Insulin-like Growth Factor-1 Concentrations Research Articles

IGF-1 Stabilizes Goat Sperm Mitochondrial Transmembrane Potential and Reduces DNA Fragmentation

BACKGROUND: Antioxidant present in sperm cells protects them from oxidative damage. However, sperm are more susceptible to peroxidative damages due to the loss of these enzymes during cryopreservation and their survival and fertility may be compromised. Insulin like growth factor-1 (IGF-1) has an antioxidant effect and could maintain sperm motility. OBJECTIVE: To improve seminal parameters, mitochondrial membrane potential (MMP), oxidative status and DNA integrity of buck semen after freeze-thawing by fortification of goat semen diluent with various concentrations of IGF-1. MATERIALS AND METHODS: Fifty ejaculates were collected and were extended with tris- citric acid- fructose diluent with 10% egg yolk and 6% glycerol with sperm concentrations of 1×108 mL– 1. Post-cryopreserved sperm were assessed for motility and a range of other functional parameters. RESULTS: In post-thaw semen sperm motility, live sperm count, acrosome integrity, hypo-osmotic swelling positive spermatozoa, malondialdehyde (MDA), protein carbonyl content (PCC), TUNEL positive sperm differed significantly (P<0.05) with the various concentrations of IGF-1 used. Sperm functional parameters post-thawing were significantly (P<0.05) better in 250 ng/mL IGF-1. IGF-1 protects against lipid peroxidation by lowering MDA and PCC production, thus reducing the harmful effect of reactive oxygen species. The kidding percentage using the artificial insemination technique was significantly higher (i.e., 40%) in the group supplemented with 250 ng/mL of IGF-1 than in the non-supplemented group (i.e., 30%). CONCLUSION: IGF-1 may be used to improve post-thaw semen quality and fertility as measured by actual kidding rate.

Exploring the Link Between Insulin-like Growth Factor-1 (IGF-1) and Body Trait Measurements in Prepubertal Goat Kids in a Humid Subtropical Climate

Background: Insulin-like growth factor 1 (IGF-1) is produced throughout life and contributes to the growth of nearly all the organs in the body. Current study investigated the relationship between IGF-1 concentrations with body trait measurements in prepubertal period of male and female Assam Hill Goat kids. Methods: Twenty-four (24) goat kids (12 male + 12 female) were used for the experiment for a period of 7 months (March-September, 2022). Climatic data points were obtained from the State Meteorological Department, Meghalaya and the temperature-humidity index (THI) was calculated. The experimental months was grouped into fourteen (14) periods (Period 1-14) based on the severity of heat stress as indicated by the THI values. Blood samples were collected at every 15 days interval for determination of serum IGF-1 levels and on the same day of collection the phenotypic growth trait measurements were recorded. Result: Results showed that the IGF-1 concentration in the experimental kids significantly (P less than 0.05) increased until Period 6; then a steady non-significant (P greater than 0.05) decline till Period 14. Correlations between IGF-1 concentrations and the phenotypic body trait measurements were significant (P less than 0.05). In conclusion, serum IGF-1 level increases with increase in THI which may be attributed to its thermos-protective effect against environmental stressors.

THU417 Associations Between Glucose Metabolism And Trabecular Bone Score In Subjects With Acromegaly

Abstract Disclosure: M. Kuzma: None. J. Payer: None. P. Vanuga: None. I. Sagova: None. D. Pavai: None. P. Jackuliak: None. Z. Killinger: None. Introduction: Previously, it was thought that increased risk of vertebral fractures (VF) in acromegaly is associated with impaired trabecular bone. More recently, cortical bone was proposed as one of the fracture risk determinant. However, trabecular compartment is still decreased. Glucose intolerance is a frequent complication of acromegaly and is directly attributable to the excess circulating growth hormone and IGF-1 concentrations and thus possibly lead to trabecular bone detoriation.Objectives: To assess effect of glucose metabolism on DXA-derived bone parameters, such as bone mineral density (BMD), trabecular bone score (TBS), cortical and trabecular vBMD, surface BMD and cortical thickness of proximal femur among patients with acromegaly. Patients and methods: In total, 70 consecutive patients (24 males/56 female, mean age = 55.6 years) with acromegaly based on current ADA guidelines were divided in two subgroups according to glucose metabolism(GM): abnormal GM (n=35; 14 males/21 females; 15 with active disease) and normal GM (n=35;10 Males /25 Females; 11 with active disease). Subjects were prospectively followed up for two years. At baseline and year 2; all subjects had pituitary hormonal measures, fasting plasma glucose (FPG), HBA1c, C-peptide, insulin resistance index (IRI) and DXA measurement performed. From DXA, BMD, TBS and 3D-Shaper parameters were derived. Results: At baseline; subjects with abnormal GM had lower TBS (1.166±0.15) in comparison to normal GM subjects (1.232±0.12; p<0.05). Insulin like growth factor 1 (IGF-1), FPG, HBA1c, C-peptide, IRI and bone parameters was correlated in simple regression model. FPG, HBA1c, C-peptide and IRI was negatively associated with TBS. No correlation between GM parameters and other bone measures was observed. Multiple regression model of all GM parameters weighted by IGF-1 revealed HBA1c as a significant predictor of TBS value (Estimate =-0,054; p=0.04). At year 2; FPG and HBA1c was negatively associated with TBS. In multiple regression IGF-1-weighted model, no significant predictor of TBS was observed. Conclusion: Acromegaly subjects with abnormal GM have lower TBS in comparison to those with normal GM. The best GM parameter to predict TBS in acromegaly was HBA1c. This study showed that trabecular bone microstructure, as indirectly assessed by TBS, is likely resulting of impaired glucose metabolism. Presentation: Thursday, June 15, 2023

