Plasma Concentrations Of Insulin-like Growth Factor Research Articles

Effects of administering exogenous bovine somatotropin to beef heifers during the first trimester on conceptus development as well as steroid- and eicosanoid-metabolizing enzymes.

The aim of this study was to evaluate the effect of bovine somatotropin (bST) on fetal and placental development during the first third of gestation in beef heifers. Angus heifers (n = 97) were randomly assigned to either receive a 500-mg injection of bST (BST) biweekly on days 0, 15, 29, 43, and 57 of gestation or not receive bST (CTL) throughout the experiment. Body weight (BW) was assessed on days -9, -3, 0, 15, 22, 29, 43, 50, 57, 64, and 77, while blood samples were collected on days 0, 22, 50, and 64. Pregnancy status was determined via transrectal ultrasonography on days 29 and 64. A subset of pregnant heifers (BST, n = 7; CTL, n = 5) were harvested on day 84, and complete gravid reproductive tracts and liver tissue were collected for analysis. Cytochrome P450 1A (CYP1A), 2C (CYP2C), 3A (CYP3A), and uridine 5'-diphospho-glucuronosyltransferase (UGT) activities were determined. Mean change in BW and average daily gain of heifers between fixed-time artificial insemination (day 0) and day 77 did not differ between treatments (P ≥ 0.05). Mean concentrations of insulin-like growth factor 1 (IGF-1) were greater (P < 0.001) in BST (347 ± 27.7 ng/mL) compared with CTL (135 ± 32.8 ng/mL) heifers. Mean placental weight, fetal membrane weight, uterine weight, and ovarian and corpus luteum (CL) weights, as well as fetal morphometric data, did not differ (P ≥ 0.05) between treatments. However, BST heifers had greater (P = 0.03) quantities of combined fetal fluid compared with CTL (521.6 ± 22.9 vs. 429.6 ± 27.14 g, respectively). Tendencies were observed for BST heifers to have reproductive tracts with fewer placentomes (P = 0.08) and fetuses with greater umbilical diameters (P = 0.09) compared with CTL. The activity of CYP1A did not differ (P ≥ 0.05) within the maternal and fetal liver, caruncle, cotyledon, or CL tissue samples between treatments. Furthermore, CYP3A activity was only observed in maternal liver samples and was not different between treatments (P ≥ 0.05). Interestingly, CYP2C activity was greater (P = 0.01) in the liver of BST vs. CTL heifers, and UGT activity was greater (P = 0.02) in the CL from BST heifers compared with CTL. In conclusion, the administration of bST during the first third of gestation increased plasma concentrations of IGF-1, which resulted in an increase in fetal fluid, decrease in placentome number, and greater umbilical diameter, but failed to alter fetal development.

Supplementation frequency and amount modulate postweaning growth and reproductive performance of Bos indicus-influenced beef heifers.

This 2-yr study evaluated the growth and puberty attainment of Bos indicus-influenced beef heifers offered 2 different postweaning concentrate supplementation amounts and delivery frequencies. On day 0 of each year, 64 Brangus crossbred heifers were stratified by initial body weight (BW) and age (mean = 244 ± 22 kg; 314 ± 17 d) and assigned into 1 of 16 bahiagrass pastures (4 heifers/pasture/yr). Treatments were randomly assigned to pastures in a 2 × 2 factorial design (4 pastures/treatment/yr) and consisted of concentrate dry matter (DM) supplementation at 1.25% or 1.75% of BW which were offered either daily (7×) or 3 times weekly (3×) for 168 d. On day 56 of each year, heifers were assigned to an estrus synchronization protocol consisting of intravaginal controlled internal drug release (CIDR) insertion on day 56, CIDR removal on day 70, i.m. injection of 25 mg of prostaglandin F2α (PGF2α) on day 86, and i.m. injection of 100 µg of gonadotropin-releasing hormone and timed-AI at 66 h after PGF2α injection (day 89). Heifers were exposed to Angus bulls from day 89 to 168 (1 bull/pasture). Pregnancy diagnosis was assessed on day 213 of each year. Supplementation amount × frequency effects were not detected (P ≥ 0.12) for any variable, except for plasma concentrations of glucose (P = 0.10) and urea nitrogen (PUN; P = 0.01). Herbage mass, herbage allowance, and nutritive value did not differ (P ≥ 0.12) among treatments. Increasing supplementation DM amount from 1.25% to 1.75% of BW increased (P ≤ 0.05) plasma concentrations of insulin-like growth factor 1 (IGF-1), overall average daily gain (ADG), final BW, percentage of pubertal heifers on day 89, pregnancy and calving percentages, and percentage of heifers calving within the first 21 d of the calving season. However, reducing the supplementation frequency from daily to 3× weekly, regardless of supplementation amount, did not impact overall pregnancy and calving percentages (P ≥ 0.42), but caused (P ≤ 0.05) fluctuations in plasma concentrations of insulin and IGF-1 and decreased (P ≤ 0.03) overall ADG, final BW, puberty attainment on days 56, 89, and 168, and percentage of heifers calving during the first 21 d of the calving season. Hence, increasing the supplement DM amount did not prevent the negative effects of reducing the frequency of supplementation (3× vs. 7× weekly) on growth and reproduction of replacement Bos indicus-influenced beef heifers.

