female controls. Samples were collected prior to pregnancy, once each trimester and 2, 16 and 36 weeks postpartum. The controls were followed in parallel. P-estradiol (E2), prolactin and 1,25-dihydroxyvitamin D (1,25(OH)2D) increased (phormone (P-PTH) and calcitonin decreased (pgrowth factor I (IGF-I) was suppressed (pbone resorption and formation rose and fall, respectively (pbone formation markers increased in association with IGF-I changes (pbone turnover markers were associated with lactation status (pbone markers indicated a negative bone balance. The rise in bone formation in late pregnancy may be initiated by a spike in IGF-I levels. The high bone turnover in lactating women may be related to high prolactin and PTH levels, low E2 levels and perhaps increased parathyroid hormone-related protein levels.

  1. Muscle atrophy in patients wirh ckd results from fgf23/klotho-mediated supression of insulin/igf-i signaling

    Directory of Open Access Journals (Sweden)

    Shinsuke Kido

    2012-06-01

    Full Text Available Muscle atrophy is a significant consequence of chronic kidney disease (CKD that increases a patient’s risk of mortality and decrease their quality of life. In CKD patients, the circulation levels of FGF23 are significantly increased, but the exact pathological significance of the increase and relationship between FGF23 and muscle atrophy are not clear. Because of Klohto, acts as a co-receptor of FGF23 is detectable in limited tissues including in kidney and brain, but not in skeletal muscles. In contrast, recently reports indicated that the extracellular domain of klohto is cleavage for some reason on the cell surface and detected in the blood in animals. In this study, we attempted to identify the causative factors responsible for the shedding of Klotho, and whether both FGF23 and Klohto induced muscle atrophy via reduction of insulin/IGF-I signaling. We first investigated by treating kidney cells with various factors related in pathological factors in CKD. As a result, we found that advanced glycation endproducts (AGEs, an accumulated in patients with CKD and diabetes mellitus, increases shedding of Klohto in kidney cells. It is common knowledge that insulin/IGF-I signaling is necessary for normal skeletal growth. As a result, we showed that both FGF23 and Klohto inhibited differentiation of cultured skeletal muscle cells through down-regulation of insulin/IGF-I signaling. These observations suggested a divergent role of FGF23 and soluble klohto in the regulation of skeletal muscle differentiation and thereby muscle atrophy under pathological conditioned in CKD patients. Our results further imply that FGF23/Klohto may serve a new therapeutic target for CKD-induced muscle atrophy.

  2. Identification of Compounds That Inhibit IGF-I Signaling in Hyperglycemia

    Directory of Open Access Journals (Sweden)

    Laura A. Maile

    2009-01-01

    Full Text Available Increased responsiveness of vascular cells to the growth factor IGF-I has been implicated in complications associated with diabetes. Here we describe the development of an assay and screening of a library of compounds for their ability to accelerate cleavage of the transmembrane protein integrin-associated protein (IAP thereby disrupting the association between IAP and SHPS-1 which we have shown as critical for the enhanced response of vascular cells to IGF-I. The cell-based ELISA utilizes an antibody that specifically detects cleaved, but not intact, IAP. Of the 1040 compounds tested, 14 were considered active by virtue of their ability to stimulate an increase in antibody-binding indicative of IAP cleavage. In experiments with smooth muscle and retinal endothelial cell cultures in hyperglycemic conditions, each active compound was shown to accelerate the cleavage of IAP, and this was associated with a decrease in IAP association with SHPS-1 as determined by coimmunoprecipitation of the proteins from cell lysates. As a consequence of the acceleration in IAP cleavage, the compounds were shown to inhibit IGF-I-stimulated phosphorylation of key signaling molecules including Shc and ERK1/2, and this in turn was associated with a decrease in IGF-I-stimulated cell proliferation. Identification of these compounds that utilize this mechanism has the potential to yield novel therapeutic approaches for the prevention and treatment of vascular complications associated with diabetes.

  3. Effect of Insulin Infusion on insulin-like growth factor I (IGF-I) during Hemodialysis

    DEFF Research Database (Denmark)

    Reinhard, Mark; Frystyk, Jan; Bjerre, Mette

    2012-01-01

    Background: Hemodialysis (HD) is a catabolic procedure probably contributing to the high frequency of protein-energy wasting among patients on maintenance HD. The aim was to investigate the effect of insulin infusion on insulin-like growth factor I (IGF-I) during HD compared with a meal alone...... infusion and followed by the only meal allowed during the study. Results: Data are presented as mean±SD. From baseline to end of HD session we observed an overall increase in both serum bioactive IGF-I (from 0.83±0.27 to 1.01±0.34 µg/L, p... in the change between the groups (p=0.43). Conclusion: A meal at the beginning of a HD session leads to an increase in bioactive IGF-I thereby assumingly counteracting the catabolic effects of HD. However, according to changes in bioactive IGF-I neither glucose nor glucose-insulin infusion during HD appear...

  4. Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Juul, Anders; Scheike, Thomas Harder; Davidsen, Michael

    2002-01-01

    Insulin-like growth factor I (IGF-I) has been suggested to be involved in the pathogenesis of atherosclerosis. We hypothesize that low IGF-I and high IGFBP-3 levels might be associated with increased risk of ischemic heart disease (IHD).......Insulin-like growth factor I (IGF-I) has been suggested to be involved in the pathogenesis of atherosclerosis. We hypothesize that low IGF-I and high IGFBP-3 levels might be associated with increased risk of ischemic heart disease (IHD)....

  5. AKT signaling mediates IGF-I survival actions on otic neural progenitors.

    Directory of Open Access Journals (Sweden)

    Maria R Aburto

    Full Text Available BACKGROUND: Otic neurons and sensory cells derive from common progenitors whose transition into mature cells requires the coordination of cell survival, proliferation and differentiation programmes. Neurotrophic support and survival of post-mitotic otic neurons have been intensively studied, but the bases underlying the regulation of programmed cell death in immature proliferative otic neuroblasts remains poorly understood. The protein kinase AKT acts as a node, playing a critical role in controlling cell survival and cell cycle progression. AKT is activated by trophic factors, including insulin-like growth factor I (IGF-I, through the generation of the lipidic second messenger phosphatidylinositol 3-phosphate by phosphatidylinositol 3-kinase (PI3K. Here we have investigated the role of IGF-dependent activation of the PI3K-AKT pathway in maintenance of otic neuroblasts. METHODOLOGY/PRINCIPAL FINDINGS: By using a combination of organotypic cultures of chicken (Gallus gallus otic vesicles and acoustic-vestibular ganglia, Western blotting, immunohistochemistry and in situ hybridization, we show that IGF-I-activation of AKT protects neural progenitors from programmed cell death. IGF-I maintains otic neuroblasts in an undifferentiated and proliferative state, which is characterised by the upregulation of the forkhead box M1 (FoxM1 transcription factor. By contrast, our results indicate that post-mitotic p27(Kip-positive neurons become IGF-I independent as they extend their neuronal processes. Neurons gradually reduce their expression of the Igf1r, while they increase that of the neurotrophin receptor, TrkC. CONCLUSIONS/SIGNIFICANCE: Proliferative otic neuroblasts are dependent on the activation of the PI3K-AKT pathway by IGF-I for survival during the otic neuronal progenitor phase of early inner ear development.

  6. PKC{eta} is a negative regulator of AKT inhibiting the IGF-I induced proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Shahaf, Galit; Rotem-Dai, Noa; Koifman, Gabriela; Raveh-Amit, Hadas; Frost, Sigal A.; Livneh, Etta, E-mail: etta@bgu.ac.il

    2012-04-15

    The PI3K-AKT pathway is frequently activated in human cancers, including breast cancer, and its activation appears to be critical for tumor maintenance. Some malignant cells are dependent on activated AKT for their survival; tumors exhibiting elevated AKT activity show sensitivity to its inhibition, providing an Achilles heel for their treatment. Here we show that the PKC{eta} isoform is a negative regulator of the AKT signaling pathway. The IGF-I induced phosphorylation on Ser473 of AKT was inhibited by the PKC{eta}-induced expression in MCF-7 breast adenocarcinoma cancer cells. This was further confirmed in shRNA PKC{eta}-knocked-down MCF-7 cells, demonstrating elevated phosphorylation on AKT Ser473. While PKC{eta} exhibited negative regulation on AKT phosphorylation it did not alter the IGF-I induced ERK phosphorylation. However, it enhanced ERK phosphorylation when stimulated by PDGF. Moreover, its effects on IGF-I/AKT and PDGF/ERK pathways were in correlation with cell proliferation. We further show that both PKC{eta} and IGF-I confer protection against UV-induced apoptosis and cell death having additive effects. Although the protective effect of IGF-I involved activation of AKT, it was not affected by PKC{eta} expression, suggesting that PKC{eta} acts through a different route to increase cell survival. Hence, our studies show that PKC{eta} provides negative control on AKT pathway leading to reduced cell proliferation, and further suggest that its presence/absence in breast cancer cells will affect cell death, which could be of therapeutic value.

  7. Lycopene inhibits IGF-I signal transduction and growth in normal prostate epithelial cells by decreasing DHT-modulated IGF-I production in co-cultured reactive stromal cells.

    Science.gov (United States)

    Liu, Xunxian; Allen, Jeffrey D; Arnold, Julia T; Blackman, Marc R

    2008-04-01

    Prostate stromal and epithelial cell communication is important in prostate functioning and cancer development. Primary human stromal cells from normal prostate stromal cells (PRSC) maintain a smooth muscle phenotype, whereas those from prostate cancer (6S) display reactive and fibroblastic characteristics. Dihydrotestosterone (DHT) stimulates insulin-like growth factor-I (IGF-I) production by 6S but not PSRC cells. Effects of reactive versus normal stroma on normal human prostate epithelial (NPE or PREC) cells are poorly understood. We co-cultured NPE plus 6S or PRSC cells to compare influences of different stromal cells on normal epithelium. Because NPE and PREC cells lose androgen receptor (AR) expression in culture, DHT effects must be modulated by associated stromal cells. When treated with camptothecin (CM), NPE cells, alone and in stromal co-cultures, displayed a dose-dependent increase in DNA fragmentation. NPE/6S co-cultures exhibited reduced CM-induced cell death with exposure to DHT, whereas NPE/PRSC co-cultures exhibited CM-induced cell death regardless of DHT treatment. DHT blocked CM-induced, IGF-I-mediated, NPE death in co-cultured NPE/6S cells without, but not with, added anti-IGF-I and anti-IGF-R antibodies. Lycopene consumption is inversely related to human prostate cancer risk and inhibits IGF-I and androgen signaling in rat prostate cancer. In this study, lycopene, in dietary concentrations, reversed DHT effects of 6S cells on NPE cell death, decreased 6S cell IGF-I production by reducing AR and beta-catenin nuclear localization and inhibited IGF-I-stimulated NPE and PREC growth, perhaps by attenuating IGF-I's effects on serine phosphorylation of Akt and GSK3beta and tyrosine phosphorylation of GSK3. This study expands the understanding of the preventive mechanisms of lycopene in prostate cancer.

  8. Normal Values of Circulating IGF-I Bioactivity in the Healthy Population: Comparison with five widely used IGF-I immunoassays

    NARCIS (Netherlands)

    M.P. Brugts (Michael); M.B. Ranke (Michael); L.J. Hofland (Leo); K. van der Wansem (Katy); K. Weber (Karin); J. Frystyk (Jan); S.W.J. Lamberts (Steven); J.A.M.J.L. Janssen (Joseph)

    2008-01-01

    textabstractBackground: IGF-I immunoassays are primarily used to estimate IGF-I bioactivity. Recently, an IGFI specific Kinase Receptor Activation Assay (KIRA) has been developed as an alternative method. However, no normative values have been established for the IGF-I KIRA. Objective: To

  9. 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

  10. IGF-I replacement therapy in children with congenital IGF-I deficiency (Laron syndrome) maintains heart dimension and function.

    Science.gov (United States)

    Scheinowitz, Mickey; Feinberg, Micha S; Laron, Zvi

    2009-06-01

    Untreated patients with congenital growth hormone deficiency (GHD) and IGF-I deficiency are characterized not only by dwarfism but also by acromicria and organomicria, such as the heart. We assessed cardiac dimensions and function in very young patients with Laron syndrome (LS) undergoing IGF-I replacement therapy. Two to seven echocardiographic measurements were performed during IGF-I replacement therapy on male (n=4) and female (n=4) LS -patients, mean+/-SD age of 7.1+/-3.6 years (range 1.6-11.6 years), weight 16.1+/-9.7 kg, and height 89.9+/-18.5 cm. As aged- and gender-matched controls served 44 healthy children, age: 8.7+/-5.5 years, weight: 36.1+/-22.4 kg, and height: 129.7+/-33.1cm. Data of LS patients were normalized to body surface area and compared to the control group as well as nomograms of normal echocardiographic parameters for this age group. Left ventricular diastolic and systolic dimensions (LVDD/ LVSD, mm) and LV mass (gr) were significantly smaller in boys and girls with IGF-I treated LS compared with controls while the shortening fraction (%) and intraventricular septum thickness (mm) were similar. When compared with standard values for this age group, all treated LS patients were within 1 standard deviation of the mean. IGF-I therapy of young patients with Laron syndrome maintain LV dimensions and function within the normal range of aged-matched controls.

  11. IGF-I: A key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain

    Directory of Open Access Journals (Sweden)

    Vanesa eNieto-Estévez

    2016-02-01

    Full Text Available The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs. This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP and the subventricular zone-olfactory bulb (SVZ-OB. By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also, by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis and neuron integration in synaptic circuits.

  12. Expression of IGF-I and Protein Degradation Markers During Hindlimb Unloading and Growth Hormone Administration in Rats

    Science.gov (United States)

    Leinsoo, T. A.; Turtikova, O. V.; Shenkman, B. S.

    2013-02-01

    It is known that hindlimb unloading or spaceflight produce atrophy and a number of phenotypic alterations in skeletal muscles. Many of these processes are triggered by the axis growth hormone/insulin-like growth factor I. However growth hormone (GH) and insulin-like growth factor I (IGF-I) expression relationship in rodent models of gravitational unloading is weakly investigated. We supposed the IGF-I is involved in regulation of protein turnover. In this study we examined the IGF-I expression by RT-PCR assay in the rat soleus, tibialis anterior and liver after 3 day of hindlimb suspension with growth hormone administration. Simultaneously were studied expression levels of MuRF-1 and MAFbx/atrogin as a key markers of intracellular proteolysis. We demonstrated that GH administration did not prevent IGF-I expression decreasing under the conditions of simulated weightlessness. It was concluded there are separate mechanisms of action of GH and IGF-I on protein metabolism in skeletal muscles. Gravitational unloading activate proteolysis independently of growth hormone activity.

  13. IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

    Science.gov (United States)

    Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

    2016-01-01

    The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

  14. Changes in IGF-I and its Binding Proteins Are Associated with Diabetes in Older Adults

    Science.gov (United States)

    Aneke, Chino S.; Parrinello, Christina M.; Rajpathak, Swapnil N.; Rohan, Thomas E.; Strotmeyer, Elsa S.; Kritchevsky, Stephen B.; Psaty, Bruce M.; Bůžková, Petra; Kizer, Jorge R.; Newman, Anne B.; Strickler, Howard D.; Kaplan, Robert C.

    2015-01-01

    Objectives Little is known about long-term changes in insulin-like growth Factor (IGF) proteins and glycemic status. We hypothesized that changes in IGF proteins are exaggerated in participants with type 2 diabetes or worsening glycemia versus those that remain normoglycemic over a 9-year follow-up period. Design Retrospective analysis of cohort study. Setting Participants were recruited from four States: North Carolina, California, Maryland and Pennsylvania. Participants 897 participants enrolled in CHS All Stars, a cohort study of community dwelling adults aged ≥65 years. Measurements Plasma IGF-I, IGFBP-1, and IGFBP-3 levels were assessed and ADA cut-points for IGT, IFG, and diabetes were used to classify participants at baseline (1996–1997) and follow-up (2005–2006). Results At baseline, mean age was 76.3 years (± 3.6) and 18.5% had diabetes. Individuals with IFG alone and IGT+IFG had the highest levels of IGF-I and lowest levels of IGFBP-1, compared to individuals with normoglycemia or diabetes. The greatest percent change in IGF levels occurred in those who had diabetes at baseline (9-year changes: −9.3% for IGF-I, 59.7% for IGFBP-1, −13.4% for IGFBP-3); the smallest in individuals who remained normoglycemic at follow-up (9-year changes: −3.7% for IGF-I, 25.6% for IGFBP-1, −6.4% for IGFBP-3); and intermediate changes in those who were normoglycemic but developed IFG at follow-up. Conclusion Our results demonstrate that degrees of glycemic impairment are associated with varying levels of changes in IGF proteins. The exaggerated changes observed in the diabetes group have been previously shown to be associated with heart failure, cancer and non-cancer mortality. PMID:25989565

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

    DEFF Research Database (Denmark)

    Skjaerbaek, Christian; Frystyk, Jan; Kaal, Andreas

    2000-01-01

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

  16. IGF-I, IGF-II, and Insulin Stimulate Different Gene Expression Responses through Binding to the IGF-I Receptor

    DEFF Research Database (Denmark)

    Versteyhe, Soetkin; Klaproth, Birgit; Borup, Rehannah

    2013-01-01

    Insulin and the insulin-like growth factors (IGF)-I and -II are closely related peptides important for regulation of metabolism, growth, differentiation, and development. The IGFs exert their main effects through the IGF-I receptor. Although the insulin receptor is the main physiological receptor...... for insulin, this peptide hormone can also bind at higher concentrations to the IGF-I receptor and exert effects through it. We used microarray gene expression profiling to investigate the gene expression regulated by IGF-I, IGF-II, and insulin after stimulation of the IGF-I receptor. Fibroblasts from mice......, knockout for IGF-II and the IGF-II/cation-independent mannose-6-phosphate receptor, and expressing functional IGF-I but no insulin receptors, were stimulated for 4 h with equipotent saturating concentrations of insulin, IGF-I, and IGF-II. Each ligand specifically regulated a group of transcripts...

  17. Experimental diabetes increases insulin-like growth factor I and II receptor concentration and gene expression in kidney

    International Nuclear Information System (INIS)

    Werner, H.; Shen-Orr, Z.; Stannard, B.; Burguera, B.; Roberts, C.T. Jr.; LeRoith, D.

    1990-01-01

    Insulinlike growth factor I (IGF-I) is a mitogenic hormone with important regulatory roles in growth and development. One of the target organs for IGF-I action is the kidney, which synthesizes abundant IGF-I receptors and IGF-I itself. To study the involvement of IGF-I and the IGF-I receptor in the development of nephropathy, one of the major complications of diabetes mellitus, we measured the expression of these genes in the kidney and in other tissues of the streptozocin-induced diabetic rat. The binding of 125I-labeled IGF-I to crude membranes was measured in the same tissues. We observed a 2.5-fold increase in the steady-state level of IGF-I-receptor mRNA in the diabetic kidney, which was accompanied by a 2.3-fold increase in IGF-I binding. In addition to this increase in IGF-I binding to the IGF-I receptor, there was also binding to a lower-molecular-weight material that may represent an IGF-binding protein. No change was detected in the level of IGF-I-peptide mRNA. Similarly, IGF-II-receptor mRNA levels and IGF-II binding were significantly increased in the diabetic kidney. IGF-I- and IGF-II-receptor mRNA levels and IGF-I and IGF-II binding returned to control values after insulin treatment. Because the IGF-I receptor is able to transduce mitogenic signals on activation of its tyrosine kinase domain, we hypothesize that, among other factors, high levels of receptor in the diabetic kidney may also be involved in the development of diabetic nephropathy. Increased IGF-II-receptor expression in the diabetic kidney may be important for the intracellular transport and packaging of lysosomal enzymes, although a role for this receptor in signal transduction cannot be excluded. Finally, the possible role of IGF-binding proteins requires further study

  18. Breast Cancer Risk in Relation to Serum IGF-I, IGFBP-3 and their Genetic Determinants: A Study Within the European Prospective Investigation into Cancer (EPIC)

    National Research Council Canada - National Science Library

    Kaaks, Rudolf

    2002-01-01

    Purpose and scope: we are conducting a large case-control study, nested within a prospective cohort, to estimate relative risks of breast cancer by levels of IGF-I and IGFBP-3, and to examine associations of IGF...

  19. The pro-Forms of Insulin-Like Growth Factor I (IGF-I) Are Predominant in Skeletal Muscle and Alter IGF-I Receptor Activation

    Science.gov (United States)

    Durzyńska, Julia; Philippou, Anastassios; Brisson, Becky K.; Nguyen-McCarty, Michelle

    2013-01-01

    IGF-I is a key regulator of muscle development and growth. The pre-pro-peptide produced by the Igf1gene undergoes several posttranslational processing steps to result in a secreted mature protein, which is thought to be the obligate ligand for the IGF-I receptor (IGF-IR). The goals of this study were to determine what forms of IGF-I exist in skeletal muscle, and whether the mature IGF-I protein was the only form able to activate the IGF-IR. We measured the proportion of IGF-I species in murine skeletal muscle and found that the predominant forms were nonglycosylated pro-IGF-I and glycosylated pro-IGF-I, which retained the C-terminal E peptide extension, instead of mature IGF-I. These forms were validated using samples subjected to viral expression of IGF-I combined with furin and glycosidase digestion. To determine whether the larger molecular weight IGF-I forms were also ligands for the IGF-IR, we generated each specific form through transient transfection of 3T3 cells and used the enriched media to perform kinase receptor activation assays. Compared with mature IGF-I, nonglycosylated pro-IGF-I had similar ability to activate the IGF-IR, whereas glycosylation of pro-IGF-I significantly reduced receptor activation. Thus, it is important to understand not only the quantity, but also the proportion of IGF-I forms produced, to evaluate the true biological activity of this growth factor. PMID:23407451

  20. Enhanced contractile force generation by artificial skeletal muscle tissues using IGF-I gene-engineered myoblast cells.

    Science.gov (United States)

    Sato, Masanori; Ito, Akira; Kawabe, Yoshinori; Nagamori, Eiji; Kamihira, Masamichi

    2011-09-01

    The aim of this study was to investigate whether insulin-like growth factor (IGF)-I gene delivery to myoblast cells promotes the contractile force generated by hydrogel-based tissue-engineered skeletal muscles in vitro. Two retroviral vectors allowing doxycycline (Dox)-inducible expression of the IGF-I gene were transduced into mouse myoblast C2C12 cells to evaluate the effects of IGF-I gene expression on these cells. IGF-I gene expression stimulated the proliferation of C2C12 cells, and a significant increase in the growth rate was observed for IGF-I-transduced C2C12 cells with Dox addition, designated C2C12/IGF (Dox+) cells. Quantitative morphometric analyses showed that the myotubes induced from C2C12/IGF (Dox+) cells had a larger area and a greater width than control myotubes induced from normal C2C12 cells. Artificial skeletal muscle tissues were prepared from the respective cells using hydrogels composed of type I collagen and Matrigel. Western blot analyses revealed that the C2C12/IGF (Dox+) tissue constructs showed activation of a skeletal muscle hypertrophy marker (Akt) and enhanced expression of muscle-specific markers (myogenin, myosin heavy chain and tropomyosin). Moreover, the creatine kinase activity was increased in the C2C12/IGF (Dox+) tissue constructs. The C2C12/IGF (Dox+) tissue constructs contracted in response to electrical pulses, and generated a significantly higher physical force than the control C2C12 tissue constructs. These findings indicate that IGF-I gene transfer has the potential to yield functional skeletal muscle substitutes that are capable of in vivo restoration of the load-bearing function of injured muscle or acting as in vitro electrically-controlled bio-actuators. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I.

    Science.gov (United States)

    Fernandez, Ana M; Hernandez-Garzón, Edwin; Perez-Domper, Paloma; Perez-Alvarez, Alberto; Mederos, Sara; Matsui, Takashi; Santi, Andrea; Trueba-Saiz, Angel; García-Guerra, Lucía; Pose-Utrilla, Julia; Fielitz, Jens; Olson, Eric N; Fernandez de la Rosa, Ruben; Garcia Garcia, Luis; Pozo, Miguel Angel; Iglesias, Teresa; Araque, Alfonso; Soya, Hideaki; Perea, Gertrudis; Martin, Eduardo D; Torres Aleman, Ignacio

    2017-01-01

    Brain activity requires a flux of glucose to active regions to sustain increased metabolic demands. Insulin, the main regulator of glucose handling in the body, has been traditionally considered not to intervene in this process. However, we now report that insulin modulates brain glucose metabolism by acting on astrocytes in concert with IGF-I. The cooperation of insulin and IGF-I is needed to recover neuronal activity after hypoglycemia. Analysis of underlying mechanisms show that the combined action of IGF-I and insulin synergistically stimulates a mitogen-activated protein kinase/protein kinase D pathway resulting in translocation of GLUT1 to the cell membrane through multiple protein-protein interactions involving the scaffolding protein GAIP-interacting protein C terminus and the GTPase RAC1. Our observations identify insulin-like peptides as physiological modulators of brain glucose handling, providing further support to consider the brain as a target organ in diabetes. © 2017 by the American Diabetes Association.

  2. Significance of determination of female sex hormones (E2, LH, FSH), insulin-like growth factor I (IGF-I) and leptin in girls with precocious puberty

    International Nuclear Information System (INIS)

    Huang Jianrong

    2004-01-01

    Objective: To investigate the diagnostic value of determination of serum levels of estradiol (E 2 ), luteinizing hormone (LH) and follicle stimulating hormone (FSH), insulin-like growth factor (IGF-I) and leptin in girls with idiopathic central precocious puberty (ICPP). Methods: Serum E 2 , LH, FSH, IGF-I (with chemiluminescence immunoassay) and leptin (with RIA) levels were determined in 35 girls with early development of breast as the sign of precocious puberty, of which, 15 was considered to be of the ICPP group and 20 of simple premature thelarche group (SPT). Criteria of diagnosis for ICPP were: peak LH value>12IU/L and LH/FSH>1 after GnRH stimulating test. Results: Serum E 2 , LH, FSH, IGF-I leptin levels in girls with ICPP were significantly higher than those in the girls with SPT (P 0.2 as the cut-off value for diagnosis of ICPP there would still be a positive rate of 86.6% suggesting that the diagnostic criteria might be set lower. Serum IGF-I levels were positively correlated to those of E 2 (r=0.47, P 2 and IGF-I. Conclusion: Determinations of serum E 2 , LH, FHS, IGF-I and leptin levels were helpful for the early diagnosis of ICPP. (author)

  3. Factor de crecimiento semejante a la insulina tipo I (IGF-I y cirrosis hepática Insulin-like growth factor I (IGF-I and liver cirrhosis

    Directory of Open Access Journals (Sweden)

    M. Conchillo

    2007-03-01

    mejoría del metabolismo energético por efecto del IGF-I. Se precisan ensayos clínicos adicionales para identificar la dosis adecuada de IGF-I, el tiempo y ritmo de administración y el subgrupo de pacientes cirróticos que obtendrán mayor beneficio de este tratamiento sustitutivo.Insulin-like growth factor I (IGF-I is a polypeptide hormone secreted by multiple tissues in response to growth hormone (GH. It is partly responsible for GH activity, and also has glucose-lowering and anabolizing effects. Ninety percent of circulating IGF-I originates in the liver and has autocrine, paracrine, and endocrine effects, the latter on multiple tissues. Liver cirrhosis results in a progressive decline of hepatic IGF-I output, and this factor may become undetectable in advanced disease. Some cirrhosis complications, mainly those nutritional and metabolic in nature (insuline resistance, malnutrition, osteopenia, hypogonadism, intestinal disorders, may be at least partly related to this IGF-I deficiency, since some IGF-I effects represent a reverse image of cirrhosis complications. Despite this, IGF-I replacement therapy has been never suggested for cirrhosis. A number of experimental studies in cirrhotic rats showed that therapy using low-dose recombinant IGF-I exerts two types of effect on experimental cirrhosis: a liver improvement driven by improved hepatocellular function, portal hypertension, and liver fibrosis; and b cirrhosis-related extrahepatic disorder improvement driven by improved food efficiency, muscle mass, bone mass, gonadal function and structure, and intestinal function and structure, with a normalization of sugar and amino acid malabsorption, and improved intstinal barrier function, manifested by reduced endotoxemia and bacterial translocation. Subsequently, the first randomized, double-blind, placebo-controlled, pilot clinical trial in a small number of cirrhotic patients showed increased serum albumin and improved energy metabolism as a result of IGF-I use

  4. 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.

  5. Differential basal and exercise-induced IGF-I system responses to resistance vs. calisthenic-based military readiness training programs.

    Science.gov (United States)

    Nindl, Bradley C; Alemany, Joseph A; Rarick, Kevin R; Eagle, Shawn R; Darnell, Mathew E; Allison, Katelyn F; Harman, Everett A

    2017-02-01

    The purpose of this study was to: 1) evaluate differential responses of the IGF-I system to either a calisthenic- or resistance exercise-based program and 2) determine if this chronic training altered the IGF-I system during an acute resistance exercise protocol. Thirty-two volunteers were randomly assigned into a resistance exercise-based training (RT) group (n=15, 27±5y, 174±6cm, 81±12kg) or a calisthenic-based training group (CT) (n=17, 29±5y, 179±8cm, 85±10kg) and all underwent 8weeks of exercise training (1.5h/d, 5d/wk). Basal blood was sampled pre- (Week 0), mid- (Week 4) and post-training (Week 8) and assayed for IGF-I system analytes. An acute resistance exercise protocol (AREP) was conducted preand post-training consisting of 6 sets of 10 repetitions in the squat with two minutes of rest in between sets and the IGF-I system analytes measured. A repeated measures ANOVA (p≤0.05) was used for statistical analysis. No interaction or within-subject effects were observed for basal total IGF-I, free IGF-I, or IGFBP-1. IGFBP-2 (pre; 578.6±295.7post-training; 14.3±1.9μg/mL; p=0.01). An interaction was observed for the RT group as IGFBP-3 increased from pre to mid (3462.4±216.4 vs. 3962.2±227.9ng/mL), but was not significant at the post-training time point (3770.3±228.7ng/mL). AREP caused all analytes except free IGF-I (40% decrease) to increase (17-27%; p=0.001) during exercise, returning to baseline concentration into recovery. Post-training, bioavailable IGF-I recovered more rapidly post-exercise. 8wks of chronic physical training resulted in increased basal IGFBP-2 and IGFBP-3, decreased ALS, increased pre-AREP free IGF-I and a more rapid free IGF-I recovery post-AREP. While total IGF-I was insensitive to chronic physical training, changes were observed with circulating IGFBPs and bioavailable IGF-I. To glean the most robust information on the effects of exercise training, studies must move beyond relying solely on total IGF-I measures and should

  6. Differential effects of hGH and IGF-I on body proportions.

    Science.gov (United States)

    Laron, Zvi; Silbergeld, Aviva; Kauli, Rivka

    2012-07-01

    The differential growth effects of hGH and IGF-I on the upper/lower (U/L) body segment in relation to height (Ht) were analyzed in 15 patients with isolated Growth hormone deficiency (IGHD,:7M, 8F) mean age 5.0 +/- 3.2 (SD) years treated with hGH; 21 patients with multiple pituitary hormone deficiency including growth hormone (MPHD: 14M, 7F) aged 10.0 +/- 3.8, treated with hGH; 9 patients with Laron Syndrome (LS) (4M,5F) aged 6.9 +/- 5.6 years treated with IGF-I; 9 boys with intrauterine growth retardation (IUGR) aged 6.3 +/- 1.25 years treated by hGH; and 22 boys with idiopathic short stature (ISS) aged 8.0 +/- 1.55 years treated by hGH. The dose of hGH was 33 microg/kg/day, that of IGF-I 180-200 microg/kg/day. the U/L body segment ratio in IGHD patients decreased from 2.3 +/- 0.7 to 1.1 +/- 0.7 (p <0.001), and the Ht SDS increased from -4.9 +/- 1.3 to 2.3 +/- 1 (p < 0.001) following treatment. In MPHD patients the U/L body segment decreased from 1.1 +/- 1.1 to -0.6 +/- 1.0 (p < 0.001), and the Ht SDS increased from -3.3 +/- 1.4 to -2.5 +/- 1.0 (p < 0.009). In the LS group the U/L body segment ratio did not change with IGF-I treatment but Ht improved from -6.1 +/- 1.3 to -4.6 +/- 1.2 (p < 0.001), The differential growth response of the children with IUGR and with ISS resembled that of the children with LS. hGH and IGF-I act differentially on the spine and limbs.

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  8. Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells

    International Nuclear Information System (INIS)

    Karnevi, Emelie; Said, Katarzyna; Andersson, Roland; Rosendahl, Ann H

    2013-01-01

    Epidemiological studies have shown direct associations between type 2 diabetes and obesity, both conditions associated with hyperglycaemia and hyperinsulinemia, and the risk of pancreatic cancer. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent population studies indicate that the incidence of pancreatic cancer is reduced among diabetics taking metformin. In this study, the effects of exposure of pancreatic cancer cells to high glucose levels on their growth and response to metformin were investigated. The human pancreatic cancer cell lines AsPC-1, BxPC-3, PANC-1 and MIAPaCa-2 were grown in normal (5 mM) or high (25 mM) glucose conditions, with or without metformin. The influence by metformin on proliferation, apoptosis and the AMPK and IGF-IR signalling pathways were evaluated in vitro. Metformin significantly reduced the proliferation of pancreatic cancer cells under normal glucose conditions. Hyperglycaemia however, protected against the metformin-induced growth inhibition. The anti-proliferative actions of metformin were associated with an activation of AMP-activated protein kinase AMPK Thr172 together with an inhibition of the insulin/insulin-like growth factor-I (IGF-I) receptor activation and downstream signalling mediators IRS-1 and phosphorylated Akt. Furthermore, exposure to metformin during normal glucose conditions led to increased apoptosis as measured by poly(ADP-ribose) polymerase (PARP) cleavage. In contrast, exposure to high glucose levels promoted a more robust IGF-I response and Akt activation which correlated to stimulated AMPK Ser485 phosphorylation and impaired AMPK Thr172 phosphorylation, resulting in reduced anti-proliferative and apoptotic effects by metformin. Our results indicate that metformin has direct anti-tumour activities in pancreatic cancer cells involving AMPK Thr172 activation and suppression of the insulin/IGF signalling pathways

  9. Local administration of insulin-like growth factor-I (IGF-I) stimulates tendon collagen synthesis in humans

    DEFF Research Database (Denmark)

    Hansen, Mette; Boesen, Anders; Holm, Lars

    2013-01-01

    Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin-like growth factor I (IGF-I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing, but t...

  10. IGF-I bioactivity might reflect different aspects of quality of life than total IGF-I in gh-deficient patients during GH treatment

    NARCIS (Netherlands)

    A.J. Varewijck (Aimee); S.W.J. Lamberts (Steven); S.J.C.M.M. Neggers (Bas); L.J. Hofland (Leo); J.A.M.J.L. Janssen (Joseph)

    2013-01-01

    textabstractContext: No relationship has been found between improvement in quality of life (QOL) and total IGF-I during GH therapy. Aim: Our aim was to investigate the relationship between IGF-I bioactivity and QOL in GH-deficient (GHD) patients receiving GH for 12 months. Methods: Of 106 GHD

  11. Potency of full-length MGF to induce maximal activation of the IGF-I R Is similar to recombinant human IGF-I at high equimolar concentrations

    NARCIS (Netherlands)

    J.A.M.J.L. Janssen (Joseph); L.J. Hofland (Leo); C.J. Strasburger; E.S.R.D. Van Dungen (Elisabeth S.R. Den); M. Thevis (Mario)

    2016-01-01

    textabstractAims To compare full-length mechano growth factor (full-length MGF) with human recombinant insulin-like growth factor-I (IGF-I) and human recombinant insulin (HI) in their ability to activate the human IGF-I receptor (IGF-IR), the human insulin receptor (IR-A) and the human insulin

  12. Phosphatidylinositol 3-Kinase (PI3K) Activity Bound to Insulin-like Growth Factor-I (IGF-I) Receptor, which Is Continuously Sustained by IGF-I Stimulation, Is Required for IGF-I-induced Cell Proliferation*

    Science.gov (United States)

    Fukushima, Toshiaki; Nakamura, Yusaku; Yamanaka, Daisuke; Shibano, Takashi; Chida, Kazuhiro; Minami, Shiro; Asano, Tomoichiro; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

    2012-01-01

    Continuous stimulation of cells with insulin-like growth factors (IGFs) in G1 phase is a well established requirement for IGF-induced cell proliferation; however, the molecular components of this prolonged signaling pathway that is essential for cell cycle progression from G1 to S phase are unclear. IGF-I activates IGF-I receptor (IGF-IR) tyrosine kinase, followed by phosphorylation of substrates such as insulin receptor substrates (IRS) leading to binding of signaling molecules containing SH2 domains, including phosphatidylinositol 3-kinase (PI3K) to IRS and activation of the downstream signaling pathways. In this study, we found prolonged (>9 h) association of PI3K with IGF-IR induced by IGF-I stimulation. PI3K activity was present in this complex in thyrocytes and fibroblasts, although tyrosine phosphorylation of IRS was not yet evident after 9 h of IGF-I stimulation. IGF-I withdrawal in mid-G1 phase impaired the association of PI3K with IGF-IR and suppressed DNA synthesis the same as when PI3K inhibitor was added. Furthermore, we demonstrated that Tyr1316-X-X-Met of IGF-IR functioned as a PI3K binding sequence when this tyrosine is phosphorylated. We then analyzed IGF signaling and proliferation of IGF-IR−/− fibroblasts expressing exogenous mutant IGF-IR in which Tyr1316 was substituted with Phe (Y1316F). In these cells, IGF-I stimulation induced tyrosine phosphorylation of IGF-IR and IRS-1/2, but mutated IGF-IR failed to bind PI3K and to induce maximal phosphorylation of GSK3β and cell proliferation in response to IGF-I. Based on these results, we concluded that PI3K activity bound to IGF-IR, which is continuously sustained by IGF-I stimulation, is required for IGF-I-induced cell proliferation. PMID:22767591

  13. Monoclonal antibody to the type I insulin-like growth factor (IGF-I) receptor blocks IGF-I receptor-mediated DNA synthesis: clarification of the mitogenic mechanisms of IGF-I and insulin in human skin fibroblasts

    International Nuclear Information System (INIS)

    Flier, J.S.; Usher, P.; Moses, A.C.

    1986-01-01

    Insulin and insulin-like growth factor type I (IGF-I) stimulate an overlapping spectrum of biological responses in human skin fibroblasts. Although insulin and IGF-I are known to stimulate the incorporation of [ 3 H]thymidine into DNA in these cells, the identify of the receptor(s) that mediates this effect has not been fully clarified. The mouse anti-human IGF-I receptor antibody αIR-3 binds with specificity to IGF-I but not to insulin receptors in human placental membranes; it also specifically inhibits the binding of 125 I-labeled IGF-I but not 125 I-labeled insulin to suspensions of human skin fibroblasts in a dose-dependent manner. αIR-3 competitively inhibits IGF-I-mediated stimulation of [ 3 H]thymidine incorporation into DNA. This inhibition is dependent on the concentration of αIR-3 and in the presence of a fixed antibody concentration can be partially overcome by high concentrations of IGF-I. In contrast, at concentrations of 3 H]thymidine incorporation is not inhibited by αIR-3. However, the incremental effects of higher concentrations (> 1 μg/ml) of insulin on [ 3 H]thymidine incorporation are inhibited by αIR-3. αIR-3 is a highly specific antagonist of IGF-I receptor-mediated mitogenesis in human skin fibroblasts. By using this antibody, it is shown directly that insulin can act through the IGF-I receptor to stimulate DNA synthesis but can also activate this effect through the insulin receptor itself

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  15. Fetal programming of insulin-like growth factor (IGF)-I and IGF-binding protein-3: evidence for an altered response to undernutrition in late gestation following exposure to periconceptual undernutrition in the sheep.

    Science.gov (United States)

    Gallaher, B W; Breier, B H; Keven, C L; Harding, J E; Gluckman, P D

    1998-12-01

    It has been demonstrated in several animal models that undernutrition in utero has significant long lasting effects on subsequent fetal and postnatal development. To address the hypothesis that the insulin-like growth factors (IGFs) may mediate such effects, our study examined whether a period of periconceptual maternal undernutrition could have a lasting influence on the IGF axis in the fetal sheep. Ewes were either allowed to feed ad libitum or kept undernourished from day 60 prior to mating until day 30 after conception, and then both groups were allowed to feed ad libitum. These groups were further divided at day 105 of gestation, either being fed ad libitum or undernourished until day 115 of gestation. Fetal and maternal blood samples were obtained at both day 105 and 115 of gestation. We describe the development of a specific homologous RIA to measure ovine IGF-binding protein-3 (IGFBP-3) in fetal and maternal sheep plasma. Fetal plasma IGFBP-3 and IGF-I concentrations were significantly (Pfetal plasma IGFBP-2 levels were unchanged. The degree of reduction in fetal plasma IGFBP-3 and IGF-I between day 105 and 115 of gestation as a response to acute maternal undernutrition was significantly greater (Pfetal plasma IGFBP-3 concentrations were not the result of increased proteolytic activity. These results suggest that exposure to maternal periconceptual undernutrition reprograms IGFBP-3 and IGF-I regulation in the developing sheep fetus, altering its response to undernutrition in late gestation.

  16. The Insulin-like Growth Factor (IGF)-I E-Peptides Modulate Cell Entry of the Mature IGF-I Protein

    OpenAIRE

    Pfeffer, Lindsay A.; Brisson, Becky K.; Lei, Hanqin; Barton, Elisabeth R.

    2009-01-01

    Insulin-like growth factor (IGF)-I is a critical protein for cell development and growth. Alternative splicing of the igf1 gene gives rise to multiple isoforms. In rodents, proIGF-IA and proIGF-IB have different carboxy-terminal extensions called the E-peptides (EA and EB) and upon further posttranslational processing, produce the identical mature IGF-I protein. Rodent EB has been reported to have mitogenic and motogenic effects independent of IGF-I. However, effects of EA or EB on mature IGF...

  17. Stimulation of proteoglycans by IGF I and II in microvessel and large vessel endothelial cells

    International Nuclear Information System (INIS)

    Bar, R.S.; Dake, B.L.; Stueck, S.

    1987-01-01

    Endothelial cells were cultured from bovine capillaries and pulmonary arteries, and the effect of insulinlike growth factor (IGF) I and II (multiplication-stimulating activity) and insulin on the synthesis of proteoglycans was determined. IGF I and II stimulated 35 SO 4 incorporation into proteoglycans in a dose-dependent manner in both microvessel and pulmonary artery endothelial cells with maximum threefold increases. In pulmonary artery cells, the IGFs caused a general stimulation of all classes of glycosaminoglycan-containing proteoglycans. In microvessel endothelial cells, the IGFs appeared to preferentially increase heparan sulfate-containing proteoglycans. Insulin, at concentrations up to 10 -6 M, had no effect on the synthesis of proteoglycans in either microvessel or pulmonary arterial endothelial cells. Thus, the IGFs stimulate the synthesis of proteoglycans in both microvessel and large vessel endothelial cells, a property that is not mimicked by insulin. Because vascular endothelial cells are bathed by IGFs in vivo, such IGF-mediated functions are likely to be significant in both the normal physiology of vascular endothelium and in disease states such as diabetes mellitus

  18. The proto-oncogene product c-Crk associates with insulin receptor substrate-1 and 4PS. Modulation by insulin growth factor-I (IGF) and enhanced IGF-I signaling.

    Science.gov (United States)

    Beitner-Johnson, D; Blakesley, V A; Shen-Orr, Z; Jimenez, M; Stannard, B; Wang, L M; Pierce, J; LeRoith, D

    1996-04-19

    The Crk proto-oncogene product is an SH2 and SH3 domain-containing adaptor protein which we have previously shown to become rapidly tyrosine phosphorylated in response to stimulation with insulin-like growth factor I (IGF-I) in NIH-3T3 cells. In order to further characterize the role of Crk in the IGF-I signaling pathway, NIH-3T3 and 293 cells were stably transfected with an expression vector containing the Crk cDNA. The various resultant 3T3-Crk clones expressed Crk at approximately 2-15-fold higher levels than parental 3T3 cells. In 3T3-Crk cells, Crk immunoreactivity was detected in insulin receptor substrate-1 (IRS-1) immunoprecipitates. Stimulation with IGF-I resulted in a dissociation of Crk protein from IRS-1. In contrast, the association of the related adaptor protein Grb2 with IRS-1 was enhanced by IGF-I stimulation. Similar results were obtained in stably transfected 293-Crk cells, which express both IRS-1 and the IRS-1-related signaling protein 4PS. In these cells, IRS-1 and 4PS both associated with Crk, and this association was also decreased by IGF-I treatment, whereas the association of Grb2 with IRS-1 and 4PS was enhanced by IGF-I. Overexpression of Crk also enhanced IGF-I-induced mitogenesis of NIH-3T3 cells, as measured by [3H]thymidine incorporation. The levels of IGF-I-induced mitogenesis were proportional to the level of Crk expression. These results suggest that Crk is a positive effector of IGF-I signaling, and may mediate its effects via interaction with IRS-1 and/or 4PS.

  19. 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)

    Yamamoto, Hiroyuki; Kato, Yuzuru; Murphy, L.J.

    1996-01-01

    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 125 I 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. 125 I-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.)

  20. Monoclonal antibodies directed to human insulin-like growth factor I (IGF I)

    International Nuclear Information System (INIS)

    Laubli, U.K.; Baier, W.; Celio, M.R.; Binz, H.; Humbel, R.E.

    1982-01-01

    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. (Auth.)

  1. Androgen receptor activation integrates complex transcriptional effects in osteoblasts, involving the growth factors TGF-β and IGF-I, and transcription factor C/EBPδ.

    Science.gov (United States)

    McCarthy, Thomas L; Centrella, Michael

    2015-11-15

    Osteoblasts respond to many growth factors including IGF-I and TGF-β, which themselves are sensitive to other bone growth regulators. Here we show that IGF-I gene promoter activity in prostaglandin E2 (PGE2) induced osteoblasts is suppressed by dihydrotestosterone (DHT) through an essential C/EBP response element (RE) in exon 1 of the igf1 gene. Inhibition by DHT fails to occur when the androgen receptor (AR) gene is mutated within its DNA binding domain. Correspondingly, DHT activated AR inhibits gene transactivation by C/EBPδ, and transgenic C/EBPδ expression inhibits AR activity. Inhibition by DHT persists when upstream Smad and Runx REs in the IGF-I gene promoter are mutated. TGF-β also enhances IGF-I gene promoter activity, although modestly relative to PGE2, and independently of the C/EBP, Smad, or Runx REs. Still, DHT suppresses TGF-β induced IGF-I promoter activity, but not its effects on DNA or collagen synthesis. Notably, DHT suppresses plasminogen activator inhibitor gene promoter activity, but synergistically increases Smad dependent gene promoter activity in TGF-β induced cells, which are differentially sensitive to AR mutations and the AR co-regulator ARA55. Finally, although the PGE2 sensitive C/EBP RE in the igf1 gene is not essential for basal TGF-β induction, C/EBPδ activity through this site is potently enhanced by TGF-β. Thus DHT suppresses the PGE2 and TGF-β induced IGF-I gene promoter and differentiates other aspects of TGF-β activity in osteoblasts. Our results extend the complex interactions among local and systemic bone growth regulators to DHT, and predict complications from anabolic steroid use in other DHT sensitive tissues. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Insulin and IGF-II, but not IGF-I, stimulate the in vitro regeneration of adult frog sciatic sensory axons

    DEFF Research Database (Denmark)

    Edbladh, M; Svenningsen, Åsa Fex; Ekström, P A

    1994-01-01

    We used the in vitro regenerating frog sciatic nerve to look for effects of insulin and insulin-like growth factors I and II (IGF-I, IGF-II) on regeneration of sensory axons and on injury induced support cell proliferation in the outgrowth region. In nerves cultured for 11 days, a physiological...... dose (10 ng/ml, approximately 2 nM) of insulin or IGF-II increased ganglionic protein synthesis (by 20% and 50%, respectively) as well as the level of newly formed, radiolabelled axonal material distal to a crush injury (both by 80%), compared to untreated, paired controls. In addition, insulin...... increased the outgrowth distance of the furthest regenerating sensory axons by 10%. The preparation was particularly sensitive to insulin during the first 5 days of culturing. Furthermore, both insulin and IGF-II were found to inhibit proliferation of support cells in the outgrowth region in a manner...