THU046 Repeated Treatment With AZP-3813, A Bicyclic, 16-Amino Acid Peptide Antagonist Of The Human Growth Hormone Receptor, Induces Enhanced Suppression Of IGF1 In Beagle Dogs

Abstract Disclosure: G. Ravel: None. C. Chalmey: None. C. Berardet: None. D. Duracher: None. H. Kurasaki: None. T. Tomiyama: None. P. Reid: None. M.D. Culler: None. Medical treatment of acromegaly is based on either suppressing pituitary growth hormone (GH) secretion or inhibiting GH action by preventing interaction with its receptor in order to suppress the elevated levels of insulin-like growth factor 1 (IGF1). AZP-3813 is a 16-amino acid, bicyclic peptide antagonist of the GH receptor (GHR) derived from peptide sequences discovered using a unique, cell-free in vitro transcription-translation system screened against the human GHR, and optimized by rational design to increase binding affinity, solubility and half-life. The KD of AZP-3813 for the human GHR is 1.9nM. In previous studies, AZP-3813 was demonstrated to suppress IGF1 secretion in juvenile rats in a dose-related manner, and to maintain IGF1 suppression when given daily for extended periods. Recently, we demonstrated that AZP-3813 is also very effective in suppressing IGF1 in normal Beagle dogs. Dogs receiving a single 0.1, 1 and 10 mg/kg subcutaneous injection of AZP-3813 responded with a dose-related 2.2 + 7.1, 21.4 + 2.7 and 27.8 + 1.5% decrease in IGF1 after 24 hours, respectively, and the decrease in IGF1 attained with a single 10 mg/kg dose was maintained for over 72 hours. The relatively small further increase in IGF1 suppression with 10 versus 1 mg/kg suggests that 10 mg/kg AZP-3813 may induce near maximal GHR antagonism. To examine the effect of repeated and higher dose treatment of dogs with AZP-3813, young adult, non-fasted, Beagle dogs were injected subcutaneously at rotated dorsal sites with AZP-3813 at doses of 10, 30 or 60 mg/kg (n=2, one male and one female) daily for seven days. Blood samples, collected prior to dosing to establish baseline IGF1 levels and 24 hour after the final, seventh AZP-3813 injection, were assayed for total IGF1 content by radioimmunoassay. Baseline IGF1 levels were lower in the female dogs (136.7 + 36.1 ng/ml) than in the male dogs (197.0 + 11.3 ng/ml); however, the percent IGF1 suppression resulting from AZP-3813 treatment was similar for both sexes. AZP-3813, injected for seven days at 10, 30 and 60 mg/kg, induced highly significant 69.0 + 4.0, 70.5 + 9.5 and 75.0 + 1.0% decreases in IGF1, respectively. The similar magnitude of IGF1 suppression attained with the three doses of AZP-3813 implies that maximal GH antagonism is essentially achieved with the 10 mg/kg dose. The substantial increase in IGF1 suppression achieved by repeated 10 mg/kg injection of AZP-3813, compared to the previously observed suppression after a single 10 mg/kg injection, likely represents compound accumulation (under investigation) as well as a progressive effect of maximal GH antagonism on IGF1 production. These results demonstrate that the potent GHR antagonist activity of AZP-3813 translates to a highly effective suppression of IGF1 in normal dogs and further support the development of AZP-3813 as a potential therapy for acromegaly. Presentation: Thursday, June 15, 2023

Mathematical Model of Insulin-like growth factor-1 estimating its cause in human bone cancer arises due to liver cancer

The insulin-like growth factor-1 (IGF-1) is a peptide hormone that is regulated by growth hormone and secreted in the liver; its prime role is to regulate the growth and proliferation of the bone cell. Our study results relate to the cause of bone cancer due to high IGF-1 levels in liver metastatic conditions. Liver cancer increases the liver volume which further increases IGF-1 secretion to a toxic level, which in turn causes uncontrolled bone cell proliferation and maturation thus leading to bone cancer. Thus, the mathematical model was designed to explain the kinetics of IGF-1 from the liver to bone and mathematically simplified using the ordinary differential equation, and IGF-1 concentration was estimated in the normal and cancerous state. The mathematical simulation was done using a high throughput technique using MATLAB (version R2020a). The model parameter condition due to liver cancer is considered as an increase in liver volume (vL), The initial mass of IGF-1(x01), and the varying rate constants (kP, kL, ke1, and ke2). The graphical results represent the volume of the liver and synthesis of IGF-1 increases with varying abnormal rate constants giving the estimation of an increase in IGF-1 concentration in plasma, and more IGF-1 deposits over the bone to a toxic level.