Association of residual feed intake with growth performance, carcass traits, meat quality, and blood variables in native chickens.

Improving feed efficiency is a primary goal in poultry breeding strategies. Residual feed intake (RFI) in chickens typically calculated during the growing period is a measure of feed efficiency that is independent of the level of production. The objective of this study was to evaluate phenotypic correlations of growth performance, carcass traits, meat quality, and blood variables with RFI in growing native chickens. A total of 1,008 chickens were selected for the experiment to derive RFI. After the RFI measurement period of 42 d, 25 chickens with low RFI values, 25 chickens with medium RFI values, and 25 chickens with high RFI values were selected. The RFI was significantly positively correlated with feed conversion ratio and average daily feed intake, while it was not significantly correlated with initial body weight (BW), final BW, average daily body weight gain, and metabolic BW0.75. The abdominal fat weight and yield of high RFI group were significantly greater than those of medium and low RFI groups, and the abdominal fat yield was significantly positively correlated with RFI. Moreover, the plasma insulin-like growth factor 1 (IGF-1) content of low RFI group was significantly greater than those of high and medium RFI groups. The plasma concentrations of adrenocorticotropic hormone, triiodothyronine (T3), and cortisol of high RFI birds were significantly greater than that of low RFI birds. RFI was significantly positively correlated with plasma concentrations of T3 and cortisol, while it was significantly negatively correlated with plasma concentration of IGF-1. In addition, the serum levels of glucose and triglyceride of high RFI birds were significantly lower than that of low RFI birds. The serum low-density lipoprotein cholesterol (LDL-C) content of high RFI group was significantly greater than that of medium and low RFI groups, and it was significantly positively correlated with RFI. Our data suggested that selection of chickens with low RFI values may be beneficial to reduce fat deposition in native chickens without affecting the meat quality. Circulating IGF-1, T3, cortisol, and LDL-C concentrations can be used as indirect selection indicators of feed efficiency in native chickens. The effect of IGF-1, T3, cortisol, and LDL-C on feed efficiency of native chickens should be carefully examined and validated in future breeding programs.

PM2.5-bound PAHs exposure linked with low plasma insulin-like growth factor 1 levels and reduced child height

BackgroundExposure to atmospheric fine particle matter (PM2.5) pollution and the absorbed pollutants is known to contribute to numerous adverse health effects in children including to growth. ObjectiveThe aim of this study was to evaluate exposure levels of atmospheric PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) in an electronic waste (e-waste) polluted town, Guiyu, and to investigate the associations between PM2.5-PAH exposure, insulin-like growth factor 1 (IGF-1) levels and child growth. MethodsThis study recruited 238 preschool children (3–6 years of age), from November to December 2017, of which 125 were from Guiyu (an e-waste area) and 113 were from Haojiang (a reference area). Levels of daily PM2.5 and PM2.5-bound ∑16 PAHs were assessed to calculate individual chronic daily intakes (CDIs). IGF-1 and IGF-binding protein 3 (IGFBP-3) concentrations in child plasma were also measured. The associations and further mediation effects between exposure to PM2.5 and PM2.5-bound PAHs, child plasma IGF-1 concentration, and child height were explored by multiple linear regression models and mediation effect analysis. ResultsElevated atmospheric PM2.5-bound ∑16 PAHs and PM2.5 levels were observed in Guiyu, and this led to more individual CDIs of the exposed children than the reference (all P < 0.001). The median level of plasma IGF-1 in the exposed group was lower than in the reference group (91.42 ng/mL vs. 103.59 ng/mL, P < 0.01). IGF-1 levels were negatively correlated with CDIs of PM2.5, but not with CDIs of PM2.5-bound ∑16 PAHs after adjustment. An increase of 1 μg/kg of PM2.5 intake per day was associated with a 0.012 cm reduction of child height (95% CI: −0.014, −0.009), and similarly, an elevation of 1 ng/kg of PM2.5-bound ∑16 PAHs intake per day was associated with a 0.022 cm decrease of child height (95% CI: −0.029, −0.015), both after adjustment of several potential confounders (age, gender, family cooking oil, picky eater, eating sweet food, eating fruits or vegetables, parental education level and monthly household income). The decreased plasma IGF-1 concentration mediated 15.8% of the whole effect associated with PM2.5 exposure and 23.9% of the whole effect associated with PM2.5-bound ∑16 PAHs exposure on child height. ConclusionExposure to atmospheric PM2.5-bound ∑16 PAHs and PM2.5 is negatively associated with child height, and is linked to reduced IGF-1 levels in plasma. This may suggest a causative negative role of atmospheric PM2.5-bound exposures in child growth.

Changes of plasma cGP/IGF-1 molar ratio with age is associated with cognitive status of Parkinson disease.

