Insulin-like Growth Factor-1 Concentrations Research Articles

The degree of maternal nutrient restriction during late gestation influences the growth and endocrine profiles of offspring from beef cows

Context Cow–calf operations in Argentina are managed under extensive grazing condition and the quality of forages is often poor during the second half of gestation. The severity of nutrient restriction in bovine gestation, caused by seasonal pasture production, often results in poor production traits in progeny. Aims The objective of the current study was to determine whether different levels of maternal nutrient intake in beef cows during late gestation affect fetal and postnatal growth, glucose metabolism, and insulin-like growth factor 1 (IGF1) concentrations in offspring of beef cattle. Methods At 180 ± 4 days of gestation, multiparous Angus cows (n = 56) were blocked by bodyweight (BW) and expected calving date, and assigned to pens (2 or 3 cows/pen). Pens (n = 8 per treatment) were then randomly assigned to the following treatments: severely restricted (SR; 50% of net energy and 58% of CP requirements), moderately restricted (MR; 75% of net energy and 85% of CP requirements), or control (CON; 100% of net energy and 116% of CP requirements). Pen was the experimental unit and data were analysed by ANOVA or repeated measures analysis, as appropriate. After calving, all cows were managed in a single group until weaning. Key results Cow BW and body condition score decreased as nutritional restriction increased (P < 0.05). At parturition, birth weight of calves from SR dams and MR dams was lower than that of calves from CON dams (P = 0.05; 4.9 kg and 2.1 kg respectively). Average daily gain of calves from birth to 24 days of age was higher (P = 0.01) in calves from SR dams than in calves from CON and MR dams. Calves from MR dams were lighter (P = 0.04) than were calves from SR and CON dams at weaning. Treatments did not affect milk production or composition (P > 0.10) or glucose–insulin metabolism of offspring during lactation (P > 0.10). Concentration of IGF1 tended to be lower in MR progeny than in SR and CON progeny during lactation (P = 0.09). Conclusions Late gestation maternal nutrient restriction, irrespective of the severity of the restriction, decreased birth weight of offspring; however, severe nutrient restriction induced early postnatal compensatory growth. Implications The severe nutritional restriction produced calves with weaning weights indistinguishable from the control cows due to early postnatal compensatory growth. However, the longer-term effects of nutritional restriction of the dam in the second half of pregnancy on metabolic and reproductive performance in replacement heifers or meat production/quality in steers is yet to be determined.

The role of insulin-like growth factor-1 in prognostication metabolic disorders in patients with arterial hypertension

The article reviews the sources of scientific literature on the role of somatomedin - insulin-like growth factor-1 (IGF-1) in predicting the development of metabolic disorders in patients with hypertension, the depth of the search for a period of 10 years. It is noted that this scientific problem has been studied in different countries, the connection between IGF-1 deficiency and the occurrence of metabolic disorders in patients with hypertension (AH) is considered to be one of the predictors of cardiovascular disease. It was experimentally established that the study of the content of IGF-1 in the blood revealed a significant decrease in the level of somatomedin in groups of patients with varying degrees of hypertension. Studies have confirmed the pathogenetic role of IGF-1 deficiency in the development of left ventricular hypertrophy and heart failure in patients with hypertension in combination with type 2 diabetes mellitus (DM). It is the deficiency of IGF-1 in the blood was associated with the development of degenerative processes. Immune-modulating ability of IGF-1 has been established, antithrombotic and antiremodeling properties of somatomedin have been proved. It was found that people with normal blood pressure and people without signs of impaired glucose tolerance had significantly higher levels of IGF-1 in the blood.
 It is established that the study of the role of IGF-1 in the prediction of metabolic disorders in patients with hypertension is a promising scientific problem.