A-049 Inter-assay Variation of Insulin-like Growth Factor-1 Remains an Issue

Abstract Background Human insulin-like growth factor-1 (IGF-1) is the main mediator of the somatotropic effects of growth hormone (GH). Accurate measurement of IGF-1 is required for the diagnosis and management of GH secretion disorders. Several commercial vendors and laboratories have standardized their IGF-1 assays to the WHO International Standard 02/254. This standardization does not prohibit the existence of significant inter-assay variability in IGF-1 measurements. Such concentration variance can lead to inaccurate patient case decision making. The IGF-1 testing performed in our laboratory was recently migrated from an Immulite 2000 platform to a CobasPro system. This shift in vendor necessitated an investigation of the inter-assay variability between these standardized tests. This relative variance was established through a validation of the analytical performance of the CobasPro IGF-1 assay. Methods Reportable range, intra-day precision and accuracy of IGF-1 measurements using the CobasPro (Roche Diagnostics) system were determined. Patient correlation studies between the CobasPro and an Immulite 2000 (Siemens Healthcare Diagnostics) instrument was also performed. The concentration of IGF-1 in a subset of these correlation study specimens was also quantified by liquid chromatography mass spectrometry (LC-MS) assays from two different reference laboratories. Results The CobasPro assay had a verified linear range of 7–1443 ng/mL (R2 = 0.9998, slope = 0.9915). At IGF-1 concentrations of 54 and 345 ng/mL the intra-day precision (%CV, N = 10) of the CobasPro assay did not exceed 0.9%. Patient specimen correlations between the CobasPro and Immulite 2000 assays showed significant bias (Deming regression: y = 1.543x − 48.61, N = 128, R = 0.9641). This method bias was exacerbated at Immulite 2000 derived IGF-1 concentrations >100 ng/mL (Deming regression: y = 1.662x − 84.29, N = 93, R = 0.9492, CobasPro range = 77–910 ng/mL, Immulite 2000 range = 103–539 ng/mL). Patient specimen correlations between the CobasPro and LC-MS assay from reference laboratory A showed a positive bias (Deming regression: y = 1.375x − 64.5, N = 19, R = 0.9210). An analogous correlation with reference laboratory B demonstrated a higher level of concordance (Deming regression: y = 1.005x + 10.2, N = 16, R = 0.9499). The CobasPro and Immulite 2000 assays both produced acceptable result when challenged by multiple external quality assurance (EQA) specimens provided by the College of American Pathologists (CAP). However, the observed relative trends in IGF-1 concentrations from these challenges were opposite to our observations with authentic patient specimens. The CobasPro assay consistently produced lower IGF-1 concentrations relative to the Immulite 2000 assay for these EQA specimens. Conclusion The CobasPro IGF-1 assay offered acceptable analytical performance. Although both assays were traceable to a reference standard, a significant positive concentration bias was observed between the CobasPro and Immulite 2000 assays. Standardization efforts have not eliminated inter-assay IGF-1 variability. A careful evaluation of the impact of this variance on the diagnosis and management of GH deficiency and acromegaly must be considered when IGF-1 testing platforms are changed.

Expressions of Insulin-like Growth Factor System among Different Breeds Impact Piglets' Growth during Weaning.

The present study investigated the insulin-like growth factors (IGFs) and their receptors and binding proteins among three pig breeds during weaning. Sixty Duroc (DR), Taoyuan black (TYB), and Xiangcun black (XCB) piglets (20 piglets per breed) were selected at 21 and 24 (3 days of post-weaning) days of age to analyze organ indices, plasma concentrations of IGF and IGF-binding proteins (IGFBPs) using ELISA kits, and gene expression of IGF-system-related components in different tissues. The plasma IGFBP-3 concentration in TYB piglets was higher (p > 0.05) than in the XCB and DR piglets at 21 days of age. At 21 days of age, compared with the DR piglets, the IGF-1 expression was lower (p < 0.05) in the kidney, but it was higher (p < 0.05) in the spleen of XCB and TYB piglets. At 24 days of age, the IGF-1 expression was higher (p < 0.05) in the kidney of TYB piglets than in the XCB and DR piglets, while IGFBP-3 in the stomach and IGFBP-4 in the liver of XCB and TYB piglets were lower (p < 0.05) compared with the DR piglets. Weaning down-regulated (p < 0.05) IGF-1 expression in the jejunum, spleen, and liver of piglets, while it up-regulated (p < 0.05) IGFBP-3 expression in the stomach, IGFBP-4 in the liver, IGFBP-5 in the ileum, and IGFBP-6 in the jejunum of DR piglets. Spearman's correlation analysis showed a negative correlation (p < 0.05) between plasma IGFBP-2 and IGFBP-5 concentration and the organ indices of piglets. Collectively, there were significant differences in the IGF system components among the three pig breeds. The IGF system components were altered during weaning, which might be involved in weaning stress to decrease the growth of piglets.