ObjectiveCognitive impairment is a common feature of Parkinson disease (PD), for which age is a major contributing factor. Insulin‐like growth factor‐1 (IGF‐1) declines with age and contributes to age‐related cognitive impairment in PD. Cyclic glycine‐proline (cGP) is a metabolite of IGF‐1 and normalizes bioavailable IGF‐1. Plasma cGP/IGF‐1 molar ratio that represents bioactive IGF‐1 in circulation, may associate with the cognitive status in PD.MethodsWe examined the association of plasma cGP/IGF‐1 molar ratio with the cognitive scores or age in PD patients with normal cognition (PD‐N, n = 74), mild cognitive impairment (PD‐MCI, n = 71), or dementia (PD‐D, n = 33), and with the cognitive scores in 23 age‐matched healthy controls. Plasma concentrations of IGF‐1, IGF binding protein‐3, and cGP were evaluated using enzyme‐linked immunosorbent assay (ELISA) and high‐performance liquid chromatography‐mass spectrometry (HPLC‐MS), respectively.ResultsThe cGP/IGF‐1 molar ratio was positively correlated with the age of PD‐N group, negatively correlated with the age of PD‐D group, and not associated with the age of PD‐MCI group. Independent of age, the cGP/IGF‐1 molar ratio was positively correlated with the cognitive scores of healthy controls, but not in PD groups.ConclusionOld healthy people with a higher cGP/IGF‐1 molar ratio showed better preserved cognition, possibly due to improved IGF‐1 function. Increased cGP/IGF‐1 molar ratio with age may contribute to cognitive retention in the PD‐N group. The absence or reversal of such association with age in the PD‐MCI and PD‐D groups may indicate the conversion of cognitive status in PD, if confirmed through longitudinal investigations within the individuals with advancing cognitive impairment.

Effects of Saccharomyces cerevisiae supplementation on growth performance, plasma metabolites and hormones, and rumen fermentation in Holstein calves during pre- and post-weaning periods.

This study aimed to evaluate the effects of supplementing Saccharomyces cerevisiae (SC) during the pre- and post-weaning periods on growth, metabolic and hormonal responses, and rumen fermentation in calves. Three-week-old Holstein calves were assigned to either control (n=12) or SC group (n=12), the latter of which received 2×109 cfu/day of SC. The experiment was conducted over a period of 7weeks around weaning. Daily gain (DG) in the SC group was higher (p<.05) than that in the control group. In the SC group, plasma glucose, insulin, and growth hormone (GH) concentrations were higher (p<.05) and concentrations of glucagon and insulin-like growth factor 1 (IGF-1) tended to be higher (p<.1) than in the control group. Proportion of rumen propionate and concentration of rumen ammonia nitrogen at 10weeks of age were greater (p<.05) in the SC group than that in the control group. Supplementation of SC around weaning may improve dietary nutrient and energy availability and increase plasma GH and IGF-1 concentrations. These changes observed in SC-supplemented calves could be closely related to the improvement of DG.

Dietary lysine affects amino acid metabolism and growth performance, which may not involve the GH/IGF-1 axis, in young growing pigs1.

Lysine is the first limiting amino acid (AA) in typical swine diets. Our previous research showed that dietary lysine restriction compromised the growth performance of late-stage finishing pigs, which was associated with the changes in plasma concentrations of nutrient metabolites and hormone insulin-like growth factor 1 (IGF-1). This study was conducted to investigate how dietary lysine restriction affects the plasma concentrations of selected metabolites and three anabolic hormones in growing pigs. Twelve individually penned young barrows (Yorkshire × Landrace; 22.6 ± 2.04 kg) were randomly assigned to two dietary treatments (n = 6). Two corn and soybean meal based diets were formulated to contain 0.65% and 0.98% standardized ileal digestible lysine as a lysine-deficient (LDD) and a lysine-adequate (LAD) diets, respectively. During the 8-week feeding trial, pigs had ad libitum access to water and their respective diets, and the growth performance parameters including average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F) were determined. At the end of the trial, jugular vein blood was collected for plasma preparation. The plasma concentrations of free AA and six metabolites were analyzed with the established chemical methods, and the hormone concentrations were analyzed with the commercial ELISA kits. Data were analyzed with Student's t-test. The ADG of LDD pigs was lower (P < 0.01) than that of LAD pigs, and so was the G:F (P < 0.05) since there was no difference in the ADFI between the two groups of pigs. In terms of free AA, the plasma concentrations of lysine, methionine, leucine, and tyrosine were lower (P < 0.05), while that of β-alanine was higher (P < 0.01), in the LDD pigs. The total plasma protein concentration was lower (P < 0.02) in the LDD pigs, whereas no differences were observed for the other metabolites between the two groups. No differences were observed in the plasma concentrations of growth hormone (GF), insulin, and IGF-1 between the two groups as well. These results indicate that the lack of lysine as a protein building block must be the primary reason for a reduced body protein synthesis and, consequently, the compromised G:F ratio and ADG. The changes in the plasma concentrations of total protein and four AA suggest that the compromised growth performance might be associated with some cell signaling and metabolic pathways that may not involve the GH/IGF-1 axis.