Effects of Administering Exogenous Bovine Somatotropin During the First Trimester of Pregnancy Altered Uterine Hemodynamics in Suckled Beef Cows

The objective of this study was to examine the effects of recombinant bovine somatotropin (bST) administration on uterine hemodynamics and subsequent fetal programming in suckled cows during the first trimester of gestation. Crossbred beef cows (n = 152) were stratified by breed, days postpartum, parity, cyclicity status, and body condition score (BCS) before being assigned to either receive injections of bST every other week (BST; 500-mg/14 d) starting at fixed-time artificial insemination (TAI; d 0) until d 97 or to receive no bST (CTL). Blood samples were collected until d 97 for analysis of plasma concentrations of insulin-like growth factor 1 (IGF-1). Pregnancy was assessed via transrectal ultrasonography on d 41 and 173. A subset of pregnant cows (BST, n = 24; CTL, n = 28) were selected for assessment of uterine arterial blood flow (BF), pulsatility index, and resistance index (RI) of the uterine arteries ipsilateral and contralateral to the conceptus via color Doppler ultrasonography on d 97 and 233 of gestation. No differences (P = 0.99) were detected in body weight (BW) or BCS of dams; however, plasma concentrations of IGF-1 were greater (P < 0.001) in BST-treated cows. Color Doppler ultrasonography parameters differed whereby a treatment × day interaction (P = 0.007) was detected for RI on d 97 (P = 0.048); however, on d 233, RI did not differ (P > 0.10) but ipsilateral BF for BST-treated cows was greater (P = 0.0319) than controls. Mean heart girth diameter, crown-to-rump length, and neonate BW at 7 ± 5 d of calf age did not differ (P > 0.10). Liver tissue samples from each calf were collected for analysis of mRNA expression of target insulin-like growth factor system ligands. There was no difference in gene expression of hepatic IGF-1 between treatments (P = 0.99). A treatment × sex interaction was determined, where BST heifers had increased mRNA expression of IGFR1 compared to BST bulls (P = 0.03). Bi-weekly administration of bST until d 97 of pregnancy increased plasma concentrations of IGF-1, altered uterine hemodynamics in dams, induced sex-specific changes in liver gene expression of the offspring but failed to alter calf morphometries or calf performance until weaning.

PSXVI-2 Response of ileal microbiota composition and immunity function to xylanase supplementation in broilers fed wheat-based diets

Abstract A total of 112 one-day-old broilers (initial BW 48.03 ± 0.33 g) were selected to investigate effects of xylanase (AT-xynA) on growth performance, ileal morphology, microbiota composition, immune response, antioxidant capacity and endocrine peptide levels in broilers [Founded by NSFC (31772612)]. Broilers were randomly allotted into 2 dietary treatments (n = 7) including a wheat-soybean basal diet (CON), and a basal diet with 4,000 U/kg AT-xynA (XY). On d 7, 14, 21 and 42, broilers were weighted and ileal tissues were sampled. Ileal digesta samples were collected for analyzing microbiota composition on d 21 and 42. The results showed that AT-xynA could improve average daily weight gain and average daily feed intake, and there were interactions between diet and age of broilers (P < 0.05). On d 21 and 42, xylanase supplementation could decrease ileal microbiota α-diversity, the relative abundance of potentially pathogenic microbiota such as phyla Proteobacteria, family Moraxellaceae, Staphylococcaceae, genus Staphylococcus, Pseudomonas, Streptococcus, Enterococcus, and increased the abundance of Lactobacillus (P < 0.05). Moreover, the reduction in acetate concentration and abundance of short chain fatty acid producing bacteria was also observed in broilers from XY group (P < 0.05). AT-xynA could increase ileal villus height, glucagon-like peptide-1 and insulin-like growth factor-1 concentrations, decreased interleukin-1β, interleukin-6, tumor necrosis factor-α and malondialdehyde content in broilers from XY group, and these positive effects on intestinal health were greater in young broilers. In conclusion, xylanase supplementation to wheat-based diets could improve intestinal health, and the positive effects of xylanase supplementation were more pronounced in young broilers, thus contributing to subsequent improvements in growth performance of broilers.

PSX-B-11 Comparing effects of FGF2 and IGF1 on the development competence of parthenogenetic activated bovine oocytes maturing in vitro