Predictors of long-term remission in acromegaly – an updated review

Abstract Acromegaly is a rare chronic disorder due to growth hormone (GH) - secreting pituitary tumor. The first-line treatment of acromegaly is a transsphenoidal adenomectomy. Surgical remission rates range from 30-50% for macroadenomas to 70-90% for microadenomas. Thus in patients with active acromegaly after surgery, medical treatment is recommended. Treatment outcome on medical therapy differs a lot depending on medications. The aim of this paper is to summerize the current knowledge of factors predicting acromegaly remission after surgery and biochemical control on medical treatment. Factors affecting treatment outcome, not related to the patient and the tumor, are neurosurgeon’s experience and visualisation tools used during surgery. Younger patients, as well as women tend to achieve acromegaly remission after surgery less often. Patients with lower GH and insulin-like growth factor-1 (IGF-1) concentrations at diagnosis, in oral glucose tolerance test (OGTT) and postoperatively have a greater chance of surgical remission. However, some publications do not confirm that. Patients presenting with larger and more invasive tumors achieve surgical remisson less often. Hypointensive tumors on T2-weighted magnetic resonance imaging (MRI) scans are associated with better response to first-generation somatostatin receptor ligands (SRLs) and to pasireotide. Pathologic factors increasing the chance of acromegaly remission are densely granulated tumors, lower Ki-67 index, high expression of somatostatin receptors (SSTRs) and high expression of E-cadherin. A thorough analysis of the abovementioned factors predicting the treatment outcome in acromegaly may be helpful for selecting the best treatment option for each patient.

Method Validation and Establishment of Reference Intervals for an Insulin-like Growth Factor-1 Chemiluminescent Immunoassay in Cats.

Previously, radioimmunoassay (RIA) has been the only assay to measure insulin-like growth factor-1 (IGF-1) to diagnose hypersomatotropism (HS). Due to radiation concerns, availability, and the cost of IGF-1 RIA, validation of assays for automated analysers such as a chemiluminescent immunoassay (CLIA) is needed. The aim of this study was to validate a CLIA for measurement of feline IGF-1 (IMMULITE 2000® XPi, Siemens Medical Solutions Diagnostics, Malvern, PA, USA) compared to IGF1 RIA, establish reference interval (RI), and determine a cut-off value for diagnosis of HS in diabetic cats. Validation of assay performance included precision, linearity, and recovery studies. Right-sided RI was determined using surplus serum of 50 healthy adult cats. Surplus serum samples of diabetic cats with known IGF-1 concentration with (n = 32/68) and without HS (n = 36/68) were used for method comparison with RIA. The cut-off for diagnosis of HS was established using receiver operating characteristic (ROC) analysis. The intra-assay coefficient of variation (CV) was ≤4.7%, and the inter-assay CV was ≤5.6% for samples with low, medium, and high IGF-1 concentration. Linearity was excellent (R2 > 0.99). The correlation between CLIA and RIA was very high (rs = 0.97), with a mean negative bias for CLIA of 24.5%. The upper limit of RI was 670 ng/mL. ROC analysis showed an area under the curve of 0.94, with best cut-off for diagnosis of HS at 746 ng/mL (sensitivity, 84.4%; specificity, 97.2%). The performance of CLIA was good, and the RI and cut-off for HS diagnosis established in this study allow for CLIA to be used in routine work-up of diabetic cats.

Combination of milk variables and on-farm data as an improved diagnostic tool for metabolic status evaluation in dairy cattle during the transition period

Milk composition, particularly milk fatty acids, has been extensively studied as an indicator of the metabolic status of dairy cows during early lactation. In addition to milk biomarkers, on-farm sensor data also hold potential in providing insights into the metabolic health status of cows. While numerous studies have explored the collection of a wide range of sensor data from cows, the combination of milk biomarkers and on-farm sensor data remains relatively underexplored. Therefore, this study aims to identify associations between metabolic blood variables, milk variables, and various on-farm sensor data. Second, it seeks to examine the supplementary or substitutive potential of these data sources. Therefore, data from 85 lactations on metabolic status and on-farm data were collected during 3 wk before calving up to 5 wk after calving. Blood samples were taken on d 3, 6, 9, and 21 after calving for determination of β-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), glucose, insulin-like growth factor-1 (IGF-1), insulin, and fructosamine. Milk samples were taken during the first 3 wk in lactation and analyzed by mid-infrared for fat, protein, lactose, urea, milk fatty acids, and BHB. Walking activity, feed intake, and body condition score (BCS) were monitored throughout the study. Linear mixed effect models were used to study the association between blood variables and (1) milk variables (i.e., milk models); (2) on-farm data (i.e., on-farm models) consisting of activity and dry matter intake analyzed during the dry period ([D]) and lactation ([L]) and BCS only analyzed during the dry period ([D]); and (3) the combination of both. In addition, to assess whether milk variables can clarify unexplained variation from the on-farm model and vice versa, Pearson marginal residuals from the milk and on-farm models were extracted and related to the on-farm and milk variables, respectively. The milk models had higher coefficient of determination (R2) than the on-farm models, except for IGF-1 and fructosamine. The highest marginal R2 values were found for BHB, glucose, and NEFA (0.508, 0.427, and 0.303 vs. 0.468, 0.358, and 0.225 for the milk models and on-farm models, respectively). Combining milk and on-farm data particularly increased R2 values of models assessing blood BHB, glucose, and NEFA concentrations with the fixed effects of the milk and on-farm variables mutually having marginal R2 values of 0.608, 0.566, and 0.327, respectively. Milk C18:1 was confirmed as an important milk variable in all models, but particularly for blood NEFA prediction. On-farm data were considerably more capable of describing the IGF-1 concentration than milk data (marginal R2 of 0.192 vs. 0.086), mainly due to dry matter intake before calving. The BCS [D] was the most important on-farm variable in relation to blood BHB and NEFA and could explain additional variation in blood BHB concentration compared with models solely based on milk variables. This study has shown that on-farm data combined with milk data can provide additional information concerning the metabolic health status of dairy cows. On-farm data are of interest to be further studied in predictive modeling, particularly because early warning predictions using milk data are highly challenging or even missing.