L-Glutamine Increases IGF-1 Liver Expression to Prevent Bone Loss in Sickle Mice

BACKGROUND: Chronic red blood cell (RBC) hemolysis that accompanies sickle cell disease (SCD) is associated with elevated iron storage in tissues, in particular the liver (Nguyen et al. 2014). Iron storage within the liver leads to oxidative stress and fibrosis, reducing circulating antioxidants (vitamin D &amp; hemopexin) and essential hormones, namely insulin-like growth factor-1 (IGF-1). We have previously shown that SCD mice progressively develop a pronounced osteopenia, although the particular drivers of this are unknown (Green et al. 2015). Outside studies suggest this is largely due to the significant decrease of IGF-1 expression, which is vital for bone growth and development (Xiao et al. 2016). FDA approval of L-glutamine (GLN) is said to reduce the acute complications of SCD by increasing antioxidant capacity of RBCs, however opposing research has led to uncertainty about the proposed therapeutic mechanism (Quinn 2018). GLN is utilized ubiquitously as a precursor for antioxidant synthesis to combat oxidative stress; therefore, the benefit experienced by sickle patients may be explained by means outside of RBC usage. Under normal conditions the liver is one of the primary sources of GLN for the body. However, the liver becomes a major site of GLN consumption during disease states to maintain homeostatic activity and reduce hepatic damage from oxidative stress (Cruzat et al. 2018). We hypothesize that GLN therapy prevents sickle bone loss by increasing liver expression of IGF-1. METHODS: Male Townes sickle mice (SS, Jackson) and littermate controls (AA) were evaluated at 4, 8, 12 and 16 wks old. (n=10/group, IACUC approved). Half the animals received GLN in drinking water (0.7% w/v) from weaning at 4 wks old until sacrifice. Changes in femoral cortical and trabecular bone were assessed by µCT. Livers were weighed, as hepatomegaly provides a clinical index for iron storage and cirrhosis in SCD. In addition, plasma concentrations of liver derived IGF-1, the antioxidant hemopexin (HPX), and gamma-glutamyl transferase (GGT) activity were measured to determine therapeutic efficacy. RESULTS: At 4wks there was no difference in bone, but SS livers were 20% larger than AA although liver plasma markers did not significantly differ. GLN therapy was effective at 8 wks, preventing cortical bone thinning in SS mice and reducing hepatomegaly by 12%; which remained consistent at all ages. IGF-1 plasma concentrations reflected this reduction in liver size with ~2 fold increase. HPX and GGT levels were similar to controls within treatment group, but were significantly reduced in untreated SS mice. At 12 wks, GLN effects split into two groups: (i) elevated IGF-1 (GLN+, like AA) or (ii) reduced IGF-1 (GLN-) consistent with loss of GLN effect in these mice. At 12 wks, cortical and trabecular bone in GLN+ mice group were similar to AA, while bone of GLN- mice were comparable to untreated SS mice. Protective effect of GLN on cortical bone remained by 16 wks, but was lost in trabecular bone, even in GLN+ mice. HPX concentrations followed a similar pattern, however GGT activity of GLN+ group reduced to GLN- rates. DISCUSSION: Our studies reveal that GLN therapy increases the expression of IGF-1 and prevents the osteopenia that develops in adolescence in SCD. However, the protective effects of GLN on trabecular bone in SS mice appears to be lost with skeletal maturity. GLN therapy increases the amount of HPX available to prevent iron absorption into the tissue; however sickle RBC hemolysis still occurs during GLN therapy, thereby delaying oxidative stress derived hepatic damage as suggested by GGT at 16 wks. Why cortical and trabecular bone respond differently to GLN in SCD at maturity is not yet clear. Previous studies have shown that systemic liver derived IGF-1 preferentially affects cortical bone growth in normal mice, while locally produced IGF-1 is responsible for trabecular. In a similar manner to the liver, we speculate that iron accumulate within sickle bone may alter local bone cell expression of IGF-1. Disclosures No relevant conflicts of interest to declare.

Comparison of the effects of high and low milk-replacer feeding regimens on health and growth of crossbred dairy heifers