Abstract The oocyte quality acquired during in vitro maturation (IVM) are the main limitative factors affecting the embryo production. The aim of the present research was to study effects of fibroblast growth factor 2 (FGF2) and insulin-like growth factor 1 (IGF1) during IVM of bovine oocytes on their developmental potential after parthenogenetic activation. Bovine cumulus-oocyte complexes (COC; n = 1176) were cultured for 22h in either standard maturation medium (TCM-199 supplemented with 10% fetal calf serum (FCS), 0.2 mM sodium pyruvate, 10 μg/ml FSH and 10 μg/ml LH; Control) or maturation medium supplemented with different concentrations (5–160 ng/ml) of FGF2 and IGF1. After IVM, matured oocytes activated by sequential treatment with ionomycin followed by DMAP and cyclohexamide and then cultured up to the blastocyst stage. The obtained blastocysts were fixed, and the total cell number and the level of apoptosis were determined using DAPI and TUNEL staining. The data from 4 replicates (77–91 oocytes per treatment) were analyzed by ANOVA. Cleavage rates of activated oocytes did not differ between groups and ranged from 63.7 to 68.1%. The addition of 10, 20 and 40 ng/ml of FGF2 to the IVM medium led to an increase in the yield of blastocysts [from 19.6±1.8% (Control) to 35.2±3.4, 29.8±1.9 and 31.1±2.1%, respectively (P<0.05)] and in the total cell number in embryos that developed to the blastocyst stage (P<0.05). Meanwhile, the blastocyst yield and the total cell number in blastocysts in the IGF1-treated groups were similar to that in the control group. No effects of both growth factors on the proportion of apoptotic nuclei in blastocysts (5.3–7.1%) were observed. Thus, FGF2 (but not IGF1) are able to maintain competence for parthenogenetic development of bovine COC during their maturation invitro. Supported by RFBR (18-29-07089) and the Ministry of Science and Higher Education of Russia.

Cost-Utility of Acromegaly Pharmacological Treatments in a French Context.

ObjectiveEfficacy of pharmacological treatments for acromegaly has been assessed in many clinical or real-world studies but no study was interested in economics evaluation of these treatments in France. Therefore, the objective of this study was to estimate the cost-utility of second-line pharmacological treatments in acromegaly patients.MethodsA Markov model was developed to follow a cohort of 1,000 patients for a lifetime horizon. First-generation somatostatin analogues (FGSA), pegvisomant, pasireotide and pegvisomant combined with FGSA (off label) were compared. Efficacy was defined as the normalization of insulin-like growth factor-1 (IGF-1) concentration and was obtained from pivotal trials and adjusted by a network meta-analysis. Costs data were obtained from French databases and literature. Utilities from the literature were used to estimate quality-adjusted life year (QALY).ResultsThe incremental cost-utility ratios (ICUR) of treatments compared to FGSA were estimated to be 562,463 € per QALY gained for pasireotide, 171,332 € per QALY gained for pegvisomant, and 186,242 € per QALY gained for pegvisomant + FGSA. Pasireotide seems to be the least cost-efficient treatment. Sensitivity analyses showed the robustness of the results.ConclusionFGSA, pegvisomant and pegvisomant + FGSA were on the cost-effective frontier, therefore, depending on the willingness-to-pay for an additional QALY, they are the most cost-effective treatments. This medico-economic analysis highlighted the consistency of the efficiency results with the efficacy results assessed in the pivotal trials. However, most recent treatment guidelines recommend an individualized treatment strategy based on the patient and disease profile.

Cardiac functions in children with growth hormone deficiency: Effects of one year of GH replacement therapy

IntroductionChildren with Growth Hormone deficiency (GHD) are prone to heart dysfunction and, if left untreated, will result in marked cardiac dysfunction in adulthood. The aim was to evaluate the effect of GHD and growth hormone (GH) therapy on cardiac structure in children and adolescents, and to investigate the role of insulin like growth factor-1 (IGF-1) in this. MethodsM-mode, pulse-wave Doppler echocardiography and tissue Doppler imaging (TDI) were performed in 49 children with GHD who were divided into those with a peak GH response < 7 μg/L and 7–10 μg/L after two GH stimulation tests, aged 8–16 years at baseline and at six and 12 months after GH initiation, and 49 healthy peers. IGF-1 concentration was measured. ResultsAlthough the left ventricular end diastolic and systolic diameters in both GH deficient groups were significantly lower than controls (p < 0.01), both diameters increased significantly with one year of treatment and achieved normal values (p > 0.05). Using TDI in both two patients group revealed increased E/A, prolonged isovolumic relaxation time, shortened ejection time, and a significant increase in myocardial performance index compared to controls (p < 0.001). Significant improvement was observed in these parameters from the sixth month of GH treatment (p < 0.001), this improvement does not match parameters measured in healthy peers, even after one year of treatment in both patients group. (p < 0.001). No correlation was found between IGF-1 concentration and any echocardiographic parameter. ConclusionEchocardiographic parameters were similar in children with a GH peak < 7 μg/L and 7–10 μg/L. In TDI, both systolic and diastolic function was impaired in GHD children compared to controls. These parameters improved after one year of GH therapy but did not recover to healthy control levels.