  3. Effects of eccentric cycling exercise on IGF-I splice variant expression in the muscles of young and elderly people

    DEFF Research Database (Denmark)

    Hameed, M.; Toft, A.D.; Harridge, S.D.

    2008-01-01

    growth factor (MGF) were studied in response to 1 h of eccentric cycling exercise in young and old individuals. Subjects (nine young, aged 20-27 years and eight elderly, aged 67-75 years) completed an eccentric exercise protocol that consisted of 60 min of reverse pedal cycling. Workloads were chosen......Recovery from micro damage resulting from intensive exercise has been shown to take longer in older muscles. To investigate the factors that may contribute to muscle repair, we have studied the expression of two splice variants of the insulin-like growth factor-I (IGF-I) gene. IGF-IEa and mechano....... No difference was observed between the baseline levels of the two splice variants between the two subject groups. Eccentric cycling exercise resulted in a significant increase in the mean MGF mRNA in both young and old subjects but did not alter IGF-IEa mRNA levels in either age group. As reported previously...

  4. Endocrine and Local IGF-I in the Bony Fish Immune System.

    Science.gov (United States)

    Franz, Anne-Constance; Faass, Oliver; Köllner, Bernd; Shved, Natallia; Link, Karl; Casanova, Ayako; Wenger, Michael; D'Cotta, Helena; Baroiller, Jean-François; Ullrich, Oliver; Reinecke, Manfred; Eppler, Elisabeth

    2016-01-26

    A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived), which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine) IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.

  5. Endocrine and Local IGF-I in the Bony Fish Immune System

    Directory of Open Access Journals (Sweden)

    Anne-Constance Franz

    2016-01-01

    Full Text Available A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived, which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.

  6. Targeting either GH or IGF-I during somatostatin analogue treatment in patients with acromegaly

    DEFF Research Database (Denmark)

    Dal, Jakob; Klose, Marianne; Heck, Ansgar

    2018-01-01

    CONTEXT: Discordant GH and IGF-I values are frequent in acromegaly. The clinical significance and its dependence on treatment modality and of glucose-suppressed GH (GHnadir) measurements remain uncertain. OBJECTIVE: To evaluate the effects of targeting either IGF-I or GH during somatostatin analog...... (SA) treatment. PATIENTS AND METHODS: 84 patients with controlled acromegaly after surgery (n=23) or SA (n=61) underwent a GH-profile including an OGTT, at baseline and after 12 months. SA patients were randomized to monitoring according to either IGF-I (n= 33) or GHnadir (n=28). SA dose escalation...

  7. Divergent frequencies of IGF-I receptor-expressing blood lymphocytes in monozygotic twin pairs discordant for Graves' disease: evidence for a phenotypic signature ascribable to nongenetic factors

    DEFF Research Database (Denmark)

    Douglas, Raymond S; Brix, Thomas H; Hwang, Catherine J

    2009-01-01

    CONTEXT: Graves' disease (GD) is an autoimmune process of the thyroid and orbital connective tissues. The fraction of T and B cells expressing IGF-I receptor (IGF-IR) is increased in GD. It is a potentially important autoantigen in GD. Susceptibility to GD arises from both genetic and acquired...

  8. Structural analysis of the interaction of IGF I with the IGF types 1 and 2 and insulin receptors

    International Nuclear Information System (INIS)

    Cascieri, M.A.; Chicchi, G.G.; Hayes, N.S.; Green, B.G.; Applebaum, J.A.; Bayne, M.L.

    1987-01-01

    A synthetic gene for human IGF I has been synthesized which directs the synthesis and secretion of fully active human IGF I (rIGF I) from yeast. rIGF I inhibits binding of 125 I-IGF I to type 1 IGF receptors from human placenta (IGF-R1, IC50 = 4 nM), binding of 125 I-insulin to insulin receptors (IR, IC50 = 881 nM), binding of 125 I-MSA to type 2 IGF receptors from rat liver (IGF-R2, IC50 = 80 nM), and binding of 125 I-IGF I to crude human serum binding protein (hBP, IC50 = 0.42 nM). rIGF I is equipotent to human IGF I in stimulating glucose transport in murine BC3H1 cells and in stimulating DNA synthesis in rat A10 cells. Site directed mutagenesis of the synthetic gene is being used to characterize the structural requirements for binding to these receptors. IGF I (FFY) B(23-25) is equipotent to rIGF I at the IGF-R1 (6.9 nM), the IGF-R2 (36 nM), and the IR (841 nM) and is less potent at the hBP (1.7 nM). In contrast, IGF I(SFY) B(23-25) is 20-fold less potent than rIGF I at the IGF-R1 and is 10-fold less potent than rIGF I at hBP. This peptide is greater than 10-fold less active at the IGF-R2 and the IR. This peptide is a full agonist in the cell assays but 20-50 fold less potent than rIGF I. These data are consistent with the hypothesis that the F to S change destabilizes the tertiary structure of IGF I

  9. Polymorphism in NPY and IGF-I genes associate with reproductive ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-05

    Oct 5, 2009 ... effects of NPY and IGF-I genes on reproductive traits of chickens. Key words: ... flavor and good egg quality are accorded with Chinese consumers' taste. ... Numerous studies in mammals and more recently in teleost fish.

  10. Comparison of Efficacy of Endogenous and Exogenous IGF-I in Stimulating Matrix Production in Neonatal and Mature Chondrocytes.

    Science.gov (United States)

    Aguilar, Izath N; Trippel, Stephen B; Shi, Shuiliang; Bonassar, Lawrence J

    2015-10-01

    The goal of this study was to compare the efficacy of endogenous upregulation of IGF-I by gene therapy and exogenous addition of insulin-like growth factor I (IGF-I) in enhancing proteoglycan synthesis by skeletally mature and neonatal chondrocytes. Chondrocyte transplantation therapy is a common treatment for focal cartilage lesions, with both mature and neonatal chondrocytes used as a cell source. Additionally, gene therapy strategies to upregulate growth factors such as IGF-I have been proposed to augment chondrocyte transplantation therapies. Both skeletally mature and neonatal chondrocytes were exposed to either an adeno-associated virus-based plasmid containing the IGF-I gene or exogenous IGF-I. Analysis of IGF-I and glycosaminoglycan production using a 4-parameter dose-response model established a clear connection between the amount of IGF-I produced by cells and their biosynthetic response. Both neonatal and mature chondrocytes showed this relationship, but the sensitivities were quite different, with EC50 of 0.57 ng/mL for neonatal chondrocytes and EC50 of 8.70 ng/mL IGF-I for skeletally mature chondrocytes. These data suggest that IGF-I gene therapy may be more effective with younger cell sources. Both cell types were less sensitive to exogenous IGF-I than endogenous IGF-I.

  11. Utility of circulating IGF-I as a biomarker for assessing body composition changes in men during periods of high physical activity superimposed upon energy and sleep restriction.

    Science.gov (United States)

    Nindl, Bradley C; Alemany, Joseph A; Kellogg, Mark D; Rood, Jennifer; Allison, Steven A; Young, Andrew J; Montain, Scott J

    2007-07-01

    Insulin-like growth factor (IGF)-I is a biomarker that may have greater utility than other conventional nutritional biomarkers in assessing nutritional, health, and fitness status. We hypothesized that the IGF-I system would directionally track a short-term energy deficit and would be more related to changes in body composition than other nutritional biomarkers. Thirty-five healthy men (24 +/- 0.3 yr) underwent 8 days of exercise and energy imbalance. Total and free IGF-I, IGF binding proteins-1, -2, and -3, the acid labile subunit, transferrin, ferritin, retinol binding protein, prealbumin, testosterone, triiodothyronine, thyroxine, and leptin responses were measured. Dual-energy X-ray absorptiometry assessed changes in body mass and composition. Repeated-measures ANOVA, correlation analysis, and receiver operator characteristic curves were used for statistical analyses (P losing >5% body mass. The IGF-I system is an important adjunct in the overall assessment of adaptation to stress imposed by high levels of physical activity superimposed on energy and sleep restriction and is more closely associated with losses in body mass and fat-free mass than other conventional nutritional biomarkers.

  12. IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function.

    Science.gov (United States)

    Pardo, Joaquín; Abba, Martin C; Lacunza, Ezequiel; Ogundele, Olalekan M; Paiva, Isabel; Morel, Gustavo R; Outeiro, Tiago F; Goya, Rodolfo G

    2018-03-14

    In rats, learning and memory performance decline during normal aging, which makes this rodent species a suitable model to evaluate therapeutic strategies. In aging rats, insulin-like growth factor-I (IGF-I), is known to significantly improve spatial memory accuracy as compared to control counterparts. A constellation of gene expression changes underlie the hippocampal phenotype of aging but no studies on the effects of IGF-I on the hippocampal transcriptome of old rodents have been documented. Here, we assessed the effects of IGF-I gene therapy on spatial memory performance in old female rats and compared them with changes in the hippocampal transcriptome. In the Barnes maze test, experimental rats showed a significantly higher exploratory frequency of the goal hole than controls. Hippocampal RNA-sequencing showed that 219 genes are differentially expressed in 28-month-old rats intracerebroventricularly injected with an adenovector expressing rat IGF-I as compared with placebo adenovector-injected counterparts. From the differentially expressed genes, 81 were down and 138 upregulated. From those genes, a list of functionally relevant genes, concerning hippocampal IGF-I expression, synaptic plasticity as well as neuronal function was identified. Our results provide an initial glimpse at the molecular mechanisms underlying the neuroprotective actions of IGF-I in the aging brain.

  13. 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...

  14. Genetic Mutations, Birth Lengths, Weights and Head Circumferences of Children with IGF-I Receptor Defects. Comparison with other Congenital Defects in the GH/IGF-I axis.

    Science.gov (United States)

    Essakow, Jenna Lee; Lauterpacht, Aharon; Lilos, Pearl; Kauli, Rivka; Laron, Zvi

    2016-09-01

    In recent years more and more genetic defects along the GHRH-GH-IGF-I axis have been reported. Mutations of the IGF-I receptor (R) are a rare abnormality of whom only the heterozygote progenies survive. To summarize, from the literature, data on birth length, weight and head circumference of neonates with IGF-I-R mutations, and to correlate the data with that of other types of mutations in the GH/IGF-I axis. Sixty seven neonates from 24 published articles were included and forty seven different mutations of the IGF-I (R) located on chromosome 15 have been identified. Mean (±SD) birth length (BL), available for 26, (10 M, 16F) neonates with a gestational age of 34-41weeks, was 44.2±4cm; one was premature (30cm at 31 weeks). There was a significant correlation between birth length and gestational age (GA) r=0.71 (p>.001). Mean birth weight (BW) of 41 neonates (18M, 23F) was 2388±743gr. Two premature neonates weighed 650gr and 950gr respectively. The BW correlated significantly with gestational age, (males: r=0.68; p=0.007, females: r=0.49; p=0.024). The BMI of 25 neonates ranged from 6 to 13. In 22 records marked microcephaly was ascertained or stated. Nine of 16 mothers were short (133 -148cm), m±SD = 150.5±7.3cm. Copyright© of YS Medical Media ltd.

  15. Insulin-like growth factor (IGF)-I binding to a cell membrane associated IGF binding protein-3 acid-labile subunit complex in human anterior pituitary gland

    NARCIS (Netherlands)

    Wilczak, N; Kuhl, N; Chesik, D; Geerts, A; Luiten, P; De Keyser, J

    The binding characteristics of [(125) I]insulin-like growth factor (IGF)-I were studied in human brain and pituitary gland. Competition binding studies with DES(1-3)IGF-I and R-3 -IGF-I, which display high affinity for the IGF-I receptor and low affinity for IGF binding proteins (IGFBPs), were

  16. Human IGF-I propeptide A promotes articular chondrocyte biosynthesis and employs glycosylation-dependent heparin binding.

    Science.gov (United States)

    Shi, Shuiliang; Kelly, Brian J; Wang, Congrong; Klingler, Ken; Chan, Albert; Eckert, George J; Trippel, Stephen B

    2018-03-01

    Insulin-like growth factor I (IGF-I) is a key regulator of chondrogenesis, but its therapeutic application to articular cartilage damage is limited by rapid elimination from the repair site. The human IGF-I gene gives rise to three IGF-I propeptides (proIGF-IA, proIGF-IB and proIGF-IC) that are cleaved to create mature IGF-I. In this study, we elucidate the processing of IGF-I precursors by articular chondrocytes, and test the hypotheses that proIGF-I isoforms bind to heparin and regulate articular chondrocyte biosynthesis. Human IGF-I propeptides and mutants were overexpressed in bovine articular chondrocytes. IGF-I products were characterized by ELISA, western blot and FPLC using a heparin column. The biosynthetic activity of IGF-I products on articular chondrocytes was assayed for DNA and glycosaminoglycan that the cells produced. Secreted IGF-I propeptides stimulated articular chondrocyte biosynthetic activity to the same degree as mature IGF-I. Of the three IGF-I propeptides, only one, proIGF-IA, strongly bound to heparin. Interestingly, heparin binding of proIGF-IA depended on N-glycosylation at Asn92 in the EA peptide. To our knowledge, this is the first demonstration that N-glycosylation determines the binding of a heparin-binding protein to heparin. The biosynthetic and heparin binding abilities of proIGF-IA, coupled with its generation of IGF-I, suggest that proIGF-IA may have therapeutic value for articular cartilage repair. These data identify human pro-insulin-like growth factor IA as a bifunctional protein. Its combined ability to bind heparin and augment chondrocyte biosynthesis makes it a promising therapeutic agent for cartilage damage due to trauma and osteoarthritis. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Thyroid hormone modulates insulin-like growth factor-I(IGF-I) and IGF-binding protein-3, without mediation by growth hormone, in patients with autoimmune thyroid diseases.

    Science.gov (United States)

    Inukai, T; Takanashi, K; Takebayashi, K; Fujiwara, Y; Tayama, K; Takemura, Y

    1999-10-01

    The expression and synthesis of insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) are regulated by various hormones and nutritional conditions. We evaluated the effects of thyroid hormones on serum levels of IGF-I and IGFBP-3 levels in patients with autoimmune thyroid diseases including 54 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis, and in 32 healthy age-matched control subjects. Patients were subdivided into hyperthyroid, euthyroid and hypothyroid groups that were untreated, or were treated with methylmercaptoimidazole (MMI) or L-thyroxine (L-T4). Serum levels of growth hormone (GH), IGF-I and IGFBP-3 were determined by radioimmunoassay. Serum GH levels did not differ significantly between the hyperthyroid and the age-matched euthyroid patients with Graves' disease. The serum levels of IGF-I and IGFBP-3 showed a significant positive correlation in the patients (R=0.616, Phyperthyroid patients with Graves' disease or in those with Hashimoto's thyroiditis induced by excess L-T4 administration than in control subjects. Patients with hypothyroid Graves' disease induced by the excess administration of MMI showed significantly lower IGFBP-3 levels as compared to those in healthy controls (Phormone modulates the synthesis and/or the secretion of IGF-I and IGFBP-3, and this function is not mediated by GH.

  18. Conditionally immortalized human pancreatic stellate cell lines demonstrate enhanced proliferation and migration in response to IGF-I

    Energy Technology Data Exchange (ETDEWEB)

    Rosendahl, Ann H., E-mail: ann.rosendahl@med.lu.se [Lund University, Department of Clinical Sciences Lund, Division of Surgery, Lund (Sweden); Lund University and Skåne University Hospital, Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund (Sweden); Gundewar, Chinmay; Said Hilmersson, Katarzyna [Lund University, Department of Clinical Sciences Lund, Division of Surgery, Lund (Sweden); Ni, Lan; Saleem, Moin A. [University of Bristol, School of Clinical Sciences, Children' s Renal Unit and Academic Renal Unit, Bristol (United Kingdom); Andersson, Roland [Lund University, Department of Clinical Sciences Lund, Division of Surgery, Lund (Sweden)

    2015-01-15

    Pancreatic stellate cells (PSCs) play a key role in the dense desmoplastic stroma associated with pancreatic ductal adenocarcinoma. Studies on human PSCs have been minimal due to difficulty in maintaining primary PSC in culture. We have generated the first conditionally immortalized human non-tumor (NPSC) and tumor-derived (TPSC) pancreatic stellate cells via transformation with the temperature-sensitive SV40 large T antigen and human telomerase (hTERT). These cells proliferate at 33°C. After transfer to 37°C, the SV40LT is switched off and the cells regain their primary PSC phenotype and growth characteristics. NPSC contained cytoplasmic vitamin A-storing lipid droplets, while both NPSC and TPSC expressed the characteristic markers αSMA, vimentin, desmin and GFAP. Proteome array analysis revealed that of the 55 evaluated proteins, 27 (49%) were upregulated ≥3-fold in TPSC compared to NPSC, including uPA, pentraxin-3, endoglin and endothelin-1. Two insulin-like growth factor binding proteins (IGFBPs) were inversely expressed. Although discordant IGFBP-2 and IGFBP-3 levels, IGF-I was found to stimulate proliferation of both NPSC and TPSC. Both basal and IGF-I stimulated motility was significantly enhanced in TPSC compared to NPSC. In conclusion, these cells provide a unique resource that will facilitate further study of the active stroma compartment associated with pancreatic cancer. - Highlights: • Generation of human conditionally immortalized human pancreatic stellate cell lines. • Temperature-sensitive SV40LT allows switch to primary PSC phenotype characteristics. • Proteome profiling revealed distinct expression patterns between TPSC and NPSC. • Enhanced IGF-I-stimulated proliferation and motility by TPSC compared to NPSC.

  19. The effect of HMB ingestion on the IGF-I and IGF binding protein response to high intensity military training.

    Science.gov (United States)

    Redd, Michael J; Hoffman, Jay R; Gepner, Yftach; Stout, Jeffrey R; Hoffman, Mattan W; Ben-Dov, Daniel; Funk, Shany; Church, David D; Avital, Guy; Chen, Yacov; Frankel, Hagai; Ostfeld, Ishay

    2017-02-01

    Insulin-like growth factor-I (IGF-I) is a metabolic and anabolic biomarker that has been proposed to reflect physiological adaptations resulting from multistressor environments. The bioactivity of IGF-I is regulated by seven different insulin-like growth factor binding proteins (IGFBPs) which act not only as carriers of IGF-1, but also function as a modulator of IGF-I availability and activity. Supplementing with β-hydroxy-β-methylbutyrate (HMB) has been shown to enhance physiological outcomes associated with intense training, and has been reported to augment the IGF-1 response. The purpose of this study was to examine the effect of 23days of HMB supplementation on circulating levels of IGF-I and IGFBPs in combat soldiers during highly intense military training. Thirteen male soldiers from an elite infantry unit volunteered to participate in this double-blind, parallel design study. Soldiers were provided 3g·day -1 of either HMB (n=6) or placebo (PL; n=7). During the study soldiers performed advanced military training with periods of restricted sleep and severe environmental stressors. Blood samples were obtained prior to (PRE) and approximately 18h following the final supplement consumption (POST). No significant differences were observed for circulating IGF-1 concentrations between HMB and PL (p=0.568). In addition, no differences were seen between the groups for IGFBP-1 (p=1.000), IGFBP-2 (p=0.855), IGFBP-3 (p=0.520), IGFBP-4 (p=0.103), IGFBP-5 (p=0.886), or IGFBP-6 (p=0.775). A significant difference was noted between HMB (169.9±23.0ng·ml -1 ) and PL (207.2±28.0ng·ml -1 ) for IGFBP-7 at POST (p=0.042). Although the results of this study do not support the influence of HMB supplementation on circulating concentrations of IGF-1 or IGFBPs1-6 during high intensity military training, it does present initial evidence that it may lower circulating IGFBP-7 concentrations. This may provide some indication of a reduced stress response, but further investigation on

  20. Comparison of acid ethanol extraction and acid gel filtration prior to IGF-I and IGF-II radioimmunoassays; Improvement of determinations in acid ethanol extracts by the use of truncated IGF-I as radioligand

    Energy Technology Data Exchange (ETDEWEB)

    Bang, P; Eriksson, U; Wivall, I -L; Hall, K [Department of Endocrinology, Karolinska Institute, Stockholm (Sweden); Sara, V [Department of Pathology, Karolinska Institute, Stockholm (Sweden)

    1991-01-01

    Insulin-like growth factor binding proteins interfere in the IGF-I and -II radioimmunoassays. In an attempt to overcome this problem, we have compared the use of truncated IGF-I, with reduced IGFBP affinity, and IGF-I as radioligands for IGF-I RIA measurements in serum separated by acid gel filtration or acid ethanol extraction followed by cryo-precipitation. With truncated IGF-I as radioligand the IGF-I measurements in acid gel filtrates and acid ethanol extracts were significantly correlated in healthy subjects (N=42, r=0.91, p<0.001) and in patients with acromegaly (N=10, r=0.85, p<0.01), GH deficiency (N=10, r=0.88, p<0.001) or Type I diabetes mellitus (N=10, r=0.90, p<0.001). In contrast, the IGF-I concentrations in acid ethanol extracts determined with IGF-I as radioligand did not correlate with those in acid gel filtrates using truncated IGF-I radioligand in patients with acromegaly (r=0.61, NS) or GH deficiency (r=0.46, NS). In the latter group the mean IGF-I concentrations measured in acid ethanol extracts were erroneously elevated by 112%. Low-affinity antibodies used for IGF-II RIA determinations failed to give reliable results in acid ethanol extracts from patients with Type I diabetes mellitus or GH deficiency. In conclusion, erroneously high IGF-I concentrations owing to binding of the radioligand to IGFBPs not completely removed by acid ethanol extraction can be avoided by the use of truncated IGF-I as radioligand. (author).

  1. Effects of Growth Hormone/IGF-I and Exercise on Unloaded Bones

    Science.gov (United States)

    Harper, J. S.; Arnaud, S. B.; Gosselink, K. L.; Grindeland, R. E.

    1994-01-01

    Growth hormone (GH) and insulin-like growth factor-I (IGF-I) in combination with exercise prevent muscle atrophy induced by unloading in the tail-suspension rat model for space flight (Gosselink et al, FASEB J 1994). This study evaluated the effects of these treatments on bone. Hypophysectomized rats were suspended (S) and treated with 1mg/kg/day CH plus IGF-I (H) or vehicle (Sal) daily by injection and exercised (Ex) by 3 climbs up a 1m ladder carrying a load equal to 30% the initial body weight (BW) 3x/day for 10 days. Tibial epiphysis (Epi) widths were measured by micrometry and femoral Bone Mineral Content (fBMC) in excised femurs by DEXA (Lunar DPX-L). Serum calcium (Ca) and phosphorus (Pi) were measured by COBAS Autoanalyzer (Roche Diag.). Ambulatory (Amb)-H treated rats showed growth rates of 6.6+-0.9 g/day, similar to S-H-Ex and higher than S-H (3.210.6, p less than 0.05) and S-Sal (-0.711.0, p less than 0.05). Epi widths were 10% lower in S-Sal, and S-Sal-Ex, and increased 100% in all H groups. fBMC was less in S than Amb, only when all S groups are compared to both Amb groups (p less than 0.03). H treatment increased fBMC (p less than 0.05) but reduced fBMC/100g BW in all H groups (p less than 0.001). The reduced density of H bone cannot be attributed to low circulating Ca. and Pi since they were higher in H than Sal (p less than 0.001). H treatment for 10 days in doses sufficient to support normal growth in BW failed to produce normal Epi widths or fBMC, even when combined with exercise. The suspension effect observed in Epi widths was not corrected by H or Ex alone, but was improved by H plus a This regimen. although effective in preventing muscle atrophy, failed to return bone measures, Epi widths and fBMC, to normal.

  2. Diabetic retinopathy in two patients with congenital IGF-I deficiency (Laron syndrome).

    Science.gov (United States)

    Laron, Zvi; Weinberger, Dov

    2004-07-01

    Animal and clinical studies have shown that excessive amounts of growth hormone or insulin-like growth factor-I (IGF-I) promote the development of diabetes and diabetic retinopathy. Forthwith, we present two patients with congenital IGF-I deficiency who developed type II diabetes and subsequently retinopathy. Eighteen adult patients with classical Laron syndrome (8 males, 10 females, aged 20-62 years) were followed by us since childhood or underwent fundus photography with a Nikon NF 505 instrument. Three had been treated in childhood with IGF-I, the rest were never treated, including the two patients reported. Two never-treated patients were diagnosed with type II diabetes (DM) at ages 39 and 41 respectively. There was no diabetes in the families. Oral treatment was followed by insulin injections. Metabolic control was not optimal and one patient developed proliferative diabetic retinopathy, necessitating laser surgery. He also has nephropathy and severe neuropathy. The other patient has background diabetic retinopathy and has developed, progressively, exudates, microaneurisms, hemorrhages and clinically significant macular edema. He also has subacute ischemic heart disease. Our findings show that congenital IGF-I deficiency, similar to excess, causes vascular complications of DM, denoting also that vascular endothelial growth factor can induce neovascularization in the presence of congenital IGF-I deficiency.

  3. Comparison of acid ethanol extraction and acid gel filtration prior to IGF-I and IGF-II radioimmunoassays

    International Nuclear Information System (INIS)

    Bang, P.; Eriksson, U.; Wivall, I.-L.; Hall, K.; Sara, V.

    1991-01-01

    Insulin-like growth factor binding proteins interfere in the IGF-I and -II radioimmunoassays. In an attempt to overcome this problem, we have compared the use of truncated IGF-I, with reduced IGFBP affinity, and IGF-I as radioligands for IGF-I RIA measurements in serum separated by acid gel filtration or acid ethanol extraction followed by cryo-precipitation. With truncated IGF-I as radioligand the IGF-I measurements in acid gel filtrates and acid ethanol extracts were significantly correlated in healthy subjects (N=42, r=0.91, p<0.001) and in patients with acromegaly (N=10, r=0.85, p<0.01), GH deficiency (N=10, r=0.88, p<0.001) or Type I diabetes mellitus (N=10, r=0.90, p<0.001). In contrast, the IGF-I concentrations in acid ethanol extracts determined with IGF-I as radioligand did not correlate with those in acid gel filtrates using truncated IGF-I radioligand in patients with acromegaly (r=0.61, NS) or GH deficiency (r=0.46, NS). In the latter group the mean IGF-I concentrations measured in acid ethanol extracts were erroneously elevated by 112%. Low-affinity antibodies used for IGF-II RIA determinations failed to give reliable results in acid ethanol extracts from patients with Type I diabetes mellitus or GH deficiency. In conclusion, erroneously high IGF-I concentrations owing to binding of the radioligand to IGFBPs not completely removed by acid ethanol extraction can be avoided by the use of truncated IGF-I as radioligand. (author)

  4. Effects of Moderate Aerobic Exercise Combined with Caloric Restriction on Circulating Estrogens and IGF-I in Premenopausal Women

    National Research Council Canada - National Science Library

    Williams, Nancy

    2003-01-01

    The proposal entitled "Effects of moderate aerobic exercise combined with caloric restriction on circulating estrogens and IGF-I in premenopausal women will provide important scientific contributions...

  5. Detection of exogenous gene doping of IGF-I by a real-time quantitative PCR assay.

    Science.gov (United States)

    Zhang, Jin-Ju; Xu, Jing-Feng; Shen, Yong-Wei; Ma, Shi-Jiao; Zhang, Ting-Ting; Meng, Qing-Lin; Lan, Wen-Jun; Zhang, Chun; Liu, Xiao-Mei

    2017-07-01

    Gene doping can be easily concealed since its product is similar to endogenous protein, making its effective detection very challenging. In this study, we selected insulin-like growth factor I (IGF-I) exogenous gene for gene doping detection. First, the synthetic IGF-I gene was subcloned to recombinant adeno-associated virus (rAAV) plasmid to produce recombinant rAAV2/IGF-I-GFP vectors. Second, in an animal model, rAAV2/IGF-I-GFP vectors were injected into the thigh muscle tissue of mice, and then muscle and blood specimens were sampled at different time points for total DNA isolation. Finally, real-time quantitative PCR was employed to detect the exogenous gene doping of IGF-I. In view of the characteristics of endogenous IGF-I gene sequences, a TaqMan probe was designed at the junction of exons 2 and 3 of IGF-I gene to distinguish it from the exogenous IGF-I gene. In addition, an internal reference control plasmid and its probe were used in PCR to rule out false-positive results through comparison of their threshold cycle (Ct) values. Thus, an accurate exogenous IGF-I gene detection approach was developed in this study. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  6. 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...

  7. Hand size and growth in untreated and IGF-I treated patients with Laron syndrome.

    Science.gov (United States)

    Konen, O; Silbergeld, A; Lilos, P; Kornreich, L; Laron, Z

    2009-03-01

    We have previously reported on the linear growth, growth of the head circumference and foot length in untreated and IGF-I treated patients with Laron syndrome (LS) (primary GH insensitivity). To assess the size and growth of the hands in patients with LS from early childhood to adult age. Ten IGF-I treated children with LS (4 M, 6 F) and 24 untreated patients (10 M, 14 F) were studied. Measurements of palm length were made on available standardized hand X-rays from infancy to adult age. The measurements were compared to normal references and SD values were calculated for each measurement. The growth of the hand was compared to the concomitant height of the body. Hand SDS in untreated patients with LS decreased with age, from a mean of -2.8 +/- 0.7 (age 1-3 years) to -7.3 +/- 0.8 (age 13-15 years) and to -9.0 +/- 3.9 (age 40-50 years). During 9 years of IGF-I treatment the hand size deficit SDS did not improve in contradistinction to the height SDS which decreased from -6.2 +/- 1.2 to -3.9 +/- 0.5. Congenital IGF-I deficiency, as in Laron syndrome, profoundly affects the size and growth of the hand as part of its growth retardation characteristics, resulting in acromicria.

  8. Detection of polymorphism of the insulin-like growth factor-I (IGF-I ...

    African Journals Online (AJOL)

    Molecular genetic selection on individual genes is a promising method to genetically improve economically important traits in chickens. The insulin-like growth factor-I (IGF-I) gene may play important roles in growth of multiple tissues, including muscle cells, cartilage and bone. In the present study, polymorphism of the ...

  9. Acute GH and IGF-I responses to short vs. long rest period between ...

    African Journals Online (AJOL)

    In order to examine the effects of different rest intervals between the sets on acute growth hormone (GH) and insulin-like growth factor-1 (IGF-I) responses, ten recreationally resistance trained men served as subjects (Mean ± SD, age=22 ± 2 years, body mass= 84 ± 8 kg). Subjects performed two heavy-resistance training ...

  10. Acute regulation of IGF-I by alterations in post-exercise macronutrients

    Science.gov (United States)

    This investigation sought to examine the contributions of exercise and nutrient replenishment on in vivo regulation of the insulin-like growth factor-I (IGF-I) axis components. Eight college-aged males completed three high-intensity interval training (HIIT) protocols followed by three post-exercise ...

  11. IGF-I en la homeostasia cerebral: implicaciones patológicas

    Directory of Open Access Journals (Sweden)

    Ignacio Torres

    2005-03-01

    Full Text Available El factor de crecimiento de la familia de la insulina tipo I (IGF-I es una proteína sérica especialmente abundante fabricada principalmente en el hígado; su producción está regulada por la hormona de crecimiento (GH hipofisario.

  12. Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3

    DEFF Research Database (Denmark)

    Juul, A; Kastrup, K W; Pedersen, S A

    1997-01-01

    .e. 45% of patients treated with GH during childhood because of isolated GHD had a normal GH response when retested in adulthood. Multiple regression analysis revealed that peak GH levels were dependent on the degree of hypopituitarism, body mass index, and duration of disease. IGF-I levels were below -2...

  13. Interaction of Mechanical Load with Growth Hormone (GH) and Insulin-Like Growth Factor I (IGF-I) on Slow-Twitch Skeletal Muscle and Bone

    Science.gov (United States)

    Linderman, Jon K.; Gosselink, Kristin L.; Wang, Tommy J.; Mukku, Venkat R.; Grindeland, Richard E.

    1994-01-01

    Exogenous humoral growth factors, combined with increased mechanical loading, reportedly induce hypertrophy of fast-, but not slow-twitch skeletal muscles, and have little effect in attenuating atrophy of slow-twitch muscle associated with exposure to microgravity in animals with intact neuroendocrine systems. These observations suggest that anabolic adjuvants and muscle tension do not interact to stimulate growth or maintenance of slow-twitch skeletal muscle. The purpose of the present study was to determine whether a chronic increase in mechanical loading (synergistic ablation) or hindlimb unweighting (hindlimb suspension) interact with exogenous GH and IGF-I (Genentech, So San Francisco, CA) in the slow-twitch soleus muscles of female rats (approx. 250 g). Bilateral ablation of the plantaris and gastrocnemius muscles induced 38% and 40% increases in the absolute (mg/pair) and relative (mg/100 g body weight) weights of the soleus, respectively (p less than or = 0.05), in ambulatory rats. GH and IGF-I interacted with chronic loading to increase absolute soleus mass an additional 20% (p less than or = 0.05), and mixed and myofibrillar protein contents an additional 12% and 7%, respectively (NS). In contrast, hindlimb suspension (HLS) resulted in 20% and 18% decreases in the absolute and relative weights of the soleus, respectively (p less than or = 0.05); GH and IGF-I did not spare loss of soleus mass or protein content in HLS rats. HLS decreased tibial plate thickness approx. 11% (p less than or = 0.05), but not weights of the tibia or femus. GH and IGF-I increased tibial plate thickness approx. 30% (p less than or = 0.05), in ambulatory and HLS rats, and increased femur and tibial weights 12% (p less than or = 0.05) and 8% (NS), respectively, in ambulatory rats, but had no effect in HLS rats. Results of the present investigation suggest that GH and IGF-I can stimulate hypertrophy of slow-twitch skeletal muscle when chronically overloaded, but can also stimulate

  14. Serum insulin-like growth factor-I (IGF-I) and growth in children born after assisted reproduction

    DEFF Research Database (Denmark)

    Kai, Claudia Mau; Main, Katharina M; Andersen, Anders Nyboe

    2006-01-01

    CONTEXT: Concern has been raised about the safety of assisted reproduction techniques for the offspring. OBJECTIVES: The objective of the study was to investigate postnatal growth and growth factors in children born after intra-cytoplasmatic sperm injection (ICSI) and in vitro fertilization (IVF...... their target height (sd score) at 3 yr of age [mean -0.91 (1.2)], compared with NC children [-0.61 (0.9), P = 0.033]. In the child cohort, target height attainment (sd score) and growth factors did not differ among the three groups. CONCLUSIONS: The overall growth pattern of ICSI and IVF children in both...... cohorts was normal. Our findings of subtle differences in target height attainment and serum IGF-I levels between infants born after assisted reproduction techniques and controls may not be clinically significant. However, these observations indicate that further systematic follow-up of growth and puberty...

  15. Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years.

    Science.gov (United States)

    Kindler, Joseph M; Pollock, Norman K; Laing, Emma M; Oshri, Assaf; Jenkins, Nathan T; Isales, Carlos M; Hamrick, Mark W; Ding, Ke-Hong; Hausman, Dorothy B; McCabe, George P; Martin, Berdine R; Hill Gallant, Kathleen M; Warden, Stuart J; Weaver, Connie M; Peacock, Munro; Lewis, Richard D

    2017-07-01

    IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  16. Insulin/IGF-I regulation of necdin and brown adipocyte differentiation via CREB- and FoxO1-associated pathways

    DEFF Research Database (Denmark)

    Cypess, Aaron M; Zhang, Hongbin; Schulz, Tim J

    2011-01-01

    is regulated by the phosphoinositide 3 kinase-Akt pathway, increased necdin promoter activity. Based on reporter gene assays using truncations of the necdin promoter and chromatin immunoprecipitation studies, we demonstrated that CREB and FoxO1 are recruited to the necdin promoter, likely interacting......Brown adipose tissue plays an important role in obesity, insulin resistance, and diabetes. We have previously shown that the transition from brown preadipocytes to mature adipocytes is mediated in part by insulin receptor substrate (IRS)-1 and the cell cycle regulator protein necdin. In this study...... with specific consensus sequences in the proximal region. Based on these results, we propose that insulin/IGF-I act through IRS-1 phosphorylation to stimulate differentiation of brown preadipocytes via two complementary pathways: 1) the Ras-ERK1/2 pathway to activate CREB and 2) the phosphoinositide 3 kinase-Akt...

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

    NARCIS (Netherlands)

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

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

  18. Treatment with N- and C-Terminal Peptides of Parathyroid Hormone-Related Protein Partly Compensate the Skeletal Abnormalities in IGF-I Deficient Mice

    Science.gov (United States)

    Portal-Núñez, Sergio; Murillo-Cuesta, Silvia; Lozano, Daniel; Cediel, Rafael; Esbrit, Pedro

    2014-01-01

    Insulin-like growth factor-I (IGF-I) deficiency causes growth delay, and IGF-I has been shown to partially mediate bone anabolism by parathyroid hormone (PTH). PTH-related protein (PTHrP) is abundant in bone, and has osteogenic features by poorly defined mechanisms. We here examined the capacity of PTHrP (1–36) and PTHrP (107–111) (osteostatin) to reverse the skeletal alterations associated with IGF-I deficiency. Igf1-null mice and their wild type littermates were treated with each PTHrP peptide (80 µg/Kg/every other day/2 weeks; 2 males and 4 females for each genotype) or saline vehicle (3 males and 3 females for each genotype). We found that treatment with either PTHrP peptide ameliorated trabecular structure in the femur in both genotypes. However, these peptides were ineffective in normalizing the altered cortical structure at this bone site in Igf1-null mice. An aberrant gene expression of factors associated with osteoblast differentiation and function, namely runx2, osteoprotegerin/receptor activator of NF-κB ligand ratio, Wnt3a , cyclin D1, connexin 43, catalase and Gadd45, as well as in osteocyte sclerostin, was found in the long bones of Igf1-null mice. These mice also displayed a lower amount of trabecular osteoblasts and osteoclasts in the tibial metaphysis than those in wild type mice. These alterations in Igf1-null mice were only partially corrected by each PTHrP peptide treatment. The skeletal expression of Igf2, Igf1 receptor and Irs2 was increased in Igf1-null mice, and this compensatory profile was further improved by treatment with each PTHrP peptide related to ERK1/2 and FoxM1 activation. In vitro, PTHrP (1–36) and osteostatin were effective in promoting bone marrow stromal cell mineralization in normal mice but not in IGF-I-deficient mice. Collectively, these findings indicate that PTHrP (1–36) and osteostatin can exert several osteogenic actions even in the absence of IGF-I in the mouse bone. PMID:24503961

  19. IGF-I during primiparous pregnancy and maternal risk of breast cancer

    OpenAIRE

    Chen, Tianhui; Lukanova, Annekatrin; Grankvist, Kjell; Zeleniuch-Jacquotte, Anne; Wulff, Marianne; Johansson, Robert; Schock, Helena; Lenner, Per; Hallmans, Goran; Wadell, Goran; Toniolo, Paolo; Lundin, Eva

    2009-01-01

    Abstract Previously, we reported that insulin-like growth factor (IGF)-I during early pregnancy is positively associated with maternal risk of breast cancer. To further explore this association, we designed a new study limited to women who donated a blood sample during their first pregnancy ending with childbirth. A case?control study was nested within the Northern Sweden Maternity Cohort in which repository since 1975, serum specimens remaining after early pregnancy screening for ...

  20. IGF-I deficiency, longevity and cancer protection of patients with Laron syndrome.

    Science.gov (United States)

    Laron, Zvi; Kauli, Rivka; Lapkina, Lena; Werner, Haim

    Laron syndrome (LS) is a unique model of congenital IGF-I deficiency. It is characterized by dwarfism and obesity, and is caused by deletion or mutations of the growth hormone receptor (GH-R) gene. It is hypothesized that LS is an old disease originating in Indonesia and that the mutated gene spread to South Asia, the Middle East, the Mediterranean region and South America. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Genetic influence on the associations between IGF-I and glucose metabolism in a cohort of elderly twins

    DEFF Research Database (Denmark)

    Jensen, Rikke Beck; Thankamony, Ajay; Holst, Klaus K.

    2018-01-01

    OBJECTIVE: IGF-I may be a marker of later metabolic and cardiovascular disease. The interactions between IGF-I and glucose metabolism are multifactorial, and there is potential confounding from several secondary effects. In this study, we examined the interaction between IGF-I and glucose...... metabolism in a large cohort of clinically well-characterized elderly twins. DESIGN: A total of 303 twin pairs of the same gender (606 twins) were included in the study; 125 monozygotic and 178 dizygotic twin pairs. METHODS: A clinical examination including a standard oral glucose tolerance test (OGTT.......11). In a multiple regression analysis (adjusting for age, gender and twin status), there was a negative association between IGF-I and insulin sensitivity (B: -0.13, SE 0.03, P cohort of 606 twins. The associations between IGF...

  2. The Effects of Systemic IGF-I on the Arterial Anastomosis in Rats

    Directory of Open Access Journals (Sweden)

    Baris Keklik

    2014-04-01

    Full Text Available Objective: In this study, we aimed to document the effects of a well-known agent and mdash; and ldquo;insulin-like growth factor (IGF-I and rdquo; and mdash; on the microvascular anastomosis site. Methods: Sixteen Sprague-Dawley rats were used in this study. The rats were classified randomly into two equally numbered groups (eight rats each: the control (Group 1 and the experiment group (Group 2. The femoral artery was dissected completely in all rats. Following division of the artery, anastomoses were conducted with microvascular techniques. Forty-five minutes after the anastomoses, an Acland milking test was performed in order to check the patency and the first surgical session was terminated. In the second stage, LONG and reg; R3 IGF-I human (Sigma-Aldrich, St. Louis, Missouri, United States solution was introduced to Group 2 (experimental group intraperitoneally in doses of 2 mg/kg on the day of the surgery in addition to the third and seventh days postoperatively. On the 4th postoperative week, the patency of the anastomoses was evaluated with the Acland milking test. In addition, one centimeter of a vascular segment including the anastomosis site was excised and stained with hematoxylin-eosin. They were evaluated for edema, inflammation, vascular wall injury, intimal hyperplasia, medial atrophy, thrombus, calcification, foreign body reactions, and the endothelial proliferation. Results: The Acland milking test showed a 100% vascular patency in both groups. A statistically significant difference was found between the experimental and control groups in terms of edema and vascular wall injury (p0.05. Conclusion: Under the light of the obtained data, IGF-I was effective in preventing the edema and vascular wall injury at the anastomosis site. However, the net positive clinical effect on anastomosis patency necessitates further studies. [Arch Clin Exp Surg 2014; 3(2.000: 87-93

  3. Retardation of fetal dendritic development induced by gestational hyperglycemia is associated with brain insulin/IGF-I signals.

    Science.gov (United States)

    Jing, Yu-Hong; Song, Yan-Feng; Yao, Ya-Ming; Yin, Jie; Wang, De-Gui; Gao, Li-Ping

    2014-10-01

    Hyperglycemia is an essential risk factor for mothers and fetuses in gestational diabetes. Clinical observation has indicated that the offspring of mothers with diabetes shows impaired somatosensory function and IQ. However, only a few studies have explored the effects of hyperglycemia on fetal brain development. Neurodevelopment is susceptible to environmental conditions. Thus, this study aims to investigate the effects of maternal hyperglycemia on fetal brain development and to evaluate insulin and insulin-like growth factor-I (IGF-I) signals in fetal brain under hyperglycemia or controlled hyperglycemia. At day 1 of pregnancy, gestational rats were intraperitoneally injected with streptozocin (60 mg/kg). Some of the hyperglycemic gestational rats were injected with insulin (20 IU, two times a day) to control hyperglycemia; the others were injected with saline of equal volume. The gestational rats were sacrificed at days 14, 16, and 18 of embryo development. The dendritic spines of subplate cortex neurons in the fetal brain were detected by Golgi-Cox staining. The mRNA levels of insulin receptors (IRs) and IGF-IR in the fetal brain were measured using qRT-PCR. The protein levels of synaptophysin, IR, and IGF-IR in the fetal brain were detected by western blot. No significant difference in fetal brain formation was observed between the maternal hyperglycemic group and insulin-treated group. By contrast, obvious retardation of dendritic development in the fetus was observed in the maternal hyperglycemic group. Similarly, synaptophysin expression was lower in the fetus of the maternal hyperglycemic group than in that of the insulin-treated group. The mRNA and protein expression levels of IRs in the fetal brain were higher in the hyperglycemic group than in the insulin-treated group. By contrast, the levels of IGF-IR in the brain were lower in the fetus of the maternal hyperglycemic group than in that of the insulin-treated group. These results suggested that

  4. strong>A novel oral preparation of human growth hormone (hGH) is absorbed and increases serum IGF-I levels after 7 days administration to GH-deficient adultsstrong>

    DEFF Research Database (Denmark)

    Laursen, Torben; Mindeholm, Linda; Haemmerle, Sibylle

    2007-01-01

    ) as carrier has recently been developed. The aim of this study was to determine if this oral formulation of hGH could be absorbed and be bioactive. Eight GHD men (mean age 50 years) receiving sc hGH therapy were withdrawn from therapy for 7 days and then treated for 7 days orally with tablets of HGH191...