Context Pre-weaning growth in dairy heifers is highly dependent on the amount of milk fed. Both milk replacer (MR) and associated labour are costly, encouraging restricted milk rations and once-a-day feeding. Aims This study compared performance relating to the growth and health of calves receiving one of two commercial feeding regimens: High or Low. Methods All heifers born during the Spring (January–March) calving block on a commercial UK farm with mixed-breed genetics were recruited at birth, randomly assigned to the High (n = 104, receiving MR-A) or Low (n = 88, receiving MR-B) feed group and reared indoors on straw bedding, with free access to concentrate. Both groups initially received MR twice daily. The High group continued to receive MR twice daily throughout the experiment, whereas the Low group calves were reduced to a single MR feed daily during Weeks 4–8. Blood samples were taken in Weeks 1 and 6 to assess passive transfer and measure circulating insulin-like growth factor 1 (IGF1). The Wisconsin calf-scoring system was used to assess health of calves in Weeks 1, 2, 4, 6 and 8 and at 6 months and size was also measured at these times. Data were analysed by univariate and multivariate models. Key results Passive transfer was good in both groups (serum total protein (mean ± s.d.) 60.9 ± 9.1 mg/mL) with no differences in pre-weaning disease incidence; diarrhoea occurred in 64.5% and bovine respiratory disease in 26.3% of calves. High group calves were significantly heavier, taller and longer at all pre-weaning examinations except recruitment owing to more growth in the first month, and remained significantly larger at 6 months: weight 157 ± 8 vs 149 ± 7 kg, height 103 ± 5 vs 100 ± 5 cm, length 90 ± 4 vs 88 ± 5 cm. Plasma IGF1 concentrations at around Week 6 were doubled in the High group (101 ± 38.6 vs 55 ± 34.1 ng/mL). Bovine respiratory disease was associated with reduced weight gain. Heifers with diarrhoea were leaner at weaning. High feed group, weight at recruitment and good passive transfer were positively associated with weight at 6 months. Conclusions Higher feeding levels pre-weaning increased growth rates and IGF1, although the disease incidence was unaffected. Implications Previous studies have shown that more growth and higher IGF1 pre-weaning are associated with a lower age at first calving and an increased chance of reaching the end of first lactation. These in turn improve long-term performance.

Artificial long-day photoperiod in the subtropics increases body weight in goat kids born in the autumn

To determine whether exposure to artificial long days increases the body weight of subtropical goat kids born in autumn, sixty-four goat kids were distributed in a completely randomized design with a factorial arrangement. Experimental groups consisted of two photoperiod treatments (natural or artificial photoperiod, 16 h light: 8 h darkness), and two suckling types (natural or artificial). The mean body weight, recorded at day 27 of age, was higher in goat kids subjected to artificial long days (7.7 ± 0.2 kg) than in those maintained under a natural photoperiod (7.0 ± 0.2 kg; P < 0.05). The mean daily gain was higher in light-treated kids (163 g/d) than in those maintained on a natural photoperiod (141 g/d; P < 0.001). Likewise, the mean blood glucose concentration was higher in goat kids submitted to artificial long days (102.0 ± 1.3 mg/dL) than in those kids maintained on the natural photoperiod (92.5 ± 1.3 mg/dL; P < 0.001). The suckling type had an effect on the plasma insulin-like growth factor-1 concentrations (IGF-1) of the kids (P < 0.01), and this effect was more pronounced in goat kids under artificial long days (P < 0.05). The results of the present study show that in subtropical goat kids born during the autumn, exposure to an artificial long-day photoperiod promotes a high body weight during the early phase of growth, independent of whether they are reared or not by their dams. In addition, these results also showed that, depending on suckling type, exposure to artificial long days increase the concentrations of IGF-1 in goat kids.

Prenatal arsenic exposure is associated with increased plasma IGFBP3 concentrations in 9-year-old children partly via changes in DNA methylation

Exposure to inorganic arsenic (As), a carcinogen and epigenetic toxicant, has been associated with lower circulating levels of insulin-like growth factor 1 (IGF1) and impaired growth in children of pre-school age. The aim of this study was to assess the potential impact of exposure to As on IGF1 and insulin-like growth factor-binding protein 3 (IGFBP3) as well as DNA methylation changes in 9-year-old children. To this end, we studied 9-year-old children from a longitudinal mother–child cohort in rural Bangladesh (n = 551). Prenatal and concurrent exposure to As was assessed via concentrations in maternal urine at gestational week 8 and in child urine at 9 years, measured by HPLC-HG-ICPMS. Plasma IGF1 and IGFBP3 concentrations were quantified with immunoassays. DNA methylation was measured in blood mononuclear cells at 9 years in a sub-sample (n = 113) using the Infinium HumanMethylation450K BeadChip. In multivariable-adjusted linear regression models, prenatal As (natural log-transformed), but not children’s concurrent urinary As, was positively associated with IGFBP3 concentrations (β = 76, 95% CI 19, 133). As concentrations were not associated with IGF1. DNA methylation analysis revealed CpGs associated with both prenatal As and IGFBP3. Mediation analysis suggested that methylation of 12 CpG sites for all children was mediator of effect for the association between prenatal As and IGFBP3. We also found differentially methylated regions, generally hypermethylated, that were associated with both prenatal As and IGFBP3. In all, our study revealed that prenatal exposure to As was positively associated with IGFBP3 concentrations in children at 9 years, independent of IGF1, and this association may, at least in part, be epigenetically mediated.

Association between male Infertility and seminal plasma levels of growth hormone and insulin-like growth factor-1.