Feeding strategies for rearing replacement beef heifers in a grazing system under tropical conditions

Our objective was to evaluate the effects of pre- and post-weaning protein supplement on the productive response and nutritional and metabolic status of replacement beef heifers grazed on tropical pasture. Fifty-six Nellore heifers (7.7 ± 0.1 months age) with an average initial body weight (BW) of 237 ± 3.5 kg were distributed in a completely randomized design in 2 × 2 factorial arrangement. The four strategies were: US-ME, unsupplemented heifers at pre-weaning and supplemented with 5 g/kg BW at post-weaning; US-HI, unsupplemented heifers at pre-weaning and supplemented with 7.5 g/kg BW at post-weaning; ME-ME, heifers supplemented with 5 g/kg BW at pre-weaning and post-weaning; and ME-HI, heifers supplemented with 5 g/kg BW at pre-weaning and 7.5 g/kg BW at post-weaning. On average, crude protein (CP) intake and CP: digested organic matter (DOM) ratio were influenced (P < 0.05) by protein supplement in the post-weaning period, with a higher intake of CP and CP:DOM ratio in HI heifers than in ME heifers (average CP of 0.812 vs 0.665 kg/day and average DOM of 204 vs 174 g CP/kg). Nonetheless, the post-weaning protein supplement did not affect the intake of total dry matter (DM), pasture DM, organic matter (OM), neutral detergent fiber corrected for ash and protein residue (apNDF), non-fibrous carbohydrates, and DOM. The CP digestibility was highest (P = 0.005) for HI heifers than for ME heifers (average of 0.732 vs 0.645 g/g DM). The pre-weaning and post-weaning protein supplement did not affect the concentration of insulin-like growth factor–1 (IGF-1), progesterone, albumin, globulins, glucose, and triglycerides, and liver mRNA expression of carbamoyl phosphate synthetase-1 (CPS-1) and phosphoenolpyruvate carboxykinase (PEPCK). Finally, the pre-weaning and post-weaning protein supplement did not affect growth performance, carcass traits, and body growth in the post-weaning. Supplementation during pre-weaning does not bring any carry-over effect on the productive performance and metabolic status of heifers supplemented during post-weaning. However, supplementation in post-weaning with 5 or 7.5 g/kg BW allows a compensatory growth of heifers that are unsupplemented at pre-weaning. Therefore, the supply of 7.5 g/kg BW of protein supplement for beef heifers only during the post-weaning period is recommended.

Effect of Growth Hormone Receptor Deficiency on Androgen-Associated Gene Expression of Hepatic Drug Metabolizing Enzymes and Drug Transporters in Pigs.

Growth hormone receptor (GHR)-deficient pigs were generated using the CRISPR/Cas9 system to investigate the involvement of GHR-mediated growth hormone (GH) signaling in androgen-associated gene expression of hepatic drug metabolizing enzymes (DMEs) and drug transporters. We initially confirmed that no wild-type GHR mRNA was present in GHR-/- (GHR-KO) pigs; in addition, as previously reported, those pigs exhibited decreases in body weight and serum insulin-like growth factor-1 concentration and an increase in serum GH concentration compared with the levels in GHR-/+ and GHR+/+ pigs with a wild-type GHR mRNA. The real-time RT-PCR results on the mRNA levels of hepatic DMEs and drug transporters in the GHR-KO pigs and the pigs with a wild-type GHR mRNA revealed that, among the examined hepatic DMEs, the mRNA levels of CYP1A2, CYP2A19, sulfotransferase (SULT) 1A1, and SULT2A1 were higher in GHR-KO pigs than in the pigs with a wild-type GHR mRNA, whereas the opposite trend was observed for the mRNA level of uridine 5'-diphospho-glucuronosyltransferase 1A6. No such significant differences in the mRNA levels of three hepatic drug transporters including multidrug resistance protein 1 were observed. In addition, the mRNA level of hepatic cut-like homeobox 2 (CUX2), which is expressed in an androgen-dependent manner and associated with the hepatic mRNA expression of several DMEs, was significantly decreased in GHR-KO pigs. The present findings strongly suggest that not only serum androgen but also GHR-mediated GH signaling contributes to the mRNA expression of several DMEs and CUX2, but not transporters, in the pig liver.

THE RELATIONSHIP OF PLASMA SOMATOMEDIN (IGF-1) WITH PERFORMANCE AND CARCASS CHARACTERISTICS OF AWASSI AND KARADI LAMBS

Lambs’ performance and some carcass traits in relation to insulin-like growth factor-1 (IGF-1) were studied in twelve lambs from each of Awassi and Karadi slaughtered at three different weights raised at the animal farm, Department of Animal Production, College of Agricultural Engineering Science, University of Duhok. Each group of lambs slaughtered at 30 kg, 40 kg, and 50kg was kept in an individual separate pen and fed concentrate ration at libitum. Weight gain and feed intake were recorded till the slaughter and blood samples were taken at the beginning of the experiment and one day before slaughter from the vena jugular for the IGF-1 analysis by using the enzyme immunoassay (EIA) method. Statistical analysis showed that the concentrations of insulin-like growth factor (IGF-1) were not affected significantly by breed. Furthermore, lambs slaughtered at 50 kg, showed numerically the highest IGF-1 concentration, compared to lambs slaughtered at 30 kg and 40kg. There was a significant positive correlation between IGF-1 concentrations and each of the average daily gain and daily feed intake of Awassi lambs slaughtered at 30. Additionally, no consistent results were found between the IGF-1 concentration and carcass composition in studied breeds.