Use of low dosage amino acid blends to prevent stress-related piglet diarrhea.

Weaning is a challenging period for piglets associated with reduced feed intake, impairment of gut integrity, and diarrhea. Previous studies demonstrate that supplementation with single functional amino acids (AA) promote piglets’ performance due to the improvement of intestinal health. Thus, we hypothesized that a combination of functional AA provided beyond the postulated requirement for growth could facilitate the weaning transition. Ninety piglets, initially stressed after weaning by 100 min overland transport, received a control diet or the same diet supplemented with a low-dosed (0.3%) mixture of AA (AAB-1: L-arginine, L-leucine, L-valine, L-isoleucine, L-cystine; AAB-2: L-arginine, L-leucine, L-valine, L-isoleucine, L-cystine, and L-tryptophan) for 28 days. Fecal consistency was ranked daily, growth performance was assessed weekly. On days 1 and 14 of the trial, blood samples were collected from a subset of 10 piglets per group to assess concentrations of insulin-like growth factor 1. After 28 days of feeding, tissues were obtained from the same piglets to analyze gut morphology and relative mRNA expression of genes related to gut function. Even if the stress response as indicated by rectal temperature was not different between the groups, pigs supplemented with AAB-2 showed firmer feces after weaning and less days with diarrhea compared to control. Furthermore, the jejunal expression of the MUC-2 gene was reduced (P < 0.05) in group AAB-2. Both AA mixtures increased crypt depth in the duodenum. Collectively, the given results indicate that 0.3% extra AA supplementation might alleviate postweaning diarrhea but did not alter growth performance of weanling piglets.

Vitamin D content in children with short stature due to intrauterine growth restriction against normosomatotropinemia

Background. There are no data about the status of vitamin D and its effect on the growth hormone/growth factors axis in prepubertal children with intrauterine growth restriction (IGR). Of particular interest is a group of patients who remain significantly short on the background of a decrease in insulin-like growth factor 1 (IGF-1) levels and normal stimulated release of growth hormone (GH). The purpose of our study was to determine the levels of 25-hydroxycalciferol in the blood plasma of prepubertal children with short stature due to IGR on the background of normosomatotropinemia. Materials and methods. We examined 34 prepubertal children (14 girls and 20 boys) with short stature (average age — 6.95 ± 0.46 years) who had signs of IGR at birth. A symmetrical type of IGR was found in 15 (44.2 %) patients, an asymmetrical type — in 19 (55.8 %). According to the results of functional tests all patients had a normal GH peak release (&gt; 10 ng/ml). Thyroid-stimulating hormone, free thyroxine levels in the blood plasma were determined by the immunoradiometric assay with standard Immunotech® kit (Czech Republic). At the time of examination, all patients were euthyroid. GH, IGF-1 and insulin-like growth factor binding protein 3 (IGFBP-3) levels were determined by enzyme-linked immunosorbent assay using Immulite 2000 Xi kits (Siemens, USA). 25-hydroxycalciferol level was determined by the immunochemiluminescent method (Abbott, USA). The results were evaluated according to the guidelines of the International Society of Endocrinology (2011). Results. It was found that in prepubertal children with IGR signs at birth, the average height standard deviation score (SDS) at the time of the examination was –2.83 ± 0.12. There were no significant differences between the height and body weight in patients with a symmetrical and an asymmetrical types of IGR at the time of examination (p &gt; 0.05). Vitamin D content in the blood plasma of children with IGR signs was 49.70 ± 2.17 nmol/l in the whole group. Vitamin D insufficiency below 75 nmol/l was found in 16 (47 %) patients, and vitamin D deficiency below 50 nmol/l — in 18 (53 %). No significant differences were found between vitamin D values in girls and boys with signs of IGR (51.79 ± 3.38 nmol/l and 48.36 ± 2.86 nmol/l, respectively, p &gt; 0.05). Height SDS in the group of patients with an asymmetrical type of IGR weakly correlates (r = 0.38) with vitamin D content. Vitamin D level significantly differed depending on IGR type (in a symmetrical type — 44.1 ± 3.2 nmol/l, in an asymmetrical type — 54.20 ± 2.56 nmol/l, p &lt; 0.05). IGF-1 SDS in the group of patients with an asymmetrical type of IGR weakly correlated (r = 0.36) with vitamin D level. On the background of a significant decrease in IGFBP-3 content in children with an asymmetrical type of IGR compared to those with a symmetrical type (–1.32 ± 0.07 SDS and –1.00 ± 0.14 SDS, p &lt; 0.05), there was a reduction in IGF-1 levels (–1.62 ± 0.10 SDS and –1.34 ± 0.14 SDS, p = 0.05). Conclusions. Patients born with signs of IGR, even against normosomatotropinemia, may still have significant growth deficit, a sharp decrease in IGF-1 and IGFBP-3 for a long time after birth. The results obtained indicate the presence of hypovitaminosis D in all prepubertal patients who were born with the signs of intrauterine growth restriction. No correlation was found between vitamin D level and the maximum peak of stimulated growth hormone release. However, patients with an asymmetrical type of IGR have a weak correlation (r = 0.36) between IGF-1 SDS and vitamin D content, a significant decrease in the content of IGF-1, IGFBP-3, as well as vitamin D compared to its level in a symmetrical type of IGR. It is recommended to include the determination of vitamin D level in the blood plasma irrespective of the type of disease and the state of somatotropic function in the list of studies for the examination of children with short stature who were born with signs of intrauterine growth restriction.