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) have been proposed to play a pivotal role in male infertility due to their anabolic effects. The aim of this study was to investigate possible associations between seminal plasma levels of GH and IGF-1 and sperm parameters. Fifty men participated in this study. Semen analysis was performed, while cell-free seminal plasma was collected following sperm centrifugation. Seminal plasma concentrations of IGF-1 and GH were determined by enzyme-linked immunosorbent assay (ELISA). Due to the presence of asthenozoospermia in all participants who presented with abnormal sperm parameters, the participants were further subdivided into normal (group A), asthenozoospermic (group B) and asthenozoospermic plus at least one additional abnormal parameter (group C). A marginally nonsignificant statistical difference (p=0.063) was revealed between the GH levels corresponding to the asthenozoospermic and the normal group with the latter presenting with higher GH levels. A statistically significant positive correlation (p<0.05) was noted between levels of GH and IGF-1 in group C. The above relationship has also been observed in men with low sperm concentration, vitality, volume and abnormal morphology. These novel findings require further investigation in order for the biological significance of those associations to be clarified.

A quantitative LC-MS/MS method for insulin-like growth factor 1 in human plasma.

Insulin-like growth factor 1 (IGF1) is a biomarker with various applications in medicine and also in doping control. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed that employs 15N-IGF1 as an internal standard. The method features urea-based IGF1/IGFBP-complex dissociation which is directly followed by tryptic digestion. Following solid-phase extraction (SPE) sample clean-up of the digest, IGF1 is detected by means of two signature peptides that enable quantification of total IGF1 as well as discrimination between IGF1 proteoforms with 'native' and modified or extended N-terminal sequences. Our method is capable of measuring plasma IGF1 concentrations over the clinically relevant range of 10-1000 ng/mL and was validated according to regulatory guidelines. Comparison with the IDS-iSYS IGF1 immunoassay revealed good correlation (R2>0.97) and no proportional bias between both assays was observed after normalizing the results against the WHO reference standard for IGF1 (02/254). Evaluation of several commercially available IGF1 preparations showed varying responses which were due to inconsistencies in purity and absolute amount of IGF1 present in these products. Our LC-MS/MS method introduces urea-based dissociation of IGF1/IGFBP-complexes to enable reliable quantification of IGF1 in plasma. Furthermore, the method is able to detect clinically relevant IGF1 levels without an enrichment procedure at the protein-level and thereby minimizes the risk of losing IGF1 proteoforms during sample preparation.

Relationships between plasma insulin-like growth factor-1 and insulin concentrations in multiparous dairy cows with cytological endometritis

Cytological endometritis (CYTO) is a uterine inflammation characterised by the percentage of polymorphonuclear neutrophils in endometrial cytology. This observational study evaluated the association of blood plasma insulin-like growth factor-1 (IGF-1)...

Assessing Indices of Growth for Field Studies of Juvenile Salmon: An Experiment and Synthesis

AbstractThe hypothesis that size‐selective mortality in the first marine year is a major regulator of recruitment in Pacific salmon Oncorhynchus spp. has led to interest in assessing the recent growth of field‐caught fish. Understanding differences in relative growth across years, regions, habitats, and prey fields may provide insights into factors influencing survival. Plasma insulin‐like growth factor 1 (IGF1), muscle RNA : DNA ratio (RD), and scale circulus spacing have all been used as indices of recent growth in juvenile salmonids. We concurrently assessed these growth rate indices in a laboratory study of postsmolt, young‐of‐the‐year, ocean‐type Chinook Salmon O. tshawytscha. We synthesized results with previous work to inform selection of appropriate growth rate indices for field studies on juvenile salmonids. Muscle samples suitable for RD analysis were obtained nonlethally and without subsequent growth impacts, even for very small juvenile salmon (75–99 mm FL). Plasma IGF1 concentration was strongly correlated with growth rate (R2 = 0.79), while loge(RD) and mean spacing of the outer two circuli were moderately correlated with growth rate (R2 = 0.47 and 0.44, respectively). Relationships between the two biochemical indices and growth rate were independent of body size at the start of the experiment. Conversely, initially larger fish formed wider circuli for a given growth rate. Insulin‐like growth factor 1 and RD responded to a change in growth conditions within 4 and 6 d, respectively. Rate of circulus formation varied positively with growth rate, meaning that outer circulus spacing indexed shorter periods of growth in faster‐growing fish. Our results confirm the value of plasma IGF1 as an index of recent growth in juvenile salmon. Although scales (marginal circulus spacing) and white muscle (RD) can both be sampled nonlethally, scale sampling presents a number of practical advantages.

L-Carnitine Supplementation in Older Women. A Pilot Study on Aging Skeletal Muscle Mass and Function.