Circulating insulin-like growth factor-1 and brain health: Evidence from 369,711 participants in the UK Biobank

BackgroundThe effects of insulin-like growth factor-1 (IGF-1) deficiency on cognitive decline have been consistently reported in animal studies, but the relationship between IGF-1 and human brain health remains controversial. Our study aimed to investigate the associations of serum IGF-1 concentrations with some brain-related disorders and neuroimaging features.MethodsThis prospective study included 369,711 participants (55.8 ± 8.1 years) from the UK biobank who had serum IGF-1 measured and were free from brain-related disorders of interest — dementia, stroke, and Parkinson’s disease (PD) — at enrollment (2006–2010). Restricted cubic splines and Cox proportional hazards models were used to detect the associations between IGF-1 concentrations and brain-related diseases. In addition, general linear regressions were applied to explore the relationship between IGF-1 concentrations and neuroimaging features (volumes of white matter, grey matter, and hippocampus and white matter hyperintensity) among a sub-sample of 36,458 participants with magnetic resonance imaging data collected since 2014.ResultsDuring a median follow-up of 12.6 years, a total of 4,857 dementia, 6,240 stroke, and 2,116 PD cases were documented. The dose–response analyses yielded U-shaped relationships between IGF-1 concentrations and risks of dementia and stroke (P < 0.001 for non-linearity), with the lowest risks at 18 nmol/L and 26 nmol/L, respectively. A positive linear relationship was observed between IGF-1 concentrations and risk of PD (P = 0.163 for non-linearity). Moreover, neuroimaging analyses showed that higher IGF-1 concentrations were associated with greater volumes of white matter (β = 2.98 × 10–4, P < 0.001) and hippocampus (β = 3.37 × 10–4, P = 0.002) and smaller white matter hyperintensity (β = -3.12 × 10–3, P < 0.001).ConclusionsApart from the diverse associations with neuroimaging features, both low and high IGF-1 concentrations are associated with increased risks of dementia and stroke and higher IGF-1 concentrations are linked to a higher risk of PD, highlighting the potential of IGF-1 as a biomarker for risk stratification of brain health.

Maternal Daidzein Supplementation during Lactation Promotes Growth Performance, Immunity, and Intestinal Health in Neonatal Rabbits

The main purpose of the present research was to evaluate the effect of varying levels of DA inclusion in maternal diet, in the form of powder, on the born-weaning growth performance (days 1–30) and intestinal health of neonatal rabbits. A total of 152 delivered maternal does (3.94 ± 0.05 kg) were allocated into four groups, with thirty-eight replicates of one doe each, and fed with a control diet (CON) supplemented with different levels of powdered DA (85 mg/kg (DA85), 170 mg/kg (DA170), and 340 mg/kg (DA340)) during lactation. The results show that dietary DA increased individual body weight at days 21 and 30 (p = 0.03 and p &lt; 0.01) and showed a linear and quadratic effect on individual body weight and average daily gain (ADG) (p &lt; 0.05), although ADG was not affected by DA. The serum progesterone (P) (p = 0.05) and glutathione peroxidase (GSH-Px) (p = 0.01) concentrations of maternal rabbits were increased in all maternal DA-supplemented groups and showed a linear and quadratic effect (p &lt; 0.05), while a linear effect was observed in estrogen (E-2) (p &lt; 0.05). Interestingly, the concentrations of the serum insulin-like growth factor-1 (IGF-I) (p &lt; 0.01) and immunoglobulin (IgA and IgG) (p &lt; 0.01 and p = 0.01) in neonatal rabbits were increased in all dietary DA groups, and both showed a linear and quadratic effect (p &lt; 0.05). In addition, the serum interleukin (IL-1β) (p = 0.03) and catalase (CAT) (p = 0.04) concentrations were affected by DA supplements, but linear and quadratic effects were only observed in the catalase (CAT) of neonatal rabbits (p &lt; 0.05). Importantly, the duodenal and jejunal villus heights (p &lt; 0.04 and p = 0.01) and the ratio of villus height to crypt depth (p = 0.02 and p = 0.01) in neonatal rabbits were elevated in all DA-supplemented treatments, while a linear and quadratic effect was observed in jejunum, but a quadratic effect was observed in duodenum (p &lt; 0.05). The ileal villus height (p &lt; 0.01) was also elevated in all DA-supplemented treatments exhibiting both linear and quadratic effects (p &lt; 0.05). Moreover, the expression levels of occludin (p = 0.04), zonula occludens-1 (ZO-1) (p &lt; 0.01), IGF-1 (p = 0.03), and solute carrier family 5 member 9 (SCL5A9) (p &lt; 0.01) in jejunum were markedly elevated in the DA175 and 340 mg/kg DA-supplemented groups and were showing linear and quadratic effects (p &lt; 0.05). Finally, inflammation-related gene expression levels such as NF-κB, TLR4, and MYD88 in jejunal (p = 0.01, p = 0.04, and p &lt; 0.01) and ileal (p = 0.04, p = 0.04, and p = 0.03) epithelium were decreased in the DA170 and DA340 groups (p &lt; 0.05), while linear and quadratic effects were observed for TLR4 in jejunum and for NF-κB and TLR4 MYD88 in ileum (p &lt; 0.05). In summary, as a functional additive, maternal DA supplementation with 170 and 340 mg/kg DA during lactation can promote the growth of neonatal rabbits, which is related to improved antioxidative capacity and immunity, as well as improved intestinal health in neonatal rabbits.