REHABILITATION THERAPY WITH INSULIN-LIKE GROWTH FACTOR AFTER ACUTE SKELETAL MUSCLE INJURY

ABSTRACT Introduction Skeletal muscle injuries account for 10% to 50% of treadmill sports injuries. Insulin-like growth factor (IGF) is a family of polypeptides with both insulin-like anabolic and growth-promoting effects. Sports play a vital role in the recovery of skeletal muscle injuries. Objective The paper analyzes the ability of insulin-like growth factor 1 (IGF-1) to repair skeletal muscle injury caused by treadmill exercise. Method We injected drugs under the wound after exercise-induced injury in rats. The control group was injected with saline, and the experimental group was injected with an insulin-like growth factor. We conduct histological and electron microscopic structural analysis of rats, Results: After an injury, the experimental group formed a basal lamina protective film earlier than the control group, activated myoblasts, formed myofilaments, formed myotubes, and fused into muscle fibers earlier than the control group. The healing quality was also better. The experimental group was endogenous. The mRNA content of sex IGF-1 and IGF-2 both increased earlier than the control group. Conclusion Local injection of exogenous insulin-like growth factor-1 can stimulate the proliferation of myoblasts and accelerate the post-traumatic repair process of skeletal muscle caused by treadmill sports. Level of evidence II; Therapeutic studies - investigation of treatment results.

Активація внутрішньоклітинних ферментних систем під впливом патогенетичних факторів канцерогенезу у хворих на цукровий діабет 2-го типу