  5. Proline-rich tyrosine kinase 2 (Pyk2 regulates IGF-I-induced cell motility and invasion of urothelial carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Marco Genua

    Full Text Available The insulin-like growth factor receptor I (IGF-IR plays an essential role in transformation by promoting cell growth and protecting cancer cells from apoptosis. We have recently demonstrated that the IGF-IR is overexpressed in invasive bladder cancer tissues and promotes motility and invasion of urothelial carcinoma cells. These effects require IGF-I-induced Akt- and MAPK-dependent activation of paxillin. The latter co-localizes with focal adhesion kinases (FAK at dynamic focal adhesions and is critical for promoting motility of urothelial cancer cells. FAK and its homolog Proline-rich tyrosine kinase 2 (Pyk2 modulate paxillin activation; however, their role in regulating IGF-IR-dependent signaling and motility in bladder cancer has not been established. In this study we demonstrate that FAK was not required for IGF-IR-dependent signaling and motility of invasive urothelial carcinoma cells. On the contrary, Pyk2, which was strongly activated by IGF-I, was critical for IGF-IR-dependent motility and invasion and regulated IGF-I-dependent activation of the Akt and MAPK pathways. Using immunofluorescence and AQUA analysis we further discovered that Pyk2 was overexpressed in bladder cancer tissues as compared to normal tissue controls. Significantly, in urothelial carcinoma tissues there was increased Pyk2 localization in the nuclei as compared to normal tissue controls. These results provide the first evidence of a specific Pyk2 activity in regulating IGF-IR-dependent motility and invasion of bladder cancer cells suggesting that Pyk2 and the IGF-IR may play a critical role in the invasive phenotype in urothelial neoplasia. In addition, Pyk2 and the IGF-IR may serve as novel biomarkers with diagnostic and prognostic significance in bladder cancer.

  6. Secondhand Smoke Exposure Reduced the Compensatory Effects of IGF-I Growth Signaling in the Aging Rat Hearts.

    Science.gov (United States)

    Wu, Jia-Ping; Hsieh, Dennis Jine-Yuan; Kuo, Wei-Wen; Han, Chien-Kuo; Pai, Peiying; Yeh, Yu-Lan; Lin, Chien-Chung; Padma, V Vijaya; Day, Cecilia Hsuan; Huang, Chih-Yang

    2015-01-01

    Secondhand smoke (SHS) exposure is associated with increased risk of cardiovascular disease. Aging is a physiological process that involves progressive impairment of normal heart functions due to increased vulnerability to damage. This study examines secondhand smoke exposure in aging rats to determine the age-related death-survival balance. Rats were placed into a SHS exposure chamber and exposed to smog. Old age male Sprague-Dawley rats were exposed to 10 cigarettes for 30 min, day and night, continuing for one week. After 4 weeks the rats underwent morphological and functional studies. Left ventricular sections were stained with hematoxylin-eosin for histopathological examination. TUNEL detected apoptosis cells and protein expression related death and survival pathway were analyzed using western blot. Death receptor-dependent apoptosis upregulation pathways and the mitochondria apoptosis proteins were apparent in young SHS exposure and old age rats. These biological markers were enhanced in aging SHS-exposed rats. The survival pathway was found to exhibit compensation only in young SHS-exposed rats, but not in the aging rats. Further decrease in the activity of this pathway was observed in aging SHS-exposed rats. TUNEL apoptotic positive cells were increased in young SHS-exposed rats, and in aging rats with or without SHS-exposure. Aging reduces IGF-I compensated signaling with accelerated cardiac apoptotic effects from second-hand smoke.

  7. DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy.

    Science.gov (United States)

    Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan

    2017-01-01

    Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95-nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95-nNOS interactions in MHE.

  8. DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Saidan Ding

    2017-09-01

    Full Text Available Insulin-like growth factor I (IGF-I has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE was shown to be induced by elevated intracranial dopamine (DA. The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95 and neuronal nitric oxide synthase (nNOS was found in neurons. Ribosomal S6 protein kinase (RSK phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2. In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95–nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95–nNOS interactions in MHE.

  9. Development and biological function of the female gonads and genitalia in IGF-I deficiency -- Laron syndrome as a model.

    Science.gov (United States)

    Laron, Zvi

    2006-01-01

    Laron syndrome (LS) or primary GH insensitivity is a unique human model to study the effects of congenital IGF-I deficiency. Within our cohort of 63 patients with LS, 15 female patients were regularly followed since birth or infancy, throughout puberty. We observed that they were short at birth, with small genitalia and gonads -- during puberty, developed delayed puberty but eventually reached between 16 and 19 1/2 years full sexual development. Reproduction is unaffected at a young adult age. It is concluded that IGF-I in concert with the sex hormones has a modulatory but not essential function on female sexual development and maturation.

  10. High-Methionine Diet Attenuates Severity of Arthritis and Modulates IGF-I Related Gene Expressions in an Adjuvant Arthritis Rats Model

    Directory of Open Access Journals (Sweden)

    Mingxin Li

    2016-01-01

    Full Text Available Rheumatoid arthritis, a synthesized form of adjuvant arthritis exhibited throughout many animal species, inhibits liver function and circulation of IGF-I and contributes to the degradation of skeletal muscle mass. One of the primary goals of the present study is determining whether a high-Methionine (high-Met diet is capable of reducing the adverse effects of arthritis, namely, loss of body mass. Following adjuvant injection, forty arthritic rats were randomly assigned to either a control group with a basal diet or a high-Met group with the same basal diet + 0.5% Methionine. After 14 days all rats were terminated. The high-Met group exhibited an increase in body weight and food intake in comparison with the control group (P<0.05. High-Met diet debilitated arthritis-induced surges in the gastrocnemius in both atrogin-1 and the MuRF1 expressions; however, it was observed to have little to no effect on atrogin-1 and MuRF1 gene expression in soleus. At the same time, high-Met diet rats experienced a rise in IGF-I, with lowering of IGFBP-3 gene expression in the gastrocnemius and the soleus. These data suggest that arthritis severity can be partly attenuated by high-Met diet.

  11. EXPRESSION OF GROWTH HORMONE (PhGH GENE AND ANALYSIS OF INSULINE-LIKE GROWTH FACTOR I (IGF-I PRODUCTION IN AFRICAN CATFISH (Clarias gariepinus TRANSGENIC F-1

    Directory of Open Access Journals (Sweden)

    Huria Marnis

    2013-12-01

    Full Text Available We have previously produced F-1 transgenic of African catfish from crosses between founder transgenic female and non transgenic male. The aim of this study was to evaluate distribution and expression PhGH growth hormone gene transgenic African catfish organs and to measure the concentration of IGF-I in plasma. Transgene was detected using the PCR method in various organs, namely pituitary, brain, liver, heart, spleen, kidney, intestine, stomach, muscle, gill, and eye. Transgene expression levels were analyzed using the method of quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR. Plasma samples were analyzed for Insuline-like Growth Factor (IGF-I using Enzyme Linked Immunosorbent Assay (ELISA method. The results showed that the PhGH was detected and expressed in all organs of the transgenic African catfish (F-1. Liver exhibited the highest level of PhGH mRNA (23 x 106 copies. The plasma IGF-I levels in transgenic individuals were not significant than non transgenic. The higher level of exogenous PhGH gene expression may not represent the production of IGF-1.

  12. Insulin-like growth factor-I raises serum procollagen levels in children and adults with Laron syndrome

    DEFF Research Database (Denmark)

    Klinger, B; Jensen, L T; Silbergeld, A

    1996-01-01

    children and 5 adults) were included in the study. The children with LS were treated with IGF-I for 3 years with daily doses of 150-200 micrograms/kg. The adult LS patients were treated for 9 months with daily doses of 50-120 micrograms/kg. Blood samples for procollagens were collected before, during...... IGF-I administration. RESULTS: Untreated patients with LS had lower than normal serum levels of PICP and PIIINP for age. IGF-I treatment increased significantly the PIIINP levels in children from 7.2 +/- 2.8 (SD) to 12.5 +/- 2.2 micrograms/l (P 3.......6 micrograms/l (P 3.7 to 14.3 +/- 5.9 micrograms/l (P

  13. Desalted deep-sea water improves cognitive function in mice by increasing the production of insulin-like growth factor-I in the hippocampus.

    Science.gov (United States)

    Harada, Naoaki; Zhao, Juan; Kurihara, Hiroki; Nakagata, Naomi; Okajima, Kenji

    2011-08-01

    The stimulation of sensory neurons in the gastrointestinal (GI) tract improves cognitive function by increasing the hippocampal production of insulin-like growth factor-I (IGF-I) in mice. In the current study, we examined whether oral administration of desalted deep-sea water (DSW) increases the hippocampal production of IGF-I by stimulating sensory neurons in the GI tract, thereby improving cognitive function in mice. Desalted DSW increased calcitonin gene-related peptide (CGRP) release from dorsal root ganglion (DRG) neurons isolated from wild-type (WT) mice by activating transient receptor potential vanilloid 1. The plasma levels of IGF-I and tissue levels of CGRP, IGF-I, and IGF-I mRNA in the hippocampus were increased by oral administration of desalted DSW in WT mice. In these animals, nociceptive information originating from the GI tract was transmitted to the hippocampus via the spinothalamic pathway. Improvement of spatial learning was observed in WT mice after administration of desalted DSW. Distilled DSW showed results similar to those of desalted DSW in vitro and in vivo. None of the effects of desalted DSW in WT mice were observed after the administration of desalted DSW in CGRP-knockout (CGRP-/-) mice. No volatile compounds were detected in distilled DSW on GC-MS analysis. These observations suggest that desalted DSW may increase the hippocampal IGF-I production via sensory neuron stimulation in the Gl tract, thereby improving cognitive function in mice. Such effects of desalted DSW might not be dependent on the minerals but are dependent on the function of the water molecule itself. Copyright © 2011 Mosby, Inc. All rights reserved.

  14. Organ-Specific and Age-Dependent Expression of Insulin-like Growth Factor-I (IGF-I) mRNA Variants: IGF-IA and IB mRNAs in the Mouse

    OpenAIRE

    Ohtsuki, Takashi; Otsuki, Mariko; Murakami, Yousuke; Maekawa, Tetsuya; Yamamoto, Takashi; Akasaka, Koji; Takeuchi, Sakae; Takahashi, Sumio

    2005-01-01

    Insulin-like growth factor-I (IGF-I) gene generates several IGF-I mRNA variants by alternative splicing. Two promoters are present in mouse IGF-I gene. Each promoter encodes two IGF-I mRNA variants (IGF-IA and IGF-IB mRNAs). Variants differ by the presence (IGF-IB) or absence (IGF-IA) of a 52-bp insert in the E domain-coding region. Functional differences among IGF-I mRNAs, and regulatory mechanisms for alternative splicing of IGF-I mRNA are not yet known. We analyzed the expression of mouse ...

  15. Reduced insulin-like growth factor-I serum levels in formerly obese women subjected to laparoscopic-adjustable gastric banding or diet-induced long-term caloric restriction.

    Science.gov (United States)

    Mitterberger, Maria C; Mattesich, Monika; Klaver, Elise; Piza-Katzer, Hildegunde; Zwerschke, Werner

    2011-11-01

    Life-span extension in laboratory rodents induced by long-term caloric restriction correlates with decreased serum insulin-like growth factor-I (IGF-I) levels. Reduced activity of the growth hormone/IGF-I signaling system slows aging and increases longevity in mutant mouse models. In the present study, we show that long-term caloric restriction achieved by two different interventions for 4 years, either laparoscopic-adjustable gastric banding or reducing diet, leads to reduced IGF-I serum levels in formerly obese women relative to normal-weight women eating ad libitum. Moreover, we present evidence that the long-term caloric restriction interventions reduce fasting growth hormone serum levels. The present study indicates that the activity of the growth hormone/IGF-I axis is reduced in long-term calorically restricted formerly obese humans. Furthermore, our findings suggest that the duration and severity of the caloric restriction intervention are important for the outcome on the growth hormone/IGF-I axis in humans.

  16. Effects of Moderate Aerobic Exercise Combined With Caloric Restriction on Circulating Estrogens and IGF-I in Premenopausal Women

    National Research Council Canada - National Science Library

    Williams, Nancy

    2002-01-01

    ... cancer, circulating estrogens and IGF-I. We will also test whether this type of diet/exercise program will produce significant reductions in the peripheral production of estrone by adipose tissue through its impact on the reduction of fat mass...

  17. Co-induction of hepatic IGF-I and progranulin mRNA by growth hormone in tilapia, Oreochromis mossambiccus

    Science.gov (United States)

    Like IGF-I, progranulin (pgrn) is a growth factor involved in tumorigenesis and wound healing. We report here the identification and characterization of pgrn cDNA in tilapia and the regulation of its expression by growth hormone(GH). The tilapia pgrn cDNA was cloned by RT-PCR ampliWcation, using g...

  18. Maternal exposure to UV filters and associations to maternal thyroid hormones and IGF-I/IGFBP3 and birth outcomes

    DEFF Research Database (Denmark)

    Krause, Marianna; Frederiksen, Hanne; Sundberg, Karin

    2018-01-01

    as birth outcomes (weight, height, and head and abdominal circumferences) were examined. RESULTS: Positive associations between maternal serum concentrations of 4-HBP and triiodothyronine (T3), thyroxine (T4), Insulin-like Growth Factor-I (IGF-I) and its binding protein IGFBP3, were observed in mothers...

  19. Systemic administration of insulin-like growth factor I (IGF-I) causes growth of the rat prostate

    DEFF Research Database (Denmark)

    Tørring, N; Vinter-Jensen, L; Pedersen, S B

    1997-01-01

    PURPOSE: To investigate the effects of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) on the rat prostate. In addition, we investigated the effect of ornithine decarboxylase (ODC) inhibition with alpha-diflouromethylornitine (DFMO) on the expected growth of the prostate.MA...

  20. Determining the normal range for IGF-I, IGFBP-3, and ALS: new reference data based on current internal standards.

    Science.gov (United States)

    Ertl, Diana-Alexandra; Gleiss, Andreas; Sagmeister, Susanne; Haeusler, Gabriele

    2014-09-01

    The measurement of insulin-like growth factors (IGF-I) and insulin-like growth factor-binding protein (IGFBP-3) often serves as first-line testing in children with growth disorders. The role of acid-labile subunit (ALS) as a screening parameter for homozygous or heterozygous mutations of the ALS gene still has to be determined. IGF-I, IGFBP-3, and ALS were measured in 252 samples from children and adolescents. Reference curves were fitted using generalized additive model for location, scale and shape (GAMLSS) models and SD-Scores were calculated. Bootstrap analysis was used to quantify the uncertainty of the estimated percentiles. Bland-Altman plots were used to investigate the discrepancy between our newly estimated standard deviation scores (SDS) and SDS calculated on the basis of previous reference data. We present reference data for enzyme-linked immunosorbent assay (ELISA) measurements based on recommended internal standard for IGF-I, IGFBP-3, and ALS suitable for calculation of SD-scores. The Bland-Altman plot shows a rough agreement between the previous SDS calculation and our new one only for SDS around 1; for SDS at -2, an average difference of 0.83 SD was noticed. Our IGF-I reference values for the interval of interest in diagnosing growth hormone deficiency (GHD) (prepubertal age) are solid as proved by bootstrap analysis. The difference in calculated SD scores by using data provided previously highlights the importance of using labor and method specific reference data.

  1. [Differential expression of IGF-I and its mRNA in mandibular condylar cartilage of rat--direct evidence for servosystem theory of facial growth].

    Science.gov (United States)

    Zhou, Z; Luo, S

    1998-05-01

    It was studied the expression of IGF-I and its mRNA in the condylar cartilage of 10 7-week-old SD male rats by using in situ hybridization and immunohisto-chemistry technique. The results showed both IGF-I and its gene expressed in growing rat condyle. IGF-I peptide was abundant in germinal zone, and positive reaction of its mRNA was strongest in transitional and maturational zones. These indicate that condylar cartilage has the capability of local production and secretion of IGF-I, mediating the command effect of STH, and differential expression of IGF-I and its mRNA might establish the local feedback loop, which supply a direct evidence for servosystem theory of facial growth.

  2. Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3.

    Science.gov (United States)

    2005-01-01

    Insmed is developing mecasermin rinfabate, a recombinant complex of insulin-like growth factor-I (rhIGF-I) and binding protein-3 (rhIGFBP-3) [insulin-like growth factor-I/insulin-like growth factor binding protein-3, rhIGF-I/rhIGFBP-3, SomatoKine], for a number of metabolic and endocrine indications. In the human body, IGF-I circulates in the blood bound to a binding protein-3 (IGFBP-3), which regulates the delivery of IGF-I to target tissues, and particular proteases clip them apart in response to stresses and release IGF-I as needed. IGF-I, a naturally occurring hormone, is necessary for normal growth and metabolism. For the treatment of IGF-I deficiency, it is desirable to administer IGF-I bound to IGFBP-3 to maintain the normal equilibrium of these proteins in the blood. Mecasermin rinfabate (rhIGF-I/rhIGFBP-3) mimics the effects of the natural protein complex in the bloodstream and would augment the natural supply of these linked compounds. The most advanced indication in development of mecasermin rinfabate is the treatment of severe growth disorders due to growth hormone insensitivity syndrome (GHIS), also called Laron syndrome. GHIS is a genetic condition in which patients do not produce adequate quantities of IGF because of a failure to respond to the growth hormone signal. This results in a slower growth rate and short stature. Mecasermin rinfabate also has potential as replacement therapy for IGF-I, which may become depleted in indications such as major surgery, organ damage/failure, traumatic injury, cachexia and severe burn trauma. It also has potential for the treatment of osteoporosis. Mecasermin rinfabate was developed by Celtrix using its proprietary recombinant protein production technology. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on 1 June 2000. Insmed and Avecia of the UK have signed an agreement for manufacturing mecasermin rinfabate and its components, rhIGF-1 and rhIGFBP-3. CGMP clinical production of mecasermin rinfabate

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  4. Effects of an evaporative cooling system on plasma cortisol, IGF-I, and milk production in dairy cows in a tropical environment

    Science.gov (United States)

    Titto, Cristiane Gonçalves; Negrão, João Alberto; Titto, Evaldo Antonio Lencioni; Canaes, Taissa de Souza; Titto, Rafael Martins; Pereira, Alfredo Manuel Franco

    2013-03-01

    Access to an evaporative cooling system can increase production in dairy cows because of improved thermal comfort. This study aimed to evaluate the impact of ambient temperature on thermoregulation, plasma cortisol, insulin-like growth factor 1 (IGF-I), and productive status, and to determine the efficiency of an evaporative cooling system on physiological responses under different weather patterns. A total of 28 Holstein cows were divided into two groups, one with and the other without access to a cooling system with fans and mist in the free stall. The parameters were analyzed during morning (0700 hours) and afternoon milking (1430 hours) under five different weather patterns throughout the year (fall, winter, spring, dry summer, and rainy summer). Rectal temperature (RT), body surface temperature (BS), base of tail temperature (TT), and respiratory frequency (RF) were lower in the morning ( P milk production during spring and summer ( P < 0.01).

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

    DEFF Research Database (Denmark)

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

    1997-01-01

    fraction of the total IGF-I circulates in its free form, which is believed to be the biologically active form. However, our knowledge of the clinical or physiological value of determination of free IGF-I in serum is limited at present. In adults, the diagnostic value of total IGF-I and IGFBP-3......, commercially available immunoradiometric assay (Diagnostic Systems Laboratories) to establish valid normative data for this analysis. We studied the diagnostic value of free IGF-I in relation to total IGF-I and IGFBP-3 determinations in adults who were suspected of GHD. A GH provocative test, using oral...... determinations in patients suspected of GHD has only been reported in a few studies, whereas no previous reports on the diagnostic value of free IGF-I levels in adults suspected of GHD exist. Serum levels of free IGF-I were determined in 1430 healthy children, adolescents, and adults by a newly developed...

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

    DEFF Research Database (Denmark)

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

    1997-01-01

    fraction of the total IGF-I circulates in its free form, which is believed to be the biologically active form. However, our knowledge of the clinical or physiological value of determination of free IGF-I in serum is limited at present. In adults, the diagnostic value of total IGF-I and IGFBP-3...... determinations in patients suspected of GHD has only been reported in a few studies, whereas no previous reports on the diagnostic value of free IGF-I levels in adults suspected of GHD exist. Serum levels of free IGF-I were determined in 1430 healthy children, adolescents, and adults by a newly developed......, commercially available immunoradiometric assay (Diagnostic Systems Laboratories) to establish valid normative data for this analysis. We studied the diagnostic value of free IGF-I in relation to total IGF-I and IGFBP-3 determinations in adults who were suspected of GHD. A GH provocative test, using oral...

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

    Science.gov (United States)

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

    2018-04-01

    Obese children are often taller than age-matched subjects. Reports on GH and IGF-I levels in obese individuals are controversial, with normal and reduced GH-IGF-I levels having been reported in this group of patients. Thus, the aim of this study was to analyse insulin-like growth factor type 1 receptor (IGF-IR) mRNA expression in obese children. Forty-seven pre-pubertal children were included in this study: 29 were obese and taller than their target height, and 18 were normal eutrophic controls. Fasting blood samples were collected for IGF-IR mRNA expression in isolated lymphocytes and serum IGF-I, ALS, IGFBP-3, and IGFBP-1 concentration analysis. Relative IGF-IR gene expression (2 -ΔΔCT ) was significantly (P=0.025) higher in obese children (median 1.87) than in controls (1.15). Fourteen of the 29 obese subjects showed 2 -ΔΔCT values greater than or equal to 2, while only 2 individuals in the control group showed values above 2 (P=0.01). Obese children showed significantly (P=0.01) higher IGF-I concentrations than the control group (237ng/ml and 144ng/ml, respectively). Among obese patients, 65.5% had IGF-I values above the 75 percentile of the control group (P=0.02). ALS concentration was significantly (P=0.04) higher in the obese group, while IGFBP-3 levels were similar in obese and control children. IGFBP-1 concentration was lower in obese children, while insulin levels and HOMA-IR index were higher than in controls. The higher IGF-IR mRNA expression observed in obese children, associated with the higher IGF-I and ALS and the lower IGFBP-1 levels, suggest that the higher stature observed in these children may be due to increased IGF-I bioactivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. CARTILAGE CONSTRUCTS ENGINEERED FROM CHONDROCYTES OVEREXPRESSING IGF-I IMPROVE THE REPAIR OF OSTEOCHONDRAL DEFECTS IN A RABBIT MODEL

    Science.gov (United States)

    Madry, Henning; Kaul, Gunter; Zurakowski, David; Vunjak-Novakovic, Gordana; Cucchiarini, Magali

    2015-01-01

    Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes over expressing a human insulin-like growth factor I (IGF-I) gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-over expressing chondrocytes markedly improved osteochondral repair compared with control (lacZ) constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects. PMID:23588785

  9. Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model

    Directory of Open Access Journals (Sweden)

    H Madry

    2013-04-01

    Full Text Available Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes overexpressing a human insulin-like growth factor I (IGF-I gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-overexpressing chondrocytes markedly improved osteochondral repair compared with control (lacZ constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects.

  10. IGF-I and IGFBP-3 levels and their correlations with ...

    African Journals Online (AJOL)

    Çiğdem Yağcıoğlu Yücel

    carcinoembryonic antigen (CEA) is the most widespreadly used tumor marker. .... for endometrium CA.33 Prostate cancer and benign prostate hyper- plasia are ..... and IGF-binding protein-3 in benign prostatic hyperplasia and prostate cancer.

  11. Peripheral blood aspirates overexpressing IGF-I via rAAV gene transfer undergo enhanced chondrogenic differentiation processes.

    Science.gov (United States)

    Frisch, Janina; Orth, Patrick; Rey-Rico, Ana; Venkatesan, Jagadeesh Kumar; Schmitt, Gertrud; Madry, Henning; Kohn, Dieter; Cucchiarini, Magali

    2017-11-01

    Implantation of peripheral blood aspirates induced towards chondrogenic differentiation upon genetic modification in sites of articular cartilage injury may represent a powerful strategy to enhance cartilage repair. Such a single-step approach may be less invasive than procedures based on the use of isolated or concentrated MSCs, simplifying translational protocols in patients. In this study, we provide evidence showing the feasibility of overexpressing the mitogenic and pro-anabolic insulin-like growth factor I (IGF-I) in human peripheral blood aspirates via rAAV-mediated gene transfer, leading to enhanced proliferative and chondrogenic differentiation (proteoglycans, type-II collagen, SOX9) activities in the samples relative to control (reporter rAAV-lacZ) treatment over extended periods of time (at least 21 days, the longest time-point evaluated). Interestingly, IGF-I gene transfer also triggered hypertrophic, osteo- and adipogenic differentiation processes in the aspirates, suggesting that careful regulation of IGF-I expression may be necessary to contain these events in vivo. Still, the current results demonstrate the potential of targeting human peripheral blood aspirates via therapeutic rAAV transduction as a novel, convenient tool to treat articular cartilage injuries. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  12. Indications, limitations and pitfalls in the determination of human growth hormone, IGF-I and their binding proteins.

    Science.gov (United States)

    Laron, Zvi; Bidlingmaier, Martin; Strasburger, Christian Joseph

    2007-10-01

    Deviations from normal growth are a major part of Pediatric Endocrinology. The principal post-natal growth promoting hormones are pituitary growth hormone (GH) and insulin-like growth factor-I (IGF-I). The GH-IGF-I axis has many links and portals, the secrets of which have been disclosed in recent years by scientific advances (genetic and biochemical technologies). In this article, we describe the players in the GH axis, the auxological indications for performing GH evaluation tests, enumerate the most frequently used tests and discuss the laboratory tests which help to define the pathological entities along the GH axis. Emphasis is put on the limitations of methods used, lack of standards, norms and the possible errors in diagnosis and treatment indications that may evolve. As both hGH and IGF-I immunoassay measurements represent cornerstones in the diagnosis and monitoring of the different etiological entities presenting with short stature, clinicians must have an insight into the variability and limitations of these analytical techniques. Interpretation of biochemical results without proper reference data and without knowledge of the assay-inherent characteristics inevitably leads to misdiagnosis, unnecessary further testing and treatment and imposes a burden on the child, family and the health care system.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  14. Identification of binding sites for an insulin-like growth factor (IGF-I) in the median eminence of the rat brain by quantitative autoradiography

    International Nuclear Information System (INIS)

    Bohannon, N.J.; Figlewicz, D.P.; Corp, E.S.; Wilcox, B.J.; Porte, D. Jr.; Baskin, D.G.

    1986-01-01

    The microanatomical location of IGF-I binding in the rat brain was determined by in vitro autoradiography with slide-mounted sections of frozen brain. Sections incubated in 0.1 nM [ 125 I]-iodo-IGF-I produced a dense grain concentration in regions of the autoradiographic image corresponding to the external palisade zone of the median eminence; other hypothalamic regions were not so heavily labeled. This reaction was significantly reduced in the presence of 100 nM IGF-I. Measurement of binding by computer digital image analysis of autoradiographic images showed that specific binding for IGF-I in the median eminence was 41.3 +/- 8 X 10(-3) fmol/mm2 (mean +/- SEM); nonspecific binding was 11.9 +/- 1.8 X 10(-3) fmol/mm2. In contrast, specific binding to other hypothalamic regions was uniformly lower. In a separate experiment, 1000 nM unlabeled insulin was added. Without insulin, specific binding was 23 +/- 0.9 X 10(-3) fmol/mm2; nonspecific binding was 8 +/- 0.5 X 10(-3) fmol/mm2. In the presence of 1000 nM unlabeled insulin, specific binding for [ 125 I]-iodo-IGF-I was 23 +/- 1 X 10(-3) fmol/mm2. The results suggest that a high concentration of receptors for an IGF-I-like molecule is present in the median eminence

  15. Polymorphism of Insulin-like growth factor-I (IGF-I gene and their effect on growth traits in Indonesia native chicken

    Directory of Open Access Journals (Sweden)

    M.A Mu'in

    2009-12-01

    Full Text Available The research was aimed is to detect Insulin-like growth factor-I (IGF-I gene polymorphism and their effect on growth traits in Indonesia natives chicken. Seventy two Indonesian native chicken are going to be used in this research. The polymorphism of IGF-I gene was detected by PCR-RFLP/Pst-I. Four growth traits (body weight at 1, 2, 3, and 4 months were recorded for analyzing the association between IGF-I gene polymorphism and growth performance.The results showed that allele A (621 bp and allele B (364 and 257 bp were found in this research. It was found that Indonesian native chicken carried high frequencies of allele A (0.82, and frequencies of IGF-I genotypes (AA, AB, BB were 68.0, 27.8, and 4,2%, respectively. When compared to the IGF-I genotypes, the BB genotype had the highest body weight at 1, 2, 3, and 4 month (P<0.05. The results showed that the B allele was positive of associated to a higher growth rate. Therefore, these results suggest that there is a possibility of IGF-I genotypes acting as a molecular marker for growth rate of Indonesia native.

  16. Increase in tendon protein synthesis in response to insulin-like growth factor-I is preserved in elderly men

    DEFF Research Database (Denmark)

    Nielsen, Rie Harboe; Holm, Lars; Malmgaard-Clausen, Nikolaj Mølkjær

    2014-01-01

    the in vivo IGF-I stimulation of tendon protein synthesis in elderly compared with young men. We injected IGF-I in the patellar tendons of young (n = 11, 20-30 yr of age) and old (n = 11, 66-75 yr of age) men, and the acute fractional synthesis rate (FSR) of tendon protein was measured with the stable isotope.......01). This increase in protein synthesis was seen in both young and old men, with no differences between age groups. The old group had markedly lower serum IGF-I levels compared with young (165 ± 17 vs. 281 ± 27 ng/ml, P protein synthesis in both young and old men...... technique and compared with the contralateral side (injected with saline as control). We found that tendons injected with IGF-I had significantly higher protein FSR compared with controls (old group: 0.018 ± 0.015 vs. 0.008 ± 0.008, young group: 0.016 ± 0.009 vs. 0.009 ± 0.006%/h, mean ± SE, P

  17. Serum insulin-like growth factor (IGF)-I and IGF binding protein-3 in relation to terminal duct lobular unit involution of the normal breast in Caucasian and African American women: The Susan G. Komen Tissue Bank.

    Science.gov (United States)

    Oh, Hannah; Pfeiffer, Ruth M; Falk, Roni T; Horne, Hisani N; Xiang, Jackie; Pollak, Michael; Brinton, Louise A; Storniolo, Anna Maria V; Sherman, Mark E; Gierach, Gretchen L; Figueroa, Jonine D

    2018-02-22

    Lesser degrees of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini/TDLU, are associated with elevated breast cancer risk. In rodent models, the insulin-like growth factor (IGF) system regulates involution of the mammary gland. We examined associations of circulating IGF measures with TDLU involution in normal breast tissues among women without precancerous lesions. Among 715 Caucasian and 283 African American (AA) women who donated normal breast tissue samples to the Komen Tissue Bank between 2009 and 2012 (75% premenopausal), serum concentrations of IGF-I and binding protein (IGFBP)-3 were quantified using enzyme-linked immunosorbent assay. Hematoxilyn and eosin-stained tissue sections were assessed for numbers of TDLUs ("TDLU count"). Zero-inflated Poisson regression models with a robust variance estimator were used to estimate relative risks (RRs) for association of IGF measures (tertiles) with TDLU count by race and menopausal status, adjusting for potential confounders. AA (vs. Caucasian) women had higher age-adjusted mean levels of serum IGF-I (137 vs. 131 ng/mL, p = 0.07) and lower levels of IGFBP-3 (4165 vs. 4684 ng/mL, p IGF-I:IGFBP-3 ratios were associated with higher TDLU count in Caucasian (RR T3vs.T1 =1.33, 95% CI = 1.02-1.75, p-trend = 0.04), but not in AA (RR T3vs.T1 =0.65, 95% CI = 0.42-1.00, p-trend = 0.05), women. Our data suggest a role of the IGF system, particularly IGFBP-3, in TDLU involution of the normal breast, a breast cancer risk factor, among Caucasian and AA women. © 2018 UICC.

  18. Postnatal Changes in Testicular Position are Associated with IGF-I and Function of Sertoli and Leydig Cells

    DEFF Research Database (Denmark)

    Koskenniemi, Jaakko J; Virtanen, Helena E; Wohlfahrt-Veje, Christine

    2018-01-01

    position during childhood. Design: Testicular position (the distance from the pubic bone to the upper pole of the testes) at birth, 3 months, 18 months, 36 months, 7 years and reproductive hormones at three months were measured. Setting: Prenatally recruited, prospective longitudinal birth cohort....... Participants: In total 2545 boys were recruited prenatally in a Danish-Finnish birth cohort and had testicular position examination available. A subset of 680 Danish and 362 Finnish boys had serum reproductive hormone concentrations and insulin-like growth factor I (IGF-I) determined at three months. Main...

  19. Salinity and temperature variations reflecting on cellular PCNA, IGF-I and II expressions, body growth and muscle cellularity of a freshwater fish larvae.

    Science.gov (United States)

    Martins, Y S; Melo, R M C; Campos-Junior, P H A; Santos, J C E; Luz, R K; Rizzo, E; Bazzoli, N

    2014-06-01

    The present study assessed the influence of salinity and temperature on body growth and on muscle cellularity of Lophiosilurus alexaxdri vitelinic larvae. Slightly salted environments negatively influenced body growth of freshwater fish larvae and we observed that those conditions notably act as an environmental influencer on muscle growth and on local expression of hypertrophia and hypeplasia markers (IGFs and PCNA). Furthermore, we could see that salinity tolerance for NaCl 4gl(-)(1) diminishes with increasing temperature, evidenced by variation in body and muscle growth, and by irregular morphology of the lateral skeletal muscle of larvae. We saw that an increase of both PCNA and autocrine IGF-II are correlated to an increase in fibre numbers and fibre diameter as the temperature increases and salinity diminishes. On the other hand, autocrine IGF-I follows the opposite way to the other biological parameters assessed, increasing as salinity increases and temperature diminishes, showing that this protein did not participate in muscle cellularity, but participating in molecular/cellular repair. Therefore, slightly salted environments may provide adverse conditions that cause some obstacles to somatic growth of this species, suggesting some osmotic expenditure with a salinity increment. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Expression of human choline kinase in NIH 3T3 fibroblasts increases the mitogenic potential of insulin and insulin-like growth factor I.

    Science.gov (United States)

    Chung, T; Huang, J S; Mukherjee, J J; Crilly, K S; Kiss, Z

    2000-05-01

    In mammalian cells, growth factors, oncogenes, and carcinogens stimulate phosphocholine (PCho) synthesis by choline kinase (CK), suggesting that PCho may regulate cell growth. To validate the role of PCho in mitogenesis, we determined the effects of insulin, insulin-like growth factor I (IGF-I), and other growth factors on DNA synthesis in NIH 3T3 fibroblast sublines highly expressing human choline kinase (CK) without increasing phosphatidylcholine synthesis. In serum-starved CK expressor cells, insulin and IGF-I stimulated DNA synthesis, p70 S6 kinase (p70 S6K) activity, phosphatidylinositol 3-kinase (PI3K) activity, and activating phosphorylation of p42/p44 mitogen-activated protein kinases (MAPK) to greater extents than in the corresponding vector control cells. Furthermore, the CK inhibitor hemicholinium-3 (HC-3) inhibited insulin- and IGF-I-induced DNA synthesis in the CK overexpressors, but not in the vector control cells. The results indicate that high cellular levels of PCho potentiate insulin- and IGF-I-induced DNA synthesis by MAPK- and p70 S6K-regulated mechanisms.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  2. Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners.

    Science.gov (United States)

    Sarfstein, Rive; Friedman, Yael; Attias-Geva, Zohar; Fishman, Ami; Bruchim, Ilan; Werner, Haim

    2013-01-01

    Accumulating epidemiological evidence shows that obesity is associated with an increased risk of several types of adult cancers, including endometrial cancer. Chronic hyperinsulinemia, a typical hallmark of diabetes, is one of the leading factors responsible for the obesity-cancer connection. Numerous cellular and circulating factors are involved in the biochemical chain of events leading from hyperinsulinemia and insulin resistance to increased cancer risk and, eventually, tumor development. Metformin is an oral anti-diabetic drug of the biguanide family used for treatment of type 2 diabetes. Recently, metformin was shown to exhibit anti-proliferative effects in ovarian and Type I endometrial cancer, although the mechanisms responsible for this non-classical metformin action remain unclear. The insulin-like growth factors (IGFs) play a prominent role in cancer biology and their mechanisms of action are tightly interconnected with the insulin signaling pathways. Given the cross-talk between the insulin and IGF signaling pathways, the aim of this study was to examine the hypothesis that the anti-proliferative actions of metformin in uterine serous carcinoma (USC) are potentially mediated via suppression of the IGF-I receptor (IGF-IR) pathway. Our results show that metformin interacts with the IGF pathway, and induces apoptosis and inhibition of proliferation and migration of USC cell lines with both wild type and mutant p53. Taken together, our results suggest that metformin therapy could be a novel and attractive therapeutic approach for human USC, a highly aggressive variant of endometrial cancer.

  3. Insulin-like growth factor (IGF) binding protein from human decidua inhibits the binding and biological action of IGF-I in cultured choriocarcinoma cells

    International Nuclear Information System (INIS)

    Ritvos, O.; Ranta, T.; Jalkanen, J.; Suikkari, A.M.; Voutilainen, R.; Bohn, H.; Rutanen, E.M.

    1988-01-01

    The placenta expresses genes for insulin-like growth factors (IGFs) and possesses IGF-receptors, suggesting that placental growth is regulated by IGFs in an autocrine manner. We have previously shown that human decidua, but not placenta, synthesizes and secretes a 34 K IGF-binding protein (34 K IGF-BP) called placental protein 12. We now used human choriocarcinoma JEG-3 cell monolayer cultures and recombinant (Thr59)IGF-I as a model to study whether the decidual 34 K IGF-BP is able to modulate the receptor binding and biological activity of IGFs in trophoblasts. JEG-3 cells, which possess type I IGF receptors, were unable to produce IGF-BPs. Purified 34 K IGF-BP specifically bound [125I]iodo-(Thr59)IGF-I. Multiplication-stimulating activity had 2.5% the potency of (Thr59)IGF-I, and insulin had no effect on the binding of [125I] iodo-(Thr59)IGF-I. 34 K IGF-BP inhibited the binding of [125I] iodo-(Thr59)IGF-I to JEG-3 monolayers in a concentration-dependent manner by forming with the tracer a soluble complex that could not bind to the cell surface as demonstrated by competitive binding and cross-linking experiments. After incubating the cell monolayers with [125I]iodo-(Thr59)IGF-I in the presence of purified binding protein, followed by cross-linking, no affinity labeled bands were seen on autoradiography. In contrast, an intensely labeled band at 40 K was detected when the incubation medium was analyzed, suggesting that (Thr59)IGF-I and 34 K IGF-BP formed a complex in a 1:1 molar ratio. Also, 34 K IGF-BP inhibited both basal and IGF-I-stimulated uptake of alpha-[3H]aminoisobutyric acid in JEG-3 cells. RNA analysis revealed that IGF-II is expressed in JEG-3 cells

  4. The relationship in Japanese infants between a genetic polymorphism in the promoter region of the insulin-like growth factor I gene and the plasma level.

    Science.gov (United States)

    Kinoshita, Yumiko; Kizaki, Zenro; Ishihara, Yasunori; Nakajima, Hisakazu; Adachi, Shinsuke; Kosaka, Kitaro; Kinugasa, Akihiko; Sugimoto, Tohru

    2007-01-01

    Evidence is accumulating that the promoter region of the insulin-like growth factor I (IGF-I) gene polymorphism and low levels of IGF-I are associated with type 2 diabetes, cardiovascular disease and birth weight; however, the number of wild-type alleles is different in each country. This study aimed to examine the 737/738 marker, a cytosine-adenine repeat in the promoter region of the IGF-I gene polymorphism, and plasma IGF-I levels in Japanese infants and analyze the genetic background. Data were collected for 15 months in Kyoto Prefectural University of Medicine. The body composition parameters of all infants were determined at birth. At 5 days after birth, we took blood samples to measure the product size of the promoter region of the IGF-I gene polymorphism and plasma IGF-I. In a population-based sample of 160 subjects, 6 different alleles and 16 genotypes were identified in the promoter region of the IGF-I gene polymorphism. The existence of a 196-bp allele has proved to result in a low plasma IGF-I level, a small head and chest circumference (p body composition parameters in Japanese infants. Our results suggest genetical influence on prenatal growth and serum IGF-I levels.

  5. An IGF-I promoter polymorphism modifies the relationships between birth weight and risk factors for cardiovascular disease and diabetes at age 36

    Directory of Open Access Journals (Sweden)

    Stehouwer Coen DA

    2005-06-01

    Full Text Available Abstract Objective To investigate whether IGF-I promoter polymorphism was associated with birth weight and risk factors for cardiovascular disease (CVD and type 2 diabetes (T2DM, and whether the birth weight – risk factor relationship was the same for each genotype. Design and participants 264 subjects (mean age 36 years had data available on birth weight, IGF-I promoter polymorphism genotype, CVD and T2DM risk factors. Student's t-test and regression analyses were applied to analyse differences in birth weight and differences in the birth weight – risk factors relationship between the genotypes. Results Male variant carriers (VCs of the IGF-I promoter polymorphism had a 0.2 kg lower birth weight than men with the wild type allele (p = 0.009. Of the risk factors for CVD and T2DM, solely LDL concentration was associated with the genotype for the polymorphism. Most birth weight – risk factor relationships were stronger in the VC subjects; among others the birth weight – systolic blood pressure relationship: 1 kg lower birth weight was related to an 8.0 mmHg higher systolic blood pressure Conclusion The polymorphism in the promoter region of the IGF-I gene is related to birth weight in men only, and to LDL concentration only. Furthermore, the genotype for this polymorphism modified the relationships between birth weight and the risk factors, especially for systolic and diastolic blood pressure.

  6. Toward the insulin-IGF-I intermediate structures: Functional and structural properties of the [TyrB25NMePheB26] insulin mutant

    Czech Academy of Sciences Publication Activity Database

    Žáková, Lenka; Brynda, Jiří; Au-Alvarez, O.; Dodson, G. D.; Whittingham, J. L.; Brzozowski, A. M.

    2004-01-01

    Roč. 43, - (2004), s. 16293-16300 ISSN 0006-2960 R&D Projects: GA MŠk LN00B030 Institutional research plan: CEZ:AV0Z4055905 Keywords : insulin * IGF -I * Structures Subject RIV: CE - Biochemistry Impact factor: 4.008, year: 2004

  7. Insulin and IGF-II, but not IGF-I, stimulate the in vitro regeneration of adult frog sciatic sensory axons

    DEFF Research Database (Denmark)

    Edbladh, M; Svenningsen, Åsa Fex; Ekström, P A

    1994-01-01

    We used the in vitro regenerating frog sciatic nerve to look for effects of insulin and insulin-like growth factors I and II (IGF-I, IGF-II) on regeneration of sensory axons and on injury induced support cell proliferation in the outgrowth region. In nerves cultured for 11 days, a physiological...

  8. The essential role of IGF-I: lessons from the long-term study and treatment of children and adults with Laron syndrome.

    Science.gov (United States)

    Laron, Z

    1999-12-01

    Fifty patients with primary GH resistance (Laron syndrome) due to molecular defects of the GH receptor or post-receptor pathways were followed from infancy through adulthood. This condition leading to long-term insulin-like growth factor-I (IGF-I) deprivation caused marked growth retardation (-4 to 8 height SD), acromicia, organomicria, retarded development of the skeletal and muscular systems, a small cranium, slow motor development, and impairment of intellectual development in some of the patients. In addition, there was progressive obesity, insulin resistance, a tendency for hypoglycemia, followed later in life by hypercholesterolemia and by glucose intolerance and even diabetes. IGF-I treatment of children with Laron syndrome, by our and other groups (150-240 microg/day sc), stimulated growth (8 cm in the first year and 4-5 cm in the following years) and normalized the biochemical abnormalities. Overdosage led to adverse effects such as hypoglycemia, edema, swelling of soft tissues, and hyperandrogenism. It is concluded that primary IGF-I deprivation induces severe auxological, biochemical, and hormonal changes, the only treatment being biosynthetic IGF-I administration.

  9. Cartilage formation measured by a novel PIINP assay suggests that IGF-I does not stimulate but maintains cartilage formation ex vivo

    DEFF Research Database (Denmark)

    Madsen, S H; Sondergaard, B C; Jensen, Anne-Christine Bay

    2009-01-01

    explants were cultured in Dulbecco's modified Eagle's medium (DMEM):F12 in the presence of 0, 0.01, 0.1, 1, 10, or 100 ng/mL of IGF-I. The viability of the chondrocytes was measured by the colorimetric Alamar blue assay. Collagen formation was assessed from the conditioned medium by the PIINP assay...

  10. Plasma IGF-I, INSL3, testosterone, inhibin concentrations and scrotal circumferences surrounding puberty in Japanese Black beef bulls with normal and abnormal semen.

    Science.gov (United States)

    Weerakoon, W W P N; Sakase, M; Kawate, N; Hannan, M A; Kohama, N; Tamada, H

    2018-07-01

    The relationships between semen abnormalities and peripheral concentrations of testicular and metabolic hormones in beef bulls are unclear. Here we compared plasma insulin-like growth factor I (IGF-I), insulin-like peptide 3 (INSL3), testosterone, inhibin concentrations, and scrotal circumferences surrounding puberty in Japanese Black beef bulls (n = 66) with normal or abnormal semen. We collected blood samples and measured scrotal circumferences monthly from 4 to 24 months of age. Semen was collected weekly from 12 months until at least 18 months of age. Fresh semen was evaluated for semen volume, sperm motility, concentrations, and morphological defects. The normal fresh semen was frozen by a standard method and examined for post-thaw sperm motility and fertility. Bulls were classified as having either normal post-thaw semen (n = 45) or abnormal semen (n = 21, when at least one of the above test items was abnormal for 6 months). Abnormal semen was classified into abnormal fresh or low-fertility post-thaw which evaluated for rates of transferable embryos. The abnormal fresh was categorized as having sperm morphological defects, low motility, and morphological defects plus low motility. Scrotal circumferences were smaller for the abnormal-semen group vs. the normal-semen group at 20 and 24 months (p IGF-I, INSL3, and inhibin concentrations in the abnormal-semen group were lower than those of the normal-semen group (p IGF-I; 6, 9, 11-14, 17, and 20-21 months for INSL3; 5, 8-13, 16, 17, 19, and 20 months for inhibin). The plasma testosterone concentrations were lower in the abnormal-semen bulls vs. normal-semen bulls only at 22 months (p IGF-I and inhibin concentrations for low-fertility post-thaw semen (p IGF-I, INSL3, and inhibin surrounding puberty may be associated with semen aberration in beef bulls. Notably, the combined sperm abnormality of morphological defects and low motility in fresh semen could involve lowered INSL3, whereas the low

  11. Insulin-like growth factor binding protein-3 induces angiogenesis through IGF-I- and SphK1-dependent mechanisms.

    Science.gov (United States)

    Granata, R; Trovato, L; Lupia, E; Sala, G; Settanni, F; Camussi, G; Ghidoni, R; Ghigo, E

    2007-04-01

    Angiogenesis is critical for development and repair, and is a prominent feature of many pathological conditions. Based on evidence that insulin-like growth factor binding protein (IGFBP)-3 enhances cell motility and activates sphingosine kinase (SphK) in human endothelial cells, we have investigated whether IGFBP-3 plays a role in promoting angiogenesis. IGFBP-3 potently induced network formation by human endothelial cells on Matrigel. Moreover, it up-regulated proangiogenic genes, such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2 and -9. IGFBP-3 even induced membrane-type 1 MMP (MT1-MMP), which regulates MMP-2 activation. Decreasing SphK1 expression by small interfering RNA (siRNA), blocked IGFBP-3-induced network formation and inhibited VEGF, MT1-MMP but not IGF-I up-regulation. IGF-I activated SphK, leading to sphingosine-1-phosphate (S1P) formation. The IGF-I effect on SphK activity was blocked by specific inhibitors of IGF-IR, PI3K/Akt and ERK1/2 phosphorylation. The disruption of IGF-I signaling prevented the IGFBP-3 effect on tube formation, SphK activity and VEGF release. Blocking ERK1/2 signaling caused the loss of SphK activation and VEGF and IGF-I up-regulation. Finally, IGFBP-3 dose-dependently stimulated neovessel formation into subcutaneous implants of Matrigel in vivo. Thus, IGFBP-3 positively regulates angiogenesis through involvement of IGF-IR signaling and subsequent SphK/S1P activation.