The skeletal safety of milk-derived proteins: A meta-analysis of randomized controlled trials.

There has been a persistent claim that dairy products contain calcium-leaching proteins, although the soundness of such a claim has been challenged. A meta-analysis of randomized controlled trials (RCTs) on the effects of milk-derived protein supplementation on bone health indices in adults was performed to reconcile the controversy surrounding the potential skeletal safety concerns of proteins of dairy origin. The PubMed and Web of Science databases were searched for relevant RCTs. A random-effects model was used to generate pooled effect sizes and 95% confidence intervals. Milk-derived protein supplementation did not significantly affect whole-body BMD (n = 7 RCTs) and BMD at the lumbar spine (n = 10), hip (n = 8), femoral neck (n = 9), trochanter (n = 5), intertrochanter (n = 2), and ultradistal radius (n = 2). The concentrations of bone formation markers (bone-specific alkaline phosphatase [n = 11], osteocalcin [n = 6], procollagen type 1 amino-terminal propeptide [n = 5]), bone resorption markers (N-terminal telopeptide of type 1 collagen [n = 7], C-terminal telopeptide of type 1 collagen [n = 7], deoxypyridinoline [n = 4]), and parathyroid hormone (n = 7) were not significantly affected. However, increased insulin-like growth factor-1 (IGF-1) concentrations (n = 13) were observed. Reduced IGF-1 concentrations were observed when soy protein was used as a comparator, and increased IGF-1 concentrations were observed when carbohydrate was used. Our findings do not support the claim that proteins of dairy origin are detrimental to bone health.

Elevated IGF-1 concentrations in children with low grade glioma: A descriptive analysis in a retrospective national cohort.

Children with low grade glioma (LGG) may present with, or develop, elevated concentrations of insulin-like growth factor 1 (IGF-1). The prevalence, pathophysiology, or its possible clinical effects are poorly understood. Our aim was to evaluate the prevalence of such elevated IGF-1 concentrations and to describe its association with linear growth, body mass index (BMI), pituitary outcome, and tumor behavior in a large retrospective national cohort. From a nationwide retrospective cohort of pediatric brain tumor survivors diagnosed between 2002 and 2012, tumor, treatment, endocrine, and auxological data of children with LGG were collected (n = 358). Prevalence and risk factors for elevated IGF-1 concentrations, as well as the association between having elevated IGF-1 concentrations and receiving tumor treatment, were explored. IGF-1 concentrations had only been measured in 45.5% of cases (n = 163/358). In 18.4% of 163 children with available IGF-1 measurements, IGF-1 concentrations were found elevated. No association was described between having an elevated IGF-1 concentration and tumor behavior or height SDS at last moment of follow-up. Multivariate logistic regression identified posterior pituitary disorder (OR 6.14 95% CI: 2.21-17.09) and BMI SDS at follow-up (OR 1.56 95% CI: 1.09-2.20) to be significantly associated with elevated IGF-1 concentrations. In this retrospective cohort of children with LGG, IGF-1 was found elevated in 18.4% of children with available IGF-1 measurements. Elevated IGF-1 seems to be related to hypothalamic dysfunction worsening over time. Larger prospective cohort studies are needed.

The Effect of Environmental Disasters on Endocrine Status, Hematology Parameters, Body Composition, and Physical Performance in Young Soccer Players: A Case Study of the Aral Sea Region.