Актуальність. У пацієнтів із цукровим діабетом (ЦД) доведено підвищений ризик онкологічних захворювань. Основними чинниками онкогенезу при ЦД визнано ожиріння, цитокіновий дисбаланс, гіпер­інсулінемію, гіперглікемію. Вказані розлади зумовлюють дисфункцію внутрішньоклітинних регуляторних сигнальних шляхів, основним з яких є шлях PI3K/Akt/mTOR. Мета. Дослідження ролі фосфорильованої Akt­протеїнкінази (фосфо­Akt) у процесах онкогенезу у пацієнтів із ЦД 2­го типу. Матеріали та методи. Обстежені 75 осіб. Хворі розподілені на групи: І — здорові, ІІ — пацієнти з ЦД 2­го типу, ІІІ — хворі на рак, IV — хворі на рак, що виник на тлі ЦД 2­го типу. Були залучені пацієнти з раком молочної залози (МЗ), ендометрія (РЕ), підшлункової залози та кишечника. Визначали рівень інсуліну, інсуліноподібного фактора росту 1 (IGF­1) та фосфо­Akt. Результати. Пацієнти ІІ і ІV груп мали декомпенсований ЦД із рівнем HbA1с &gt; 8,0 %. Вірогідну гіперінсулінемію виявлено у хворих на ЦД ІІ та IV груп (p &lt; 0,05), а підвищений рівень IGF­1 — в усіх групах дослідження (p &lt; 0,05). Показники фосфо­Akt у пацієнтів ІІІ групи були підвищеними (p &lt; 0,05), а в ІV групі — зниженими (p &lt; 0,05). У ІІІ групі виявлено гіперінсулінемію у хворих на РЕ, МЗ і кишечника (p &lt; 0,05) та підвищення рівня IGF­1 незалежно від локалізації (p &lt; 0,05). У ІV групі підвищені рівні інсуліну та IGF­1 виявлені у хворих на рак МЗ та РЕ (p &lt; 0,05). У жінок ІІІ групи, хворих на рак МЗ та РЕ, рівень IGF­1 був вищим від показників ІV групи (p &lt; 0,05). У пацієнтів IV групи, які отримували монотерапію метформіном, рівень фосфо­Akt був вірогідно нижчим (p &lt; 0,05). Виявлено прямий кореляційний зв’язок між фосфо­Akt та IGF­1 у пацієнтів ІІ групи (r = 0,50, p &lt; 0,05) і між фосфо­Akt та інсуліном у ІІІ групі (r = 0,45, p &lt; 0,05). Висновки. ГІ та IGF­1 є спільними патогенетичними факторами ЦД 2­го типу та онкологічних захворювань. Підвищений рівень фосфо­Akt може бути лабораторною ознакою онкоризику в здорових осіб. Поєднання ЦД 2­го типу та онкологічних захворювань зумовлює зниження рівня фосфо­Akt через конкурентну взаємодію внутрішньоклітинних сигнальних шляхів. Терапія метформіном сприяє зниженню рівня фосфо­Akt та може розглядатись як один із засобів протиракової профілактики.

The effects of organic grass and grass-birdsfoot trefoil pastures on Jersey heifer development: Heifer growth, performance, and economic impact

Dairy heifers developed in certified organic programs, especially those utilizing pasture-based management schemes, have lower rates of gain than heifers raised in nonorganic confinement production systems in temperate climates, such as in the Intermountain West region of the United States. This study investigates the effects that different forages in a rotational grazing system have on development of organically raised Jersey heifers. Over 3 years, 210 yearling Jersey heifers were randomly assigned to one of 9 treatments, including a conventional confinement control where animals were fed a total mixed ration or one of 8 pasture treatments: Cache Meadow bromegrass (Bromus riparius Rehmann), QuickDraw orchard grass (Dactylis glomerata L.), Amazon perennial ryegrass (Lolium perenne L.), or Fawn tall fescue (Schendonorus arundinaceus [Schreb.] Dumort) and each individual grass interseeded with birdsfoot trefoil (Lotus corniculatus L., BFT). Each treatment had 3 blocks/yr over the 3-yr period, with each block having a 0.4 ha pasture of each treatment. Every 35 d, over a 105-d period, heifers were weighed and measured for hip height, and blood samples were collected to determine serum insulin-like growth factor-1 and blood urea nitrogen concentrations. Fecal egg counts were also assessed. Heifer body weight (BW), blood urea nitrogen, and insulin-like growth factor-1 concentrations were affected by treatment when analyzed over time. Heifers on grass-BFT pastures had increased BW compared with heifers on monoculture grass pastures. Heifers receiving a total mixed ration or perennial ryegrass+BFT had increased BW gain over the 105-d period compared with heifers grazing tall fescue+BFT, orchard grass, perennial ryegrass, meadow bromegrass, or tall fescue. Individually for all grass species, heifers grazing +BFT pastures had greater ending BW and weight gain than heifers grazing the respective grass monocultures. Furthermore, weight gain for heifers on perennial ryegrass+BFT, meadow bromegrass+BFT, and orchard grass+BFT were not different from those on a total mixed ration. Heifers grazing grass-BFT pastures had increased blood urea nitrogen compared with heifers grazing monoculture grass pastures. Heifer hip height and fecal egg counts were not affected by treatment. These results show that the addition of BFT to organic pasture improves growth of grazing replacement heifers. Economic analyses also demonstrate that interseeding grass pastures with BFT results in an increased economic return compared with grazing monoculture grass pastures. Grass pastures interseeded with BFT may be a sustainable option to achieve adequate growth of Jersey heifers raised in an organic pasture scenario in a temperate climate.

Small for Gestational Age Preterm Neonates Exhibit Defective GH/IGF1 Signaling Pathway.