  12. Exogenous estrogen as mediator of racial differences in bioactive insulin-like growth factor-I levels among postmenopausal women.

    Science.gov (United States)

    Jung, Su Yon; Vitolins, Mara Z; Paskett, Electra D; Chang, Shine

    2015-04-01

    The role of exogenous estrogen use in racial differences in insulin-like growth factor-I (IGF-I) levels which affect cancer risk is unclear. We investigated whether the relationship between race and circulating bioactive IGF-I proteins was mediated by exogenous estrogen and the extent to which exogenous estrogen influenced the race-IGF-I relationship in postmenopausal women. This cross-sectional study included 636 white and 133 African American postmenopausal women enrolled in an ancillary study of the Women's Health Initiative Observational Study. To assess exogenous estrogen use (nonusers [n = 262] vs users [n = 507]) as a mediator of the race-IGF-I relationship, we used the Baron-Kenny method and an estimation of the proportional change in the odd ratios for IGF-I levels on race plus a bootstrapping test for the significance of the mediation effect. Compared with white women, African American women were more likely to have high IGF-I levels and less likely to use exogenous estrogen. After accounting for race, estrogen nonusers had higher IGF-I levels than estrogen users did. Among oral contraceptive ever users, exogenous estrogen had a strong mediation effect (67%; p = .018) in the race-IGF-I relationship. In the women with a history of hypertension, exogenous estrogen explained racial differences in IGF-I levels to a modest degree (23%; p = .029). Exogenous estrogen use has a potentially important role in disparities in IGF-I bioactivity between postmenopausal African American and white women. A history of oral contraceptive use and hypertension may be part of the interconnected hormonal pathways related to racial differences in IGF-I levels. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Expression of insulin-like growth factor I receptors at mRNA and protein levels during metamorphosis of Japanese flounder (Paralichthys olivaceus).

    Science.gov (United States)

    Zhang, Junling; Shi, Zhiyi; Cheng, Qi; Chen, Xiaowu

    2011-08-01

    Insulin-like growth factor I (IGF-I) is an important regulator of fish growth and development, and its biological actions are initiated by binding to IGF-I receptor (IGF-IR). Our previous study has revealed that IGF-I could play an important role during metamorphosis of Japanese flounder, Paralichthys olivaceus. The analysis of IGF-IR expression thus helps further elucidate the IGF-I regulation of metamorphic processes. In this study, the spatial-temporal expression of two distinct IGF-IR mRNAs was investigated by real-time RT-PCR. The spatial distribution of two IGF-IR mRNAs in adult tissues is largely overlapped, but they exhibit distinct temporal expression patterns during larval development. A remarkable decrease in IGF-IR-2 mRNA was detected during metamorphosis. In contrast, a significant increase in IGF-IR-1 mRNA was determined from pre-metamorphosis to metamorphic completion. These indicate that they may play different function roles during the flounder metamorphosis. The levels and localization of IGF-IR proteins during larval development were further studied by Western blotting and immunohistochemistry. Immunoreactive IGF-IRs were detected throughout larval development, and the IGF-IR proteins displayed a relatively abundant expression during metamorphosis. Moreover, the IGF-IR proteins appeared in key tissues, such as thickened skin beneath the migrating eye, developing intestine, gills and kidney during metamorphosis. These results further suggest that the IGF-I system may be involved in metamorphic development of Japanese flounder. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Kaneko, Haruna; Yu, Dong; Miura, Masahiko

    2007-01-01

    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

  15. Insulin-like growth factors (IGFs) as autocrine/paracrine regulators of granulosa cell differentiation and growth: Studies with a neutralizing monoclonal antibody to IGF-I

    International Nuclear Information System (INIS)

    Mondschein, J.S.; Canning, S.F.; Miller, D.Q.; Hammond, J.M.

    1989-01-01

    Evidence that granulosa cells secrete and respond to insulin-like growth factors (IGFs) suggests, but does not prove, the importance of IGFs as intraovarian regulators. To further assess the role of these peptides in ovarian function, a neutralizing monoclonal antibody to IGF-I was employed to block the actions of IGFs in porcine follicular fluid and in granulosa cell-conditioned medium. In one series of experiments, granulosa cells from immature porcine follicles were cultured in medium containing porcine follicular fluid that had been charcoal-treated to remove steroids. As noted before, fluid from large follicles (LFF) stimulated progesterone production in a dose-dependent manner. The stimulatory effect of LFF (30% v/v) could be inhibited by greater than 50% by the anti-IGF monoclonal antibody. This inhibitory action was specific for the anti-IGF antibody and could be overcome by the addition of excess exogenous IGFs. In another series of experiments, granulosa cells were made dependent on endogenously produced IGFs by culturing them in a serum-free medium without exogenous growth factors. The effects of follicle-stimulating hormone (FSH), estradiol (E2), growth hormone (GH), and combinations thereof on progesterone production were inhibited by approximately 50% by the anti-IGF antibody. The effects of IGFs on indices of cell growth (judged by the criterion of being inhibited by the anti-IGF antibody) were less dramatic. A modest 18% increase in cell number was observed with FSH and E2 treatment in serum-free medium; this effect was virtually abolished by the antibody

  16. Head circumference in untreated and IGF-I treated patients with Laron syndrome: comparison with untreated and hGH-treated children with isolated growth hormone deficiency.

    Science.gov (United States)

    Laron, Zvi; Iluz, Moshe; Kauli, Rivka

    2012-04-01

    Head circumference (HC) is a simple and practical measure of brain size, development and longitudinal measurements of the HC in childhood are an index of brain growth. To determine the effects of long IGF-I deficiency and treatment on HC in patients with Laron syndrome (LS). 20 untreated adult LS patients, aged 48.4±11.2 years and 13 LS patients treated between ages of 5.6±4 to 11.3±3 years were studied. 15 patients with congenital IGHD treated between age 6.1±4 and 13±4 by hGH served as controls. HC was expressed as standard deviation (SD) and Ht as SDS. HC was measured and plotted on Nellhaus charts. Linear height (Ht) was measured by a Harpenden Stadiometer. The mean HC deficit of the adult untreated LS males was -2.9±0.6 SD compared to a Ht deficit of -7.0±1.7 SDS. The HC of the LS adult females was -3.6±1 SD compared to a Ht SDS of -6.9±1.5 (pdeficit decreased only by 1.5 SDS. hGH treatment of cIGHD children increased the HC from -2.0±1.8 to 0.3±1.2 SD and the Ht SDS from -4.8±1.6 to 1.6±1.0. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Insulin-like growth factors (IGFs) as autocrine/paracrine regulators of granulosa cell differentiation and growth: Studies with a neutralizing monoclonal antibody to IGF-I

    Energy Technology Data Exchange (ETDEWEB)

    Mondschein, J.S.; Canning, S.F.; Miller, D.Q.; Hammond, J.M. (Pennsylvania State Univ., Hershey (USA))

    1989-07-01

    Evidence that granulosa cells secrete and respond to insulin-like growth factors (IGFs) suggests, but does not prove, the importance of IGFs as intraovarian regulators. To further assess the role of these peptides in ovarian function, a neutralizing monoclonal antibody to IGF-I was employed to block the actions of IGFs in porcine follicular fluid and in granulosa cell-conditioned medium. In one series of experiments, granulosa cells from immature porcine follicles were cultured in medium containing porcine follicular fluid that had been charcoal-treated to remove steroids. As noted before, fluid from large follicles (LFF) stimulated progesterone production in a dose-dependent manner. The stimulatory effect of LFF (30% v/v) could be inhibited by greater than 50% by the anti-IGF monoclonal antibody. This inhibitory action was specific for the anti-IGF antibody and could be overcome by the addition of excess exogenous IGFs. In another series of experiments, granulosa cells were made dependent on endogenously produced IGFs by culturing them in a serum-free medium without exogenous growth factors. The effects of follicle-stimulating hormone (FSH), estradiol (E2), growth hormone (GH), and combinations thereof on progesterone production were inhibited by approximately 50% by the anti-IGF antibody. The effects of IGFs on indices of cell growth (judged by the criterion of being inhibited by the anti-IGF antibody) were less dramatic. A modest 18% increase in cell number was observed with FSH and E2 treatment in serum-free medium; this effect was virtually abolished by the antibody.

  18. Eco RV RFLP at the insulin-like growth factor I (IGF I) locus on chromosome 12

    Energy Technology Data Exchange (ETDEWEB)

    Schneid, H; Noguiez, P; Girard, F; Binoux, M; Le Bouc, Y [INSERM U 142, Paris (France)

    1988-09-26

    The human liver IFG I cDNA insert from the {lambda}TG03 (1) was subcloned in PGEM4 (pTG 3906). The 660 bp Eco RI-Bam HI fragment containing the 5{prime} untranslated, the coding and the 3{prime} untranslated region of the IGF IA gene (exons 1, 2, 3 and 5) was used. Eco RV digestion of genomic DNA and hybridization with the IGF I probe reveals invariant fragments of 20; 8, 7 and 5 kb and polymorphic fragments of 13 kb (allele 1) and 11, 5 kb (allele 2). The frequency of alleles was studied in 51 unrelated European Caucasians. Co-dominant segregation was observed in 2 European families (9 individuals). Hind III and Pvu II digestions show previous described RFLP. Allelic frequencies however were: Hind III (5, 2 kb allele = 0, 14 and 4, 9 kb allele = 0, 86) and Pvu II (5 kb allele = 0, 14 and 4, 7 kb allele = 0, 86). Hind III and Pvu II RFLPs are linked. Among the DNA of the 14 individuals, where Eco RV RFLP was found, only one exhibited Hind III and Pvu II RFLPs.

  19. Growth and Growth hormone - Insulin Like Growth Factor -I (GH-IGF-I) Axis in Chronic Anemias.

    Science.gov (United States)

    Soliman, Ashraf T; De Sanctis, Vincenzo; Yassin, Mohamed; Adel, Ashraf

    2017-04-28

    Anaemia is a global public health problem affecting both developing and developed countries with major consequences for human health as well as social and economic development. It occurs at all stages of the life cycle, but is more prevalent in pregnant women and young children. Iron deficiency anaemia (IDA) was considered to be among the most important contributing factors to the global burden of disease. Prolonged and/or chronic anemia has a negative effect on linear growth especially during the rapid phases (infancy and puberty). Additionally infants with chronic IDA have delayed cognitive, motor, and affective development that may be long-lasting. In view of the significant impact of chronic anemias on growth, pediatricians endocrinologists and hematologists should advocate primary prevention and screening for growth disturbance in these forms of anemias. The extent of the negative effect of different forms of chronic anemias on linear growth and its possible reversibilty is addressed in this review. The possible mechanisms that may impair growth in the different forms of anemias are addressed with special attention to their effect on the growth hormone (GH) - insulin like growth factor -I (IGF-I).

  20. Oral contraceptives increase insulin-like growth factor binding protein-1 concentration in women with polycystic ovarian disease.

    Science.gov (United States)

    Suikkari, A M; Tiitinen, A; Stenman, U H; Seppälä, M; Laatikainen, T

    1991-05-01

    Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. To investigate the effect of oral contraceptive (OC) pills, given for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in seven women with polycystic ovarian disease (PCOD) and in five healthy control subjects. Seven women with PCOD and five healthy control subjects. An oral glucose tolerance test (OGTT) was performed before and after treatment with OC. After treatment with OC, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentration increased in the women with PCOD as well as in the control subjects. The cumulative response of serum insulin to OGTT was larger in the women with PCOD than in the control subjects both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from basal level of 326 +/- 70 micrograms/L to 199 +/- 28 micrograms/L after treatment with OC in the women with PCOD, whereas no change was found in the control subjects (from 235 +/- 11 micrograms/L to 226 +/- 11 micrograms/L). Treatment with OC caused an increase of the mean basal IGFBP-1 concentration from 24 +/- 7 micrograms/L to 73 +/- 14 micrograms/L in the women with PCOD. This increase was constant during the OGTT. In the control subjects, treatment with OC did not result in any significant change in IGFBP-1 concentrations (from 44 +/- 11 micrograms/L to 61 +/- 9 micrograms/L). The combination of decreased total IGF-I concentration and increased IGFBP-1 concentration induced by OC may decrease ovarian androgen production in PCOD.

  1. 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...

  2. The potential role of IGF-I receptor mRNA in rats with diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    匡洪宇; 邹伟; 刘丹; 史榕荇; 程丽华; 殷慧清; 刘晓民

    2003-01-01

    Objective To evaluate the potential role of insulin-like growth factor-1 receptor mRNA(IGF-IR mRNA) in the onset and development of retinopathy in diabetic rats.Methods A diabetic model was duplicated in Wistar rats. The early changes in the retina were examined using light and transmission electron microscopy. Expression of IGF-IR mRNA was analyzed using in situ hybridization.Results Weak expression of IGF-IR mRNA(5%) was found in retinas of normal rats, but was significantly increased (15% and 18%) in the retinas of diabetic rats after 3 and 6 months of diabetes (P<0.01). In situ hybridization and morphological study demonstrated that there was a positive correlation between IGF-IR mRNA expression and retinal changes at various stages.Conclusion Increased IGF-IR mRNA might play an important role in the onset and development of diabetic retinopathy.

  3. Regulation of insulin-like growth factor (IGF) I receptor expression during muscle cell differentiation. Potential autocrine role of IGF-II.

    OpenAIRE

    Rosenthal, S M; Brunetti, A; Brown, E J; Mamula, P W; Goldfine, I D

    1991-01-01

    Muscle is an important target tissue for insulin-like growth factor (IGF) action. The presence of specific, high affinity IGF receptors, as well as the expression of IGF peptides and binding proteins by muscle suggest that a significant component of IGF action in this tissue is mediated through autocrine and/or paracrine mechanisms. To explore autocrine/paracrine action of IGFs in muscle, we studied the regulation of the IGF-I receptor and the expression of IGF peptides during differentiation...

  4. Clonage de l'IGF-I et de son récepteur chez le turbot (Psetta maxima

    Directory of Open Access Journals (Sweden)

    ELIES G.

    1998-07-01

    Full Text Available Les IGF, leurs récepteurs et leurs protéines de liaison constituent une famille moléculaire qui joue un rôle essentiel dans la régulation de la croissance et du développement. Nous nous sommes intéressés à la caractérisation moléculaire de l'IGF-l et de son récepteur (IGF-1R chez le turbot (Psetta maxima, un poisson plat téléostéen. Par RT-PCR, nous avons clone un ADNc codant pour les quatre domaines de l'IGF-l mature. La protéine présente 70 à 96 % d'identité avec les autres IGF-I de vertébrés. Le clonage de la séquence codante entière du récepteur a nécessité la construction d'une banque d'ADNc d'embryons de turbots. Le récepteur est organisé en domaines dont la taille et les caractéristiques sont semblables à celles des autres récepteurs aux IGF de type 1 décrits chez les mammifères et le poulet. La région catalytique est particulièrement conservée. Dans certains domaines, notamment dans la région C-terminale du précurseur, quelques différences qui pourraient avoir une importance fonctionnelle sont cependant observées. Enfin, par RT-PCR, nous avons mis en évidence une régulation ontogénique du statut de polyadénylation des ARNm IGF-1R.

  5. Maternal exposure to UV filters: associations with maternal thyroid hormones, IGF-I/IGFBP3 and birth outcomes.

    Science.gov (United States)

    Krause, M; Frederiksen, H; Sundberg, K; Jørgensen, F S; Jensen, L N; Nørgaard, P; Jørgensen, C; Ertberg, P; Petersen, J H; Feldt-Rasmussen, U; Juul, A; Drzewiecki, K T; Skakkebaek, N E; Andersson, A M

    2018-02-01

    Several chemical UV filters/absorbers ('UV filters' hereafter) have endocrine-disrupting properties in vitro and in vivo . Exposure to these chemicals, especially during prenatal development, is of concern. To examine maternal exposure to UV filters, associations with maternal thyroid hormone, with growth factor concentrations as well as to birth outcomes. Prospective study of 183 pregnant women with 2nd trimester serum and urine samples available. Maternal concentrations of the chemical UV filters benzophenone-1 (BP-1) and benzophenone-3 (BP-3) in urine and 4-hydroxy-benzophenone (4-HBP) in serum were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relationships between 2nd trimester maternal concentrations of the three chemical UV filters and maternal serum concentrations of thyroid hormones and growth factors, as well as birth outcomes (weight, height, and head and abdominal circumferences) were examined. Positive associations between maternal serum concentrations of 4-HBP and triiodothyronine (T 3 ), thyroxine (T 4 ), insulin-like growth factor I (IGF-I) and its binding protein IGFBP3 were observed in mothers carrying male fetuses. Male infants of mothers in the middle 4-HBP exposure group had statistically significantly lower weight and shorter head and abdominal circumferences at birth compared to the low exposure group. Widespread exposure of pregnant women to chemical UV filters and the possible impact on maternal thyroid hormones and growth factors, and on fetal growth, calls for further studies on possible long-term consequences of the exposure to UV filters on fetal development and children's health. © 2018 The authors.

  6. Biochemical and hormonal changes induced by one week of administration of rIGF-I to patients with Laron type dwarfism

    DEFF Research Database (Denmark)

    Laron, Z; Klinger, B; Jensen, L T

    1991-01-01

    ) aged 3 1/2 to 37 3/4 years were submitted to seven daily s.c. injections of recombinant IGF-I in doses of 120 or 150 micrograms/kg/day. MEASUREMENTS: Blood samples were drawn before, after three and seven injections, and one week after stopping the trial. RESULTS: The main biochemical and hormonal...... changes registered were (mean +/- SD): a marked rise in serum type III procollagen (PIIINP) from 4.2 +/- 0.9 to 7.3 +/- 2 micrograms/l (P less than 0.0003) and decrease in the following blood components: plasma hGH from 32.51 +/- 43.77 to 4.02 +/- 2.48 mU/l (P less than 0.001), serum cholesterol from 5...... of these effects were transitory, and were found after 3 days therapy but afterwards decreased (insulin, cholesterol and liver tests), others persisted throughout the whole treatment period (hGH, PIINP). CONCLUSIONS: IGF-I mimics the biochemical and hormonal changes described after administration of h...

  7. Niveles séricos de IGF-I e IGFBP-3 en adolescentes embarazadas provenientes de un sector socioeconómico de bajos ingresos

    Directory of Open Access Journals (Sweden)

    Stella Carrasco Rodríguez

    2001-12-01

    Full Text Available El eje de la hormona de crecimiento (GH/factor de crecimiento similar a la insulina tipo-l (IGF-I participa en el crecimiento durantela vida postnatal y fetal y se encuentra regulado por la nutrición. Sin embargo, muy pocos estudios se han adelantado con el fin de comprender los efectos de la mala nutrición sobre dicho eje durante el embarazo en la adolescencia. En este estudio se determinaron los niveles séricos del IGF-I y de IGFBP-3 en un grupo (n=62 de adolescentes en el segundo trimestre de embarazo y provenientes de un estrato pobre de la ciudad de Bogotá y se compararon con los de un grupo (n=36 de adolescentes del mismo estrato. Como referencia se tomaron los valores obtenidos en un grupo (n=20 de adolescentes de un estrato de clase media de la misma ciudad. Se encontró que las adolescentes del estrato pobre presentaban un crecimiento por debajo del percentil 3 con talla y peso significativamente (p

  8. Short- and long-term metabolic effects of recombinant human IGF-I treatment in patients with severe insulin resistance and diabetes mellitus

    DEFF Research Database (Denmark)

    Vestergaard, H; Rossen, M; Urhammer, S A

    1997-01-01

    In patients suffering from the genetic syndromes of severe insulin resistance it appears that diabetes develops when the adaptive hypersecretion of insulin fails and often these forms of diabetes will be insensitive to insulin treatment. The objective of the present study was to examine......-resistant diabetes mellitus and (b) during a long-term (10 weeks) period with rhIGF-I given once a day in a low dose (40 micrograms/kg body weight) in three of the four patients. Two siblings had known mutations in the tyrosine kinase domain of the insulin receptor and a deletion of exon 17 in part of their insulin......-50%), proinsulin (40-50%) and C-peptide (10-65%) and an improvement in glycaemic control as evaluated by decreased glycosylated haemoglobin and serum fructosamine. During the long-term study period blood glucose-lowering effects of rhIGF-I were seen after 2 weeks of treatment and fasting plasma glucose and serum...

  9. Regional level approach for increasing energy efficiency

    International Nuclear Information System (INIS)

    Viholainen, Juha; Luoranen, Mika; Väisänen, Sanni; Niskanen, Antti; Horttanainen, Mika; Soukka, Risto

    2016-01-01

    Highlights: • Comprehensive snapshot of regional energy system for decision makers. • Connecting regional sustainability targets and energy planning. • Involving local players in energy planning. - Abstract: Actions for increasing the renewable share in the energy supply and improving both production and end-use energy efficiency are often built into the regional level sustainability targets. Because of this, many local stakeholders such as local governments, energy producers and distributors, industry, and public and private sector operators require information on the current state and development aspects of the regional energy efficiency. The drawback is that an overall view on the focal energy system operators, their energy interests, and future energy service needs in the region is often not available for the stakeholders. To support the local energy planning and management of the regional energy services, an approach for increasing the regional energy efficiency is being introduced. The presented approach can be seen as a solid framework for gathering the required data for energy efficiency analysis and also evaluating the energy system development, planned improvement actions, and the required energy services at the region. This study defines the theoretical structure of the energy efficiency approach and the required steps for revealing such energy system improvement actions that support the regional energy plan. To demonstrate the use of the approach, a case study of a Finnish small-town of Lohja is presented. In the case example, possible actions linked to the regional energy targets were evaluated with energy efficiency analysis. The results of the case example are system specific, but the conducted study can be seen as a justified example of generating easily attainable and transparent information on the impacts of different improvement actions on the regional energy system.

  10. Differential roles of MAPK-Erk1/2 and MAPK-p38 in insulin or insulin-like growth factor-I (IGF-I) signaling pathways for progesterone production in human ovarian cells.

    Science.gov (United States)

    Seto-Young, D; Avtanski, D; Varadinova, M; Park, A; Suwandhi, P; Leiser, A; Parikh, G; Poretsky, L

    2011-06-01

    Insulin and insulin like-growth factor-I (IGF-I) participate in the regulation of ovarian steroidogenesis. In insulin resistant states ovaries remain sensitive to insulin because insulin can activate alternative signaling pathways, such as phosphatidylinositol-3-kinase (PI-3 kinase) and mitogen-activated protein-kinase (MAPK) pathways, as well as insulin receptors and type 1 IGF receptors. We investigated the roles of MAPK-Erk1/2 and MAPK-p38 in insulin and IGF-I signaling pathways for progesterone production in human ovarian cells. Human ovarian cells were cultured in tissue culture medium in the presence of varying concentrations of insulin or IGF-I, with or without PD98059, a specific MAPK-Erk1/2 inhibitor, with or without SB203580, a specific MAPK-p38 inhibitor or with or without a specific PI-3-kinase inhibitor LY294002. Progesterone concentrations were measured using radioimmunoassay. PD98059 alone stimulated progesterone production in a dose-dependent manner by up to 65% (pprogesterone production by 13-18% (pprogesterone production by 17-20% (pprogesterone production by 20-30% (pprogesterone production by 40-60% (pprogesterone synthesis while SB203580 abolished insulin-induced progesterone production. Either PD98059 or SB203580 abolished IGF-I-induced progesterone production. Both MAPK-Erk1/2 and MAPK-p38 participate in IGF-I-induced signaling pathways for progesterone production, while insulin-induced progesterone production requires MAPK-p38, but not MAPK-Erk1/2. These studies provide further evidence for divergence of insulin and IGF-I signaling pathways for human ovarian cell steroidogenesis. © Georg Thieme Verlag KG Stuttgart · New York.

  11. 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....

  12. Increased abundance of insulin/insulin-like growth factor-I hybrid receptors in skeletal muscle of obese subjects is correlated with in vivo insulin sensitivity.

    Science.gov (United States)

    Federici, M; Porzio, O; Lauro, D; Borboni, P; Giovannone, B; Zucaro, L; Hribal, M L; Sesti, G

    1998-08-01

    We reported that in noninsulin-dependent diabetes melitus (NIDDM) patients expression of insulin/insulin-like growth factor I (IGF-I) hybrid receptors is increased in insulin target tissues. Whether this is a defect associated with NIDDM or represents a generalized abnormality associated with insulin resistant states is still unsettled. To address this, we applied a microwell-based immunoassay to measure abundance of insulin receptors, type 1 IGF receptors, and hybrid receptors in muscle of eight normal and eight obese subjects. Maximal insulin binding to insulin receptors was lower in obese than in control subjects (B/T = 1.8 +/- 0.20 and 2.6 +/- 0.30; P < 0.03, respectively) and was negatively correlated with insulinemia (r = -0.60; P < 0.01). Maximal IGF-I binding to type 1 IGF receptors was higher in obese than in controls (B/T = 1.9 +/- 0.20 and 0.86 +/- 0.10; P < 0.0001, respectively) and was negatively correlated with plasma IGF-I levels (r = -0.69; P < 0.003). Hybrid receptor abundance was higher in obese than in normal subjects (B/T = 1.21 +/- 0.14 and 0.44 +/- 0.06; P < 0.0003, respectively) and was negatively correlated with insulin binding (r = -0.60; P < 0.01) and positively correlated with IGF-I binding (r = 0.92; P < 0.0001). Increased abundance of hybrids was correlated with insulinemia (r = 0.70; P < 0.002) and body mass index (r = 0.71; P < 0.0019), whereas it was negatively correlated with in vivo insulin sensitivity measured by ITT (r = -0.67; P < 0.016). These results indicate that downregulation of insulin receptors or upregulation of type 1 IGF receptors because of changes in plasma insulin and IGF-I levels may result in modifications in hybrid receptor abundance.

  13. Association between insulin-like growth factor I (IGF-I microsatellite polymorphisms and important economic traits in pigs Associação entre polimorfismos no marcador microssatélite do gene do fator de crescimento semelhante à insulina I (IGF-I com características de interesse econômico em suínos

    Directory of Open Access Journals (Sweden)

    Danielle Assis de Faria

    2009-02-01

    Full Text Available This study investigated the association between IGF-I microsatellite marker in an F2 population (N=459 generated by mating of native boars to Brazilian commercial sows with performance, carcass cut, and meat quality traits. Association analyses were carried out using a statistical model that included genotype, sex, and group as fixed effects and sire as random effect. The IGF-I genotypes were significantly associated with different quantitative traits and these results corroborate with previous QTL analyses obtained for this chromosome region in swine. Additive and dominance effects, as well as a genotype-sex interaction, were estimated and discussed in the text. According to the results obtained, this marker is suitable for QTL search in the genotyped population.Investigou-se neste trabalho a associação entre o marcador microssatélite IGF-I em uma população F2 (N=459 gerada pelo acasalamento entre suínos nativos brasileiros e fêmeas comerciais com características de desempenho, cortes de carcaça e qualidade da carne. A análise de associação foi feita por meio de um modelo que incluiu genótipo, sexo e grupo como efeitos fixos e pais como efeito aleatório. Os genótipos do IGF-I apresentaram associação significativa com nove características quantitativas, resultados que corroboram análises prévias de QTL obtidas para essa região cromossômica em suínos. Efeitos aditivos de dominância, assim como a interação genótipo × sexo, foram estimados e estão descritos neste trabalho. De acordo com os resultados obtidos, este marcador será útil nas análises de QTL na população analisada.

  14. Do building wakes increase ground level concentrations?

    International Nuclear Information System (INIS)

    Taylor, T.J.; Melbourne, W.H.

    1996-01-01

    As part of the EPRI Plume Rise and Downwash Project to develop and evaluate new mathematical algorithms representing plume rise and downwash, physical model studies were performed on the plume dispersion from Combustion Turbine Unit 4, (CT 4), at the Jersey Central Power and Light Sayreville Generating Station, Sayreville, New Jersey. Studies were performed both in neutral and stably stratified model atmospheric boundary layer conditions with the primary objective being to determine the behavior of the combustion turbine plume under high and low ambient wind speed conditions within the wake region produced by the combustion turbine itself. Field measurements were also performed at the site and to this end a base case wind direction of β = 335 degree was chosen for both the field and model studies in an attempt to minimize the effects of other building wakes on the plume. This paper looks at the flow and dispersion characteristics with and without these large structures in the model in an attempt to explain why the differences in concentration levels occurred

  15. IGF-I generation test in prepubertal children with Noonan syndrome due to mutations in the PTPN11 gene.

    Science.gov (United States)

    Bertelloni, Silvano; Baroncelli, Giampiero I; Dati, Eleonora; Ghione, Silvia; Baldinotti, Fulvia; Toschi, Benedetta; Simi, Paolo

    2013-01-01

    Short stature represents one of the main features of children with Noonan syndrome. The reason for impaired growth remains largely unknown. To assess GH and IGF1 secretion in children with Noonan syndrome. 12 prepubertal children with Noonan syndrome due to mutations in the PTPN11 gene [7 males, 6 females; median age, years: 8.6 (range 5.1-13.4)] were studied; 12 prepubertal children with short stature (SS) [7 males, 5 females; median age, years: 8.1 (range 4.8-13.1)] served as the control group. GH secretion after arginine stimulation test; IGF1 generation test by measurement of IGF1 levels before and after recombinant GH (rGH) administration (0.05 mg/kg/day for 4 days). Baseline and stimulated peak values of GH were not significantly different between the two groups. At +120 minutes, GH levels remained significantly higher (p = 0.0121) in comparison with baseline values in children with Noonan syndrome. Baseline IGFI levels in patients and in SS controls were not significantly different, in contrast to values after the rGH generation test [205 ng/mL (interquartiles 138.2-252.5 ng/mL) and 284.5 ng/mL (interquartiles 172-476 ng/mL), respectively; p = 0.0248]. IGF1 values were significantly related to height (baseline: r = 773, p = 0.0320; peak: r = 0.591, p = 0.0428) in children with Noonan syndrome. Blunted increase of IGF1 after the rGH generation test was present in children with Noonan syndrome due to mutations in the PTPN11 gene in comparison with SS children. This finding may be due to partial GH resistance in the former likely related to altered Ras-MAPK signaling pathway.

  16. Short-term strength training and the expression of myostatin and IGF-I isoforms in rat muscle and tendon

    DEFF Research Database (Denmark)

    Heinemeier, K M; Olesen, J L; Schjerling, P

    2007-01-01

    In skeletal muscle, an increased expression of insulin like growth factor-I isoforms IGF-IEa and mechano-growth factor (MGF) combined with downregulation of myostatin is thought to be essential for training-induced hypertrophy. However, the specific effects of different contraction types on regul......In skeletal muscle, an increased expression of insulin like growth factor-I isoforms IGF-IEa and mechano-growth factor (MGF) combined with downregulation of myostatin is thought to be essential for training-induced hypertrophy. However, the specific effects of different contraction types...... on regulation of these factors in muscle are still unclear, and in tendon the functions of myostatin, IGF-IEa, and MGF in relation to training are unknown. Female Sprague-Dawley rats were subjected to 4 days of concentric, eccentric, or isometric training (n = 7-9 per group) of the medial gastrocnemius......, by stimulation of the sciatic nerve during general anesthesia. mRNA levels for myostatin, IGF-IEa, and MGF in muscle and Achilles' tendon were measured by real-time RT-PCR. Muscle myostatin mRNA decreased in response to all types of training (2- to 8-fold) (P

  17. Clinical ssignificance of determination of changes of serum 1GF-1 CA125 and TSGF levels after operation in patients with ovarian cancer

    International Nuclear Information System (INIS)

    Liu Suming

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IGF-I, CA125 and TSGF levels after operation in patients with ovarian cancer. Methods: Serum IGF-I, CA125 (with RIA) and TSGF (with bio-chemistry) levels were determined in 34 patients with ovarian cancer both before and after operation as well as in 35 controls. Results: Before operation the serum IGF-I, CA125 and TSGF levels were significantly higher in the patients than those in the controls (P 0.05). Conclusion: Detection of serum IGF-I, CA125 and TSGF levels after operation might be of progno stic importance in patients with ovarian cancer. (authors)

  18. [EFECTOS NEUROENDOCRINOS DE INSULINA, IGF-I Y LEPTINA SOBRE LA SECRECIÓN DE HORMONA LIBERADORA DE GONADOTROPINAS (GnRH

    Directory of Open Access Journals (Sweden)

    Ana Maria Rosales-Torres

    2011-10-01

    Full Text Available El balance energético del individuo determina en gran medida su eficiencia reproductiva. Bajo condiciones de balance negativo de energía, en la mayoría de los mamíferos, hay una reducción en la síntesis de hormona liberadora de gonadotropinas (GnRH, lo cual disminuye la actividad del eje hipotálamo-hipófisis-gónadas. Cuando el balance energético es revertido, el hipotálamo puede monitorear este cambio y restablecer la secreción de GnRH. La Insulina, el Factor de Crecimiento similar a la Insulina I (IGF-I y Leptina parecen ser los principales mensajeros que informan al hipotálamo sobre el estado energético del animal puesto que las concentraciones periféricas de estas hormonas en situaciones energéticas negativas o positivas, se han asociado con los cambios en la secreción de GnRH. En la presente revisión se muestra como IGF-I actúa directamente sobre neuronas secretoras de GnRH, afectando su síntesis, en tanto que insulina y leptina actúan sobre neuronas en el núcleo arcuato, las cuales hacen sinapsis con neuronas GnRH en el área preóptica medial. Sobre neuronas productoras de neuropéptido Y (NPY insulina y leptina reducen su expresión y por lo tanto el efecto negativo del NPY sobre neuronas GnRH. En cambio insulina y leptina estimulan la síntesis de péptido similar a la galanina (GLAP y propiomelanocortina (POMC. Tanto GALP como los metabolitos de POMC (hormona estimulante de melanocitos principalmente incrementan la síntesis de GnRH. Finalmente, la leptina, incrementa la expresión de kispeptina en neuronas del núcleo ARC. Kispeptina por su parte también tiene un efecto positivo sobre la síntesis y secreción de GnRH.

  19. Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.

    Science.gov (United States)

    Young, Lindsay R; Kurzer, Mindy S; Thomas, William; Redmon, J Bruce; Raatz, Susan K

    2013-07-01

    The insulin-like growth factor pathway plays a central role in the normal and abnormal growth of tissues; however, nutritional determinants of insulin-like growth factor I (IGF-I) and its binding proteins in healthy individuals are not well defined. Three test diets-high-fat diet (40% energy as fat), low-fat diet (LF; 20% energy as fat), and a diet with low fat and high omega-3 fatty acid (LFn3; 23% energy as fat)--were tested in a randomized crossover designed controlled feeding trial in healthy postmenopausal women. Plasma IGF-I, IGF binding protein-3 (IGFBP-3), insulin, glucose, and ratio of IGF-I/IGFBP-3 concentrations were measured in response to diets. Insulin sensitivity was calculated using the homeostatic model assessment of insulin resistance We hypothesized that IGF-I, insulin, and glucose concentrations would decrease and IGFBP-3 concentration would increase in response to the low-fat diets. Eight weeks of the LFn3 diet increased circulating IGF-I (P diet increased IGFBP-3 (P = .04), resulting in trends toward an increased IGF-I/IGFBP-3 ratio with the LFn3 diet and a decreased IGF-I/IGFBP-3 ratio with the LF diet (P = .13 for both comparisons). No statistically significant differences were detected between treatments at baseline or 8 weeks for IGF-1, IGFBP-3, or the ratio of IGF-1/IGFBP-3. Insulin, glucose, and the homeostatic model assessment of insulin resistance were not altered by the interventions. Low-fat diet with high n-3 fatty acids may increase circulating IGF-I concentrations without adversely affecting insulin sensitivity in healthy individuals. Published by Elsevier Inc.

  20. Pre-treatment growth and IGF-I deficiency as main predictors of response to growth hormone therapy in neural models

    Directory of Open Access Journals (Sweden)

    Urszula Smyczyn´ska

    2018-01-01

    Full Text Available Mathematical models have been applied in prediction of growth hormone treatment effectiveness in children since the end of 1990s. Usually they were multiple linear regression models; however, there are also examples derived by empirical non-linear methods. Proposed solution consists in application of machine learning technique – artificial neural networks – to analyse this problem. This new methodology, contrary to previous ones, allows detection of both linear and non-linear dependencies without assuming their character a priori. The aims of this work included: development of models predicting separately growth during 1st year of treatment and final height as well as identification of important predictors and in-depth analysis of their influence on treatment’s effectiveness. The models were derived on the basis of clinical data of 272 patients treated for at least 1 year, 133 of whom have already attained final height. Starting from models containing 17 and 20 potential predictors, respectively for 1st year and final height model, we were able to reduce their number to 9 and 10. Basing on the final models, IGF-I concentration and earlier growth were indicated as belonging to most important predictors of response to GH therapy, while results of GH secretion tests were automatically excluded as insignificant. Moreover, majority of the dependencies were observed to be non-linear, thus using neural networks seems to be reasonable approach despite it being more complex than previously applied methods.

  1. Effects of Moderate Aerobic Exercise Combined with Caloric Restriction on Circulating Estrogens and IGF-I in Premenopausal Women

    National Research Council Canada - National Science Library

    Williams, Nancy

    2002-01-01

    ...) to support her development as a breast cancer researcher, and to conduct a study to test whether a program of moderate aerobic exercise that is combined with a moderate level of dietary restriction...

  2. Minireview: Mechano-Growth Factor: A Putative Product of IGF-I Gene Expression Involved in Tissue Repair and Regeneration

    Science.gov (United States)

    2010-03-01

    Ec in humans) has been the topic of several research studies, particularly in skeletal muscle. It has been proposed that age-related sarcopenia results...performed in elderly men (74 yr old), increases in IGF-IEc mRNA were seen after 5 and 12 wk GH administration or resistance training compared with the...increased after mechanical stress is not entirely clear. In elderly men, IGF-IEc (MGF) mRNA is increased after long-term exer- cise and GH administration but

  3. Exercise-dependent IGF-I, IGFBPs, and type I collagen changes in human peritendinous connective tissue determined by microdialysis

    DEFF Research Database (Denmark)

    Olesen, Jens L; Heinemeier, Katja M; Gemmer, Carsten

    2007-01-01

    Microdialysis studies indicate that mechanical loading of human tendon during exercise elevates type I collagen production in tendon. However, the possibility that the insertion of microdialysis fibers per se may increase the local collagen production due to trauma has not been explored. Insulin......-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen] were measured by microdialysis in peritendinous tissue of the human Achilles tendon in an exercise group (performing a 36-km run, n = 6) and a control group (no intervention, n = 6). An increase in local PICP concentration was seen in both...... and exercise groups after 48 h (P human peritendinous tissue in response to prolonged mechanical loading with part of the increase due to trauma from the sampling...

  4. Effects of Moderate Aerobic Exercise Combined with Caloric Restriction on Circulating Estrogens and IGF-I in Premenopausal Women

    Science.gov (United States)

    2002-10-01

    monkeys during strenuous exercise training: rapid transition to exercise - induced amenorrhea £Mrfocnnotogy 142:2381-2389,2001 Williams NI, DL...reversal of exercise - induced amenorrhea : Temporal correlation with plasma T3 levels, (presented at the 76th Proceedings of the National Endocrine Society...changes during long-term training, and no studies have attempted to differentiate between the exercise - induced changes in ovarian vereus adipose sources

  5. Effects of Moderate Aerobic Exercise Combined With Calorie Restriction on Circulating Estrogens and IGF-I in Premenopausal Women

    Science.gov (United States)

    2004-10-01

    rapid transition to exercise - induced amenorrhea Endocrinology 142: 2381-2389, 2001 Williams N.I., DL Helmreich DL, DB Parfitt, Caston-Balderrama AL...N.I., A.L. Caston, and J.L. Cameron. Induction and reversal of exercise - induced amenorrhea : Temporal correlation with plasma T3 levels, (presented at...deficit required for these changes during long-term training, and no studies have attempted to differentiate between the exercise - induced changes in

  6. Effects of long term feeding diets differing in protein source and pre-slaughter starvation on biometry, qualitative traits and liver IGF-I expression in large rainbow trout

    Directory of Open Access Journals (Sweden)

    Emilio Tibaldi

    2010-01-01

    Full Text Available The effects of feeding two complete extruded diets differing in protein source (fish meal-FM vs. vegetable proteins-VP over 30 weeks and subsequent 30 days of starvation on biometry, fillet composition and liver IGF-I mRNA were studied in large rainbow trout. At the end of the feeding period, the dietary protein source little affected major biometry traits, dressing out yields and overall adiposity (P>0.05 but fish given the VP diet resulted in higher content of PUFA n-6 fatty acids in mus- cle (0.46 vs. 0.22 g/100g fillet, P0.05 and of all fatty acids in fillet (P<0.05, except DHA. Liver IGF-I mRNA content was little affected by the test diet and starvation.

  7. Liver-Derived Insulin-Like Growth Factor-I is Involved in the Regulation of Blood Pressure in Mice

    DEFF Research Database (Denmark)

    Tivesten, Asa; Bollano, Entela; Andersson, Irene

    2002-01-01

    IGF-I has been suggested to be of importance for cardiovascular structure and function, but the relative role of locally produced and liver-derived endocrine IGF-I remains unclear. Using the Cre-LoxP recombination system, we have previously created transgenic mice with a liver-specific, inducible...... IGF-I knockout (LI-IGF-I-/-). To examine the role of liver-derived IGF-I in cardiovascular physiology, liver-derived IGF-I was inactivated at 4 wk of age, resulting in a 79% reduction of serum IGF-I levels. At 4 months of age, systolic blood pressure (BP) was increased in LI-IGF-I-/- mice...... to endothelial dysfunction associated with increased expression of endothelin-1 and impaired vasorelaxation of resistance vessels. In conclusion, our findings suggest that liver-derived IGF-I is involved in the regulation of BP in mice....

  8. Effect of recombinant human insulin-like growth factor-I on progression of ALS. A placebo-controlled study. The North America ALS/IGF-I Study Group.

    Science.gov (United States)

    Lai, E C; Felice, K J; Festoff, B W; Gawel, M J; Gelinas, D F; Kratz, R; Murphy, M F; Natter, H M; Norris, F H; Rudnicki, S A

    1997-12-01

    The objective of this study was to investigate the safety and efficacy of recombinant human insulinlike growth factor-I (rhIGF-I) in the treatment of sporadic ALS. A double-blind, placebo-controlled, randomized study of 266 patients was conducted at eight centers in North America. Placebo or rhIGF-I (0.05 mg/kg/day or 0.10 mg/kg/day) was administered for 9 months. The primary outcome measure was disease symptom progression, assessed by the rate of change (per patient slope) in the Appel ALS rating scale total score. The Sickness Impact Profile (SIP), a patient-perceived, health-related quality of life assessment, was a secondary outcome variable. Progression of functional impairment in patients receiving high-dose (0.10 mg/kg/day) rhIGF-I was 26% slower than in patients receiving placebo (p = 0.01). The high-dose treatment group was less likely to terminate the study due to protocol-defined markers of disease symptom progression, and members in this group exhibited a slower decline in quality of life, as assessed by the SIP. Patients receiving 0.05 mg/kg/day of rhIGF-I exhibited trends similar to those associated with high-dose treatment, suggesting a dose-dependent response. The incidence of clinically significant adverse experiences was comparable among the three treatment groups. Recombinant human insulin-like growth factor-I slowed the progression of functional impairment and the decline in health-related quality of life in patients with ALS with no medically important adverse effects.

  9. Effects of growth hormone (GH) administration on homocyst(e)ine levels in men with GH deficiency: a randomized controlled trial.