The Aral Sea region (Uzbekistan) is infamous because of the ecological disaster characterized by the disappearance of the Aral Sea due to excessive uncontrolled water intake for agriculture needs. A new desert occurrence, soil and climate aridization led to pesticide and toxic metals environment pollution. The impact of environmental conditions in some areas of Uzbekistan on the health of soccer players is not as noticeable as, for example, the effectiveness of training, so it is not widely discussed in scientific papers. The aim of the present study was to study the features of endocrine status, hematology parameters (e.g., red blood cells (RBC) and hemoglobin (Hb)), and their influence on body composition and physical fitness performance in local young soccer players of the Aral Sea region as the territory of ecological disaster. The study involved 60 male soccer players aged from 18 to 22 years. Participants were divided into two groups: the experimental group (EG), which consisted of 30 soccer players living on the territory of the Aral ecological disaster region, and the control group (CG), which included 30 soccer players, natives of the ecologically favorable region of Uzbekistan. All volunteers had anthropometric measurements, concentrations of insulin-like growth factor-1 (IGF-1), total testosterone (TT), estradiol (E2), cortisol (C), RBC, and Hb count. Moreover, Yo-Yo Intermittent Recovery Test Level 1 (YYIRT1) and professional skills tests such as dribbling shuttle test (DSt) and goal accuracy test (GAt) were assessed. When comparing the CG group to the EG group, it was observed that the EG group exhibited statistically significantly reduced levels of TT and E2 (p < 0.05). No significant statistical difference was observed between the two groups in terms of IGF-1 and C (p > 0.05). Regarding hematological parameters, Hb, Ht, and mean corpuscular volume (MCV) were found to be significantly lower in the EG compared with the CG (p < 0.05). Moreover, the distance covered in the YYIR1 test was found to be significantly lower in soccer players within the EG compared with the CG (p < 0.05). Additionally, it was determined that there was no significant difference between the groups in terms of DSt and GAt values (p > 0.05). Lastly, significant differences were observed between the EG and CG in terms of anthropometric characteristics (diameters, skinfold, and somatotype profile) (p < 0.05). The present study showed that the changes in evaluated characteristics might result from the complex influence of endocrine-disrupting chemicals, the content of which is high in the environment of the Aral Sea region. The results obtained may help monitor the health of athletes living in an environmentally unfriendly environment.

Insulin Like Growth Factor Binding Protein 7 as a Novel Diagnostic Marker in Sera of Iraqi Patients with Acromegaly

The purpose of this study was to measure serum levels of insulin-like growth factor-binding protein (IGFBP7), Insulin-like Growth Factor 1 (IGF-1), Growth Hormone (GH), Interleukin 6 (IL-6) and insulin in acromegaly patients and healthy controls. The acromegaly group had 60 patients, while the population group had 30 people who had never had acromegaly before. The concentration of IGFBP7, IGF-1, GH, IL-6, and insulin were determined. The results of the present study indicate that IGFBP7 level in the acromegaly group was significantly lower (1.690.07 ng/mL vs. 2.740.12 ng/mL, respectively, p = 0.001). IGF-1, GH, IL-6, and insulin concentrations were also significantly higher in acromegaly patients. The diagnostic accuracy (2.194) was excellent in separating acromegaly from the healthy patient group, and the area under the curve (AUC = 0.871, p = 0.001). From the results of the present study, we can conclude that serum IGFBP7 can be used to distinguish acromegaly patients from healthy individuals.

134-OR: Associations of Growth Hormone (GH) Mediators with Loss of Glycemic Control in Youth with Type 2 Diabetes (T2D)

T2D in youth has a more severe phenotype than in adults, with puberty as a potential contributor to this difference. Pubertal changes in GH mediators (e.g., insulin-like growth factor 1 (IGF-1), growth hormone receptor (GHR), insulin-like growth factor binding protein 1 (IGFBP-1)) may impact insulin sensitivity and beta cell function. We examined associations of GH mediators with loss of glycemic control in youth with T2D using the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort (N= 310). We performed paired comparison of plasma concentrations of IGF-1, GHR, and IGFBP-1 (ELISA), between 0mo and 36mo based on TODAY primary outcome of loss of glycemic control vs. maintained glycemic control (LGC vs MGC), with LGC defined as HbA1c ≥ 8% for 6 months and/or insulin dependence. We studied associations of GH mediators with HbA1c, insulinogenic index, oral disposition index, and 1/fasting insulin. Models were adjusted for age, sex, race, treatment arm, and baseline HbA1c (linear regression). Mean plasma IGF-1 (ng/mL) was lower in LGC group at 0mo (LGC: 451 ± 141, MGC: 485 ± 155, p = 0.04), and at 36mo (LGC: 340 ± 117, MGC: 400 ± 136, p&amp;lt; 0.0001). Increase in IGF-1 between 0-36mo predicted lower HbA1c at 36mo (B = -3.2E-3, SE = 9.0E-4, p &amp;lt; 0.001). Higher GHR was associated with higher HbA1c (B = 1.2E-2, SE = 3.0E-3, p &amp;lt; 0.001) and lower 1/fasting insulin (B = -6.6E-4, SE = 2.1E-4, P &amp;lt; 0.01) at 0mo. Increase in GHR between 0-36mo predicted higher 36mo HbA1c (B = 3.0E-2, SE = 9.4E-3, p &amp;lt; 0.01). IGFBP-1 was positively associated with 1/fasting insulin at 0m (B = 1.1E-3, SE = 4.9E-4, p = 0.03). In exploratory analyses stratified by Tanner stage (TS) at study entry, GH mediators changed differentially between TS 1-3 (n = 31) vs TS 4-5 (n = 274). In conclusion, GH mediators differed based on primary outcome in TODAY, and were associated with HbA1c and insulin sensitivity. Whether changes in GH mediators contribute to, or are the result of, changes in glucose metabolism is a key area for future studies. Disclosure C.Lu: None. D.Wolfs: None. L.El ghormli: None. L.M.Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. M.Patti: Consultant; MBX Biosciences, AstraZeneca, Hanmi Pharm. Co., Ltd., Other Relationship; Fractyl Health, Inc. E.M.Isganaitis: None. Funding National Institutes of Health (2T32DK007260-46); National Institute of Diabetes and Digestive and Kidney Diseases (5U01DK061230-16)