Skeletal muscle wasting, associated with aging, may be regulated by the inflammatory cytokines as well as by insulin-like growth factor 1 (IGF-1). l-carnitine possesses anti-inflammatory properties and increases plasma IGF-1 concentration, leading to the regulation of the genes responsible for protein catabolism and anabolism. The purpose of the present study was to evaluate the effect of a 24-week l-carnitine supplementation on serum inflammatory markers, IGF-1, body composition and skeletal muscle strength in healthy human subjects over 65 years of age. Women between 65 and 70 years of age were supplemented for 24 weeks with either 1500 mg l-carnitine-l-tartrate or an isonitrogenous placebo per day in a double-blind fashion. Before and after the supplementation protocol, body mass and composition, as well as knee extensor and flexor muscle strength were determined. In the blood samples, free carnitine, interleukin-6, tumor necrosis factor-α, C-reactive protein and IGF-1 were determined. A marked increase in free plasma carnitine concentration was observed due to l-carnitine supplementation. No substantial changes in other parameters were noted. In the current study, supplementation for 24 weeks affected neither the skeletal muscle strength nor circulating markers in healthy women over 65 years of age. Positive and negative aspects of l-carnitine supplementation need to be clarified.

Effect of zinc and vitamin E supplementation on hormones and blood biochemicals in peri-partum Sahiwal cows

Thirty-two advanced pregnant multiparous Sahiwal cows were used to study the effect of additional zinc (Zn) and vitamin E (VE) supplementation on hormonal and biochemical changes. Cows were randomly assigned to four groups and fed a basal diet of compounded concentrate, berseem fodder, and wheat straw in a ratio of 60:20:20. The groups were: (1) the basal diet with no supplement (control treatment); (2) the basal diet supplemented with 60 mg/kg DM/cow daily of Zn (Zn treatment); (3) the basal diet supplemented with 1000 IU/cow daily of vitamin E (VE treatment); and (4) the basal diet supplemented with a combination of 60 mg Zn/kg DM/cow and 1000 IU vitamin E/cow/d (Zn + VE treatment). Blood samples were collected on −60, −45, −30, −15, −7, −3, 0, 3, 7, 15, 30, 45, 60, 90, and 120 d in relation to expected date of calving and were analyzed for endocrine variables and biochemical changes. Plasma concentrations of leptin, insulin, insulin like growth factor-1 (IGF-1), triidothyronine (T3), and tetraiodothyronine (T4) were decreased toward calving and observed lowest (P < 0.05) on 3 d post-partum. However, plasma levels of growth hormone (GH) and cortisol increased toward calving and were found highest (P < 0.05) on 3 d post-partum. Pre-partum concentrations of leptin and IGF-1 were higher (P < 0.05) than its respective concentration observed during post-partum. Post-partum concentrations of GH and cortisol were higher (P < 0.05) than its respective pre-partum concentration. Pre-partum concentrations of urea, triglycerides, Zn, and VE were higher (P < 0.05) and total cholesterol and HDL cholesterol were lower than its values observed in post-partum among all the groups. Treatments had significant (P < 0.05) effect on plasma hormonal levels and levels of Zn and VE but no effect on biochemical attributes. Cows fed on diet supplemented with Zn + VE had highest (P < 0.05) pre as well as post-calving concentrations of leptin (6.38 vs 5.01 ng/ml), insulin (1.39 vs 1.33 ng/ml), GH (9.29 vs 13.72 ng/ml), IGF-1 (14.55 vs 12.59 nmol/l), T3 (1.45 vs 1.40 ng/ml), T4 (32.44 vs 31.79 ng/ml) whereas as lowest concentration of cortisol hormone (3.05 vs 3.44 ng/ml). Cows supplemented with combination of Zn and VE showed minimum decline in plasma concentration of leptin, insulin, GH, IGF-1, T3, and T4, and minimum increase in cortisol concentration. In conclusion, dairy cows around parturition faces various endocrine and biochemical alterations and supplementation of Zn in combination with VE can ameliorate adverse effect of calving stress by maintaining circulatory concentration of hormone and biochemicals towards the basal levels.

Effects of Transport Duration and Environmental Conditions in Winter or Summer on the Concentrations of Insulin-Like Growth Factors and Insulin-Like Growth Factor-Binding Proteins in the Plasma of Market-Weight Pigs.

In previous work using market-weight pigs, we had demonstrated that insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) are regulated during shipment characterized by changing conditions of stress due to loading or unloading, transportation, lairage, and slaughter. In addition, we found in a previous study that IGFBP-2 concentrations were lower in pigs transported for longer periods of time. Therefore, we performed a more detailed study on the effects of transport duration and season on the plasma concentrations of IGFs and IGFBPs in adult pigs. For the study, exsanguination blood was collected from 240 market-weight barrows that were transported for 6, 12, or 18 h in January or July. IGF-I and -II were detected using commercial ELISAs whereas IGFBPs were quantified by quantitative Western ligand blotting. In addition, established markers of stress and metabolism were studied in the animals. The results show that plasma concentrations of IGFBP-3 were significantly reduced after 18 h of transport compared to shorter transport durations (6 and 12 h; p < 0.05). The concentrations of IGF-I in plasma were higher (p < 0.001) in pigs transported 12 h compared to shorter or longer durations. Season influenced plasma concentrations of IGFBP-3 and IGF-II (p < 0.05 and p < 0.01, respectively). Neither transport duration nor differential environmental conditions of winter or summer had an effect on glucocorticoids, albumin, triglycerides, or glucose concentrations (p > 0.05). However, low-density lipoprotein concentrations decreased after 18 h compared to 6 h of transport (p < 0.05), whereas high-density lipoprotein concentrations were higher (p < 0.05) in pigs transported for 12 or 18 h compared to those transported for only 6 h. Our findings indicate differential regulation of IGF-compounds in response to longer transport duration or seasonal changes and support current evidence of IGFs and IGFBPs as innovative animal-based indicators of psycho-social or metabolic stress in pigs.