    Science.gov (United States)

    Sesmilo, G; Biller, B M; Llevadot, J; Hayden, D; Hanson, G; Rifai, N; Klibanski, A

    2001-04-01

    GH deficiency is associated with increased cardiovascular mortality and early manifestations of atherosclerosis. Elevated serum homocyst(e)ine levels have been found to be associated with increased cardiovascular risk. The effect of GH replacement on homocyst(e)ine has not been investigated to date. We evaluated the effect of GH replacement on fasting homocyst(e)inemia in a group of men with adult-onset GH deficiency in a randomized, single blind, placebo-controlled trial. Forty men with adult-onset GH deficiency were randomized to GH or placebo for 18 months, with dose adjustments made according to serum insulin-like growth factor I (IGF-I) levels. Fasting serum homocyst(e)ine, folate, vitamin B12, and total T(3) levels were determined at baseline and 6 and 18 months. Anthropometry, IGF-I levels, insulin, and glucose were measured at 1, 3, 6, 12, and 18 months. Nutritional assessment, body composition, total T(4), thyroid hormone binding index, and free T(4) index were assessed every 6 months. Homocyst(e)ine decreased in the GH-treated group compared with that in the placebo group (net difference, -1.2 +/- 0.6 micromol/L; confidence interval, -2.4, -0.02 micromol/L; P = 0.047). Homocyst(e)ine at baseline was negatively correlated with plasma levels of folate (r = -0.41; P = 0.0087). Total T(3) increased in the GH-treated group vs. that in the placebo group (net difference, 0.17 +/- 0.046 ng/dL; confidence interval, 0.071, 0.26 nmol/L; P = 0.0012). Folate and vitamin B12 levels did not significantly change between groups. Changes in homocyst(e)ine were negatively correlated with changes in IGF-I. For each 1 nmol/L increase in IGF-I, homocyst(e)ine decreased by 0.04 +/- 0.02 micromol/L (P = 0.029). In contrast, changes in homocyst(e)ine did not correlate with changes in folate, vitamin B12, total T(3), C-reactive protein, interleukin-6, or insulin levels. This study shows that GH replacement decreases fasting homocyst(e)ine levels compared with placebo. This may be

  10. Changes in calcitropic hormones, bone markers and insulin-like growth factor I (IGF-I) during pregnancy and postpartum

    DEFF Research Database (Denmark)

    Møller, U K; við Streym, Susanna; Mosekilde, L

    2013-01-01

    physiological changes in calcium homeostasis, calcitropic hormones and bone metabolism during pregnancy and lactation. METHODS: We studied 153 women planning pregnancy (n=92 conceived) and 52 non-pregnant, age-matched female controls. Samples were collected prior to pregnancy, once each trimester and 2, 16...... and 36 weeks postpartum. The controls were followed in parallel. RESULTS: P-estradiol (E2), prolactin and 1,25-dihydroxyvitamin D (1,25(OH)2D) increased (p... resorption and formation rose and fall, respectively (p

  11. Potassium Bicarbonate Attenuates the Urinary Nitrogen Excretion That Accompanies an Increase in Dietary Protein and May Promote Calcium Absorption

    Science.gov (United States)

    Ceglia, Lisa; Harris, Susan S.; Abrams, Steven A.; Rasmussen, Helen M.; Dallal, Gerard E.; Dawson-Hughes, Bess

    2009-01-01

    Context: Protein is an essential component of muscle and bone. However, the acidic byproducts of protein metabolism may have a negative impact on the musculoskeletal system, particularly in older individuals with declining renal function. Objective: We sought to determine whether adding an alkaline salt, potassium bicarbonate (KHCO3), allows protein to have a more favorable net impact on intermediary indices of muscle and bone conservation than it does in the usual acidic environment. Design: We conducted a 41-d randomized, placebo-controlled, double-blind study of KHCO3 or placebo with a 16-d phase-in and two successive 10-d metabolic diets containing low (0.5 g/kg) or high (1.5 g/kg) protein in random order with a 5-d washout between diets. Setting: The study was conducted in a metabolic research unit. Participants: Nineteen healthy subjects ages 54–82 yr participated. Intervention: KHCO3 (up to 90 mmol/d) or placebo was administered for 41 d. Main Outcome Measures: We measured 24-h urinary nitrogen excretion, IGF-I, 24-h urinary calcium excretion, and fractional calcium absorption. Results: KHCO3 reduced the rise in urinary nitrogen excretion that accompanied an increase in protein intake (P = 0.015) and was associated with higher IGF-I levels on the low-protein diet (P = 0.027) with a similar trend on the high-protein diet (P = 0.050). KHCO3 was also associated with higher fractional calcium absorption on the low-protein diet (P = 0.041) with a similar trend on the high-protein diet (P = 0.064). Conclusions: In older adults, KHCO3 attenuates the protein-induced rise in urinary nitrogen excretion, and this may be mediated by IGF-I. KHCO3 may also promote calcium absorption independent of the dietary protein content. PMID:19050051

  12. Hypothalamic neurogenesis persists in the aging brain and is controlled by energy-sensing IGF-I pathway.

    Science.gov (United States)

    Chaker, Zayna; George, Caroline; Petrovska, Marija; Caron, Jean-Baptiste; Lacube, Philippe; Caillé, Isabelle; Holzenberger, Martin

    2016-05-01

    Hypothalamic tanycytes are specialized glial cells lining the third ventricle. They are recently identified as adult stem and/or progenitor cells, able to self-renew and give rise to new neurons postnatally. However, the long-term neurogenic potential of tanycytes and the pathways regulating lifelong cell replacement in the adult hypothalamus are largely unexplored. Using inducible nestin-CreER(T2) for conditional mutagenesis, we performed lineage tracing of adult hypothalamic stem and/or progenitor cells (HySC) and demonstrated that new neurons continue to be born throughout adult life. This neurogenesis was targeted to numerous hypothalamic nuclei and produced different types of neurons in the dorsal periventricular regions. Some adult-born neurons integrated the median eminence and arcuate nucleus during aging and produced growth hormone releasing hormone. We showed that adult hypothalamic neurogenesis was tightly controlled by insulin-like growth factors (IGF). Knockout of IGF-1 receptor from hypothalamic stem and/or progenitor cells increased neuronal production and enhanced α-tanycyte self-renewal, preserving this stem cell-like population from age-related attrition. Our data indicate that adult hypothalamus retains the capacity of cell renewal, and thus, a substantial degree of structural plasticity throughout lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The growth hormone-insulin-like growth factor axis in glycogen storage disease type 1: evidence of different growth patterns and insulin-like growth factor levels in patients with glycogen storage disease type 1a and 1b.

    Science.gov (United States)

    Melis, Daniela; Pivonello, Rosario; Parenti, Giancarlo; Della Casa, Roberto; Salerno, Mariacarolina; Balivo, Francesca; Piccolo, Pasquale; Di Somma, Carolina; Colao, Annamaria; Andria, Generoso

    2010-04-01

    To investigate the growth hormone (GH)-insulin-like growth factor (IGF) system in patients with glycogen storage disease type 1 (GSD1). This was a prospective, case-control study. Ten patients with GSD1a and 7 patients with GSD1b who were given dietary treatment and 34 sex-, age-, body mass index-, and pubertal stage-matched control subjects entered the study. Auxological parameters were correlated with circulating GH, either at basal or after growth hormone releasing hormone plus arginine test, insulin-like growth factors (IGF-I and IGF-II), and anti-pituitary antibodies (APA). Short stature was detected in 10.0% of patients with GSD1a, 42.9% of patients with GSD1b (P = .02), and none of the control subjects. Serum IGF-I levels were lower in patients with GSD1b (P = .0001). An impaired GH secretion was found in 40% of patients with GSD1a (P = .008), 57.1% of patients with GSD1b (P = .006), and none of the control subjects. Short stature was demonstrated in 3 of 4 patients with GSD1b and GH deficiency. The prevalence of APA was significantly higher in patients with GSD1b than in patients with GSD1a (P = .02) and control subjects (P = .03). The GH response to the provocative test inversely correlated with the presence of APA (P = .003). Compared with levels in control subjects, serum IGF-II and insulin levels were higher in both groups of patients, in whom IGF-II levels directly correlated with height SD scores (P = .003). Patients with GSD1a have an impaired GH secretion associated with reference range serum IGF-I levels and normal stature, whereas in patients with GSD1b, the impaired GH secretion, probably because of the presence of APA, was associated with reduced IGF-I levels and increased prevalence of short stature. The increased IGF-II levels, probably caused by increased insulin levels, in patients with GSD1 are presumably responsible for the improved growth pattern observed in patients receiving strict dietary treatment. Copyright 2010 Mosby, Inc. All

  14. Decreased total antioxidant levels and increased oxidative stress in ...

    African Journals Online (AJOL)

    21–25 ... Decreased total antioxidant levels and increased oxidative stress in South ... antioxidant-rich diet and lifestyle changes in T2DM patients would help to avert the .... glycation of proteins and the formation of advanced glycosylation.

  15. Dietary guanidinoacetic acid increases brain creatine levels in healthy men

    DEFF Research Database (Denmark)

    Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik

    2017-01-01

    OBJECTIVE: Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA......, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity. RESULTS: Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation......, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8...

  16. Niacin treatment increases plasma homocyst(e)ine levels.

    Science.gov (United States)

    Garg, R; Malinow, M; Pettinger, M; Upson, B; Hunninghake, D

    1999-12-01

    Studies have reported high levels of plasma homocyst(e)ine as an independent risk factor for arterial occlusive disease. The Cholesterol Lowering Atherosclerosis Study reported an increase in plasma homocyst(e)ine levels in patients receiving both colestipol and niacin compared with placebo. Thus the objective of this study was to examine the effect of niacin treatment on plasma homocyst(e)ine levels. The Arterial Disease Multiple Intervention Trial, a multicenter randomized, placebo-controlled trial, examined the effect of niacin compared with placebo on homocyst(e)ine in a subset of 52 participants with peripheral arterial disease. During the screening phase, titration of niacin dose from 100 mg to 1000 mg daily resulted in a 17% increase in mean plasma homocyst(e)ine level from 13.1 +/- 4.4 micromol/L to 15.3 +/- 5.6 micromol/L (P ine levels in the niacin group and a 7% decrease in the placebo group (P =.0001). This difference remained statistically significant at the end of follow-up at 48 weeks. Niacin substantially increased plasma homocyst(e)ine levels, which could potentially reduce the expected benefits of niacin associated with lipoprotein modification. However, plasma homocyst(e)ine levels can be decreased by folic acid supplementation. Thus further studies are needed to determine whether B vitamin supplementation to patients undergoing long-term niacin treatment would be beneficial.

  17. Emotionally arousing pictures increase blood glucose levels and enhance recall.

    Science.gov (United States)

    Blake, T M; Varnhagen, C K; Parent, M B

    2001-05-01

    Arousal enhances memory in human participants and this enhancing effect is likely due to the release of peripheral epinephrine. As epinephrine does not readily enter the brain, one way that peripheral epinephrine may enhance memory is by increasing circulating blood glucose levels. The present study investigated the possibility that emotionally arousing color pictures would improve memory and elevate blood glucose levels in human participants. Blood glucose levels were measured before, 15 min, and 30 min after male university students viewed 60 emotionally arousing or relatively neutral pictures. Participants viewed each picture for 6 s and then had 10 s to rate the arousal (emotional intensity) and valence (pleasantness) of each picture. A free-recall memory test was given 30 min after the last picture was viewed. Although the emotionally arousing and neutral picture sets were given comparable valence ratings, participants who viewed the emotionally arousing pictures rated the pictures as being more arousing, recalled more pictures, and had higher blood glucose levels after viewing the pictures than did participants who viewed the neutral pictures. These findings indicate that emotionally arousing pictures increase blood glucose levels and enhance memory, and that this effect is not due to differences in the degree of pleasantness of the stimuli. These findings support the possibility that increases in circulating blood glucose levels in response to emotional arousal may be part of the biological mechanism that allows emotional arousal to enhance memory. Copyright 2001 Academic Press.

  18. Increased carboxyhemoglobin level during liver resection with inflow occlusion.

    Science.gov (United States)

    Godai, Kohei; Hasegawa-Moriyama, Maiko; Kuniyoshi, Tamotsu; Matsunaga, Akira; Kanmura, Yuichi

    2013-04-01

    Controlling stress responses associated with ischemic changes due to bleeding and ischemia/reperfusion injury is essential for anesthetic management. Endogenous carboxyhemoglobin (COHb) is produced in the oxidative degradation of heme proteins by the stress-response enzyme heme oxygenase. Although the COHb level is elevated in critically ill patients, changes in endogenous COHb during anesthesia have not been well investigated. Therefore, we evaluated changes in endogenous COHb levels in patients undergoing liver resections with inflow occlusion. Levels of COHb were significantly increased after the Pringle maneuver. The inflow occlusion time in patients with increased COHb after the Pringle maneuver (∆COHb > 0.3 %) was significantly longer than in patients without increased COHb (∆COHb < 0.3 %) (P = 0.01). In addition, COHb changes were correlated with inflow occlusion time (P = 0.005, R(2) = 0.21). Neither total blood loss, transfusion volume of packed red blood cells, operation time, nor anesthetic time differed between patients with and without increased COHb. The results indicated that endogenous COHb levels were increased by inflow occlusion in patients undergoing liver resections, which suggests that changes in COHb may correlate with hepatic ischemia/reperfusion injury induced by inflow occlusion.

  19. Enhanced insulin-like growth factor I gene expression in regenerating rat pancreas

    International Nuclear Information System (INIS)

    Smith, F.E.; Rosen, K.M.; Villa-Komaroff, L.; Weir, G.C.; Bonner-Weir, S.

    1991-01-01

    Insulin-like growth factor I (IGF-I) mRNA expression was studied after 90% partial pancreatectomy in the rat to determine whether IGF-I was associated with pancreatic regeneration. The level of IGF-I mRNA was maximally increased (4-fold above control value) 3 days after pancreatectomy, but thereafter gradually decreased, returning to control levels by 14 days after surgery. By in situ hybridization, IGF-I mRNA in both pancreatectomized and sham-operated rats was localized to capillary endothelial cells, indicating that this is the site of IGF-I expression in the normal rat pancreas. However, enhanced IGF-I mRNA expression was localized to focal areas of regeneration unique to pancreatectomized rats. In these areas, epithelial cells of proliferating ductules and individual connective tissue cells expressed IGF-I, suggesting that IGF-I may play an important role in the growth or differentiation of pancreatic tissue

  20. Enhanced insulin-like growth factor I gene expression in regenerating rat pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Smith, F.E.; Rosen, K.M.; Villa-Komaroff, L.; Weir, G.C.; Bonner-Weir, S. (E. P. Joslin Research Laboratory, Joslin Diabetes Center, Harvard Medical School, Boston, MA (USA))

    1991-07-15

    Insulin-like growth factor I (IGF-I) mRNA expression was studied after 90% partial pancreatectomy in the rat to determine whether IGF-I was associated with pancreatic regeneration. The level of IGF-I mRNA was maximally increased (4-fold above control value) 3 days after pancreatectomy, but thereafter gradually decreased, returning to control levels by 14 days after surgery. By in situ hybridization, IGF-I mRNA in both pancreatectomized and sham-operated rats was localized to capillary endothelial cells, indicating that this is the site of IGF-I expression in the normal rat pancreas. However, enhanced IGF-I mRNA expression was localized to focal areas of regeneration unique to pancreatectomized rats. In these areas, epithelial cells of proliferating ductules and individual connective tissue cells expressed IGF-I, suggesting that IGF-I may play an important role in the growth or differentiation of pancreatic tissue.

  1. Decreased total antioxidant levels and increased oxidative stress in ...

    African Journals Online (AJOL)

    Background: Chronic hyperglycaemia in diabetes mellitus leads to increased lipid peroxidation in the body, followed by the development of chronic complications due to oxidative stress. Objective: The aim of this study was to compare total antioxidant (TAO) levels and oxidative stress in type 2 diabetes mellitus (T2DM) ...

  2. Effect of the association of IGF-I, IGF-II, bFGF, TGF-beta1, GM-CSF, and LIF on the development of bovine embryos produced in vitro.

    Science.gov (United States)

    Neira, J A; Tainturier, D; Peña, M A; Martal, J

    2010-03-15

    This study examined the influence of the following growth factors and cytokines on early embryonic development: insulin-like growth factors I and II (IGF-I, IGF-II), basic fibroblast growth factor (bFGF), transforming growth factor (TGF-beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), and leukemia inhibitory factor (LIF). Synthetic oviduct fluid (SOF) was used as the culture medium. We studied the development of bovine embryos produced in vitro and cultured until Day 9 after fertilization. TGF-beta1, bFGF, GM-CSF, and LIF used on their own significantly improved the yield of hatched blastocysts. IGF-I, bFGF, TGF-beta1, GM-CSF, and LIF significantly accelerated embryonic development, especially the change from the expanded blastocyst to hatched blastocyst stages. Use of a combination of these growth factors and cytokines (GF-CYK) in SOF medium produced higher percentages of blastocysts and hatched blastocysts than did use of SOF alone (45% and 22% vs. 24% and 12%; PGM-CSF, produces similar results to 10% fetal calf serum for the development of in vitro-produced bovine embryos. This entirely synthetic method of embryo culture has undeniable advantages for the biosecurity of embryo transfer. Copyright 2010 Elsevier Inc. All rights reserved.

  3. Endozepine-4 levels are increased in hepatic coma.

    Science.gov (United States)

    Malaguarnera, Giulia; Vacante, Marco; Drago, Filippo; Bertino, Gaetano; Motta, Massimo; Giordano, Maria; Malaguarnera, Michele

    2015-08-14

    To evaluate the serum levels of endozepine-4, their relation with ammonia serum levels, the grading of coma and the severity of cirrhosis, in patients with hepatic coma. In this study we included 20 subjects with Hepatic coma, 20 subjects with minimal hepatic encephalopathy (MHE) and 20 subjects control. All subjects underwent blood analysis, Child Pugh and Model for End - stage liver disease (MELD) assessment, endozepine-4 analysis. Subjects with hepatic coma showed significant difference in endozepine-4 (P blood ammonia concentration was noted to be raised in patients with hepatic coma, with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia (P < 0.001). In patients with grade IV hepatic coma, endozepine levels were significantly higher compared to other groups. This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion, data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations.

  4. Ghrelin administered spinally increases the blood glucose level in mice.

    Science.gov (United States)

    Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

    2014-04-01

    Ghrelin is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of ghrelin located in the spinal cord in the regulation of the blood glucose level were investigated in ICR mice. We found that intrathecal (i.t.) injection with ghrelin (from 1 to 10 μg) caused an elevation of the blood glucose level. In addition, i.t. pretreatment with YIL781 (ghrelin receptor antagonist; from 0.1 to 5 μg) markedly attenuated ghrelin-induced hyperglycemic effect. The plasma insulin level was increased by ghrelin. The enhanced plasma insulin level by ghrelin was reduced by i.t. pretreatment with YIL781. However, i.t. pretreatment with glucagon-like peptide-1 (GLP-1; 5 μg) did not affect the ghrelin-induced hyperglycemia. Furthermore, i.t. administration with ghrelin also elevated the blood glucose level, but in an additive manner, in d-glucose-fed model. Our results suggest that the activation of ghrelin receptors located in the spinal cord plays important roles for the elevation of the blood glucose level. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Increased plasma agmatine levels in patients with schizophrenia.

    Science.gov (United States)

    Uzbay, Tayfun; Goktalay, Gokhan; Kayir, Hakan; Eker, Salih S; Sarandol, Asli; Oral, Sema; Buyukuysal, Levent; Ulusoy, Gokhan; Kirli, Selcuk

    2013-08-01

    Agmatine is an endogenous substance, synthesized from l-arginine, and it is proposed to be a new neurotransmitter. Preclinical studies indicated that agmatine may have an important role in the pathophysiology of schizophrenia. This study was organized to investigate plasma agmatine in patients with schizophrenia and in healthy controls. Eighteen patients with schizophrenia and 19 healthy individuals constituted the subjects. Agmatine levels in the plasma were measured using the HPLC method. The S100B protein level, which is a peripheral biomarker for brain damage, was also measured using the ELISA method. While plasma levels of agmatine in patients with schizophrenia were significantly increased (p agmatine levels as a clinical diagnostic test would significantly differentiate between patients with schizophrenia and those in the control group (predictive value: 0.969; p  0.05). A multiple regression analysis revealed that the age of the patient and the severity of the illness, as indicated by the PANSS score, significantly contributed the plasma agmatine levels in patients with schizophrenia. These results support the hypothesis that an excess agmatine release is important in the development of schizophrenia. The findings also imply that the plasma agmatine level may be a potential biomarker of schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Efficiency of fisheries is increasing at the ecosystem level

    DEFF Research Database (Denmark)

    Jacobsen, Nis Sand; Burgess, Matthew G; Andersen, Ken Haste

    2017-01-01

    examine the efficiency of North Sea and Baltic Sea fisheries with respect to economic rent and ecosystem impact, finding both to be inefficient but steadily improving. Our results suggest the following: (i) a broad and encouraging trend towards ecosystem-level efficiency of fisheries; (ii) that ecosystem......Managing fisheries presents trade-offs between objectives, for example yields, profits, minimizing ecosystem impact, that have to be weighed against one another. These trade-offs are compounded by interacting species and fisheries at the ecosystem level. Weighing objectives becomes increasingly...... regressing at least one other. We investigate the ecosystem-level efficiency of fisheries in five large marine ecosystems (LMEs) with respect to yield and an aggregate measure of ecosystem impact using a novel calibration of size-based ecosystem models. We estimate that fishing patterns in three LMEs (North...

  7. Increased Plasma Levels of Heme Oxygenase-1 in Human Brucellosis.

    Science.gov (United States)

    Chen, Zhe; Zhang, Yu-Xue; Fu, Dong-Wei; Gao, Qing-Feng; Ge, Feng-Xia; Liu, Wei-Hua

    2016-08-01

    Brucellosis is associated with inflammation and the oxidative stress response. Heme oxygenase-1 (HO-1) is a cytoprotective stress-responsive enzyme that has anti-inflammatory and anti-oxidant effects. Nevertheless, the role of HO-1 in human brucellosis has not yet been studied. The aim of this study was to examine the plasma levels of HO-1 in patients with brucellosis and to evaluate the ability of plasma HO-1 levels as an auxiliary diagnosis, a severity predictor, and a monitor for brucellosis treatments. A total of 75 patients with brucellosis were divided into the acute, subacute, chronic active, and chronic stable groups. An additional 20 volunteers were included as the healthy control group. The plasma HO-1 levels and other laboratory parameters were measured in all groups. Furthermore, the plasma levels of HO-1 in the acute group were compared before and after treatment. The plasma HO-1 levels were considerably increased in the acute (4.97 ± 3.55), subacute (4.98 ± 3.23), and chronic active groups (4.43 ± 3.00) with brucellosis compared to the healthy control group (1.03 ± 0.63) (p brucellosis (r = 0.707, p brucellosis status and may be used as a supplementary plasma marker for diagnosing brucellosis and monitoring its treatment.

  8. Increased levels of metallothionein in placenta of smokers

    International Nuclear Information System (INIS)

    Ronco, Ana Maria; Arguello, Graciela; Suazo, Myriam; Llanos, Miguel N.

    2005-01-01

    Experiments were designed to evaluate and compare metallothionein (MT), zinc and cadmium levels in human placentas of smoking and non-smoking women. Smoking was assessed by self-reported cigarette consumption and urine cotinine levels before delivery. Smoking pregnant women with urine cotinine levels higher than 130 ng/ml were included in the smoking group. Determination of placental MT was performed by western blot analysis after tissue homogenization and saturation with cadmium chloride (1000 ppm). Metallothionein was analyzed with a monoclonal antibody raised against MT-1 and MT-2 and with a second anti mouse antibody conjugated to alkaline phosphatase. Zinc and cadmium were determined by neutron activation analysis and atomic absorption spectrometry respectively. Smokers showed higher placental MT and cadmium levels, together with decreased newborn birth weights, as compared to non-smokers. The semi-quantitative analysis of western blots by band densitometry indicated that darker bands corresponded to MT present in smokers' samples. This study confirms that cigarette smoking increases cadmium accumulation in placental tissue and suggests that this element has a stimulatory effect on placental MT production

  9. Transgenic cells with increased plastoquinone levels and methods of use

    Energy Technology Data Exchange (ETDEWEB)

    Sayre, Richard T.; Subramanian, Sowmya; Cahoon, Edgar

    2016-12-27

    Disclosed herein are transgenic cells expressing a heterologous nucleic acid encoding a prephenate dehydrogenase (PDH) protein, a heterologous nucleic acid encoding a homogentisate solanesyl transferase (HST) protein, a heterologous nucleic acid encoding a deoxyxylulose phosphate synthase (DXS) protein, or a combination of two or more thereof. In particular examples, the disclosed transgenic cells have increased plastoquinone levels. Also disclosed are methods of increasing cell growth rates or production of biomass by cultivating transgenic cells expressing a heterologous nucleic acid encoding a PDH protein, a heterologous nucleic acid encoding an HST protein, a heterologous nucleic acid encoding a DXS protein, or a combination of two or more thereof under conditions sufficient to produce cell growth or biomass.

  10. Effects of increased CO{sub 2} levels on monsoons

    Energy Technology Data Exchange (ETDEWEB)

    Cherchi, Annalisa; Masina, Simona; Navarra, Antonio [Centro Euro-Mediterraneo per i Cambiamenti Climatici and Istituto Nazionale di Geofisica e Vulcanologia, Bologna (Italy); Alessandri, Andrea [Centro Euro-Mediterraneo per i Cambiamenti Climatici, Bologna (Italy)

    2011-07-15

    Increased atmospheric carbon dioxide concentration provided warmer atmospheric temperature and higher atmospheric water vapor content, but not necessarily more precipitation. A set of experiments performed with a state-of-the-art coupled general circulation model forced with increased atmospheric CO{sub 2} concentration (2, 4 and 16 times the present-day mean value) were analyzed and compared with a control experiment to evaluate the effect of increased CO{sub 2} levels on monsoons. Generally, the monsoon precipitation responses to CO{sub 2} forcing are largest if extreme concentrations of carbon dioxide are used, but they are not necessarily proportional to the forcing applied. In fact, despite a common response in terms of an atmospheric water vapor increase to the atmospheric warming, two out of the six monsoons studied simulate less or equal summer mean precipitation in the 16 x CO{sub 2} experiment compared to the intermediate sensitivity experiments. The precipitation differences between CO{sub 2} sensitivity experiments and CTRL have been investigated specifying the contribution of thermodynamic and purely dynamic processes. As a general rule, the differences depending on the atmospheric moisture content changes (thermodynamic component) are large and positive, and they tend to be damped by the dynamic component associated with the changes in the vertical velocity. However, differences are observed among monsoons in terms of the role played by other terms (like moisture advection and evaporation) in shaping the precipitation changes in warmer climates. The precipitation increase, even if weak, occurs despite a weakening of the mean circulation in the monsoon regions (''precipitation-wind paradox''). In particular, the tropical east-west Walker circulation is reduced, as found from velocity potential analysis. The meridional component of the monsoon circulation is changed as well, with larger (smaller) meridional (vertical) scales. (orig.)

  11. Tolerance of soil flagellates to increased NaCl levels

    DEFF Research Database (Denmark)

    Ekelund, Flemming

    2002-01-01

    The ability of heterotrophic flagellates to survive and adapt to increasing salinities was investigated in this study. Whole soil samples were subjected to salinities corresponding to marine conditions and clonal cultures were used to perform growth and adaptation experiments at a wide range...... of different salinities (0-50 ppm). More morphotypes tolerant to elevated NaCl levels were found in road verge soil that was heavily exposed to de-icing salt than in less exposed soils, though there were fewer tolerant than intolerant morphotypes in all soils examined. Heterotrophic flagellates isolated...... on a freshwater medium from a non-exposed soil were unable to thrive at salinities above 15 ppt, and showed reduced growth rates even at low salt salinities (1-5 ppt). The findings suggest that heterotrophic soil flagellates are less tolerant to NaCl than their aquatic relatives, possibly due to their long...

  12. Artificially Increased Yolk Hormone Levels and Neophobia in Domestic Chicks

    Directory of Open Access Journals (Sweden)

    Aline Bertin

    2015-11-01

    Full Text Available In birds there is compelling evidence that the development and expression of behavior is affected by maternal factors, particularly via variation in yolk hormone concentrations of maternal origin. In the present study we tested whether variation in yolk hormone levels lead to variation in the expression of neophobia in young domestic chicks. Understanding how the prenatal environment could predispose chicks to express fear-related behaviors is essential in order to propose preventive actions and improve animal welfare. We simulated the consequences of a maternal stress by experimentally enhancing yolk progesterone, testosterone and estradiol concentrations in hen eggs prior to incubation. The chicks from these hormone-treated eggs (H and from sham embryos (C that received the vehicle-only were exposed to novel food, novel object and novel environment tests. H chicks approached a novel object significantly faster and were significantly more active in a novel environment than controls, suggesting less fearfulness. Conversely, no effect of the treatment was found in food neophobia tests. Our study highlights a developmental influence of yolk hormones on a specific aspect of neophobia. The results suggest that increased yolk hormone levels modulate specifically the probability of exploring novel environments or novel objects in the environment.

  13. [Severely increased serum lipid levels in diabetic ketoacidosis - case report].

    Science.gov (United States)

    Stefansson, Hrafnkell; Sigvaldason, Kristinn; Kjartansson, Hilmar; Sigurjonsdottir, Helga Águsta

    2017-01-01

    Severe hypertriglyceridemia is a known, but uncommon complication of diabetic ketoacidosis. We discuss the case of a 23-year-old, previously healthy, woman who initially presented to the emergency department with abdominal pain. Grossly lipemic serum due to extremely high triglyceride (38.6 mmol/L) and cholesterol (23.2 mmol/L) levels were observed with a high blood glucose (23 mmol/L) and a low pH of 7.06 on a venous blood gas. She was treated successfully with fluids and insulin and had no sequale of pancreatitis or cerebral edema. Her triglycerides and cholesterol was normalized in three days and she was discharged home on insulin therapy after five days. Further history revealed a recent change in diet with no meat, fish or poultry consumption in the last 12 months and concomitantly an increase in carbohydrate intake which might have contributed to her extremely high serum lipid levels. This case demonstrates that clinicians should be mindful of the different presentations of diabetic ketoacidosis. Key words: diabetic ketoacidosis, hypertriglyceridemia, hyperlipidemia, vegan diet, carbohydrate diet. Correspondence: Hrafnkell Stefansson, hrafnkell.stefans@gmail.com.

  14. Increased Blood-Reelin-Levels in First Episode Schizophrenia.

    Directory of Open Access Journals (Sweden)

    Tobias Hornig

    Full Text Available Reelin is an extracellular glycoprotein involved in several functions of brain development, synaptogenesis and dendritic proliferation. Numerous studies found perturbation in the reelin system and altered serum reelin levels in neuropsychiatric patients using the western blot procedure. In the international literature, this is the first study that made use of an enzyme-linked immunosorbent assay to analyze serum reelin protein concentration quantitatively.In order to study possible alterations in reelin blood levels in schizophrenia, we analyzed this signal in schizophrenic patients with a first episode hallucinatory and paranoid syndrome and control subjects in a pilot study design.We found increased blood reelin protein concentration in schizophrenic patients compared to healthy controls.Our findings point to a relevant role of reelin metabolism in the pathogenesis of schizophrenia.Reelin could be a biomarker for the course of disease or psychopharmacological treatment.We conclude that the reelin protein blood concentration might be a relevant signal with respect to the pathophysiology of schizophrenia.

  15. The survey of dwellings with increased radon levels in Slovakia

    International Nuclear Information System (INIS)

    Vicanova, M.

    1998-01-01

    This national survey of indoor radon measurements in a sample of dwellings in Slovakia was organised by the Institute of Preventive and Clinical Medicine in Bratislava. The aim was to find districts and type of dwellings with the highest indoor radon concentrations and to estimate the radiation load of the Slovak population owing the indoor radon exposure. Passive solid state nuclear track detectors were used to measure indoor radon concentrations. The detectors were polyallyldiglycolcarbonate CR-39 which were placed in about 6,000 selected houses (minimum two detectors for every residence). After six months exposed detectors and questionnaires were returned to for analysis. Electrochemical etching combined with a chemical pre-etching process was used for evaluating detectors. Present results are from 3,657 residents (0.2% of total dwellings in Slovakia). It was found that the arithmetic mean of equilibrium equivalent concentration (EEC) was 86 ± 119 Bq m -3 , the geometric mean was about 41 ± 2.22 Bq m -3 and 11% of dwellings (N = 409) have a greater EEC of radon than the action level (200 Bq m -3 ). The national survey results suggest that Slovakia may be among the countries with high radon risk in Central Europe. The population-weighted arithmetic mean is 48 Bq m -3 , the maximum value found was 1500 Bq m -3 and the average annual effective dose from indoor radon exposure is 2.1 mSv. The district with the highest indoor radon concentrations correlate with known presence of uranium in the soil, therefore the soil is probably the main source of radon in Slovak dwellings. This survey of dwellings with increased radon levels supported this conclusion, because the highest radon levels were found in older family houses without cellars. (author)

  16. Prospects of increasing the engineering level of NPP components

    International Nuclear Information System (INIS)

    Filippov, G.A.

    1987-01-01

    Consideration is being given to main problems related to development and industrial introduction of NPP components corresponding to the perspective world-wide engineering level. The nearest task in this field is to elevate the engineering level of developed and being produced power equipment up to the level of similar equipment, manufactured by leading foreign companies

  17. Prediction of the outcome of growth hormone provocative testing in short children by measurement of serum levels of insulin-like growth factor I and insulin-like growth factor binding protein 3

    DEFF Research Database (Denmark)

    Juul, A; Skakkebaek, N E

    1997-01-01

    Serum levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) reflect the secretion of endogenous growth hormone (GH) in healthy children and exhibit little diurnal variation, which makes them potential candidates for screening of GH deficiency (GHD......). We evaluated serum IGF-I and IGFBP-3 levels in relation to the outcome of GH provocative testing in 203 children and adolescents (111 boys and 92 girls) in whom GHD was suspected. A total of 1030 children served as control subjects. In children less than 10 years of age, IGF-I levels were below...... with a normal GH response (specificity 97.9%). Consequently the predictive value of a positive test result in prepubertal children was 88.8% for IGF-I and 90% for IGFBP-3. In children and adolescents between 10 and 20 years of age, IGF-I levels were below the cutoff limit in 34 of 46 children with GHD...

  18. Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model

    Science.gov (United States)

    Canelles, Sandra; Argente, Jesús; Barrios, Vicente

    2016-01-01

    ABSTRACT Insulin receptor substrate-2-deficient (IRS2−/−) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2−/− mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2−/− mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2−/− mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2−/− mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. PMID:27013528

  19. Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults

    DEFF Research Database (Denmark)

    Juul, A; Bang, P; Hertel, Niels

    1994-01-01

    Serum levels of insulin-like growth factor-I (IGF-I) increase with age and pubertal development. The large variation in circulating IGF-I levels in adolescence makes it difficult to use the IGF-I value of a single child in the assessment of his growth status. In addition, the interference of IGF......-binding proteins in many IGF-I assays contributes to this problem. We measured IGF-I in acid-ethanol-extracted serum from 1030 healthy children, adolescents, and adults, employing a RIA that reduces interference of IGF-binding proteins by using monoiodinated Tyr31-[125I]des-(1-3)IGF-I as radioligand. Mean serum...... volume. Multiple regression analysis revealed that serum IGF-I levels predicted height velocity in the following year (r = 0.33; P

  20. Increased serum procalcitonin levels in pregnant patients with asymptomatic bacteriuria.

    Science.gov (United States)

    Bilir, Filiz; Akdemir, Nermin; Ozden, Selcuk; Cevrioglu, A Serhan; Bilir, Cemil

    2013-09-05

    Among the pregnancy urinary tract infections, asymptomatic bacteriuria (ASB) is the most common one. Untreated ASB can progress to pyelonephritis in 30-50% of the patients and can also result in prematurity in 27% of the pregnancy so it needs immediate diagnosis and treatment. In this study, we wanted to evaluate procalcitonin levels, compared to other inflammatory in pregnant women with ASB. The study was designed between the period of January 2012 and February 2013 at Sakarya University School of Medicine, Department of Gynecology and Obstetrics. The study population included 30 pregnant patients with asymptomatic bacteriuria and 39 healthy pregnant controls. Mean age was 28 (SD, 5.5) of the study population; mean maternal weight was 70 (SD, 8) kilogram. There were no statically significant differences between the groups according to the routine biochemical parameters, but gestational age was significantly lower in the ASB group compared to the controls (20.4 vs 28.6, respectively; p 0.05 ng/ml and 21(70%) patients had negative procalcitonin levels (Chi-squrae, p treatment of the first ASB diagnosis. Procalcitonin levels were significantly higher in ASB group than the control group and serum procalcitonin levels were higher in pregnant women with recurrent ASB. This finding is an important result revealed that high procalcitonin level can predict the further urinary tract infection risk. Finally, serum procalcitonin levels were normal in healthy pregnant women while other inflammatory markers such as WBC, ESR and CRP levels were higher.

  1. Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects

    DEFF Research Database (Denmark)

    Rasmussen, M H; Hvidberg, A; Juul, A

    1995-01-01

    levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), as well as insulin in obese subjects before and after a massive weight loss. We studied 18 obese subjects (age, 26 +/- 1 yr; body mass index, 40.9 +/- 1.1 kg/m2); 18 normal age-, and sex-matched control subjects; and 9...... using anthropometric measurements and dual energy x-ray absorptiometry scanning (DXA). In the obese subjects, 24-h spontaneous GH release profiles and the GH responses to insulin-induced hypoglycemia and L-arginine as well as basal IGF-I levels and the IGF-I/IGFBP-3 molar ratio were decreased, whereas...

  2. Increased Cortisol and Cortisone Levels in Overweight Children

    OpenAIRE

    Chu, Lanling; Sheng, Kangwei; Liu, Ping; Ye, Kan; Wang, Yu; Li, Chen; Kang, Xuejun; Song, Yuan

    2017-01-01

    Background It has been unclear whether relatively high cortisol and cortisone levels are related to overweight in childhood, parental body mass index (BMI), and family dietary habits. The aim of this study was to compare cortisol and cortisone levels in urine and saliva from overweight and normal children, as well as correlations between children?s BMI, parental BMI and family dietary behavior questionnaire score (QS). Material/Methods We analyzed the data from 52 overweight children and 53 a...

  3. Feed restriction and insulin-like growth factor-I (IGF-I) affect the oocyte maturation in matrinxã Brycon amazonicus.

    Science.gov (United States)

    Montrezor, Luís Henrique; Urbinati, Elisabeth Criscuolo

    2017-02-01

    The feeding and nutrition of breeders are crucial aspects in the reproductive process. During the maturation period, metabolic changes occur aiming at mobilizing energy for growth and follicular development. The involvement of IGF-1 in metabolic and reproductive events is important. The aim of this work was to evaluate if alternate feed restriction and re-feeding have permissive effects on in vitro actions of IGF-1 on oocytes development of matrinxã. In vivo experiments were performed during vitellogenesis period. Females (n = 60) were fed with a commercial feed (2% of biomass) and they were divided into two treatments: fish receiving food daily (control - fed), and fish submitted to cycles of 3 days of feed restriction and 2 days of re-feeding (no-fed group). For the in vitro experiments, oocytes (n = 20) were obtained from the ovaries removed at the end of the in vivo experiment and were divided into four groups: fed -IGF-1; fed +IGF-1; no-fed -IGF-1 and no-fed +IGF-1. Fish under restriction had lower body weights, decreased plasma glucose, increased triglycerides levels, and their final maturation and mature oocyte were reduced and the atresic ones were in higher number. Moreover, IGF-1, in vitro, increased the percentage of mature oocytes in fed females and decreased the atresic ones. In no-fed females, IGF-1 increased the final maturation and mature oocytes and reduced the atresic ones. This study demonstrates the importance of the feeding management of female breeders of matrinxã during the vitellogenesis period.

  4. Ocean acidification increases fatty acids levels of larval fish.

    Science.gov (United States)

    Díaz-Gil, Carlos; Catalán, Ignacio A; Palmer, Miquel; Faulk, Cynthia K; Fuiman, Lee A

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  7. Pavlovian autoshaping procedures increase plasma corticosterone levels in rats.

    Science.gov (United States)

    Tomie, Arthur; Silberman, Yuval; Williams, Kayon; Pohorecky, Larissa A

    2002-06-01

    Pavlovian autoshaping conditioned responses (CRs) are complex sequences of conditioned stimulus (CS)-directed skeletal-motor responses that are elicited by CS objects predictive of food unconditioned stimulus (US). Autoshaping CRs are observed under conditions known to be conducive to elevations in plasma corticosterone levels, as, for example, in response to the eating of food as well as in response to signals predictive of food. Two experiments investigated the relationships between Pavlovian autoshaping procedures, the performance of Pavlovian autoshaping CRs, and plasma corticosterone levels in male Long-Evans rats. In Experiment 1, rats in the CS-US paired group (n=30) were given 20 daily sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of the food US. Tail blood samples obtained after the 20th autoshaping session revealed higher plasma corticosterone levels in the CS-US paired group than in the CS-US random control group (n=10). In Experiment 2, rats (n=35) were assessed for basal plasma corticosterone levels 2 weeks prior to autoshaping training. Plasma samples obtained immediately following the first autoshaping session, and prior to the acquisition of lever-press autoshaping CR performance, revealed higher plasma corticosterone levels in the CS-US paired group (n=24) relative to basal levels. This effect was not observed in the CS-US random control group (n=11). Data suggest that corticosterone release is a physiological endocrine Pavlovian CR induced by lever CS-food US pairings during Pavlovian autoshaping procedures, rather than a by-product of autoshaping CR performance. Implications of the link between autoshaping procedures and corticosterone release are discussed.

  8. Effects of increasing dietary protein levels on growth, feed utilization ...

    African Journals Online (AJOL)

    Yomi

    2012-01-05

    Jan 5, 2012 ... The effect of different dietary protein levels on growth performance and on feed utilization of catfish. (Heterobranchus ... (Legendre, 1991) because of its taste, fast growth rate ..... diet containing 40% protein had high growth with low food intake and feed ... protein rate (45%) combined with a bad utilization of.

  9. Short-term strength training and the expression of myostatin and IGF-I isoforms in rat muscle and tendon: differential effects of specific contraction types.

    Science.gov (United States)

    Heinemeier, K M; Olesen, J L; Schjerling, P; Haddad, F; Langberg, H; Baldwin, K M; Kjaer, M

    2007-02-01

    In skeletal muscle, an increased expression of insulin like growth factor-I isoforms IGF-IEa and mechano-growth factor (MGF) combined with downregulation of myostatin is thought to be essential for training-induced hypertrophy. However, the specific effects of different contraction types on regulation of these factors in muscle are still unclear, and in tendon the functions of myostatin, IGF-IEa, and MGF in relation to training are unknown. Female Sprague-Dawley rats were subjected to 4 days of concentric, eccentric, or isometric training (n = 7-9 per group) of the medial gastrocnemius, by stimulation of the sciatic nerve during general anesthesia. mRNA levels for myostatin, IGF-IEa, and MGF in muscle and Achilles' tendon were measured by real-time RT-PCR. Muscle myostatin mRNA decreased in response to all types of training (2- to 8-fold) (P effect of eccentric training was greater than concentric and isometric training (P tendon, myostatin mRNA was detected, but no changes were seen after exercise. IGF-IEa and MGF increased in muscle (up to 15-fold) and tendon (up to 4-fold) in response to training (P tendon no difference was seen between training types, but in muscle the effect of eccentric training was greater than concentric training for both IGF-IEa and MGF (P effect than concentric (P tendon to training, and the combined changes in myostatin and IGF-IEa/MGF expression could explain the important effect of eccentric actions for muscle hypertrophy.

  10. Increased Cortisol and Cortisone Levels in Overweight Children.

    Science.gov (United States)

    Chu, Lanling; Shen, Kangwei; Liu, Ping; Ye, Kan; Wang, Yu; Li, Chen; Kang, Xuejun; Song, Yuan

    2017-02-09

    BACKGROUND It has been unclear whether relatively high cortisol and cortisone levels are related to overweight in childhood, parental body mass index (BMI), and family dietary habits. The aim of this study was to compare cortisol and cortisone levels in urine and saliva from overweight and normal children, as well as correlations between children's BMI, parental BMI and family dietary behavior questionnaire score (QS). MATERIAL AND METHODS We analyzed the data from 52 overweight children and 53 age- and sex-matched normal-weight children aged 4-5 years. The concentrations of salivary cortisol (SF), salivary cortisone (SE), urinary cortisol (UF) and urinary cortisone (UE) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The family dietary behavior QS was answered by the parent mainly responsible for the family diet. RESULTS Average cortisol and cortisone levels were significantly higher in overweight children. There was no significant difference in the ratio of cortisol to cortisone (Rcc) and the marker of 11b-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activities. The results displayed correlations among cortisol, cortisone, and Rcc. Positive correlations were weak-to-moderate between BMI and SF, SE, UF, and UE. There were correlations between BMI and maternal BMI (mBMI), and BMI was significantly associated with QS. CONCLUSIONS Our results suggest that cortisol and cortisone levels are associated with overweight in children, but the 11β-HSD2 activities showed no significant differences. Unhealthy family diet was associated with higher BMI, UF, and UE, and families with maternal overweight or obesity had a higher prevalence of children's overweight or obesity.

  11. Increasing zinc levels in phytase-supplemented diets improves the ...

    African Journals Online (AJOL)

    Marjina Akter

    2017-09-02

    Sep 2, 2017 ... This result indicate that the Zn concentrations used in this study were not ... levels of phytase, the concentrations of Zn in the experimental diets of these studies ... combustion technique, as described by Sweeney (1989) using a LECO® ... Premix A. 2.0. 2.0. 2.0. 2.0. 2.0. 2.0. Choline Cl. 0.9. 0.9. 0.9. 1.1. 0.9.

  12. Both hypothyroidism and hyperthyroidism increase plasma irisin levels in rats.

    Science.gov (United States)

    Atici, Emine; Mogulkoc, Rasim; Baltaci, Abdulkerim Kasim; Menevse, Esma

    2017-11-28

    Background A recently discovered hormone, irisin is accepted to be significantly involved in the regulation of body weight. Thyroid functions may be, directly or indirectly, associated with irisin. Aim The aim of the present study is to determine the effect of experimental thyroid dysfunction on irisin levels in rats. Methods The study registered 40 adult male Sprague-Dawley rats, which were allocated to groups as follows: 1. Control; 2. Hypothyroidism induced by injection of 10 mg/kg/day intraperitoneal propylthiouracil (PTU) for 3 weeks; 3. Hypothyroidism (PTU 2 weeks) + L-thyroxin (1.5 mg/kg/day for 1 week); 4. Hyperthyroidism induced in rats by 3-week thyroxin (0.3 mg/kg/day); 5. Hyperthyroidism + PTU. At the end of the study, blood samples were collected to quantify free triiodothyronine (FT3), free triiodothyronine (FT4) and irisin levels. Results FT3 and FT4 levels were reduced in hypothyroidism and were significantly elevated in hyperthyroidism (p hyperthyroidism groups (p hyperthyroidism, and that when hypothyroidism is corrected by thyroxin administration and hyperthyroidism by PTU injection, plasma irisin values go back to normal.

  13. High epitope expression levels increase competition between T cells.

    Directory of Open Access Journals (Sweden)

    Almut Scherer

    2006-08-01

    Full Text Available Both theoretical predictions and experimental findings suggest that T cell populations can compete with each other. There is some debate on whether T cells compete for aspecific stimuli, such as access to the surface on antigen-presenting cells (APCs or for specific stimuli, such as their cognate epitope ligand. We have developed an individual-based computer simulation model to study T cell competition. Our model shows that the expression level of foreign epitopes per APC determines whether T cell competition is mainly for specific or aspecific stimuli. Under low epitope expression, competition is mainly for the specific epitope stimuli, and, hence, different epitope-specific T cell populations coexist readily. However, if epitope expression levels are high, aspecific competition becomes more important. Such between-specificity competition can lead to competitive exclusion between different epitope-specific T cell populations. Our model allows us to delineate the circumstances that facilitate coexistence of T cells of different epitope specificity. Understanding mechanisms of T cell coexistence has important practical implications for immune therapies that require a broad immune response.

  14. Increased concentrations of serum nesfatin-1 levels in childhood

    Science.gov (United States)

    Acar, Sezer; Çatlı, Gönül; Küme, Tuncay; Tuhan, Hale; Gürsoy Çalan, Özlem; Demir, Korcan; Böber, Ece; Abacı, Ayhan

    2018-04-30

    Background/aim: Nesfatin-1, an anorexigenic molecule, seems to play a role in appetite regulation and energy homeostasis. The goal of this study was to evaluate the relation of nesfatin-1 with anthropometric and metabolic (ghrelin, leptin) parameters in children with idiopathic chronic malnutrition. Materials and methods: The study included 37 underweight and 38 healthy children who were similar regarding age, sex, and pubertal status. Anthropometric and biochemical (nesfatin-1, ghrelin, and leptin levels) variables were assessed. Results: A total of 37 underweight subjects (mean age 10.5 ± 2.6 years) and 38 heathy subjects (mean age 10.3 ± 2.3 years) were recruited. Underweight children had significantly higher nesfatin-1 (2.76 ± 0.4 vs. 1.56 ± 0.7, P malnutrition, who were subsequently found to have significantly higher nesfatin-1 levels. Our study underlines that nesfatin-1 may play a role in the development of malnutrition by inhibiting food intake in children.

  15. INCREASING EMPLOYMENT LEVELS THROUGH THE USE OF CREATIVE JOBS

    Directory of Open Access Journals (Sweden)

    Anne-Marie Andreea HORDAU

    2015-06-01

    Full Text Available In this paper we want to raise awareness of how important is for an economy the existence of creative jobs. In the last years the employment rate has grown in the sector of creative jobs. This research came out due the need of creative jobs contribution to the development of an economy, in particular Romanian economy. In this paper we want to stress on the importance of creative industry and also to propose some solutions for increasing employment in this sectors , being well-known that creative industry is attractive to smart and talented people. Nevertheless, it is important to point out the development of IT as part of creative industry. Not at last, we will take in consideration the role that small and medium enterprises have, the impact of fiscal facilities in the economy and the need for appropriate financial instruments to support this kind of business.

  16. Does natural gas increase the indoor radon levels?

    International Nuclear Information System (INIS)

    Abdel-Ghany, H.A.; Shabaan, D.H.

    2015-01-01

    The natural gas is naturally occurring hydrocarbon consists mainly of methane and includes varying amounts of other hydrocarbons, carbon dioxide and other impurities such as: nitrogen, and hydrogen sulfide. It is used domestically and industrially as a preferable energy source compared to coal and oil. Because natural gas is found in deep underground natural formations or associated with other underground hydrocarbon reservoirs, there is a potential to contain radon as a contaminant. This work was designated to measure indoor radon concentrations in dwellings supplied with natural gas compared with those not supplied with it, where radon level was estimated using solid state nuclear track detectors (CR-39). The results showed that radon concentration was significantly higher in dwellings supplied with natural gas, where it was 252.30 versus 136.19 Bqm -3 in dwelling not supplied with natural gas (P < 0.001). The mean values of radon exhalation rate was 0.02 ± 6.34 · 10 -4 Bq · m -2 · h -1 in dwellings supplied with natural gas and 0.01 +- 0.008 Bq · m -2 · h -1 in dwellings lacking it. In addition, a significant difference was observed in the mean annual effective doses (4.33 and 2.34 mSv · y -1 , respectively) between both groups. Conclusively, the data indicate that natural gas may represent a potential source of indoor radon

  17. Increased Pathological Worry Levels in Patients with Alopecia Areata

    Directory of Open Access Journals (Sweden)

    Basak Sahin

    2017-01-01

    Full Text Available Aim: Alopecia Areata (AA is a type of hair loss that has been considered to have associations with various psychiatric disorders. In this study, we aimed to compare pathological worry levels between patients with AA and healthy controls (HC. Material and Method: Sixty-three patients with AA and 90 HCs were included in the present study after applying inclusion and exclusion criteria. The socio-demographic characteristics, some clinical characteristics, and the scores from the Penn State Worry Questionnaire (PSWQ were compared between groups. Results: The demographic characteristics were found to be similar between groups except for gender. The family history of AA was significantly higher in the AA group. The mean score of PSWQ in the AA group was 44.02 ± 11.59, compared to 39.71 ± 7.77 in the HC group. The mean score of PSWQ was significantly higher in the AA group (t=-3.27, p= 0.001.Discussion: The present study is the first to compare pathological worry between patients with AA and HCs. We suggest that pathological worry should be more thoroughly investigated in patients with AA to improve their quality of life. Also, this can be an effective approach to targeting the patients who may develop anxiety disorder.

  18. High Level Waste (HLW) Processing Experience with Increased Waste Loading

    International Nuclear Information System (INIS)

    JANTZEN, CAROL

    2004-01-01

    The Defense Waste Processing Facility (DWPF) Engineering requested characterization of glass samples that were taken after the second melter had been operational for about 5 months. After the new melter had been installed, the waste loading had been increased to about 38 weight percentage after a new quasicrystalline liquidus model had been implemented. The DWPF had also switched from processing with refractory Frit 200 to a more fluid Frit 320. The samples were taken after DWPF observed very rapid buildup of deposits in the upper pour spout bore and on the pour spout insert while processing the high waste loading feedstock. These samples were evaluated using various analytical techniques to determine the cause of the crystallization. The pour stream sample was homogeneous, amorphous, and representative of the feed batch from which it was derived. Chemical analysis of the pour stream sample indicated that a waste loading of 38.5 weight per cent had been achieved. The data analysis indicated that surface crystallization, induced by temperature and oxygen fugacity gradients in the pour spout, caused surface crystallization to occur in the spout and on the insert at the higher waste loadings even though there was no crystallization in the pour stream

  19. Basal levels and diurnal variations of some hormones and metabolites in blood of dairy cows treated daily with rbSTin early and late lactation

    Directory of Open Access Journals (Sweden)

    Jurgen Blum

    2010-01-01

    Full Text Available The variations of basal value (before morning feeding at 3-4 days interval and daily pattern (on 4and 18day of treat-  ment with 8 blood collections within 24h of hormones and metabolites were studied in four dairy cows; 2 in early and  2 in late lactation, which were alternatively injected daily for a period of 21 days with 26.3 mg rbST or saline.  The rbST  injection significantly increased the basal and daily levels of GH, IGF-I in both stages of lactation. Daily levels of NEFA  were significantly increased by rbST in both stages of lactation and their variations, due to the effect of meals, were coun-  teracted by the rbST; the higher level of NEFA allowed a greater sparing of glucose, the blood level of which resulted  higher (P  blood urea level (P  ticular the high availability of glucose, determined a significantly higher blood level of insulin and T3, and lower level of  glucagon. Despite the similar GH, IGF-I and NEFA increases observed in the cows treated in early and late lactation, other  metabolic and endocrine consequences resulted more evident in late lactation. Furthermore, some of these variations  were affected by the forage meals. It can be concluded, therefore, that the changes occurring in the blood subsequent  to a rbST treatment are not equal to those which occur at the start of lactation; moreover, they are affected by the daily  feeding pattern and perhaps by the stage of  lactation. 

  20. The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men

    DEFF Research Database (Denmark)

    Hameed, M; Lange, K H W; Andersen, J L

    2004-01-01

    in response to resistance training only. The subjects (age 74 +/- 1 years, mean +/- S.E.M) were assigned to either resistance training with placebo, resistance training combined with GH administration or GH administration alone. Real-time quantitative RT-PCR was used to determine mRNA levels in biopsies from...

  1. Early origins of the metabolic syndrome: Role of small size at birth, early postnatal weight gain, and adult IGF-I

    NARCIS (Netherlands)

    G.F. Kerkhof (Gerthe); R.W.J. Leunissen (Ralph); A.C.S. Hokken-Koelega (Anita)

    2012-01-01

    textabstractBackground: The relationship between low birth weight and increased risk for metabolic syndrome (MetS) in later life has been frequently described, but mechanisms underlying this association remain unknown. Methods: In 280 young adults of the PROGRAM study, aged 18-24 yr, we investigated

  2. Growth hormone increases vascular cell adhesion molecule 1 expression

    DEFF Research Database (Denmark)

    Hansen, Troels Krarup; Fisker, Sanne; Dall, Rolf

    2004-01-01

    We investigated the impact of GH administration on endothelial adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, in vivo and in vitro. Soluble VCAM-1, E-selectin, and C-reactive protein concentrations were measured before and after treatment in 25 healthy subjects...... and 25 adult GH-deficient (GHD) patients randomized to GH treatment or placebo. Furthermore, we studied the direct effect of GH and IGF-I and serum from GH-treated subjects on basal and TNF alpha-stimulated expression of VCAM-1 and E-selectin on cultured human umbilical vein endothelial cells. Baseline......% confidence interval: 95.0-208.7 microg/liter); P cells, there was no direct stimulatory effect of either GH or IGF-I on the expression of VCAM-1 and E-selectin, but serum from GH-treated healthy subjects significantly increased the expression of VCAM-1 (P

  3. Hypothalamic growth hormone-releasing hormone (GHRH) cell number is increased in human illness, but is not reduced in Prader-Willi syndrome or obesity

    NARCIS (Netherlands)

    Goldstone, Anthony P.; Unmehopa, Unga A.; Swaab, Dick F.

    2003-01-01

    Acute illness leads to increased GH, but reduced IGF-I secretion, while both are reduced in chronic illness. Prader-Willi syndrome (PWS) is a genetic obesity syndrome, with GH deficiency a feature independent of obesity. Reduced GH secretion may result from decreased hypothalamic release of

  4. Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association with increased insulin-like growth factor-I responses in rats

    DEFF Research Database (Denmark)

    Liu, Xiaowen; Murali, Sangita G; Holst, Jens Juul

    2008-01-01

    of GLP-2 and IGF-I system components are increased with the mucosal growth induced by enteral nutrient (EN) and/or a low dose of GLP-2 in parentally-fed rats. Rats were randomized to 4 treatment groups using a 2x2 design and maintained with parental nutrition (PN) for 7 days: PN alone, EN, GLP-2, EN...

  5. Changes in calcitropic hormones, bone markers and insulin-like growth factor I (IGF-I) during pregnancy and postpartum: a controlled cohort study

    DEFF Research Database (Denmark)

    Liendgaard, Ulla Kristine Møller; við Streym, Susanna; Mosekilde, Leif

    2012-01-01

    changes in calcium homeostasis, calcitropic hormones and bone metabolism during pregnancy and lactation. METHODS: We studied 153 women planning pregnancy (n = 92 conceived) and 52 non-pregnant, age-matched female controls. Samples were collected prior to pregnancy, once each trimester and 2, 16 and 36...... weeks postpartum. The controls were followed in parallel. RESULTS: P-estradiol (E(2)), prolactin and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) increased (p ..., markers of bone resorption and formation rose and fall, respectively (p 

  6. Overexpression of insulin-like growth factor (IGF)-I receptor enhances inhibition of DNA replication in mouse cells exposed to x-rays

    International Nuclear Information System (INIS)

    Wang, Y.; Cheong, N.; Miura, M.; Iliakis, G.

    1997-01-01

    Previous studies from our laboratory provided evidence for the operation of signal transduction pathways involving ras, myc, and staurosporine-sensitive protein kinases in the regulation of DNA replication in irradiated cells. Because ras and myc are also involved in the signal transduction elicited in response to ligand activation of growth factor receptors, we wondered whether growth factor receptors are upstream elements in the regulation of DNA replication in irradiated cells. Here, we report on the role of insulin-like growth factor I receptor (IGF-IR) in the regulation of DNA replication in irradiated cells. We compare radiation-induced inhibition of DNA replication in BALB/c 3T3 cells with that in P6 cells. P6 cells are derived from BALB/c 3T3 cells by transfection with a vector expressing IGF-IR, leading to 30-fold overexpression. We observe a significantly stronger inhibition of DNA replication after irradiation in P6 as compared with BALB/c 3T3 cells at all doses examined. Sedimentation in alkaline sucrose gradients shows that the increased inhibition in P6 cells is due to an increased inhibition of replicon initiation, the main controlling event in DNA replication. Staurosporine at 20 nM reduces radiation-induced inhibition of DNA replication in BALB/c 3T3 cells, but has only a small effect in P6 cells. Caffeine at a concentration of 1 mM, on the other hand, removes over 60% of the inhibition in both cell lines. The results implicate IGF-IR in the regulation of DNA replication in irradiated cells, but also suggest differences between cells of different origins in the proteins involved in the regulating signal transduction pathway. (orig.). With 5 figs

  7. Effects of dietary corn gluten meal on growth performance and protein metabolism in relation to IGF-I and TOR gene expression of juvenile cobia ( Rachycentron canadum)

    Science.gov (United States)

    Luo, Yiwen; Ai, Qinghui; Mai, Kangsen; Zhang, Wenbing; Xu, Wei; Zhang, Yanjiao; Liufu, Zhiguo

    2013-09-01

    A growth experiment was conducted on cobia ( Rachycentron canadum, initial weight 108.2 g ± 3.0 g) to investigate the effects of dietary corn gluten meal (CGM) levels on the fish growth, whole body composition and protein metabolism in relation to specific gene expression. Five isonitrogenous (crude protein 45%) and isoenergetic (gross energy 20 kJ g-1) practical diets were formulated by replacing 0% (the control), 17.5%, 35.0%, 52.5%, and 70.0% of fish meal (FM) protein with CGM protein. No significant differences were observed in the survival, feed intake (FI), specific growth rate (SGR), feed efficiency (FE) and protein productive value (PPV) among fish fed diets with 0%, 17.5%, 35.0%, and 52.5% of CGM protein. However, these indices were significantly lower in fish fed the diet with 70.0% of CGM protein than those in fish fed the control diet ( P cobia. The present results might be useful for developing cost effective and sustainable cobia dietary formulations.

  8. Deep sea minerals prolong life span of streptozotocin-induced diabetic rats by compensatory augmentation of the IGF-I-survival signaling and inhibition of apoptosis.

    Science.gov (United States)

    Liao, Hung-En; Shibu, Marthandam Asokan; Kuo, Wei-Wen; Pai, Pei-Ying; Ho, Tsung-Jung; Kuo, Chia-Hua; Lin, Jing-Ying; Wen, Su-Ying; Viswanadha, Vijaya Padma; Huang, Chih-Yang

    2016-07-01

    Consumption of deep sea minerals (DSM), such as magnesium, calcium, and potassium, is known to reduce hypercholesterolemia-induced myocardial hypertrophy and cardiac-apoptosis and provide protection against cardiovascular diseases. Heart diseases develop as a lethal complication among diabetic patients usually due to hyperglycemia-induced cardiac-apoptosis that causes severe cardiac-damages, heart failure, and reduced life expectancy. In this study, we investigated the potential of DSM and its related cardio-protection to increase the life expectancy in diabetic rats. In this study, a heart failure rat model was developed by using streptozotocin (65 mg kg(-1) ) IP injection. Different doses of DSM-1× (37 mg kg(-1) day(-1) ), 2× (74 mg kg(-1) day(-1) ) and 3× (111 mg kg(-1) day(-1) ), were administered to the rats through gavages for 4 weeks. The positive effects of DSM on the survival rate of diabetes rats were determined with respect to the corresponding effects of MgSO4 . Further, to understand the mechanism by which DSM enhances the survival of diabetic rats, their potential to regulate cardiac-apoptosis and control cardiac-dysfunction were examined. Echocardiogram, tissue staining, TUNEL assay, and Western blotting assay were used to investigate modulations in the myocardial contractile function and related signaling protein expression. The results showed that DSM regulate apoptosis and complement the cardiomyocyte proliferation by enhancing survival mechanisms. Moreover DSM significantly reduced the mortality rate and enhanced the survival rate of diabetic rats. Experimental results show that DSM administration can be an effective strategy to improve the life expectancy of diabetic subjects by improving cardiac-cell proliferation and by controlling cardiac-apoptosis and associated cardiac-dysfunction. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 769-781, 2016. © 2015 Wiley Periodicals, Inc.

  9. Plasma insulin-like growth factor I as predictor of progression and all cause mortality in chronic heart failure

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Kistorp, Caroline; Raymond, Ilan

    2009-01-01

    , renal function and LVEF) IGF-I levels did not influence the overall mortality risk or the admission rate to hospital, hazard ratio (HR) (95% confidence intervals) 1.05 (0.75-1.47) (P=0.77) and 1.00 (0.80-1.26) (P=0.96), respectively per each SD increase in log IGF-I levels. CONCLUSIONS: IGF-I levels...

  10. Balanced Physical Exercise Increase Physical Fitness, Optimize Endorphin Levels, and Decrease Malondialdehyde Levels

    Directory of Open Access Journals (Sweden)

    Erwin Adams Pangkahila

    2016-10-01

    Full Text Available Background: Physical fitness determines the level of human health. A good physical fitness can be achieved if conducted with a balance and active physical fitness. The aims of this study was to elucidate the effect of balanced physical exercise on physical fitness, endorphin levels, and malondialdehyde (MDA levels. Methods: This study was a true experimental with pretest-posttest control group design using 24 students of IKIP PGRI Denpasar. Selected samples divided into two groups: the control group given conventional physical training (P0 and the treatment group given balanced physical training (P1. Physical fitness tests was performed using Cooper method and blood sampling was done to evaluate the level of endorphins and MDA before (pre test and after (post test treatment of 8 weeks. The data of endorphin and MDA levels were analyzed using independent T test. Whereas, the physical fitness was analyzed using Mann-Whitney U test. Results: Physical fitness of the group given a balanced physical training was significantly higher compare to the group given a conventional physical training (p < 0.05. Balanced physical training was proven to enhance physical fitness as measured by the Cooper method better than conventional physical training. In contrast, the levels of endorphins of the balanced physical training group did not different with the conventional physical training group (p > 0.05. Levels of MDA of balanced physical training group also did not different with the conventional physical training group (p > 0.05. Conclusions: balanced physical training can maintain physical fitness of people and improve the health and quality of life. 

  11. Long-term insulin-like growth factor-I expression in skeletal muscles attenuates the enhanced in vitro proliferation ability of the resident satellite cells in transgenic mice

    Science.gov (United States)

    Chakravarthy, M. V.; Fiorotto, M. L.; Schwartz, R. J.; Booth, F. W.

    2001-01-01

    Insulin-like growth factor-I (IGF-I) overexpression for 1-month in mouse skeletal muscle increases satellite cell proliferation potential. However, it is unknown whether this beneficial enhancement by IGF-I expression would persist over a longer-term duration in aged mice. This is an important issue to address if a prolonged course of IGF-I is to be used clinically in muscle-wasting conditions where satellite cells may become limiting. Using the IGF-I transgenic (IGF-I Tg) mouse that selectively expresses the IGF-I transgene in striated muscles, we found that 18-months of continuous IGF-I overexpression led to a loss in the enhanced in vitro proliferative capacity of satellite cells from Tg skeletal muscles. Also 18-month-old IGF-I Tg satellite cells lost the enhanced BrdU incorporation, greater pRb and Akt phosphorylations, and decreased p27(Kip1) levels initially observed in cells from 1-month-old IGF-I Tg mice. The levels of those biochemical markers reverted to similar values seen in the 18-months WT littermates. These findings, therefore, suggest that there is no further beneficial effect on enhancing satellite cell proliferation ability with persistent long-term expression of IGF-I in skeletal muscles of these transgenic mice.

  12. 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

    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...

  13. Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects.

    Science.gov (United States)

    Martina, Valentino; Benso, Andrea; Gigliardi, Valentina Ramella; Masha, Andi; Origlia, Carla; Granata, Riccarda; Ghigo, Ezio

    2006-03-01

    Several clinical and population-based studies suggest that dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) play a protective role against atherosclerosis and coronary artery disease in human. However, the mechanisms underlying this action are still unknown. It has recently been suggested that DHEA-S could delay atheroma formation through an increase in nitric oxide (NO) production. Twenty-four aged male subjects [age (mean +/- SEM): 65.4 +/- 0.7 year; range: 58.2-67.6 years] underwent a blinded placebo controlled study receiving DHEA (50 mg p.o. daily at bedtime) or placebo for 2 months. Platelet cyclic guanosine-monophosphate (cGMP) concentration (as marker of NO production) and serum levels of DHEA-S, DHEA, IGF-I, insulin, glucose, oestradiol (E(2)), testosterone, plasminogen activator inhibitor (PAI)-1 antigen (PAI-1 Ag), homocysteine and lipid profile were evaluated before and after the 2-month treatment with DHEA or placebo. At the baseline, all variables in the two groups were overlapping. All parameters were unchanged after treatment with placebo. Conversely, treatment with DHEA (a) increased (P < 0.001 vs. baseline) platelet cGMP (111.9 +/- 7.1 vs. 50.1 +/- 4.1 fmol/10(6) plts), DHEA-S (13.6 +/- 0.8 vs. 3.0 +/- 0.3 micromol/l), DHEA (23.6 +/- 1.7 vs. 15.3 +/- 1.4 nmol/l), testosterone (23.6 +/- 1.0 vs. 17.7 +/- 1.0 nmol/l) and E(2) (72.0 +/- 5.0 vs. 60.0 +/- 4.0 pmol/l); and (b) decreased (P < 0.05 vs. baseline) PAI-1 Ag (27.4 +/- 3.8 vs. 21.5 +/- 2.5 ng/ml) and low-density lipoprotein (LDL) cholesterol (3.4 +/- 0.2 vs. 3.0 +/- 0.2 mmol/l). IGF-I, insulin, glucose, triglycerides, total cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and homocysteine levels were not modified by DHEA treatment. This study shows that short-term treatment with DHEA increased platelet cGMP production, a marker of NO production, in healthy elderly subjects. This effect is coupled with a decrease in PAI-1

  14. Estimated Cost of the Administration's Proposal to Increase the Army's and the Marine Corps's Personnel Levels

    National Research Council Canada - National Science Library

    Schmit, Matt; Wheelock, Jason; Newman, David

    2007-01-01

    .... The Administration also plans to increase the size of the Army Reserve and National Guard. The cost of the Administration's proposal to increase the size of the armed forces depends on the personnel levels it is being measured against...

  15. Do levels of perceived stress increase with increasing age after age 65? A population-based study.

    Science.gov (United States)

    Osmanovic-Thunström, Almira; Mossello, Enrico; Åkerstedt, Torbjörn; Fratiglioni, Laura; Wang, Hui-Xin

    2015-09-01

    psychological and health-related stressors often occur in advanced ages, but little is known about perceived stress in adults aged 65 and over. This study aimed to test the hypothesis that levels of perceived stress increase with increasing age and to detect factors that may account for the association. a dementia-free cohort of 1,656 adults aged 66-97 years living at home or in institutions, participating in the Swedish National Aging and Care study, Kungsholmen (SNAC-K) was assessed for levels of perceived stress using the 10-item perceived stress scale (PSS). prevalence of high stress according to the top tertile of the population (PSS score 20+) was 7.8% in adults aged 81+ years, 7.5% in adults aged 72-78 and 6.2% in adults aged 66 years (P = 0.020). More women than men reported high stress, 8.3 versus 5.4% (P = 0.001). Levels of stress increased with increasing age (P = 0.001) in the linear regression model. This association remained after adjustment for demographic and psychosocial factors, but no longer was present after adjusting for health-related factors. health-related stress is highly prevalent in older adults and seems to play an important role in the association between levels of perceived stress and age in older adults. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Effects of Water Level Increase on Phytoplankton Assemblages in a Drinking Water Reservoir

    Directory of Open Access Journals (Sweden)

    Yangdong Pan

    2018-03-01

    Full Text Available Excessive water level fluctuation may affect physico-chemical characteristics, and consequently ecosystem function, in lakes and reservoirs. In this study, we assessed the changes of phytoplankton assemblages in response to water level increase in Danjiangkou Reservoir, one of the largest drinking water reservoirs in Asia. The water level increased from a low of 137 m to 161 m in 2014 as a part of the South–North Water Diversion Project. Phytoplankton assemblages were sampled four times per year before, during and after the water level increase, at 10 sites. Environmental variables such as total nitrogen as well as phytoplankton biomass decreased after the water level increase. Non-metric multi-dimensional scaling analysis indicated that before the water level increase, phytoplankton assemblages showed distinct seasonal variation with diatom dominance in both early and late seasons while such seasonal variation was much less evident after the water level increase. Month and year (before and after explained 13% and 6% of variance in phytoplankton assemblages (PERMANOVA, p < 0.001 respectively, and phytoplankton assemblages were significantly different before and after the water level increase. Both chlorophytes and cyanobacteria became more abundant in 2015. Phytoplankton compositional change may largely reflect the environmental changes, such as hydrodynamics mediated by the water level increase.

  17. Glycine facilitates gamma-glutamylcysteinylethyl ester-mediated increase in liver glutathione level.

    Science.gov (United States)

    Nishida, K; Ohta, Y; Ishiguro, I

    1997-08-27

    gamma-Glutamylcysteinylethyl ester (gamma-GCE) increases reduced glutathione (GSH) levels in GSH-depleted rat hepatocytes. Because glycine, a constituent of GSH, exists at 0.3 to 0.4 mM in rat plasma, we examined the influence of glycine added to the medium on the action of gamma-GCE to increase GSH levels in the rat hepatocytes. Glycine (0.2-0.8 mM) dose-dependently enhanced gamma-GCE-mediated increase in intracellular GSH levels with an increase in intracellular gamma-GCE levels. These results indicate that exogenous glycine facilitates gamma-GCE-mediated increase in intracellular GSH levels in rat hepatocytes possibly by enhancing the uptake of gamma-GCE into the cells.

  18. Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor.

    Directory of Open Access Journals (Sweden)

    Masato Furuhashi

    Full Text Available Fatty acid-binding protein 4 (FABP4/A-FABP/aP2 is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP. Sodium-glucose cotransporter 2 (SGLT2 inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level.Canagliflozin (100 mg/day was administered to type 2 diabetic patients (n = 39 for 12 weeks. Serum FABP4 level was measured before and after treatment.At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008, though elevation of FABP4 level after treatment was observed in 26 (66.7% out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044, HbA1c (r = 0.329, P = 0.044 and noradrenaline (r = 0.329, P = 0.041 but was not significantly correlated with change in adiposity or other variables.Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2.UMIN-CTR Clinical Trial UMIN000018151.

  19. Influence of fatigue time and level on increases in postural sway.

    Science.gov (United States)

    Pline, Kevin M; Madigan, Michael L; Nussbaum, Maury A

    2006-12-15

    The purpose of this study was to investigate the influence of fatigue time and fatigue level on the increases in postural sway during quiet standing. Centre of pressure-based measures of postural sway were collected both before and after fatiguing participants using three different fatigue levels and two different fatigue times. Results showed increasing fatigue time increased sway velocity and sway area, and increasing fatigue level increased sway velocity. Fatigue time effects are important to consider when applying laboratory-based findings to the field given that the fatigue time can differ substantially between the two. Fatigue level effects imply a dose - response relationship between localized muscle fatigue and risk of falling that can have important implications in work/rest cycle scheduling for occupations at risk of injurious falls.

  20. Trophic assimilation efficiency markedly increases at higher trophic levels in four-level host-parasitoid food chain.

    Science.gov (United States)

    Sanders, Dirk; Moser, Andrea; Newton, Jason; van Veen, F J Frank

    2016-03-16

    Trophic assimilation efficiency (conversion of resource biomass into consumer biomass) is thought to be a limiting factor for food chain length in natural communities. In host-parasitoid systems, which account for the majority of terrestrial consumer interactions, a high trophic assimilation efficiency may be expected at higher trophic levels because of the close match of resource composition of host tissue and the consumer's resource requirements, which would allow for longer food chains. We measured efficiency of biomass transfer along an aphid-primary-secondary-tertiary parasitoid food chain and used stable isotope analysis to confirm trophic levels. We show high efficiency in biomass transfer along the food chain. From the third to the fourth trophic level, the proportion of host biomass transferred was 45%, 65% and 73%, respectively, for three secondary parasitoid species. For two parasitoid species that can act at the fourth and fifth trophic levels, we show markedly increased trophic assimilation efficiencies at the higher trophic level, which increased from 45 to 63% and 73 to 93%, respectively. In common with other food chains, δ(15)N increased with trophic level, with trophic discrimination factors (Δ(15)N) 1.34 and 1.49‰ from primary parasitoids to endoparasitic and ectoparasitic secondary parasitoids, respectively, and 0.78‰ from secondary to tertiary parasitoids. Owing to the extraordinarily high efficiency of hyperparasitoids, cryptic higher trophic levels may exist in host-parasitoid communities, which could alter our understanding of the dynamics and drivers of community structure of these important systems. © 2016 The Authors.

  1. Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals.

    Directory of Open Access Journals (Sweden)

    Shashi Bala

    Full Text Available Binge drinking, the most common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its biological consequences are poorly defined. Previous studies demonstrated that chronic alcohol use results in increased gut permeability and increased serum endotoxin levels that contribute to many of the biological effects of chronic alcohol, including alcoholic liver disease. In this study, we evaluated the effects of acute binge drinking in healthy adults on serum endotoxin levels. We found that acute alcohol binge resulted in a rapid increase in serum endotoxin and 16S rDNA, a marker of bacterial translocation from the gut. Compared to men, women had higher blood alcohol and circulating endotoxin levels. In addition, alcohol binge caused a prolonged increase in acute phase protein levels in the systemic circulation. The biological significance of the in vivo endotoxin elevation was underscored by increased levels of inflammatory cytokines, TNFα and IL-6, and chemokine, MCP-1, measured in total blood after in vitro lipopolysaccharide stimulation. Our findings indicate that even a single alcohol binge results in increased serum endotoxin levels likely due to translocation of gut bacterial products and disturbs innate immune responses that can contribute to the deleterious effects of binge drinking.

  2. Both experimental hypothyroidism and hyperthyroidism increase cardiac irisin levels in rats.

    Science.gov (United States)

    Atici, E; Menevse, E; Baltaci, A K; Mogulkoc, R

    2018-01-01

    Irisin is a newly discovered myokine and adipokine that increases total body energy expenditure. The aim of this study was to determine the effect of experimental hypothyroidism and hyperthyroidism on the levels of irisin in heart tissue in rats. The study was performed on the 40 male Sprague-Dawley rats. Experimental groups were designed as; Control, Hypothyroidism, Hypothyroidism+L-Thyroxine, Hyperthyroidism and Hyperthyroidism + PTU. Following 3 weeks experimental period, irisin levels were determined in heart tissues. Hypothyroidism group values of irisin were higher than in the control group, but lower than in the hyperthyroidism group. The hyperthyroidism group had the highest levels of cardiac irisin. The results of the study showed that the experimental hypothyroidism and hyperthyroidism increased the heart irisin levels, but the increase in the hyperthyroidism group was much higher than in the hypothyroidism group. However, treatment of hypothyroidism and hyperthyroidism corrected cardiac irisin levels (Fig. 1, Ref. 28).

  3. Increasing seat belt use through state-level demonstration projects : a compendium of initial findings

    Science.gov (United States)

    2008-08-01

    This report summarizes the efforts and results from four of six State-level demonstration projects supported with cooperative agreements from the National Highway Traffic Safety Administration. The projects were intended to increase seat belt use sta...

  4. Strategies for Mitigating the Reduction in Economic Value of Variable Generation with Increasing Penetration Levels

    Energy Technology Data Exchange (ETDEWEB)

    Mills, Andrew; Wiser, Ryan

    2014-03-03

    In this report, we evaluate individual options that have the potential to stem the decline in the marginal value of variable generation (VG) with increasing penetration levels. We focus only on the effectiveness of mitigation measures for wind and PV.

  5. Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury [v1; ref status: indexed, http://f1000r.es/2lf

    Directory of Open Access Journals (Sweden)

    Laura Genis

    2014-01-01

    Full Text Available Oxidative stress is a proposed mechanism in brain aging, making the study of its regulatory processes an important aspect of current neurobiological research. In this regard, the role of the aging regulator insulin-like growth factor I (IGF-I in brain responses to oxidative stress remains elusive as both beneficial and detrimental actions have been ascribed to this growth factor. Because astrocytes protect neurons against oxidative injury, we explored whether IGF-I participates in astrocyte neuroprotection and found that blockade of the IGF-I receptor in astrocytes abrogated their rescuing effect on neurons. The protection mediated by IGF-I against oxidative stress (H2O2 in astrocytes is probably needed for these cells to provide adequate neuroprotection. Indeed, in astrocytes but not in neurons, IGF-I helps decrease the pro-oxidant protein thioredoxin-interacting protein 1 and normalizes the levels of reactive oxygen species. Furthermore, IGF-I cooperates with trophic signals produced by astrocytes in response to H2O2 such as stem cell factor (SCF to protect neurons against oxidative insult. After stroke, a condition associated with brain aging where oxidative injury affects peri-infarcted regions, a simultaneous increase in SCF and IGF-I expression was found in the cortex, suggesting that a similar cooperative response takes place in vivo. Cell-specific modulation by IGF-I of brain responses to oxidative stress may contribute in clarifying the role of IGF-I in brain aging.

  6. Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury [v2; ref status: indexed, http://f1000r.es/38u

    Directory of Open Access Journals (Sweden)

    Laura Genis

    2014-04-01

    Full Text Available Oxidative stress is a proposed mechanism in brain aging, making the study of its regulatory processes an important aspect of current neurobiological research. In this regard, the role of the aging regulator insulin-like growth factor I (IGF-I in brain responses to oxidative stress remains elusive as both beneficial and detrimental actions have been ascribed to this growth factor. Because astrocytes protect neurons against oxidative injury, we explored whether IGF-I participates in astrocyte neuroprotection and found that blockade of the IGF-I receptor in astrocytes abrogated their rescuing effect on neurons. We found that IGF-I directly protects astrocytes against oxidative stress (H2O2. Indeed, in astrocytes but not in neurons, IGF-I decreases the pro-oxidant protein thioredoxin-interacting protein 1 and normalizes the levels of reactive oxygen species. Furthermore, IGF-I cooperates with trophic signals produced by astrocytes in response to H2O2 such as stem cell factor (SCF to protect neurons against oxidative insult. After stroke, a condition associated with brain aging where oxidative injury affects peri-infarcted regions, a simultaneous increase in SCF and IGF-I expression was found in the cortex, suggesting that a similar cooperative response takes place in vivo. Cell-specific modulation by IGF-I of brain responses to oxidative stress may contribute in clarifying the role of IGF-I in brain aging.

  7. Serum apolipoprotein e level is not increased in Alzheimer's disease : The Rotterdam study

    NARCIS (Netherlands)

    Slooter, A.J.C.; Knijff, P. de; Hofman, A.; Cruts, M.; Breteler, M.M.B.; Broeckhoven, C. van; Havekes, L.M.; Duijn, C.M. van

    1998-01-01

    The APOE*4 allele of the apolipoprotein E gene (APOE) is an important risk factor for Alzheimer's disease. It has been suggested that levels of apolipoprotein E (apoE) in plasma are increased in Alzheimer's disease. In this population-based study, we found that serum apoE levels were lower in

  8. High LDL levels lead to increased synovial inflammation and accelerated ectopic bone formation during experimental osteoarthritis

    NARCIS (Netherlands)

    Munter, W. de; Bosch, M.H. van den; Sloetjes, A.W.; Croce, K.J.; Vogl, T.; Roth, J.; Koenders, M.I.; Loo, F.A.J. van de; Berg, W.B. van den; Kraan, P.M. van der; Lent, P.L.E.M. van

    2016-01-01

    OBJECTIVE: A relation between osteoarthritis (OA) and increased cholesterol levels is apparent. In the present study we investigate OA pathology in apolipoprotein E (ApoE)(-)(/-) mice with and without a cholesterol-rich diet, a model for high systemic low density lipoprotein (LDL) cholesterol levels

  9. Ingestive behavior of grazing steers fed increasing levels of concentrate supplementation with different crude protein contents.

    Science.gov (United States)

    Mendes, Fabrício Bacelar Lima; Silva, Robério Rodrigues; de Carvalho, Gleidson Giordano Pinto; da Silva, Fabiano Ferreira; Lins, Túlio Otávio Jardim D Almeida; da Silva, Anderson Luiz Nascimento; Macedo, Venício; Abreu Filho, George; de Souza, Sinvaldo Oliveira; Guimarães, Joanderson Oliveira

    2015-02-01

    This study aimed to evaluate the ingestive behavior of steers on Brachiaria brizantha pasture fed diets with increasing levels of concentrate supplementation. Thirty-two crossbred steers in the finishing phase with average weight of 420 ± 8 kg were distributed in a completely randomized design with four treatments and eight replicates per treatment. Their behavior was assessed every 5 min for 24 h, in the middle of the experimental period. Variance and regression analyses at 0.05 % probability were adopted. The times spent grazing and ruminating reduced linearly (P <0.05), whereas the times spent at the trough (eating) and on other activities increased linearly (P <0.05) as the supplementation levels were elevated. The total feeding and chewing times decreased linearly (P <0.05) as the concentrate levels in the diet were elevated. By increasing the supplementation levels, the number of bites per day decreased linearly (P <0.05), and the feed efficiency of dry matter increased quadratically. Rumination efficiency of dry matter increased linearly (P <0.05) with increasing levels of concentrate supplementation. Grazing and rumination activities are reduced when the time devoted to other activities and at the trough are increased, as a result of the substitution effect.

  10. Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette Nørmølle; Demontis, Ditte; Ollendorff, Mathias Kaas

    2015-01-01

    measured by immunoassay, and potential determinants of the serum sortilin level were assessed by generalized linear models. Serum levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were measured in previous studies. We identified a significant increase of serum...... sortilin levels in depressed individuals compared with controls (P = 0.0002) and significant positive correlation between serum sortilin levels and the corresponding levels of BDNF and VEGF. None of the genotyped SNPs were associated with depression. Additional analyses showed that the serum sortilin level...... was influenced by several other factors. Alcohol intake and body mass index, as well as depression, serum BDNF and serum VEGF were identified as predictors of serum sortilin levels in our final multivariate model. In conclusion, the results suggest a role of circulating sortilin in depression which may relate...

  11. Serum levels of polyamine synthesis enzymes increase in diabetic patients with breast cancer

    Directory of Open Access Journals (Sweden)

    V Kenan Çelik

    2017-09-01

    Full Text Available In this study, it was aimed to investigate the relationship between diabetes and breast cancer and the detection of enzymes and ornithine levels in polyamine synthesis pathway in diabetes, breast cancer and diabetic breast cancer patients. Methods: Ornithine, arginine decarboxylase, ornithine decarboxylase and agmatinase levels have been measured in serum of all groups. Ornithine levels were measured spectrophotometrically. Arginine decarboxylase, ornithine decarboxylase and agmatinase levels were determined by ELISA kits. Results: Except for the diabetic group, the levels of enzymes in the polyamine synthesis pathway were increased in all and statistically significant (P < 0.05. The increase in the levels of agmatinase was very important among the enzymes (P < 0.001. Conclusions: Decreased levels of polyamine synthase enzymes in diabetes mellitus were found to be increased patients with breast cancer. Whether and how diabetes-based breast cancer development relates to increase activity of enzymes responsible for polyamine synthesis requires further mechanistic and prospective monitoring studies in larger patient cohorts.

  12. INCREASED TISSUE TRANSGLUTAMINASE LEVELS ARE ASSOCIATED WITH INCREASED EPILEPTIFORM ACTIVITY IN ELECTROENCEPHALOGRAPHY AMONG PATIENTS WITH CELIAC DISEASE

    Directory of Open Access Journals (Sweden)

    Sedat IŞIKAY

    2015-12-01

    Full Text Available Background - Celiac disease is an autoimmune systemic disorder in genetically predisposed individuals precipitated by gluten ingestion. Objective - In this study, we aimed to determine asymptomatic spike-and-wave findings on electroencephalography in children with celiac disease. Methods - A total of 175 children with the diagnosis of celiac disease (study group and 99 age- and sex-matched healthy children as controls (control group were included in the study. In order to determine the effects of gluten free diet on laboratory and electroencephalography findings, the celiac group is further subdivided into two as newly-diagnosed and formerly-diagnosed patients. Medical histories of all children and laboratory findings were all recorded and neurologic statuses were evaluated. All patients underwent a sleep and awake electroencephalography. Results - Among 175 celiac disease patients included in the study, 43 were newly diagnosed while 132 were formerly-diagnosed patients. In electroencephalography evaluation of patients the epileptiform activity was determined in 4 (9.3% of newly diagnosed and in 2 (1.5% of formerly diagnosed patients; on the other hand the epileptiform activity was present in only 1 (1.0% of control cases. There was a statistically significant difference between groups in regards to the presence of epileptiform activity in electroencephalography. Pearson correlation analysis revealed that epileptiform activity in both sleep and awake electroencephalography were positively correlated with tissue transglutaminase levels (P=0.014 and P=0.019, respectively. Conclusion - We have determined an increased epileptiform activity frequency among newly-diagnosed celiac disease patients compared with formerly-diagnosed celiac disease patients and control cases. Moreover the tissue transglutaminase levels were also correlated with the presence of epileptiform activity in electroencephalography. Among newly diagnosed celiac disease patients

  13. A Forest Tent Caterpillar Outbreak Increased Resource Levels and Seedling Growth in a Northern Hardwood Forest.

    Directory of Open Access Journals (Sweden)

    Danaë M A Rozendaal

    Full Text Available In closed-canopy forests, gap formation and closure are thought to be major drivers of forest dynamics. Crown defoliation by insects, however, may also influence understory resource levels and thus forest dynamics. We evaluate the effect of a forest tent caterpillar outbreak on understory light availability, soil nutrient levels and tree seedling height growth in six sites with contrasting levels of canopy defoliation in a hardwood forest in northern lower Michigan. We compared resource levels and seedling growth of six hardwood species before, during and in the three years after the outbreak (2008-2012. Canopy openness increased strongly during the forest tent caterpillar outbreak in the four moderately and severely defoliated sites, but not in lightly defoliated sites. Total inorganic soil nitrogen concentrations increased in response to the outbreak in moderately and severely defoliated sites. The increase in total inorganic soil nitrogen was driven by a strong increase in soil nitrate, and tended to become stronger with increasing site defoliation. Seedling height growth increased for all species in the moderately and severely defoliated sites, but not in lightly defoliated sites, either during the outbreak year or in the year after the outbreak. Growth increases did not become stronger with increasing site defoliation, but were strongest in a moderately defoliated site with high soil nutrient levels. Growth increases tended to be strongest for the shade intolerant species Fraxinus americana and Prunus serotina, and the shade tolerant species Ostrya virginiana. The strong growth response of F. americana and P. serotina suggests that recurring forest tent caterpillar outbreaks may facilitate the persistence of shade intolerant species in the understory in the absence of canopy gaps. Overall, our results suggest that recurrent canopy defoliation resulting from cyclical forest insect outbreaks may be an additional driver of dynamics in

  14. A Forest Tent Caterpillar Outbreak Increased Resource Levels and Seedling Growth in a Northern Hardwood Forest.

    Science.gov (United States)

    Rozendaal, Danaë M A; Kobe, Richard K

    2016-01-01

    In closed-canopy forests, gap formation and closure are thought to be major drivers of forest dynamics. Crown defoliation by insects, however, may also influence understory resource levels and thus forest dynamics. We evaluate the effect of a forest tent caterpillar outbreak on understory light availability, soil nutrient levels and tree seedling height growth in six sites with contrasting levels of canopy defoliation in a hardwood forest in northern lower Michigan. We compared resource levels and seedling growth of six hardwood species before, during and in the three years after the outbreak (2008-2012). Canopy openness increased strongly during the forest tent caterpillar outbreak in the four moderately and severely defoliated sites, but not in lightly defoliated sites. Total inorganic soil nitrogen concentrations increased in response to the outbreak in moderately and severely defoliated sites. The increase in total inorganic soil nitrogen was driven by a strong increase in soil nitrate, and tended to become stronger with increasing site defoliation. Seedling height growth increased for all species in the moderately and severely defoliated sites, but not in lightly defoliated sites, either during the outbreak year or in the year after the outbreak. Growth increases did not become stronger with increasing site defoliation, but were strongest in a moderately defoliated site with high soil nutrient levels. Growth increases tended to be strongest for the shade intolerant species Fraxinus americana and Prunus serotina, and the shade tolerant species Ostrya virginiana. The strong growth response of F. americana and P. serotina suggests that recurring forest tent caterpillar outbreaks may facilitate the persistence of shade intolerant species in the understory in the absence of canopy gaps. Overall, our results suggest that recurrent canopy defoliation resulting from cyclical forest insect outbreaks may be an additional driver of dynamics in temperate closed

  15. Modeling Caspian Sea water level oscillations under different scenarios of increasing atmospheric carbon dioxide concentrations

    Directory of Open Access Journals (Sweden)

    Roshan GholamReza

    2012-12-01

    Full Text Available Abstract The rapid rise of Caspian Sea water level (about 2.25 meters since 1978 has caused much concern to all five surrounding countries, primarily because flooding has destroyed or damaged buildings and other engineering structures, roads, beaches and farm lands in the coastal zone. Given that climate, and more specifically climate change, is a primary factor influencing oscillations in Caspian Sea water levels, the effect of different climate change scenarios on future Caspian Sea levels was simulated. Variations in environmental parameters such as temperature, precipitation, evaporation, atmospheric carbon dioxide and water level oscillations of the Caspian sea and surrounding regions, are considered for both past (1951-2006 and future (2025-2100 time frames. The output of the UKHADGEM general circulation model and five alternative scenarios including A1CAI, BIASF, BIMES WRE450 and WRE750 were extracted using the MAGICC SCENGEN Model software (version 5.3. The results suggest that the mean temperature of the Caspian Sea region (Bandar-E-Anzali monitoring site has increased by ca. 0.17°C per decade under the impacts of atmospheric carbon dioxide changes (r=0.21. The Caspian Sea water level has increased by ca. +36cm per decade (r=0.82 between the years 1951-2006. Mean results from all modeled scenarios indicate that the temperature will increase by ca. 3.64°C and precipitation will decrease by ca. 10% (182 mm over the Caspian Sea, whilst in the Volga river basin, temperatures are projected to increase by ca. 4.78°C and precipitation increase by ca. 12% (58 mm by the year 2100. Finally, statistical modeling of the Caspian Sea water levels project future water level increases of between 86 cm and 163 cm by the years 2075 and 2100, respectively.

  16. Modeling Caspian Sea water level oscillations under different scenarios of increasing atmospheric carbon dioxide concentrations.

    Science.gov (United States)

    Roshan, Gholamreza; Moghbel, Masumeh; Grab, Stefan

    2012-12-12

    The rapid rise of Caspian Sea water level (about 2.25 meters since 1978) has caused much concern to all five surrounding countries, primarily because flooding has destroyed or damaged buildings and other engineering structures, roads, beaches and farm lands in the coastal zone. Given that climate, and more specifically climate change, is a primary factor influencing oscillations in Caspian Sea water levels, the effect of different climate change scenarios on future Caspian Sea levels was simulated. Variations in environmental parameters such as temperature, precipitation, evaporation, atmospheric carbon dioxide and water level oscillations of the Caspian sea and surrounding regions, are considered for both past (1951-2006) and future (2025-2100) time frames. The output of the UKHADGEM general circulation model and five alternative scenarios including A1CAI, BIASF, BIMES WRE450 and WRE750 were extracted using the MAGICC SCENGEN Model software (version 5.3). The results suggest that the mean temperature of the Caspian Sea region (Bandar-E-Anzali monitoring site) has increased by ca. 0.17°C per decade under the impacts of atmospheric carbon dioxide changes (r=0.21). The Caspian Sea water level has increased by ca. +36cm per decade (r=0.82) between the years 1951-2006. Mean results from all modeled scenarios indicate that the temperature will increase by ca. 3.64°C and precipitation will decrease by ca. 10% (182 mm) over the Caspian Sea, whilst in the Volga river basin, temperatures are projected to increase by ca. 4.78°C and precipitation increase by ca. 12% (58 mm) by the year 2100. Finally, statistical modeling of the Caspian Sea water levels project future water level increases of between 86 cm and 163 cm by the years 2075 and 2100, respectively.

  17. Increased prolactin levels are associated with impaired processing speed in subjects with early psychosis.

    Science.gov (United States)

    Montalvo, Itziar; Gutiérrez-Zotes, Alfonso; Creus, Marta; Monseny, Rosa; Ortega, Laura; Franch, Joan; Lawrie, Stephen M; Reynolds, Rebecca M; Vilella, Elisabet; Labad, Javier

    2014-01-01

    Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for psychosis. Recent studies in non-psychiatric populations suggest that increased prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma prolactin levels are associated with poorer cognitive functioning in subjects with early psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects with an early psychosis (55 psychotic disorders with levels were determined as well as total cortisol levels in plasma. Psychopathological status was assessed and the use of psychopharmacological treatments (antipsychotics, antidepressants, benzodiazepines) recorded. Prolactin levels were negatively associated with cognitive performance in processing speed, in patients with a psychotic disorder and high-risk subjects. In the latter group, increased prolactin levels were also associated with impaired reasoning and problem solving and poorer general cognition. In a multiple linear regression analysis conducted in both high-risk and psychotic patients, controlling for potential confounders, prolactin and benzodiazepines were independently related to poorer cognitive performance in the speed of processing domain. A mediation analysis showed that both prolactin and benzodiazepine treatment act as mediators of the relationship between risperidone/paliperidone treatment and speed of processing. These results suggest that increased prolactin levels are associated with impaired processing speed in early psychosis. If these results are confirmed in future studies, strategies targeting reduction of prolactin levels may improve cognition in this population.