Decreased plasma concentrations of BDNF and IGF-1 in abstinent patients with alcohol use disorders.

The identification of growth factors as potential biomarkers in alcohol addiction may help to understand underlying mechanisms associated with the pathogenesis of alcohol use disorders (AUDs). Previous studies have linked growth factors to neural plasticity in neurocognitive impairment and mental disorders. In order to further clarify the impact of chronic alcohol consumption on circulating growth factors, a cross-sectional study was performed in abstinent AUD patients (alcohol group, N = 91) and healthy control subjects (control group, N = 55) to examine plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and IGF-1 binding protein-3 (IGFBP-3). The association of these plasma peptides with relevant AUD-related variables and psychiatric comorbidity was explored. The alcohol group was diagnosed with severe AUD and showed an average of 13 years of problematic use and 10 months of abstinence at the moment of participating in the study. Regarding common medical conditions associated with AUD, we observed an elevated incidence of alcohol-induced liver and pancreas diseases (18.7%) and psychiatric comorbidity (76.9%). Thus, AUD patients displayed a high prevalence of dual diagnosis (39.3%) [mainly depression (19.9%)] and comorbid substance use disorders (40.7%). Plasma BDNF and IGF-1 concentrations were significantly lower in the alcohol group than in the control group (p<0.001). Remarkably, there was a negative association between IGF-1 concentrations and age in the control group (r = -0.52, p<0.001) that was not found in the alcohol group. Concerning AUD-related variables, AUD patients with liver and pancreas diseases showed even lower concentrations of BDNF (p<0.05). In contrast, the changes in plasma concentrations of these peptides were not associated with abstinence, problematic use, AUD severity or lifetime psychiatric comorbidity. These results suggest that further research is necessary to elucidate the role of BDNF in alcohol-induced toxicity and the biological significance of the lack of correlation between age and plasma IGF-1 levels in abstinent AUD patients.

Consequences of dietary energy source and energy level on energy balance, lactogenic hormones, and lactation curve characteristics of cows after a short or omitted dry period

Omitting the dry period (DP) generally reduces milk production in the subsequent lactation. The aim of this study was to evaluate the effect of dietary energy source-glucogenic (G) or lipogenic (L)-and energy level-standard (std) or low-on milk production; energy balance (EB); lactogenic hormones insulin, insulin-like growth factor 1 (IGF-1), and growth hormone (GH); and lactation curve characteristics between wk 1 and 44 postpartum in cows after a 0-d or 30-d DP. Cows (n = 110) were assigned randomly to 3 transition treatments: a 30-d DP with a standard energy level required for expected milk yield [30-d DP(std)], a 0-d DP with the same energy level as cows with a 30-d DP [0-d DP(std)], and a 0-d DP with a low energy level [0-d DP(low)]. In wk 1 to 7, cows were fed the same basal ration but the level of concentrate increased to 6.7 kg/d for cows fed the low energy level and to 8.5 kg/d for cows fed the standard energy level in wk 4. From wk 8 postpartum onward, cows received a G ration (mainly consisting of corn silage and grass silage) or an L ration (mainly consisting of grass silage and sugar beet pulp) with the same energy level contrast (low or std) as in early lactation. Cows fed the G ration had greater milk, lactose, and protein yields, lower milk fat percentage, greater dry matter and energy intakes, and greater plasma IGF-1 concentration compared with cows fed the L ration. Dietary energy source did not affect EB or lactation curve characteristics. In cows with a 0-d DP, the reduced energy level decreased energy intake, EB, and weekly body weight gain, but did not affect milk production or lactation curve characteristics. A 30-d DP resulted in a greater total predicted lactation yield, initial milk yield after calving, peak milk yield, energy intake, energy output in milk, days to conception [only when compared with 0-d DP(low)], plasma GH concentration [only when compared with 0-d DP(std)], and decreased weekly body weight gain compared with a 0-d DP. A 30-d DP decreased both the increasing and the declining slope parameters of the lactation curve and the relative rate of decline in milk yield (indicating greater lactation persistency) compared with a 0-d DP, and decreased plasma insulin and IGF-1 concentration, and EB. In conclusion, feeding a G ration after wk 7 in milk improved energy intake and milk production, but did not affect EB compared with an L ration. For cows without a DP, a reduced dietary energy level did not affect milk production and lactation curve characteristics, but did decrease EB and weekly body weight gain. A 30-d DP increased milk yield and lactation persistency, but decreased milk fat and protein content, EB, and plasma insulin and IGF-1, compared with a 0-d DP.