  18. Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury.

    Science.gov (United States)

    Sawicki, Konrad Teodor; Shang, Meng; Wu, Rongxue; Chang, Hsiang-Chun; Khechaduri, Arineh; Sato, Tatsuya; Kamide, Christine; Liu, Ting; Naga Prasad, Sathyamangla V; Ardehali, Hossein

    2015-07-31

    Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to nontransgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to nonischemic cardiomyopathy. Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a novel approach for protection against the

  19. Higher Maternal Protein Intake during Pregnancy Is Associated with Lower Cord Blood Concentrations of Insulin-like Growth Factor (IGF)-II, IGF Binding Protein 3, and Insulin, but Not IGF-I, in a Cohort of Women with High Protein Intake.

    Science.gov (United States)

    Switkowski, Karen M; Jacques, Paul F; Must, Aviva; Hivert, Marie-France; Fleisch, Abby; Gillman, Matthew W; Rifas-Shiman, Sheryl; Oken, Emily

    2017-07-01

    Background: Prenatal exposure to dietary protein may program growth-regulating hormones, consequently influencing early-life growth patterns and later risk of associated chronic diseases. The insulin-like growth factor (IGF) axis is of particular interest in this context given its influence on pre- and postnatal growth and its sensitivity to the early nutritional environment. Objective: Our objective was to examine associations of maternal protein intake during pregnancy with cord blood concentrations of IGF-I, IGF-II, IGF binding protein-3 (IGFBP-3), and insulin. Methods: We studied 938 mother-child pairs from early pregnancy through delivery in the Project Viva cohort. Using multivariable linear regression models adjusted for maternal race/ethnicity, education, income, smoking, parity, height, and gestational weight gain and for child sex, we examined associations of second-trimester maternal protein intake [grams per kilogram (weight before pregnancy) per day], as reported on a food frequency questionnaire, with IGF-I, IGF-II, IGFBP-3, and insulin concentrations in cord blood. We also examined how these associations may differ by child sex and parity. Results: Mothers were predominantly white (71%), college-educated (64%), and nonsmokers (67%). Mean ± SD protein intake was 1.35 ± 0.35 g ⋅ kg -1 ⋅ d -1 Each 1-SD increment in second-trimester protein intake corresponded to a change of -0.50 ng/mL (95% CI: -2.26, 1.26 ng/mL) in IGF-I and -0.91 μU/mL (95% CI: -1.45, -0.37 μU/mL) in insulin. Child sex and parity modified associations of maternal protein intake with IGF-II and IGFBP-3: protein intake was inversely associated with IGF-II in girls ( P -interaction = 0.04) and multiparous mothers ( P -interaction = 0.05), and with IGFBP-3 in multiparous mothers ( P -interaction = 0.04). Conclusions: In a cohort of pregnant women with relatively high mean protein intakes, higher intake was associated with lower concentrations of growth-promoting hormones in cord

  20. Thrombotic thrombocytopenic purpura with decreased level of ADAMTS-13 activity and increased level of ADAMTS-13 inhibitor in an adolescent

    Directory of Open Access Journals (Sweden)

    Eun Mi Yang

    2010-03-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a thrombotic microangiopathy characterized by endothelial cell damage, resulting in microangiopathic hemolytic anemia, thrombocytopenia, and various degrees of neurological and renal impairment caused by microvascular thrombi. It is rare in children and frequently follows a fatal course. TTP is divided into 2 types: one is inherited and associated with ADAMTS-13 gene mutations and the other is acquired and associated with anti-ADAMTS-13 autoantibodies. The measurement of ADAMTS-13 activity in plasma, identification of ADAMTS-13 circulating inhibitor, anti-ADAMTS-13 IgG, and ADAMTS-13 gene sequencing are crucial to the diagnosis of TTP. Plasma exchanges are the first-line treatment for acquired TTP, combined with steroids and immunosuppressive drugs. Here, we describe the case of an adolescent patient with TTP, confirmed by decreased level of ADAMTS-13 activity and an increased level of ADAMTS-13 inhibitor, who was successfully treated by plasma exchanges.

  1. Growth hormone increases vascular cell adhesion molecule 1 expression

    DEFF Research Database (Denmark)

    Hansen, Troels Krarup; Fisker, Sanne; Dall, Rolf

    2004-01-01

    and 25 adult GH-deficient (GHD) patients randomized to GH treatment or placebo. Furthermore, we studied the direct effect of GH and IGF-I and serum from GH-treated subjects on basal and TNF alpha-stimulated expression of VCAM-1 and E-selectin on cultured human umbilical vein endothelial cells. Baseline...... levels of VCAM-1, but not E-selectin, were significantly lower in GHD patients than in healthy subjects (362 +/- 15 microg/liter vs. 516 +/- 21 microg/liter, P liter (95......% confidence interval: 95.0-208.7 microg/liter); P

  2. Increased abdominal fat levels measured by bioelectrical impedance are associated with histological lesions of nonalcoholic steatohepatitis.

    Science.gov (United States)

    Margariti, Aikaterini; Kontogianni, Meropi D; Tileli, Nafsika; Georgoulis, Michael; Deutsch, Melanie; Zafeiropoulou, Rodessa; Tiniakos, Dina; Manios, Yannis; Pectasides, Dimitrios; Papatheodoridis, George V

    2015-08-01

    Abdominal fat is considered to play an important role in nonalcoholic fatty liver disease (NAFLD), although it is not adequately studied because abdominal fat levels cannot be estimated easily. In this study, associations between abdominal obesity, as assessed by abdominal bioelectrical impedance analysis (BIA), and the characteristics of patients with NAFLD were explored. Seventy-four consecutive NAFLD patients who underwent measurement of abdominal fat levels by BIA were included. Levels of abdominal fat 12.5 or less and more than 12.5 were considered to be average and increased, respectively. The mean±SD BMI was 30±4 kg/m and the mean abdominal fat levels were 16±5, whereas 26% of patients had average abdominal fat levels. Patients with average compared with those with increased abdominal fat levels were more frequently women (50 vs. 12%, P=0.001), had lower BMI (27±3 vs. 31±4 kg/m, Pabdominal fat levels (78 vs. 38%, P=0.030) and in patients with BMI 30 or more compared with less than 30 kg/m (87 vs. 48%, P=0.033), but similar in patients with increased or normal waist circumference (67 vs. 56%, P=0.693). Average levels of abdominal fat, as assessed by abdominal BIA, are mainly present in female patients with NAFLD and are associated with a lower degree of insulin resistance. Increased abdominal fat as assessed by BIA and obesity seem to represent strong risk factors for histological steatohepatitis.

  3. IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

    Science.gov (United States)

    Akirov, Amit; Greenman, Yona; Glaser, Benjamin; S'chigol, Irena; Mansiterski, Yossi; Eizenberg, Yoav; Shraga-Slutzky, Ilana; Shimon, Ilan

    2018-05-04

    Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

  4. Effect of increasing levels of apparent metabolizable energy on laying hens in barn system.

    Science.gov (United States)

    Kang, Hwan Ku; Park, Seong Bok; Jeon, Jin Joo; Kim, Hyun Soo; Park, Ki Tae; Kim, Sang Ho; Hong, Eui Chul; Kim, Chan Ho

    2018-04-12

    This experiment was to investigate the effect of increasing levels of apparent metabolizable energy (AMEn) on the laying performance, egg quality, blood parameter, blood biochemistry, intestinal morphology, and apparent total tract digestibility (ATTD) of energy and nutrients in diets fed to laying hens. A total of three-hundred twenty 33-week-old Hy-Line Brown laying hens (Gallus domesticus) were evenly assigned to four experimental diets of 2,750, 2,850, 2,950, and 3,050 kcal AMEn/kg in floor with deep litter of rice hulls. There were four replicates of each treatment, each consisting of 20 birds in a pen. AMEn intake was increased (linear, p Feed intake and feed conversion ratio were improved (linear, p hen-day egg production tended to be increased as increasing level of AMEn in diets increased. During the experiment, leukocyte concentration and blood biochemistry (total cholesterol, triglyceride, glucose, total protein, calcium, asparate aminotransferase (AST), and alanine transferase (ALT) were not influenced by increasing level of AMEn in diets. Gross energy and ether extract were increased (linear, p hens fed high AMEn diet (i.e., 3,050 kcal/kg in the current experiment) tended to overconsume energy with a positive effect on feed intake, feed conversion ratio, nutrient digestibility, and intestinal morphology but not in egg production and egg mass.

  5. Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination.

    Directory of Open Access Journals (Sweden)

    Henning Hagmann

    Full Text Available RATIONALE: Preeclampsia is a devastating medical complication of pregnancy which leads to maternal and fetal morbidity and mortality. While the etiology of preeclampsia is unclear, human and animal studies suggest that excessive circulating levels of soluble fms-like tyrosine-kinase-1 (sFlt-1, an alternatively spliced variant of VEGF-receptor1, contribute to the signs and symptoms of preeclampsia. Since sFlt-1 binds to heparin and heparan sulfate proteoglycans, we hypothesized that the anticoagulant heparin, which is often used in pregnancy, may interfere with the levels, distribution and elimination of sFlt-1 in vivo. OBJECTIVE: We systematically determined serum and urine levels of angiogenic factors in preeclamptic women before and after administration of low molecular weight heparin and further characterized the interaction with heparin in biochemical studies. METHODS AND RESULTS: Serum and urine samples were used to measure sFlt-1 levels before and after heparin administration. Serum levels of sFlt-1 increased by 25% after heparin administration in pregnant women. The magnitude of the increase in circulating sFlt-1 correlated with initial sFlt-1 serum levels. Urinary sFlt-1 levels were also elevated following heparin administration and levels of elimination were dependent on the underlying integrity of the glomerular filtration barrier. Biochemical binding studies employing cation exchange chromatography revealed that heparin bound sFlt-1 had decreased affinity to negatively charged surfaces when compared to sFlt-1 alone. CONCLUSION: Low molecular weight heparin administration increased circulating sFlt1 levels and enhanced renal elimination. We provide evidence that both effects may be due to heparin binding to sFlt1 and masking the positive charges on sFlt1 protein.

  6. Enteral nutrition increases interstitial brain glucose levels in poor-grade subarachnoid hemorrhage patients.

    Science.gov (United States)

    Kofler, Mario; Schiefecker, Alois J; Beer, Ronny; Gaasch, Maxime; Rhomberg, Paul; Stover, John; Pfausler, Bettina; Thomé, Claudius; Schmutzhard, Erich; Helbok, Raimund

    2018-03-01

    Low brain tissue glucose levels after acute brain injury are associated with poor outcome. Whether enteral nutrition (EN) reliably increases cerebral glucose levels remains unclear. In this retrospective analysis of prospectively collected observational data, we investigate the effect of EN on brain metabolism in 17 poor-grade subarachnoid hemorrhage (SAH) patients undergoing cerebral microdialysis (CMD) monitoring. CMD-values were obtained hourly. A nutritional intervention was defined as the clinical routine administration of EN without supplemental parenteral nutrition. Sixty-three interventions were analyzed. The mean amount of EN per intervention was 472.4 ± 10.7 kcal. CMD-glucose levels significantly increased from 1.59 ± 0.13 mmol/l at baseline to a maximum of 2.03 ± 0.2 mmol/l after 5 h (p  40) and the microdialysis probe location. The increase in CMD-glucose was directly dependent on the magnitude of increase of serum glucose levels (p = 0.007). No change in CMD-lactate, CMD-pyruvate, CMD-LPR, or CMD-glutamate (p > 0.4) was observed. Routine EN also increased CMD-glucose even if baseline concentrations were critically low ( < 0.7 mmol/l, neuroglucopenia; p < 0.001). These results may have treatment implications regarding glucose management of poor-grade aneurysmal SAH patients.

  7. Core design experience of WWER-440 reactors when they working on increased power level

    International Nuclear Information System (INIS)

    Adeev, V.; Panov, A.; Melenchuk, I.

    2015-01-01

    The Kola NPP continues commercial operation of 2nd generation fuel (FA-2) and trial operation of 3rd generation fuel (FA-3), which has a number of design features providing the best operational characteristics. This report gives the results of VVER-440 core operation with FA-2 and FA-3 with enrichment increased up to 4.87%, and at the power level uprated to 107% of nominal power level. Brief analysis of obtained data is carried out. Peculiarities and techniques of developing loading patterns with new types of nuclear fuel for operation at the uprated power level are reviewed. (authors)

  8. Respiratory Deleted in Malignant Brain Tumours 1 (DMBT1) levels increase during lung maturation and infection

    DEFF Research Database (Denmark)

    Müller, H; End, C; Weiss, C

    2007-01-01

    .0179). An increase of respiratory DMBT1 levels was detected in neonatal infections (P ...Deleted in Malignant Brain Tumours 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds and aggregates various bacteria and viruses in vitro. Studies in adults have shown that DMBT1 is expressed mainly by mucosal epithelia and glands, in particular within the respiratory...... tract, and plays a role in innate immune defence. We hypothesized that respiratory DMBT1 levels may be influenced by various developmental and clinical factors such as maturity, age and bacterial infection. DMBT1 levels were studied in 205 tracheal aspirate samples of 82 ventilated preterm and full...

  9. Relationship between increased serum tumor necrosis factor levels and insulin resistance in patients with essential hypertension

    International Nuclear Information System (INIS)

    Wang Weimin; Li Jinliang; Huang Yongqiang

    2010-01-01

    Objective: To investigate the relationship between serum tumor necrosis factor-α (TNF-α) levels and insulin resistance (IR) in patients with essential by pertension. Methods: Serum TNF-α and free insulin (fINS)levels were measured with RIA in 41 patients with essential hypertension and 38 controls. Insulin resistance was calculated with insulin resistance index (HOMA-IR). Results: The serum TNF-α levels were significantly higher in patients with essential hypertension than those in the controls (P<0.001). The HOMA-IR was also significantly higher in hypertension group than that in controls (P<0.001). Serum TNF-α levels was positively correlated with BMI, HOMA-IR and SBP both in hypertension group and control group (P<0.05). Conclusion: Serum TNF-α level was increased in hypertensive patients and positively correlated with obesity and IR. (authors)

  10. Elevated fasting insulin levels increase the risk of abdominal obesity in Korean men.

    Science.gov (United States)

    Park, Sung Keun; Oh, Chang-Mo; Jung, Taegi; Choi, Young-Jun; Chung, Ju Youn; Ryoo, Jae-Hong

    2017-04-01

    This study was designed to investigate whether an elevated fasting insulin level predicts abdominal obesity. A cohort study was conducted with 13,707 non-obese Korean men. They were categorized into 4 groups according to the quartile of fasting insulin level, and followed up from 2005 to 2010. Incidence rates of obesity were compared among the 4 groups during follow-up, and a Cox proportional hazards model was used to calculate hazard ratios (HRs) for abdominal obesity according to fasting insulin level. The overall incidence rate of obesity was 16.2%, but the rate increased in proportion to the fasting insulin level (quartiles 1-4: 9.8%, 12.4%, 16.9%, 25.5%, Pobesity increased proportionally to baseline fasting insulin level in an unadjusted model. However, after adjustment for covariates, including baseline waist circumference (WC), only in the quartile 4 group was the statistical significance of the association maintained [quartile 2-4; abdominal obesity: 0.89 (0.76-1.02), 1.00 (0.86-1.14) and 1.24 (1.08-1.43), P for trend obesity was highest in the group with the highest fasting insulin levels, an overall proportional relationship between fasting insulin level and incident abdominal obesity was not found. Additionally, this association was largely accounted for by baseline WC. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Growth hormone receptor deficiency in mice results in reduced systolic blood pressure and plasma renin, increased aortic eNOS expression, and altered cardiovascular structure and function

    DEFF Research Database (Denmark)

    Egecioglu, E; Andersson, I J; Bollano, E

    2007-01-01

    To study the role of the growth hormone receptor (GHR) in the development of cardiovascular structure and function, female GHR gene-disrupted or knockout (KO) and wild-type (WT) mice at age 18 wk were used. GHR KO mice had lower plasma renin levels (12 +/- 2 vs. 20 +/- 4 mGU/ml, P < 0.05) and inc....... These data suggest an important role for an intact GH/IGF-I axis in the maintenance of a normal cardiovascular system....

  12. Apelin-13 increased food intake with serum ghrelin and leptin levels in male rats.

    Science.gov (United States)

    Saral, S; Alkanat, M; Sumer, A; Canpolat, S

    2018-01-01

    In this study, we aimed to explain the role of apelin-13 on body weight, food and water intake with serum leptin, ghrelin, neuropeptid Y (NPY) and peptid YY (PYY) levels in male rat. Thirty-two Sprague-Dawley male rats were used for the study. The rats were injected SP (0.9 %) intraperitoneally (i.p) in the control group and 30 (AP30), 100 (AP100) and 300 (AP300) µg/kg apelin-13 in the study groups, respectively, 10 min before the transition to dark period, for 10 days. During the experimental period, with light and dark periods of food and water intake, body weights were recorded in rats. Rats were euthanized and serum samples were obtained. In serum samples leptin, ghrelin, NPY and PYY levels were measured with specific ELISA kit. Apelin-13 was increased body weights in all three (AP30, AP100 and AP300) groups compared with the control group. AP100 and AP300 groups had increased food intake in the dark and the cumulative period, but in the light period food intake values were not significantly increased (p > 0.05). As for the value of water intake, compared with the control group, all dose of apelin-13 increased water intake during the dark and the cumulative period. There was no significant change in water intake in the light period. On the other hand, compared with the control group, serum leptin levels were found to increase in the groups administered 100 and 300 µg/kg of apelin-13 (p Ghrelin levels were found high in all groups treated with apelin-13. Serum levels of NPY decreased only in the 300 µg/kg apelin-13 treated group (p 0.05). Apelin-13 increases body weight in rats as well as food and water intake (dark and cumulative period). Additionally, ghrelin can mediate the orexigenic effect of apelin-13 in the regulation of food intake (Fig. 4, Ref. 37).

  13. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels

    Science.gov (United States)

    Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B.; Dong, Xiao; Wang, Hongjun

    2015-01-01

    Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice. PMID:26017184

  14. Respirometry increases cortisol levels in rainbow trout Oncorhynchus mykiss: implications for measurements of metabolic rate

    DEFF Research Database (Denmark)

    Murray, L.; Rennie, M. D.; Svendsen, Jon Christian

    2017-01-01

    This study aimed to assess the extent to which chasing, handling and confining Oncorhynchus mykiss to a small respirometer chamber during respirometric experiments is stressful and affects metabolic measurements. The study observed increased cortisol levels in animals tested using a chase protocol...

  15. Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome

    DEFF Research Database (Denmark)

    Dixon, J; Brakebusch, C; Fässler, R

    2000-01-01

    mice die perinatally as a result of severe craniofacial anomalies that include agenesis of the nasal passages, abnormal development of the maxilla, exencephaly and anophthalmia. These defects arise due to a massive increase in the levels of apoptosis in the prefusion neural folds, which are the site...

  16. Increased osteopontin plasma levels in multiple sclerosis patients correlate with bone-specific markers

    NARCIS (Netherlands)

    Vogt, M.H.J.; ten Kate, J.; Drent, R.J.M.; Polman, C.H.; Hupperts, R.

    2010-01-01

    The pro-inflammatory cytokine osteopontin has been found to be highly expressed in multiple sclerosis lesions and plasma levels are increased during relapses in relapse-onset multiple sclerosis patients. The objective was to determine the relationship between osteopontin plasma and cerebrospinal

  17. 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

    BACKGROUND: Low GH levels, probably due to insulin resistance and increased abdominal fat mass, are well described in polycystic ovary syndrome (PCOS). GH acts as an important ovarian cogonadotropin, and GH disturbances may be an additional pathogenic factor in PCOS. Decreased abdominal fat mass...

  18. Acceptability and storage stability of pork products with increased levels of polyunsaturated fatty acids

    NARCIS (Netherlands)

    Houben, J.H.; Krol, B.

    1980-01-01

    Several batches of back bacon, belly bacon, Dutch-style cervelat sausage, pork loin roll, shoulder with fat, Bologna, Guelders ring sausage, Saxon liver sausage and luncheon meat were produced with increasing PUFA-levels using raw materials containing up to 30% linoleic acid in their fats. Only

  19. Epalrestat increases intracellular glutathione levels in Schwann cells through transcription regulation

    Directory of Open Access Journals (Sweden)

    Keisuke Sato

    2014-01-01

    Full Text Available Epalrestat (EPS, approved in Japan, is the only aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Here we report that EPS at near-plasma concentration increases the intracellular levels of glutathione (GSH, which is important for protection against oxidative injury, through transcription regulation. Treatment of Schwann cells with EPS caused a dramatic increase in intracellular GSH levels. EPS increased the mRNA levels of γ-glutamylcysteine synthetase (γ-GCS, the enzyme catalyzing the first and rate-limiting step in de novo GSH synthesis. Nuclear factor erythroid 2-related factor 2 (Nrf2 is a key transcription factor that plays a central role in regulating the expression of γ-GCS. ELISA revealed that EPS increased nuclear Nrf2 levels. Knockdown of Nrf2 by siRNA suppressed the EPS-induced GSH biosynthesis. Furthermore, pretreatment with EPS reduced the cytotoxicity induced by H2O2, tert-butylhydroperoxide, 2,2'-azobis (2-amidinopropane dihydrochloride, and menadione, indicating that EPS plays a role in protecting against oxidative stress. This is the first study to show that EPS induces GSH biosynthesis via the activation of Nrf2. We suggest that EPS has new beneficial properties that may prevent the development and progression of disorders caused by oxidative stress.

  20. Elevated levels of homocysteine increase IL-6 production in monocytic Mono Mac 6 cells

    NARCIS (Netherlands)

    van Aken, B. E.; Jansen, J.; van Deventer, S. J.; Reitsma, P. H.

    2000-01-01

    Hyperhomocysteinemia is a risk factor for atherosclerosis and thrombosis. The aim of this study was to analyze if exposure of monocytic cells to increased levels of homocysteine (HCY) induces the accumulation of inflammatory mediators. Interleukin (IL)-6 production by monocytic cell line Mono Mac 6

  1. Modeling Effectiveness of Gradual Increases in Source Level to Mitigate Effects of Sonar on Marine Mammals

    NARCIS (Netherlands)

    Benda-Beckmann, A.M. von; Wensveen, P.J.; Kvadsheim, P.H.; Lam, F.P.A.; Miller, P.J.O.; Tyack, P.L.; Ainslie, M.A.

    2013-01-01

    Ramp-up or soft-start procedures (i.e., gradual increase in the source level) are used to mitigate the effect of sonar sound on marine mammals, although no one to date has tested whether ramp-up procedures are effective at reducing the effect of sound on marine mammals. We investigated the

  2. Plasma insulin levels are increased by sertraline in rats under oral glucose overload

    Directory of Open Access Journals (Sweden)

    Gomez R.

    2001-01-01

    Full Text Available Recognition and control of depression symptoms are important to increase patient compliance with treatment and to improve the quality of life of diabetic patients. Clinical studies indicate that selective serotonin reuptake inhibitors (SSRI are better antidepressants for diabetic patients than other drugs. However, preclinical trials have demonstrated that not all SSRI reduce plasma glucose levels. In fact, fluoxetine increases and sertraline decreases glycemia in diabetic and non-diabetic rats. In the present study we evaluated plasma insulin levels during fasting and after glucose overload after treatment with sertraline. Adult male Wistar rats were fasted and treated with saline or 30 mg/kg sertraline and submitted or not to glucose overload (N = 10. Blood was collected and plasma insulin was measured. The mean insulin levels were: fasting group: 25.9 ± 3.86, sertraline + fasting group: 31.10 ± 2.48, overload group: 34.1 ± 3.40, and overload + sertraline group: 43.73 ± 5.14 µU/ml. Insulinemia was significantly increased in the overload + sertraline group. There were no differences between the other groups. No difference in glucose/insulin ratios could be detected between groups. The overload + sertraline group was the only one in which a significant number of individuals exceeded the upper confidence limit of insulin levels. This study demonstrates that sertraline increases glucose-stimulated insulin secretion without any change in peripheral insulin sensitivity.

  3. Increased DHT levels in androgenic alopecia have been selected for to protect men from prostate cancer.

    Science.gov (United States)

    Bhargava, Shiva

    2014-04-01

    Androgenic alopecia, a condition characterized by increased levels of DHT could have been selected for due to the benefits that prostaglandin D2 (PGD(2)) has on the prostate. A DHT metabolite can increase the transcription of prostaglandin D2 synthase through estrogen receptor beta. The increase of PGD(2) can decrease the risk of prostate cancer and proliferation of prostate cancer cells. Therefore, the mechanisms behind male pattern baldness may also curtail the advancement of prostate cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Increased 5-hydroxymethylation levels in the sub ventricular zone of the Alzheimer's brain

    Directory of Open Access Journals (Sweden)

    Diego Mastroeni

    2016-06-01

    Full Text Available The subventricular zone (SVZ is a site of neurogenesis in the aging brain, and epigenetic mechanisms have been implicated in regulating the “normal” distribution of new nerve cells into the existing cellular milieu. In a case-control study of human primary SVZ cultures and fixed tissue from the same individuals, we have found significant increases in DNA hydroxymethylation levels in the SVZ of Alzheimer's disease patients compared with nondiseased control subjects. We show that this increase in hydroxymethylation directly correlates to an increase in cellular proliferation in Alzheimer's disease precursor cells, which implicates the hydroxymethylation tag to a higher degree of cellular proliferation.

  5. Increasing occurrence of multiple sclerosis in women correlates to hygiene level

    Directory of Open Access Journals (Sweden)

    Wojciech Cendrowski

    2014-12-01

    Full Text Available Introduction: The increasing incidence of multiple sclerosis, particularly among women in Europe and North America, has a multifactorial aetiology. Method: The aim of the current study was to ascertain the relation between the hygiene level and occurrence of multiple sclerosis in women in Poland. The study was based on a large cohort of 14,200 multiple sclerosis individuals (male – 6,106, female – 8,094 who died in the years 1981–2010 in Poland. The female to male ratio (the F:M ratio in the multiple sclerosis group was calculated using the number of deaths per year. The rate of late mortality in infants (LMI per 1,000 live births yearly was used as a marker of the hygiene level. A correlation analysis was carried out between the rate of LMI and the F:M ratio in the multiple sclerosis cohort in the years 1981–2010. Demographic data were obtained from the Central Statistical Office in Warsaw. Results: The F:M ratio in the multiple sclerosis group evidently increased (range 1.08–1.79 in the years 1981–2010, showing increasing occurrence of multiple sclerosis in women (p < 0.0001. A significant, strong and inverse correlation was found between the marker of the hygiene level (LMI rate and the F:M ratio in the multiple sclerosis group over three decades: linear correlation coefficient by Pearson: r = –0.693, p < 0.0001. By contrast with this result, no correlation was established between the hygiene level marker and proportion of women to men in the general population on account of extremely low variance of the F:M ratio (0.000025. Conclusion: The improvement of the hygiene level showed association with the increasing occurrence of multiple sclerosis in women in the years 1981–2010. The higher the hygiene level was, the greater the occurrence of female multiple sclerosis in Poland.

  6. Little effects of Insulin-like Growth Factor-I on testicular atrophy induced by hypoxia

    Directory of Open Access Journals (Sweden)

    Casares Amelia

    2006-02-01

    Full Text Available Abstract Background Insulin-like Growth Factor-I (IGF-I supplementation restores testicular atrophy associated with advanced liver cirrhosis that is a condition of IGF-I deficiency. The aim of this work was to evaluate the effect of IGF-I in rats with ischemia-induced testicular atrophy (AT without liver disease and consequently with normal serum level of IGF-I. Methods Testicular atrophy was induced by epinephrine (1, 2 mg/Kg intra-scrotal injection five times per week during 11 weeks. Then, rats with testicular atrophy (AT were divided into two groups (n = 10 each: untreated rats (AT receiving saline sc, and AT+IGF, which were treated with IGF-I (2 μg.100 g b.w.-1.day-1, sc. for 28d. Healthy controls (CO, n = 10 were studied in parallel. Animals were sacrificed on day 29th. Hypophyso-gonadal axis, IGF-I and IGFBPs levels, testicular morphometry and histopathology, immuno-histochemical studies and antioxidant enzyme activity phospholipid hydroperoxide glutathione peroxidase (PHGPx were assessed. Results Compared to controls, AT rats displayed a reduction in testicular size and weight, with histological testicular atrophy, decreased cellular proliferation and transferrin expression, and all of these alterations were slightly improved by IGF-I at low doses. IGF-I therapy increased signifincantly steroidogenesis and PHGPx activity (p Conclusion In testicular atrophy by hypoxia, condition without IGF-I deficiency, IGF-treatment induces only partial effects. These findings suggest that IGF-I therapy appears as an appropriate treatment in hypogonadism only when this is associated to conditions of IGF-I deficiency (such as Laron Syndrom or liver cirrhosis.

  7. Increased levels of unscheduled DNA synthesis in UV-irradiated human fibroblasts pretreated with sodium butyrate

    International Nuclear Information System (INIS)

    Williams, J.I.; Friedberg, E.C.

    1982-01-01

    Pretreatment of growing normal and xeroderma pigmentosum (XP) human fibroblasts with sodium butyrate at concentrations of 5-20 mM results in increased levels of DNA repair synthesis measured by autoradiography after exposure of the cells to 254 nm UV radiation in the fluence range 0-25 J/m 2 . The phenomenon manifests as an increased extent and an increased initial rate of unscheduled DNA synthesis (UDS). This experimental result is not due to an artifact of autoradiography related to cell size. Xeroderma pigmentosum cells from complementation groups A, C, D and E and XP variant cells all exhibit increases in the levels of UV-induced UDS in response to sodium butyrate proportional to those observed with normal cells. These UDS increases associated with butyrate pretreatment correlate with demonstrable changes in intracellular thymidine pool size and suggest that sodium butyrate enhances uptake of exogenous radiolabeled thymidine during UV-induced repair synthesis by reducing endogenous levels of thymidine. (author)

  8. Trans fatty acids increase nitric oxide levels and pancreatic beta-cell necrosis in rats

    Directory of Open Access Journals (Sweden)

    Kusmiyati Tjahjono DK

    2013-04-01

    Full Text Available Background The prevalence of diabetes in Indonesia is increasing due to various factors, including life style changes such as trans fatty acid (TFA intake. High TFA intake is known to be related to blood lipid profile changes resulting in cardiovascular disorders. This study was to identify the effect of TFA on nitric oxide (NO production and on necrosis of pancreatic beta cells. Methods A study of randomized pre-test post–test design with control group. Thirty Sprague Dawley rats were divided into 3 groups, i.e. group K (control, group P1 receiving a diet with 5% TFA, and P2 receiving 10% TFA. The intervention was performed for 8 weeks. NO level and pancreatic beta-cell necrosis were analyzed using Pearson’s chi square test. Results After 4 weeks of treatment there was no change in NO levels in group K, but increased NO in P2 (2.6-3.8 ìM. At 8 weeks after treatment, NO levels in groups P1 and P2 increased to 2.6-3.4 ìM and 4.2-14.3 ìM, respectively, while in group K only 2 rats had increased NO levels of 2.8-2.9 ìM. With Pearson’s chi-square test, there was a signifant difference in the proportions of necrotic pancreatic beta cells after 4 weeks and 8 weeks (p=0.000. No necrosis of beta cells was found in group K, mild necrosis in group P1 (1-25% and moderate necrosis in group P2 (26-50%. Conclusion TFA consumption significantly increases NO levels in Sprague Dawley rats and also results in moderate grades of necrosis of pancreatic beta cells.

  9. Trans fatty acids increase nitric oxide levels and pancreatic beta-cell necrosis in rats

    Directory of Open Access Journals (Sweden)

    Kusmiyati Tjahjono DK

    2015-12-01

    Full Text Available BACKGROUND The prevalence of diabetes in Indonesia is increasing due to various factors, including life style changes such as trans fatty acid (TFA intake. High TFA intake is known to be related to blood lipid profile changes resulting in cardiovascular disorders. This study was to identify the effect of TFA on nitric oxide (NO production and on necrosis of pancreatic beta cells. METHODS A study of randomized pre-test post–test design with control group. Thirty Sprague Dawley rats were divided into 3 groups, i.e. group K (control, group P1 receiving a diet with 5% TFA, and P2 receiving 10% TFA. The intervention was performed for 8 weeks. NO level and pancreatic beta-cell necrosis were analyzed using Pearson’s chi square test. RESULTS After 4 weeks of treatment there was no change in NO levels in group K, but increased NO in P2 (2.6-3.8 ìM. At 8 weeks after treatment, NO levels in groups P1 and P2 increased to 2.6-3.4 ìM and 4.2-14.3 ìM, respectively, while in group K only 2 rats had increased NO levels of 2.8-2.9 ìM. With Pearson’s chi-square test, there was a signifant difference in the proportions of necrotic pancreatic beta cells after 4 weeks and 8 weeks (p= 0.000. No necrosis of beta cells was found in group K, mild necrosis in group P1 (1-25% and moderate necrosis in group P2 (26-50%. CONCLUSION TFA consumption significantly increases NO levels in Sprague Dawley rats and also results in moderate grades of necrosis of pancreatic beta cells

  10. Increased prolactin levels are associated with impaired processing speed in subjects with early psychosis.

    Directory of Open Access Journals (Sweden)

    Itziar Montalvo

    Full Text Available Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for psychosis. Recent studies in non-psychiatric populations suggest that increased prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma prolactin levels are associated with poorer cognitive functioning in subjects with early psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects with an early psychosis (55 psychotic disorders with <3 years of illness, 23 high-risk subjects. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery, and prolactin levels were determined as well as total cortisol levels in plasma. Psychopathological status was assessed and the use of psychopharmacological treatments (antipsychotics, antidepressants, benzodiazepines recorded. Prolactin levels were negatively associated with cognitive performance in processing speed, in patients with a psychotic disorder and high-risk subjects. In the latter group, increased prolactin levels were also associated with impaired reasoning and problem solving and poorer general cognition. In a multiple linear regression analysis conducted in both high-risk and psychotic patients, controlling for potential confounders, prolactin and benzodiazepines were independently related to poorer cognitive performance in the speed of processing domain. A mediation analysis showed that both prolactin and benzodiazepine treatment act as mediators of the relationship between risperidone/paliperidone treatment and speed of processing. These results suggest that increased prolactin levels are associated with impaired processing speed in early psychosis. If these results are confirmed in future studies, strategies targeting reduction of prolactin levels may improve cognition in this population.

  11. Autism and increased paternal age related changes in global levels of gene expression regulation.

    Directory of Open Access Journals (Sweden)

    Mark D Alter

    2011-02-01

    Full Text Available A causal role of mutations in multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations in global levels of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for changes in the overall distribution of gene expression levels. For instance, in mice, variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in variance might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on RNA from peripheral blood lymphocytes (PBL of children with autism (n = 82 and controls (n = 64. Variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance. A decrease in the variance in the distribution of gene expression levels in PBL was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Global regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other

  12. Increasing cadmium and zinc levels in wild common eiders breeding along Canada's remote northern coastline

    International Nuclear Information System (INIS)

    Mallory, Mark L.; Braune, Birgit M.; Robertson, Gregory J.; Gilchrist, H. Grant; Mallory, Conor D.; Forbes, Mark R.; Wells, Regina

    2014-01-01

    The common eider (Somateria mollissima) is an abundant sea duck breeding around the circumpolar Arctic, and is an important component of subsistence and sport harvest in some regions. We determined hepatic cadmium (Cd) and zinc (Zn) concentrations in the livers of breeding females sampled during three time periods including 1992/3, 2001/2 and 2008 at three sites spanning 53.7°N–75.8°N in the eastern Canadian Arctic. At all sites, concentrations of both Cd and Zn increased ∼ 300% over this time period. The reasons for this rapid increase in concentrations are unclear. - Highlights: • Cd and Zn analyzed in common eider (Somateria mollissima) liver tissue in Canadian Arctic from sites spanning 3000 km. • ∼ 300% increase in concentrations observed over ∼ 20 years • Levels of both elements considered high and near levels thought to pose concerns for wildlife health

  13. Blood parameters in growing pigs fed increasing levels of bacterial protein meal

    DEFF Research Database (Denmark)

    Hellwing, Anne Louise Frydendahl; Tauson, Anne-Helene; Skrede, Anders

    2007-01-01

    The experiment investigated the effects of increasing dietary levels of bacterial protein meal (BPM) on various blood parameters reflecting protein and fat metabolism, liver function, and purine base metabolism in growing pigs. Sixteen barrows were allocated to four different experimental diets....... The control diet was based on soybean meal. In the other three diets soybean meal was replaced with increasing levels of BPM, approximately 17%, 35%, and 50% of the nitrogen being derived from BPM. Blood samples from the jugular vein were taken when the body weights of the pigs were approximately 10 kg, 21 kg......, 45 kg, and 77 kg. The blood parameters reflecting fat metabolism and liver funtion were not affected by diet. Both the plasma albumin and uric acid concentrations tended to decrease (P = 0.07 and 0.01, respectively) with increasing dietary BPM content, whereas the plasma glucose concentration tended...

  14. Steroid injection for shoulder pain causes prolonged increased glucose level in type 1 diabetics.

    Science.gov (United States)

    Povlsen, Bo; Povlsen, Sebastian D

    2014-09-08

    Shoulder pain is very common in diabetic patients and often treated with steroid injections, with subsequent increases in blood glucose levels or the need for additional insulin being questioned. We report a case of significant and prolonged elevation of blood glucose levels and resultant insulin requirement in a type 1 diabetic man after a single 40 mg injection of triamcinolone for shoulder pain. Within 48 h, the shoulder pain as assessed by a visual analogue scale (0-10) was reduced to zero, but the elevated insulin requirements continued for 4 weeks after the injection. This finding suggests that steroid injections for shoulder pain in diabetics may not always be as safe as previously thought. We propose that medical practitioners advise their patients to monitor their glucose levels more carefully after such injections and that caution is exercised when considering administrating these injections to those who have poorly controlled blood glucose levels preinjection to avoid ketoacidosis. 2014 BMJ Publishing Group Ltd.

  15. Utility of baseline serum phosphorus levels for predicting remission in acromegaly patients.

    Science.gov (United States)

    Yalin, G Y; Tanrikulu, S; Gul, N; Uzum, A K; Aral, F; Tanakol, R

    2017-08-01

    High GH and IGF I levels increase tubular phosphate reabsorption in patients with acromegaly. We aimed to investigate the utility of serum phosphorus levels as an indicator for predicting chance of remission in acromegaly patients. Fifty-one patients (n: 51; F: 24, M: 27) with diagnosis of acromegaly were included in the study. Plasma IGF-1, Phosphorus (P) and nadir GH levels on oral glucose tolerance test (OGTT) at the time of diagnosis were analysed retrospectively. Patients were classified into two groups according to their plasma P levels; P ≤ 4.5 mg/dl (Group-1, n: 23, 45.1%), P > 4.5 mg/dl (Group-2, n: 28, 54.9%). Two groups were compared according to remission status; remission (n: 27) and non-remission (n: 24). Remission was defined with absence of clinical symptoms, normal plasma IGF-1 (adjusted for age and gender) and GH levels (acromegaly patients. Further studies with wider spectrum are needed to make specific suggestions.

  16. Which Exercise Is Better for Increasing Serum Testosterone Levels in Patients with Erectile Dysfunction?

    Directory of Open Access Journals (Sweden)

    Jeong Kyun Yeo

    2018-05-01

    Full Text Available Purpose: We investigated the correlations of serum total testosterone (TT levels with body composition and physical fitness parameters in patients with erectile dysfunction (ED to know the best exercise for testosterone deficiency. Materials and Methods: Eighty-seven ED patients underwent serum TT assessment as well as body composition and basic exercise testing. The bioelectrical impedance analysis was used to assess body composition. Seven types of basic exercise tests were used to determine physical fitness. Correlations between serum TT levels and body composition/physical function parameters were evaluated using partial correlation analyses. A serum TT cut-off value was obtained for the parameters significantly correlated with serum TT levels. Results: The subjects had a mean serum TT level of 342.1 ng/dL. Among the body composition parameters, body and abdominal fat percentages showed statistically significant negative correlations with serum TT levels. Among the basic exercise test parameters, only the cycle ergometer test for cardiorespiratory fitness showed a statistically significant positive correlation with serum TT levels. Conclusions: Serum TT levels in patients with ED, may be increased by reducing fat percentage and improving cardiorespiratory fitness via aerobic exercise.

  17. Low oxygen level increases proliferation and metabolic changes in bovine granulosa cells.

    Science.gov (United States)

    Shiratsuki, Shogo; Hara, Tomotaka; Munakata, Yasuhisa; Shirasuna, Koumei; Kuwayama, Takehito; Iwata, Hisataka

    2016-12-05

    The present study addresses molecular backgrounds underlying low oxygen induced metabolic changes and 1.2-fold change in bovine granulosa cell (GCs) proliferation. RNA-seq revealed that low oxygen (5%) upregulated genes associated with HIF-1 and glycolysis and downregulated genes associated with mitochondrial respiration than that in high oxygen level (21%). Low oxygen level induced high glycolytic activity and low mitochondrial function and biogenesis. Low oxygen level enhanced GC proliferation with high expression levels of HIF-1, VEGF, AKT, mTOR, and S6RP, whereas addition of anti-VEGF antibody decreased cellular proliferation with low phosphorylated AKT and mTOR expression levels. Low oxygen level reduced SIRT1, whereas activation of SIRT1 by resveratrol increased mitochondrial replication and decreased cellular proliferation with reduction of phosphorylated mTOR. These results suggest that low oxygen level stimulates the HIF1-VEGF-AKT-mTOR pathway and up-regulates glycolysis, which contributes to GC proliferation, and downregulation of SIRT1 contributes to hypoxia-associated reduction of mitochondria and cellular proliferation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Increased serum level of prolactin is related to autoantibody production in systemic lupus erythematosus.

    Science.gov (United States)

    Yang, J; Li, Q; Yang, X; Li, M

    2016-04-01

    Prolactin (PRL) is known to aid effector B cells and augment autoimmunity, but the role of PRL in systemic lupus erythematosus (SLE) is not fully elucidated. The aim of this study was to determine the correlation between the serum levels of PRL and autoantibody production in SLE. Blood levels of PRL, anti-double-stranded DNA (ds-DNA) antibody, immunoglobulin M (IgM) and immunoglobulin G (IgG) were determined in samples from 30 adult patients with SLE and 25 healthy controls. The relationships between the serum level of PRL and SLE disease activity, as well as the titres of the ds-DNA antibody, IgM and IgG were determined. The serum level of PRL was higher in the SLE patients than in the healthy controls. PRL concentration increased during SLE flares-ups and decreased following disease remission. There was a positive correlation between the PRL concentration and serum levels of IgM, IgG and ds-DNA antibody titre. These data suggest that the serum level of PRL was closely related to the antibody production and disease activity of SLE patients. PRL concentration was dramatically reduced upon the remission of disease activity, indicating that PRL levels might be a promising predictor of SLE disease severity. © The Author(s) 2015.

  19. Increased Cord Blood Betatrophin Levels in the Offspring of Mothers with Gestational Diabetes

    Science.gov (United States)

    Wu, Shimin; Zhao, Yue; Du, Caiqi; Yuan, Guandou; Ning, Qin; McCormick, Kenneth; Luo, Xiaoping

    2016-01-01

    Aim Exposing a fetus to hyperglycemia can increase the risk for later-life metabolic disorders. Betatrophin has been proposed as a key regulator of pancreatic beta cell proliferation and lipid regulation. Highly responsive to nutritional signals, serum betatrophin concentrations have been found to be altered by various physiological and pathological conditions. We hypothesized that betatrophin levels are increased in the cord blood in offspring exposed to intrauterine hyperglycemia. Methods This was a cross-sectional study including 54 mothers who underwent uncomplicated Cesarean delivery in a university hospital. Maternal gestational glucose concentration was determined at 24–48 weeks gestation after a 75-g OGTT. Cord blood and placental tissue was collected immediately post delivery. Metabolic parameters were determined in the Clinical Laboratory. Cord blood betatrophin levels were assayed using a commercially available ELISA kit. Placental mitochondrial content was determined by real-time PCR. Results Cord blood betatrophin levels were increased in the gestational diabetes mellitus (GDM) group compared with the normoglycemic group. Furthermore, betatrophin levels were positively correlated with maternal gestational 2h post-OGTT glucose, cord blood insulin, HOMA-IR, and inversely correlated with placental mitochondrial content. Conclusions Cord blood betatrophin may function as a potential biomarker of maternal intrauterine hyperglycemia and fetal insulin resistance, which may presage for long-term metabolic impact of GDM on offspring. PMID:27196053

  20. [Increased oxidized LDL cholesterol levels in peritoneal fluid of women with advanced-stage endometriosis].

    Science.gov (United States)

    Polak, Grzegorz; Mazurek, Diana; Rogala, Ewelina; Nowicka, Aldona; Derewianka-Polak, Magdalena; Kotarski, Jan

    2011-03-01

    Proinflammatory and prooxidative environment in the peritoneal cavity may be involved in the pathogenesis of endometriosis. Imbalance between reactive oxygen species levels and the antioxidant capacity leads to oxidation of low-density lipoproteins (LDL). The importance of oxidized LDL (Ox-LDL) in the development of atherosclerosis is well recognized. The aim of our study was to evaluate for the presence of ox-LDL in the peritoneal fluid (PF) of women with and without endometriosis. A total of 60 women who underwent laparoscopy were divided into groups: endometriosis sufferers with minimal to mild (n 20) and moderate to severe (n 20) stages, and the reference group (n 20) with functional follicle ovarian cysts. Oxidized LDL levels were determined in the PF using enzyme immunoassay Oxidized LDL levels were detectable in all peritoneal fluid samples. Significantly increased levels of ox-LDL were observed in PF of women with stage III/IV endometriosis compared to the reference group (p = 0.03). However peritoneal fluid ox-LDL concentrations did not differ significantly between patients with minimal/mild and women with moderate/severe stage of the disease (p = 0.2). No significant difference in the PF ox-LDL concentrations was also found between women with stage I/II endometriosis and patients with follicle cysts (p = 0.3). Increased peritoneal fluid ox-LDL levels observed in women with advanced-stage endometriosis suggest the important role of oxidative stress in the pathogenesis of the disease.

  1. Cigarette smoking increases radon working level exposures to all occupants of the smoker's home

    International Nuclear Information System (INIS)

    Johnson, R.H. Jr.; Rosario, A. Jr.

    1990-01-01

    This paper reports that the 1988 National Academy of Sciences report on radon health risks evaluated the combined effects of radon exposures and cigarettes on the lung cancer risk to smokers. This report showed that the risk of lung cancer is about 10 times greater for smokers than for nonsmokers at the same Working Level exposures. In 1986, the Surgeon General reported that 106,000 lung cancer deaths occurred among smokers. Therefore, the health risks of cigarettes alone or in combination with radon exposures are well recognized. What has not been studied is the effect of cigarette smoke on the Working Levels in homes that increases the exposure to radon decay products to all occupants, both smokers and nonsmokers. Preliminary studies in a radon chamber at Radon QC showed that the smoke from a single cigarette increased the Working Levels by a factor of five within four hours. Furthermore, the Working Levels remained at an elevated level for more than 24 hours. The equilibrium ratio of radon decay products to radon gas also went from about 14% up to 71%, with a slow decrease over 24 hours. Similar studies in the homes of a smoker and nonsmoker confirmed the laboratory observations. The studies in homes also showed the effects of thoron decay products

  2. Diffuse radiation increases global ecosystem-level water-use efficiency

    Science.gov (United States)

    Moffat, A. M.; Reichstein, M.; Cescatti, A.; Knohl, A.; Zaehle, S.

    2012-12-01

    Current environmental changes lead not only to rising atmospheric CO2 levels and air temperature but also to changes in air pollution and thus the light quality of the solar radiation reaching the land-surface. While rising CO2 levels are thought to enhance photosynthesis and closure of stomata, thus leading to relative water savings, the effect of diffuse radiation on transpiration by plants is less clear. It has been speculated that the stimulation of photosynthesis by increased levels of diffuse light may be counteracted by higher transpiration and consequently water depletion and drought stress. Ultimately, in water co-limited systems, the overall effect of diffuse radiation will depend on the sensitivity of canopy transpiration versus photosynthesis to diffuse light, i.e. whether water-use efficiency changes with relative levels of diffuse light. Our study shows that water-use efficiency increases significantly with higher fractions of diffuse light. It uses the ecosystem-atmosphere gas-exchange observations obtained with the eddy covariance method at 29 flux tower sites. In contrast to previous global studies, the analysis is based directly on measurements of diffuse radiation. Its effect on water-use efficiency was derived by analyzing the multivariate response of carbon and water fluxes to radiation and air humidity using a purely empirical approach based on artificial neural networks. We infer that per unit change of diffuse fraction the water-use efficiency increases up to 40% depending on diffuse fraction levels and ecosystem type. Hence, in regions with increasing diffuse radiation positive effects on primary production are expected even under conditions where water is co-limiting productivity.

  3. Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Mazière, Cécile, E-mail: maziere.cecile@chu-amiens.fr [Biochemistry Laboratory, South Hospital University, René Laennec Avenue, Amiens 80000 (France); Salle, Valéry [Internal Medicine, North Hospital University, Place Victor Pauchet, Amiens 80000 (France); INSERM U1088 (EA 4292), SFR CAP-Santé (FED 4231), University of Picardie – Jules Verne (France); Gomila, Cathy; Mazière, Jean-Claude [Biochemistry Laboratory, South Hospital University, René Laennec Avenue, Amiens 80000 (France)

    2013-10-18

    Highlights: •Oxidized LDL enhances RANKL level in human smooth muscle cells. •The effect of OxLDL is mediated by the transcription factor NFAT. •UVA, H{sub 2}O{sub 2} and buthionine sulfoximine also increase RANKL level. •All these effects are observed in human fibroblasts and endothelial cells. -- Abstract: Receptor Activator of NFκB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) have been shown to play a role not only in bone remodeling but also in inflammation, arterial calcification and atherosclerotic plaque rupture. In human smooth muscle cells, Cu{sup 2+}-oxidized LDL (CuLDL) 10–50 μg/ml increased reactive oxygen species (ROS) and RANKL level in a dose-dependent manner, whereas OPG level was not affected. The lipid extract of CuLDL reproduced the effects of the whole particle. Vivit, an inhibitor of the transcription factor NFAT, reduced the CuLDL-induced increase in RANKL, whereas PKA and NFκB inhibitors were ineffective. LDL oxidized by myeloperoxidase (MPO-LDL), or other pro-oxidant conditions such as ultraviolet A (UVA) irradiation, incubation with H{sub 2}O{sub 2} or with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis{sub ,} also induced an oxidative stress and enhanced RANKL level. The increase in RANKL in pro-oxidant conditions was also observed in fibroblasts and endothelial cells. Since RANKL is involved in myocardial inflammation, vascular calcification and plaque rupture, this study highlights a new mechanism whereby OxLDL might, by generation of an oxidative stress, exert a deleterious effect on different cell types of the arterial wall.

  4. Increased sorbitol levels in the hypertrophic ligamentum flavum of diabetic patients with lumbar spinal canal stenosis.

    Science.gov (United States)

    Luo, Jiaquan; Huang, Lu; Chen, Zhuo; Zeng, Zhaoxun; Miyamoto, Takeshi; Wu, Hao; Zhang, Zhongzu; Pan, Zhimin; Fujita, Nobuyuki; Hikata, Tomohiro; Iwanami, Akio; Tsuji, Takashi; Ishii, Ken; Nakamura, Masaya; Matsumoto, Morio; Watanabe, Kota; Cao, Kai

    2017-05-01

    The pathomechanism of the ligamentum flavum (LF) hypertrophy in diabetic patients with lumbar spinal canal stenosis (LSCS) remains unclear. A cross-sectional study was undertaken to investigate the mechanism of LF hypertrophy in these patients. Twenty-four diabetic and 20 normoglycemic patients with LSCS were enrolled in the study. The structure of the LF in the study subjects was evaluated using histological and immunohistochemical methods, and the levels of sorbitol, pro-inflammatory cytokines, and the fibrogenic factor, TGF-β1, in the LF were analyzed. In vitro experiments were performed using NIH3T3 fibroblasts to evaluate the effect of high-glucose conditions and an aldose reductase inhibitor on the cellular production of sorbitol, pro-inflammatory factors, and TGF-β1. We found that the LF of diabetic patients exhibited significantly higher levels of sorbitol and pro-inflammatory cytokines, TGF-β1 and of CD68-positive staining than that of the normoglycemic subjects. The diabetic LF was significantly thicker than that of the controls, and showed evidence of degeneration. The high glucose-cultured fibroblasts exhibited significantly higher levels of sorbitol, pro-inflammatory factors, and TGF-β1 compared to the low glucose-cultured cells, and these levels were dose-dependently reduced by treatment with the aldose reductase inhibitor. Taken together, our data suggests that increased sorbitol levels in the LF of diabetic patients results in increased production of pro-inflammatory and fibrogenic factor, which contribute to LF hypertrophy, and could increase the susceptibility of diabetic patients to LSCS. Furthermore, aldose reductase inhibition effectively reduced the levels of sorbitol and sorbitol-induced pro-inflammatory factor expression in high glucose-cultured fibroblasts. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1058-1066, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  5. Chronic lithium treatment increased intracellular S100ß levels in rat primary neuronal culture.

    Directory of Open Access Journals (Sweden)

    Masoumeh Emamghoreishi

    2015-02-01

    Full Text Available S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenesis of bipolar disorder. Thus, lithium may exert its neuroprotective effects to some extent through S100ß. Furthermore, the possible effects of lithium on astrocytes as well as on interactions between neurons and astrocytes as a part of its mechanisms of actions are unknown. This study was undertaken to determine the effect of lithium on S100β in neurons, astrocytes and a mixture of neurons and astrocytes. Rat primary astrocyte, neuronal and mixed neuro-astroglia cultures were prepared from cortices of 18-day's embryos. Cell cultures were exposed to lithium (1mM or vehicle for 1day (acute or 7 days (chronic. RT-PCR and ELISA determined S100β mRNA and intra- and extracellular protein levels. Chronic lithium treatment significantly increased intracellular S100β in neuronal and neuro-astroglia cultures in comparison to control cultures (P<0.05. Acute and chronic lithium treatments exerted no significant effects on intracellular S100β protein levels in astrocytes, and extracellular S100β protein levels in three studied cultures as compared to control cultures. Acute and chronic lithium treatments did not significantly alter S100β mRNA levels in three studied cultures, compared to control cultures. Chronic lithium treatment increased intracellular S100ß protein levels in a cell-type specific manner which may favor its neuroprotective action. The findings of this study suggest that lithium may exert its neuroprotective action, at least partly, by increasing neuronal S100ß level, with no effect on astrocytes or interaction between neurons and astrocytes.

  6. Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

    Science.gov (United States)

    De Capite, Annette; Lancaster, Tyler; Puthoff, David

    2016-01-01

    Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it.

  7. Suramin Inhibits Osteoarthritic Cartilage Degradation by Increasing Extracellular Levels of Chondroprotective Tissue Inhibitor of Metalloproteinases 3.

    Science.gov (United States)

    Chanalaris, Anastasios; Doherty, Christine; Marsden, Brian D; Bambridge, Gabriel; Wren, Stephen P; Nagase, Hideaki; Troeberg, Linda

    2017-10-01

    Osteoarthritis is a common degenerative joint disease for which no disease-modifying drugs are currently available. Attempts to treat the disease with small molecule inhibitors of the metalloproteinases that degrade the cartilage matrix have been hampered by a lack of specificity. We aimed to inhibit cartilage degradation by augmenting levels of the endogenous metalloproteinase inhibitor, tissue inhibitor of metalloproteinases (TIMP)-3, through blocking its interaction with the endocytic scavenger receptor, low-density lipoprotein receptor-related protein 1 (LRP1). We discovered that suramin (C 51 H 40 N 6 O 23 S 6 ) bound to TIMP-3 with a K D value of 1.9 ± 0.2 nM and inhibited its endocytosis via LRP1, thus increasing extracellular levels of TIMP-3 and inhibiting cartilage degradation by the TIMP-3 target enzyme, adamalysin-like metalloproteinase with thrombospondin motifs 5. NF279 (8,8'-[carbonyl bis (imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)] bis -1,3,5-naphthalenetrisulfonic acid hexasodium salt), a structural analog of suramin, has an increased affinity for TIMP-3 and increased ability to inhibit TIMP-3 endocytosis and protect cartilage. Suramin is thus a promising scaffold for the development of novel therapeutics to increase TIMP-3 levels and inhibit cartilage degradation in osteoarthritis. Copyright © 2017 by The Author(s).

  8. Steroid injection for shoulder pain causes prolonged increased glucose level in type 1 diabetics

    OpenAIRE

    Povlsen, Bo; Povlsen, Sebastian D

    2014-01-01

    Shoulder pain is very common in diabetic patients and often treated with steroid injections, with subsequent increases in blood glucose levels or the need for additional insulin being questioned. We report a case of significant and prolonged elevation of blood glucose levels and resultant insulin requirement in a type 1 diabetic man after a single 40 mg injection of triamcinolone for shoulder pain. Within 48 h, the shoulder pain as assessed by a visual analogue scale (0–10) was reduced to zer...

  9. Smoking is associated with increased levels of extracellular peptidylarginine deiminase 2 (PAD2) in the lungs

    DEFF Research Database (Denmark)

    Damgaard, Dres; Friberg Bruun Nielsen, Michael; Quisgaard Gaunsbaek, Maria

    2015-01-01

    lavage (BAL) fluid from smokers, but intracellularly located PAD cannot be responsible for citrullination of extracellular self-antigens. We aimed to establish a link between smoking and extracellular PAD2 in the lungs. METHODS: BAL fluid samples were obtained from 13 smokers and 11 nonsmoking controls...... fluids from smokers as compared to non-smokers (p=0.018). The PAD2 content correlated with the overall CRP levels (p=0.009) and cell count (p=0.016). CONCLUSIONS: This first demonstration of increased levels of extracellular PAD2 in the lungs of smokers supports the hypothesis that smoking promotes...

  10. Clusterin levels are increased in Alzheimer's disease and influence the regional distribution of Aβ.

    Science.gov (United States)

    Miners, J Scott; Clarke, Polly; Love, Seth

    2017-05-01

    Clusterin, also known as apoJ, is a lipoprotein abundantly expressed within the CNS. It regulates Aβ fibril formation and toxicity and facilitates amyloid-β (Aβ) transport across the blood-brain barrier. Genome-wide association studies have shown variations in the clusterin gene (CLU) to influence the risk of developing sporadic Alzheimer's disease (AD). To explore whether clusterin modulates the regional deposition of Aβ, we measured levels of soluble (NP40-extracted) and insoluble (guanidine-HCl-extracted) clusterin, Aβ40 and Aβ42 by sandwich ELISA in brain regions with a predilection for amyloid pathology-mid-frontal cortex (MF), cingulate cortex (CC), parahippocampal cortex (PH), and regions with little or no pathology-thalamus (TH) and white matter (WM). Clusterin level was highest in regions with plaque pathology (MF, CC, PH and PC), approximately mirroring the regional distribution of Aβ. It was significantly higher in AD than controls, and correlated positively with Aβ42 and insoluble Aβ40. Soluble clusterin level rose significantly with severity of cerebral amyloid angiopathy, and in MF and PC regions was highest in APOE ɛ4 homozygotes. In the TH and WM (areas with little amyloid pathology) clusterin was unaltered in AD and did not correlate with Aβ level. There was a significant positive correlation between the concentration of clusterin and the regional levels of insoluble Aβ42; however, the molar ratio of clusterin : Aβ42 declined with insoluble Aβ42 level in a region-dependent manner, being lowest in regions with predilection for Aβ plaque pathology. Under physiological conditions, clusterin reduces aggregation and promotes clearance of Aβ. Our findings indicate that in AD, clusterin increases, particularly in regions with most abundant Aβ, but because the increase does not match the rising level of Aβ42, the molar ratio of clusterin : Aβ42 in those regions falls, probably contributing to Aβ deposition within the tissue. © 2016

  11. Plasma adiponectin levels correlate positively with an increasing number of components of frailty in male elders.

    Directory of Open Access Journals (Sweden)

    Jaw-Shiun Tsai

    Full Text Available OBJECTIVE: Frailty is an important geriatric syndrome. Adiponectin is an important adipokine that regulates energy homeostasis. The aim of this study is to investigate the relationship between plasma adiponectin levels and frailty in elders. METHODS: The demographic data, body weight, metabolic and inflammatory parameters, including plasma glucose, total cholesterol, triglyceride, tumor necrosis factor alpha (TNF-α, c-reactive protein (CRP and adiponectin levels, were assessed. The frailty score was assessed using the Fried Frailty Index (FFI. RESULTS: The mean (SD age of the 168 participants [83 (49.4% men and 85 (50.6% women] was 76.86 (6.10 years. Judged by the FFI score, 42 (25% elders were robust, 92 (54.7% were pre-frail, and 34 (20.3% were frail. The mean body mass index was 25.19 (3.42 kg/m(2. The log-transformed mean (SD plasma adiponectin (µg/mL level was 1.00 (0.26. The log-transformed mean plasma adiponectin (µg/mL levels were 0.93 (0.23 in the robust elders, 1.00 (0.27 in the pre-frail elders, and 1.10 (0.22 in the frail elders, and the differences between these values were statistically significant (p  = 0.012. Further analysis showed that plasma adiponectin levels rose progressively with an increasing number of components of frailty in all participants as a whole (p for trend  = 0.024 and males (p for trend  = 0.037, but not in females (p for trend  = 0.223. CONCLUSION: Plasma adiponectin levels correlate positively with an increasing number of components of frailty in male elders. The difference between the sexes suggests that certain sex-specific mechanisms may exist to affect the association between adiponectin levels and frailty.

  12. The Common Inhalational Anesthetic Sevoflurane Induces Apoptosis and Increases β-Amyloid Protein Levels

    Science.gov (United States)

    Dong, Yuanlin; Zhang, Guohua; Zhang, Bin; Moir, Robert D.; Xia, Weiming; Marcantonio, Edward R.; Culley, Deborah J.; Crosby, Gregory; Tanzi, Rudolph E.; Xie, Zhongcong

    2009-01-01

    Objective: To assess the effects of sevoflurane, the most commonly used inhalation anesthetic, on apoptosis and β-amyloid protein (Aβ) levels in vitro and in vivo. Subjects: Naive mice, H4 human neuroglioma cells, and H4 human neuroglioma cells stably transfected to express full-length amyloid precursor protein. Interventions: Human H4 neuroglioma cells stably transfected to express full-length amyloid precursor protein were exposed to 4.1% sevoflurane for 6 hours. Mice received 2.5% sevoflurane for 2 hours. Caspase-3 activation, apoptosis, and Aβ levels were assessed. Results: Sevoflurane induced apoptosis and elevated levels of β-site amyloid precursor protein-cleaving enzyme and Aβ in vitro and in vivo. The caspase inhibitor Z-VAD decreased the effects of sevoflurane on apoptosis and Aβ. Sevoflurane-induced caspase-3 activation was attenuated by the γ-secretase inhibitor L-685,458 and was potentiated by Aβ. These results suggest that sevoflurane induces caspase activation which, in turn, enhances β-site amyloid precursor protein–cleaving enzyme and Aβ levels. Increasedlevels then induce further rounds of apoptosis. Conclusions: These results suggest that inhalational anesthetic sevoflurane may promote Alzheimer disease neuropathogenesis. If confirmed in human subjects, it may be prudent to caution against the use of sevoflurane as an anesthetic, especially in those suspected of possessing excessive levels of cerebral Aβ. PMID:19433662

  13. Benefits and costs of increased levels of corticosterone in seabird chicks

    Science.gov (United States)

    Kitaysky, A.S.; Kitaiskaia, E.V.; Piatt, John F.; Wingfield, J.C.

    2003-01-01

    Seabird chicks respond to food shortages by increasing corticosterone (cort) secretion, which is probably associated with fitness benefits and costs. To examine this, we experimentally increased levels of circulating cort in captive black-legged kittiwake chicks fed ad libitum. We found that cort-implanted chicks begged more frequently and were more aggressive compared to controls. These behavioral modifications must be beneficial to chicks as they facilitate acquisition of food from the parents and might trigger brood reduction and reduced competition for food. Cort-implanted chicks also increased food intake; however, their growth rates were similar to controls. To examine the costs of chronically increased circulating levels of cort, we removed cort implants and, after a 10-day recovery period, tested cognitive abilities of young kittiwakes. We found that the ability of kittiwakes to associate a visual cue with the presence of food in a choice situation was compromised by the experimental elevation of cort during development. To examine the long-term costs of increased levels of cort, 8 months later we tested the performance of the same individuals in a spatial task requiring them to make a detour around a barrier in order to escape from an enclosure. Individuals treated with cort during development took significantly more time to solve this task compared to controls. The results of this study suggest that the adrenocortical response of a developing bird to environmental stressors is associated with both benefits (increased food intake, foraging behavior, and aggression) and costs (low growth efficiency and compromised cognitive abilities later in life). This provides an evolutionary framework for relating juvenile physiological traits to fitness of birds in subsequent life-history stages. ?? 2003 Elsevier Science (USA). All rights reserved.

  14. Widespread recent increases in county-level heart disease mortality across age groups.

    Science.gov (United States)

    Vaughan, Adam S; Ritchey, Matthew D; Hannan, Judy; Kramer, Michael R; Casper, Michele

    2017-12-01

    Recent national trends show decelerating declines in heart disease mortality, especially among younger adults. National trends may mask variation by geography and age. We examined recent county-level trends in heart disease mortality by age group. Using a Bayesian statistical model and National Vital Statistics Systems data, we estimated overall rates and percent change in heart disease mortality from 2010 through 2015 for four age groups (35-44, 45-54, 55-64, and 65-74 years) in 3098 US counties. Nationally, heart disease mortality declined in every age group except ages 55-64 years. County-level trends by age group showed geographically widespread increases, with 52.3%, 58.5%, 69.1%, and 42.0% of counties experiencing increases with median percent changes of 0.6%, 2.2%, 4.6%, and -1.5% for ages 35-44, 45-54, 55-64, and 65-74 years, respectively. Increases were more likely in counties with initially high heart disease mortality and outside large metropolitan areas. Recent national trends have masked local increases in heart disease mortality. These increases, especially among adults younger than age 65 years, represent challenges to communities across the country. Reversing these trends may require intensification of primary and secondary prevention-focusing policies, strategies, and interventions on younger populations, especially those living in less urban counties. Published by Elsevier Inc.

  15. Blood parameters in growing pigs fed increasing levels of bacterial protein meal

    Directory of Open Access Journals (Sweden)

    Tauson Anne-Helene

    2007-11-01

    Full Text Available Abstract The experiment investigated the effects of increasing dietary levels of bacterial protein meal (BPM on various blood parameters reflecting protein and fat metabolism, liver function, and purine base metabolism in growing pigs. Sixteen barrows were allocated to four different experimental diets. The control diet was based on soybean meal. In the other three diets soybean meal was replaced with increasing levels of BPM, approximately 17%, 35%, and 50% of the nitrogen being derived from BPM. Blood samples from the jugular vein were taken when the body weights of the pigs were approximately 10 kg, 21 kg, 45 kg, and 77 kg. The blood parameters reflecting fat metabolism and liver function were not affected by diet. Both the plasma albumin and uric acid concentrations tended to decrease (P = 0.07 and 0.01, respectively with increasing dietary BPM content, whereas the plasma glucose concentration tended to increase (P = 0.07 with increasing dietary BPM content. It was concluded that up to 50% of the nitrogen could be derived from BPM without affecting metabolic function, as reflected in the measured blood parameters.

  16. Increased cleavage and blastocyst rate in ewes treated with bovine somatotropin 5 days before the end of progestin-based estrous synchronization.

    Science.gov (United States)

    Montero-Pardo, A; Hernández-Cerón, J; Rojas-Maya, S; Valencia, J; Rodríguez-Cortez, A; Gutiérrez, C G

    2011-05-01

    Treatment with bovine somatotropin (bST) during estrous synchronization increased fertility and prolificacy in sheep. In the present study, a single dose of bST 5 days before the end of progestin treatment improved cleavage and embryo development. Stage of estrous cycle was synchronized in ewes (n=32) with progestin and superovulation was induced by use of FSH. Five days before the end of progestin treatment, ewes were randomly assigned to two groups: bST group (n=16) received a depot injection of 125 mg of bST sc (Lactotropina, Elanco, México) and the control group (n=16) received saline solution. Estrous was detected with rams fitted with an apron every 2 h and estrous sheep were mated every 8 h whilst in estrous. Embryos were recovered on Day 7 post mating, assessed microscopically and fixed in 4% paraformaldehyde. Cell number in blastocysts was counted after Hoechst 33342 staining. Plasma concentrations of IGF-I, insulin and progesterone were determined in eight sheep per group from the day of bST treatment to the day of embryo recovery. Cleavage rate, percentage of transferable embryos (transferable embryos/cleaved) and percentage of embryos reaching the blastocyst stage (blastocyst/cleaved) were compared between groups by logistic regression. IGF-I, insulin and progesterone plasma concentrations were analyzed by ANOVA for repeated measurements and cell number by ANOVA. Cleavage rate was greater (Psheep. Plasma concentrations of IGF-I and insulin were greater (Pprogesterone concentrations (P=0.5). It is concluded that bST injection 5 days before progestin removal increases cleavage rate and the proportion of embryos that reach the blastocyst stage. These effects are associated with an increase in IGF-I and insulin concentrations. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Protein synthesis levels are increased in a subset of individuals with Fragile X syndrome

    DEFF Research Database (Denmark)

    Jacquemont, Sébastien; Pacini, Laura; Jønch, Aia E

    2018-01-01

    architecture and plasticity. Preclinical studies revealed that pharmacological interventions restore those deficits, which are thought to mediate the FXS cognitive and behavioral symptoms. Here we characterized the de novo rate of protein synthesis in patients with FXS and their relationship with clinical...... severity. We measured the rate of protein synthesis in fibroblasts derived from 32 individuals with FXS and from 17 controls as well as in fibroblasts and primary neurons of 27 Fmr1 KO mice and 20 controls. Here we show that levels of protein synthesis are increased in fibroblasts of individuals with FXS...... and Fmr1 KO mice. However, this cellular phenotype displays a broad distribution and a proportion of fragile X individuals and Fmr1 KO mice do not show increased levels of protein synthesis, having measures in the normal range. Because the same Fmr1 KO animal measures in fibroblasts predict those...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  19. Increasing Resilience Through Engagement In Sea Level Rise Community Science Initiatives.

    Science.gov (United States)

    Chilton, L. A.; Rindge, H.

    2017-12-01

    Science literate and engaged members of the public, including students, are critical to building climate resilient communities. USC Sea Grant facilitates programs that work to build and strengthen these connections. The Urban Tides Community Science Initiative (Urban Tides) and the Youth Exploring Sea Level Rise Science Program (YESS) engage communities across the boundaries of public engagement, K-12 education, and informal education. YESS is an experiential sea level rise education program that combines classroom learning, field investigations and public presentations. Students explore sea level rise using a new curricula, collect their own data on sea level rise, develop communication products, and present their findings to city governments, researchers, and others. Urban Tides engages community members, informal education centers, K-12 students, and local government leaders in a citizen science program photo- documenting extreme high tides, erosion and coastal flooding in Southern California. Images provide critical information to help calibrate scientific models used to identify locations vulnerable to damage from future sea level rise. These tools and information enable community leaders and local governments to set priorities, guidelines, and update policies as they plan strategies that will help the region adapt. The program includes a mobile app for data collection, an open database to view photos, a lesson plan, and community beach walks. Urban Tides has led to an increase in data and data-gathering capacity for regional scientists, an increase in public participation in science, and an increase in ocean and climate literacy among initiative participants. Both of these programs bring informed and diverse voices into the discussion of how to adapt and build climate resilient communities. USC Sea Grant will share impacts and lessons learned from these two unique programs.

  20. The increasing of beta-defensin-2 level in saliva after probiotic Lactobacillus reuteri administration

    Directory of Open Access Journals (Sweden)

    Tuti Kusumaningsih

    2015-03-01

    Full Text Available Background: Commesal bacteria is an excellent inducer for beta defensin-2 (BD-2. Probiotics bacteria Lactobacillus reuteri (L. reuteri as commensal bacteria may play the same role as an excellent inducer for BD-2. Beta defensin is natural antimicrobial peptides widely expressed in oral cavity, including in epithelium salivary gland. Streptococcus mutans (S. mutans as the main of bacteria causing caries are sensitive to BD-2. Purpose: This research was aimed to determine whether administration of probiotic L. reuteri can increase salivary BD-2 level in Wistar rats. Methods: This research can be considered as a laboratory experimental research with a randomized control group post test only design. Twenty-four male Rattus norvegicus Wistar strain rats aged 3 months were used. They were randomly divided into four groups, namely two control groups (negative control group that was not induced and positive control group induced with S. mutans, and two treatment groups (K1: induced with L. reuteri for 14 days and S. mutans for 7 days, and K2: induced with L. reuteri and S. mutans simultaneously for 14 days. L. reuteri culture at a concentration of 108 CFU/ml and S. mutans culture at a concentration of 1010CFU/ml were induced into the oral cavity of Wistar rats. An examination of BD-2 level was then conducted by using Elisa techniques. results: There was significant difference of salivary BD-2 level among those treatment groups (p=0.001. BD-2 level in saliva was increased after the administration of L. reuteri. Conclusion: L. reuteri probiotic can increase salivary BD-2 level in Wistar rats.

  1. Myoclonic epilepsy with ragged-red fibers without increased lactate levels.

    Science.gov (United States)

    Kimura, Shigemi; Ozasa, Shiro; Nakamura, Kyoko; Nomura, Keiko; Kosuge, Hirofumi

    2009-07-01

    Myoclonic epilepsy associated with ragged-red fibers is one of the mitochondrial encephalomyopathies. Pathogenic mitochondrial DNA mutations have been identified in the mitochondrial transfer RNA (tRNA)(Lys) at positions 8344 and 8356. Characteristics of myoclonic epilepsy associated with ragged-red fibers include myoclonic epilepsy, generalized epilepsy, hearing loss, exercise intolerance, lactic acidosis, and ragged-red fibers. The elevated lactate level is one of the most important symptoms needed to make a diagnosis of mitochondrial encephalomyopathy. In the present case, however, myoclonic epilepsy was associated with ragged-red fibers but without increased lactate levels. Therefore, myoclonic epilepsy associated with ragged-red fibers should be suspected in a patient who has myoclonic epilepsy that is difficult to control with antiepileptic medications and who has other symptoms of mitochondrial disease, such as mental retardation, even if the patient's lactate level is normal.

  2. Taenia pisiformis cysticercosis induces decreased prolificacy and increased progesterone levels in rabbits.

    Science.gov (United States)

    Hallal-Calleros, Claudia; Morales-Montor, Jorge; Orihuela-Trujillo, Agustín; Togno-Peirce, Cristián; Murcia-Mejía, Clara; Bielli, Alejandro; Hoffman, Kurt L; Flores-Pérez, Fernando Iván

    2016-10-15

    Reproductive alterations in hosts infected by parasites have been recognized in several phyla, especially in arthropods and mollusks, but it has been less studied in higher vertebrates, particularly in mammals. In the present study, ten eight week-old female New Zealand rabbits (Oryctolagus cuniculus) were either infected with Taenia pisiformis eggs or uninfected, and 7 weeks later they were mated. We found that serum progesterone levels were increased during pregnancy in infected does. At birth, litter size of infected does was reduced by half as compared to the control group, and, at weaning, the number of kits and the weight of litters was lower. Since serum progesterone levels have a key role in the maintenance of pregnancy and implantation, we propose that the observed prolificacy alterations in does infected with T. pisiformis infection were due to changes in the levels of circulating progesterone during pregnancy. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Increased levels of circulating arginase I in overweight compared to normal weight adolescents.

    Science.gov (United States)

    Jung, Christian; Figulla, Hans R; Lichtenauer, Michael; Franz, Marcus; Pernow, John

    2014-02-01

    Overweight and the metabolic syndrome have become major problems, especially in children and adolescents. Obesity at a young age increases the risk for cardiovascular diseases and diabetes mellitus later in life. An early event in the development of cardiovascular disease is endothelial dysfunction which is found in obese young individuals. Increased activity of the enzyme arginase has been described as a central mechanism for endothelial dysfunction, especially in patients with diabetes mellitus. The aim of the study was to determine plasma levels of arginase in overweight adolescents. Sixty-six male German adolescents (age: 15.2 ± 1.1 years old) were included. Thirty-one of them were overweight (>90th age-specific weight percentile). Plasma arginase I and tumor necrosis factor alpha (TNFα) were determined. In addition, clinical data were recorded and anthropometrical measurements of obesity were performed. Overweight adolescents had a higher systolic blood pressure, lower high-density lipoprotein and increased levels of high-sensitive C-reactive protein (CRP). Circulating arginase I was elevated in overweight adolescents (95.8 ± 68.2 ng/ml) compared to normal weight adolescents (39.3 ± 26.9 ng/ml, p obesity. There was no difference between the two groups regarding TNFα. We demonstrate that arginase I levels are increased in obese adolescents. Knowing the important role for arginase in endothelial dysfunction, elevated levels of arginase I may represent a link between obesity, endothelial dysfunction and related comorbidities. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Increased Prolactin Levels Are Associated with Impaired Processing Speed in Subjects with Early Psychosis

    OpenAIRE

    Montalvo, Itziar; Gutiérrez-Zotes, Alfonso; Creus, Marta; Monseny, Rosa; Ortega, Laura; Franch, Joan; Lawrie, Stephen M.; Reynolds, Rebecca M.; Vilella, Elisabet; Labad, Javier

    2014-01-01

    Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for psychosis. Recent studies in non-psychiatric populations suggest that increased prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma prolactin levels are associated with poorer cognitive functioning in subjects with early psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects w...

  5. Temporal aspects of increases in eye-neck activation levels during visually deficient near work.

    Science.gov (United States)

    Richter, Hans O; Camilla, Lodin; Forsman, Mikael

    2012-01-01

    In an experimental study two levels of oculomotor load were induced via optical trial lenses. Trapezius muscle activity was measured with bipolar surface electromyography and normalized to a submaximal contraction. Sixty-six subjects with a median age of 36 (range 19-47, std 8) viewed a black and white Gabor grating (5 c/deg) for two 7-min periods monocularly through a 0 D lens or binocularly through -3.5 D lenses. The effect of time was separately regressed to EMG in two different subgroups of responders: a High-Oculomotor-Load (HOL) and a Low-Oculomotor-Load (LOL) group. A linear regression model was fitted on group level with exposure time on the x-axis and normalized trapezius muscle EMG (%RVE) on the y-axis. The slope coefficient was significantly positive in the -D blur condition for only the HOL subgroup of responders: 0.926 + Time(min 1-7) × 0.088 (p = 0.002, r(2)=0.865). There was no obvious sign of this activity to level off or to stabilize. These results suggest that professional information technology users that are exposed to a high level of oculomotor load, during extended times, are at an increased risk of exhibiting an increased trap.m. activity.

  6. Increased Sclerostin Levels after Further Ablation of Remnant Estrogen by Aromatase Inhibitors

    Directory of Open Access Journals (Sweden)

    Wonjin Kim

    2015-03-01

    Full Text Available BackgroundSclerostin is a secreted Wnt inhibitor produced almost exclusively by osteocytes, which inhibits bone formation. Aromatase inhibitors (AIs, which reduce the conversion of steroids to estrogen, are used to treat endocrine-responsive breast cancer. As AIs lower estrogen levels, they increase bone turnover and lower bone mass. We analyzed changes in serum sclerostin levels in Korean women with breast cancer who were treated with an AI.MethodsWe included postmenopausal women with endocrine-responsive breast cancer (n=90; mean age, 57.7 years treated with an AI, and compared them to healthy premenopausal women (n=36; mean age, 28.0 years. The subjects were randomly assigned to take either 5 mg alendronate with 0.5 µg calcitriol (n=46, or placebo (n=44 for 6 months.ResultsPostmenopausal women with breast cancer had significantly higher sclerostin levels compared to those in premenopausal women (27.8±13.6 pmol/L vs. 23.1±4.8 pmol/L, P0.05.ConclusionSerum sclerostin levels increased with absolute deficiency of residual estrogens in postmenopausal women with endocrine-responsive breast cancer who underwent AI therapy with concurrent bone loss.

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

    Directory of Open Access Journals (Sweden)

    Krystina eSorwell

    2014-06-01

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

  8. Comparing Canadian and American cybersecurity awareness levels: Educational strategies to increase public awareness

    Science.gov (United States)

    Hoggard, Amy

    Cybersecurity awareness is an important issue that affects everyone who uses a computer or a mobile device. Canada and the United States both recognize the value of mitigating cybersecurity risks in terms of national safety, economic stability and protection of their citizens. The research performed compared the levels of cybersecurity awareness in Canadian and American Internet users. Canadian and American users were equally aware of cybersecurity measures, but were not implementing best practices to keep themselves safe. The research suggested users needed to understand why a cybersecurity measure was important before being motivated to implement it. Educational strategies were reviewed in both Canada and the United States and it was determined that although there were significant resources available, they were not being utilized by both the educators and the public. In order to increase cybersecurity awareness levels, nations should focus on increasing the public's awareness by using various types of messaging, such as cartoons, in media. One possible consideration is a compulsory awareness model before accessing the Internet. Cybersecurity topics should be included in the curriculum for students at all levels of education and a focus on providing training and resources to teachers will help increase the cybersecurity knowledge of children and youth.

  9. Specific Increase of Protein Levels by Enhancing Translation Using Antisense Oligonucleotides Targeting Upstream Open Frames.

    Science.gov (United States)

    Liang, Xue-Hai; Shen, Wen; Crooke, Stanley T

    2017-01-01

    A number of diseases are caused by low levels of key proteins; therefore, increasing the amount of specific proteins in human bodies is of therapeutic interest. Protein expression is downregulated by some structural or sequence elements present in the 5' UTR of mRNAs, such as upstream open reading frames (uORF). Translation initiation from uORF(s) reduces translation from the downstream primary ORF encoding the main protein product in the same mRNA, leading to a less efficient protein expression. Therefore, it is possible to use antisense oligonucleotides (ASOs) to specifically inhibit translation of the uORF by base-pairing with the uAUG region of the mRNA, redirecting translation machinery to initiate from the primary AUG site. Here we review the recent findings that translation of specific mRNAs can be enhanced using ASOs targeting uORF regions. Appropriately designed and optimized ASOs are highly specific, and they act in a sequence- and position-dependent manner, with very minor off-target effects. Protein levels can be increased using this approach in different types of human and mouse cells, and, importantly, also in mice. Since uORFs are present in around half of human mRNAs, the uORF-targeting ASOs may thus have valuable potential as research tools and as therapeutics to increase the levels of proteins for a variety of genes.

  10. Elevated levels of serum IL-5 are associated with an increased likelihood of major depressive disorder.

    Science.gov (United States)

    Elomaa, Antti-Pekka; Niskanen, Leo; Herzig, Karl-Heinz; Viinamäki, Heimo; Hintikka, Jukka; Koivumaa-Honkanen, Heli; Honkalampi, Kirsi; Valkonen-Korhonen, Minna; Harvima, Ilkka T; Lehto, Soili M

    2012-01-09

    Inflammatory mediators in both the peripheral circulation and central nervous system (CNS) are dysregulated in major depressive disorder (MDD). Nevertheless, relatively little is known about the role of the T-helper (Th)-2 effector cytokines interleukin (IL)-5 and IL-13 in MDD. We examined the serum levels of these cytokines and a Th-1 comparison cytokine, interferon (IFN)-γ, in 116 individuals (MDD, n = 58; controls, n = 58). In our basic multivariate model controlling for the effects of potential confounders on the associations between MDD and the examined cytokines, each 1-unit increase in the serum IL-5 level increased the likelihood of belonging to the MDD group by 76% (OR 1.76, 95% CI 1.03-2.99, p = 0.04; model covariates: age, gender, marital status, daily smoking and alcohol use). The likelihood further increased in models additionally controlling for the effects of the use of antidepressants and NSAIDS, and a diagnosis of asthma. No such associations were detected with regard to IL-13 (OR 1.08, 95% CI 0.96-1.22, p = 0.22) or IFN-γ (OR 1.02, 95% CI 0.99-1.05, p = 0.23). Elevated levels of IL-5, which uses the neural plasticity-related RAS GTPase-extracellular signal-regulated kinase (Ras-ERK) pathway to mediate its actions in the central nervous system (CNS), could be one of the factors underlying the depression-related changes in CNS plasticity.

  11. A single dose of bovine somatotropin 5 days before the end of progestin-based estrous synchronization increases prolificacy in sheep.

    Science.gov (United States)

    Carrillo, F; Hernández-Cerón, J; Orozco, V; Hernández, J A; Gutiérrez, C G

    2007-11-01

    Bovine somatotropin (bST) enhances ovarian follicular and embryonic development in sheep and cattle. In the present study, the objective was to assess whether bST given 5 days before the end of progestin-based estrous synchronization improves prolificacy and lambing rate in sheep. Pelibuey ewes (n=92) exhibiting estrous cycles at regular intervals received an intravaginal sponge containing 45mg of FGA for 12 days. Five days before sponge withdrawal, ewes were treated with either 125mg of bST sc (bST group; n=47) or saline solution (control; n=45). After the sponge was removed, ewes were observed for estrus and subsequently mated twice. Lambing rate and prolificacy was determined at birth. Blood samples were taken from the time of treatment until day 15 after estrus in eight ewes from the bST group and nine from the control group. Concentrations of IGF-I were determined by immunoradiometric assay and progesterone by RIA. Treatment with bST increased (P0.05). IGF-I concentrations were greater (PProgesterone concentrations did not vary (P>0.05) between groups. It is concluded that a single dose of bST 5 days before progestin withdrawal increases lambing rate and prolificacy in sheep. These effects are associated with an increase in circulating concentrations of IGF-I.

  12. Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma

    Science.gov (United States)

    Hurabielle, Charlotte; Pillebout, Evangéline; Stehlé, Thomas; Pagès, Cécile; Roux, Jennifer; Schneider, Pierre; Chevret, Sylvie; Chaffaut, Cendrine; Boutten, Anne; Mourah, Samia; Basset-Seguin, Nicole; Vidal-Petiot, Emmanuelle; Lebbé, Céleste; Flamant, Martin

    2016-01-01

    Context Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. Objective We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. Methods We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. Results 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Conclusion Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective. PMID:26930506

  13. Matrix metalloproteinase 2 (MMP-2) levels are increased in active acromegaly patients.

    Science.gov (United States)

    Karci, Alper Cagri; Canturk, Zeynep; Tarkun, Ilhan; Cetinarslan, Berrin

    2017-07-01

    During follow-up of acromegaly patients, there is a discordance rate of 30% between the measurements of growth hormone and insulin-like growth factor-1 levels. Further tests are required to determine disease activity in patients with discordant results. This study was planned to investigate an association of serum levels of matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B with disease activity in acromegaly patients. In this study, 64 acromegaly patients followed in our clinic were divided into two groups according to the 2010 consensus criteria for cure of acromegaly as patients with active disease (n = 24) and patients with controlled disease (n = 40). Serum matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B levels were measured by the enzyme-linked immunosorbent assay method. The mean serum matrix metalloproteinase-2 level was significantly higher in the active acromegaly patients than in the controlled acromegaly patients (150.1 ± 54.5 ng/mL vs. 100.2 ± 44.6 ng/mL; p matrix metalloproteinase-9 and cathepsin B levels (p = 0.205 and p = 0.598, respectively). Serum matrix metalloproteinase-2 levels of 118.3 ng/mL and higher had a sensitivity of 75% and a specificity of 77.5% in determining active disease. The risk of active acromegaly was 3.3 fold higher in the patients with a matrix metalloproteinase-2 level of >118.3 ng/mL than in the patients with a matrix metalloproteinase-2 level of matrix metalloproteinase-2 level is increased in the active acromegaly patients and a threshold value in determining active disease was defined for serum matrix metalloproteinase-2 level. This study is the first to compare acromegaly patients having active or controlled disease in terms of matrix metalloproteinase-2 and matrix metalloproteinase-9 levels. The results need to be confirmed by a study that will be conducted in a larger patient group also including a healthy control group to demonstrate the

  14. Increased Mercury Levels in Patients with Celiac Disease following a Gluten-Free Regimen

    Directory of Open Access Journals (Sweden)

    Luca Elli

    2015-01-01

    Full Text Available Background and Aim. Although mercury is involved in several immunological diseases, nothing is known about its implication in celiac disease. Our aim was to evaluate blood and urinary levels of mercury in celiac patients. Methods. We prospectively enrolled 30 celiac patients (20 treated with normal duodenal mucosa and 10 untreated with duodenal atrophy and 20 healthy controls from the same geographic area. Blood and urinary mercury concentrations were measured by means of flow injection inductively coupled plasma mass spectrometry. Enrolled patients underwent dental chart for amalgam fillings and completed a food-frequency questionnaire to evaluate diet and fish intake. Results. Mercury blood/urinary levels were 2.4±2.3/1.0±1.4, 10.2±6.7/2.2±3.0 and 3.7±2.7/1.3±1.2 in untreated CD, treated CD, and healthy controls, respectively. Resulting mercury levels were significantly higher in celiac patients following a gluten-free diet. No differences were found regarding fish intake and number of amalgam fillings. No demographic or clinical data were significantly associated with mercury levels in biologic samples. Conclusion. Data demonstrate a fourfold increase of mercury blood levels in celiac patients following a gluten-free diet. Further studies are needed to clarify its role in celiac mechanism.

  15. Antisense oligonucleotides targeting translation inhibitory elements in 5' UTRs can selectively increase protein levels.

    Science.gov (United States)

    Liang, Xue-Hai; Sun, Hong; Shen, Wen; Wang, Shiyu; Yao, Joyee; Migawa, Michael T; Bui, Huynh-Hoa; Damle, Sagar S; Riney, Stan; Graham, Mark J; Crooke, Rosanne M; Crooke, Stanley T

    2017-09-19

    A variety of diseases are caused by deficiencies in amounts or activity of key proteins. An approach that increases the amount of a specific protein might be of therapeutic benefit. We reasoned that translation could be specifically enhanced using trans-acting agents that counter the function of negative regulatory elements present in the 5' UTRs of some mRNAs. We recently showed that translation can be enhanced by antisense oligonucleotides (ASOs) that target upstream open reading frames. Here we report the amount of a protein can also be selectively increased using ASOs designed to hybridize to other translation inhibitory elements in 5' UTRs. Levels of human RNASEH1, LDLR, and ACP1 and of mouse ACP1 and ARF1 were increased up to 2.7-fold in different cell types and species upon treatment with chemically modified ASOs targeting 5' UTR inhibitory regions in the mRNAs encoding these proteins. The activities of ASOs in enhancing translation were sequence and position dependent and required helicase activity. The ASOs appear to improve the recruitment of translation initiation factors to the target mRNA. Importantly, ASOs targeting ACP1 mRNA significantly increased the level of ACP1 protein in mice, suggesting that this approach has therapeutic and research potentials. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Increased high-density lipoprotein cholesterol levels in mice with XX versus XY sex chromosomes.

    Science.gov (United States)

    Link, Jenny C; Chen, Xuqi; Prien, Christopher; Borja, Mark S; Hammerson, Bradley; Oda, Michael N; Arnold, Arthur P; Reue, Karen

    2015-08-01

    The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels. We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the four core genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male-female gonadal sex and XX-XY chromosome complement. Gonadectomy of adult mice revealed that the male-female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male-female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared with a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an X and Y chromosome. By generating mice with XX, XY, and XXY chromosome complements, we determined that the presence of 2 X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration. We demonstrate that having 2 X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels. © 2015 American Heart Association, Inc.

  17. Experimental increase in baseline corticosterone level reduces oxidative damage and enhances innate immune response.

    Directory of Open Access Journals (Sweden)

    Csongor I Vágási

    Full Text Available Glucocorticoid (GC hormones are significant regulators of homeostasis. The physiological effects of GCs critically depend on the time of exposure (short vs. long as well as on their circulating levels (baseline vs. stress-induced. Previous experiments, in which chronic and high elevation of GC levels was induced, indicate that GCs impair both the activity of the immune system and the oxidative balance. Nonetheless, our knowledge on how mildly elevated GC levels, a situation much more common in nature, might influence homeostasis is limited. Therefore, we studied whether an increase in GC level within the baseline range suppresses or enhances condition (body mass, hematocrit and coccidian infestation and physiological state (humoral innate immune system activity and oxidative balance. We implanted captive house sparrows Passer domesticus with either 60 days release corticosterone (CORT or control pellets. CORT-treated birds had elevated baseline CORT levels one week after the implantation, but following this CORT returned to its pre-treatment level and the experimental groups had similar CORT levels one and two months following the implantation. The mass of tail feathers grown during the initial phase of treatment was smaller in treated than in control birds. CORT implantation had a transient negative effect on body mass and hematocrit, but both of these traits resumed the pre-treatment values by one month post-treatment. CORT treatment lowered oxidative damage to lipids (malondialdehyde and enhanced constitutive innate immunity at one week and one month post-implantation. Our findings suggest that a relatively short-term (i.e. few days elevation of baseline CORT might have a positive and stimulatory effect on animal physiology.

  18. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

    KAUST Repository

    Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W.; Riebesell, Ulf; Gao, Kunshan

    2015-01-01

    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46–212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130–160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28–48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

  19. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

    KAUST Repository

    Jin, Peng

    2015-10-27

    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46–212% the productio