Objective: To investigate the impact of fetal growth restriction (FGR) on hormonal regulation of post-natal growth and glucose metabolism [via insulin and growth hormone (GH)/Insulin-like Growth factor 1 (IGF1) axis pathways] in small for gestational age (SGA) neonates.Methods: We conducted a monocentric observational prospective comparative study on 73 singleton babies born with a weight inferior to 2,000 g. We analyzed auxological (weight, height and head circumference), and hormonal (GH, IGF1, and insulin plasma concentrations) data comparing SGA and appropriate for gestational age (AGA) neonates, between day 1 and 60.Results: One third (23/73) of the neonates were SGA. Twenty-five percent (18/73) required insulin for idiopathic hyperglycemia of prematurity and were smaller in weight and head circumference at discharge. In the SGA group compared with the AGA group, GH plasma concentrations were higher at day 3 (70.1 vs. 38.0 mIU/L) and IGF1 plasma concentrations were higher at day 10 (29.0 vs. 18.7 ng/ml).Conclusions: SGA neonates displayed resistance to GH and IGF1, concomitant to insulin resistance. This could partially explain the initial defective catch-up growth and, later in life, the higher prevalence of metabolic syndrome in this population.

Copeptin and insulin-like growth factor-1 predict long-term outcomes after aneurysmal subarachnoid hemorrhage: A large prospective cohort study

ObjectiveThe predictive roles of copeptin and insulin-like growth factor-1 (IGF-1) in aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. We aimed to define the relationship between copeptin and IGF-1 levels and functional outcome as well as quality of life (QoL) after aSAH. MethodsPatients with aSAH were prospectively enrolled in a tertiary university hospital. Controls were sex- and age-matched healthy subjects. Plasma concentrations of copeptin and IGF-1 were measured on admission. Demographics and clinical, radiological and laboratory characteristics of the patients were collected. Favorable functional outcome was defined as modified Rankins≤2, and QoL was evaluated by the 36-Item Short Form Health Survey (SF-36) 1 year after aSAH. Uni- and multivariable analyses were performed. ResultsOne hundred eighteen patients were eligible, with 122 healthy controls were included in this study. Plasma copeptin levels were significantly higher and plasma IGF-1 was lower in patients than in controls. Both copeptin (adjusted HR 4.143 [1.120–15.328], p = 0.033) and IGF-1 levels (adjusted HR 0.089 [0.013–0.602], p = 0.013) were positively associated with 1-year mortality, while only single copeptin and IGF-1 concentrations were independent predictors of poor functional outcome and QoL, respectively. ConclusionsPlasma copeptin and IGF-1 levels are abnormal in patients with acute aSAH, and this may reliably predict long-term mortality, functional outcome and QoL.

3: IGF-1 Hydrogel-based Nanofiber Drug Delivery System to Improve Nerve Regeneration and Functional Recovery After Peripheral Nerve Repair

Purpose:Insulin-like growth factor 1 (IGF-1) is a potent mitogen with the potential to enhance axonal regeneration and minimize muscle atrophy and Schwann cell senescence following prolonged denervation after peripheral nerve injury. IGF-1 is a small protein with a half-life of 5 min, making local delivery a challenge. Our group has demonstrated over 6 weeks of sustained release of bioactive IGF-1 encapsulated within biodegradable nanoparticles (NP) and subsequently developed a nanofiber fiber hydrogel composite (NHC) carrier to retain IGF-1 NPs at target tissue locally for the duration of drug release. The aim of this study was to further characterize and refine the IGF-1 NP-NHC drug delivery and then investigate its efficacy in both rodent and non-human primate (NHP) median nerve injury models.Methods:IGF-1 was encapsulated in biodegradable PCL NPs and then embedded within the NHC composed of hyaluronic acid and PCL nanofibers. Release kinetics and biocompatibility were evaluated and optimized both in vitro and in vivo. The drug delivery system was assessed using a chronic denervation median nerve injury rat model and an acute median nerve repair NHP model. IGF-1NP/NHC was injected along the median nerve and within denervated muscle. In rodents, a range of IGF-1 doses (300, 900 and 1500 μg/mL) were investigated to evaluate dose-response relationships. Axonal regeneration, muscle atrophy, neuromuscular junction reinnervation and recovery of grip strength were assessed.Results:The refined NP-NHC delivery system provided sustained release of bioactive IGF-1, in vivo, for at least 42 days by serial ELISA. IGF-1 treated rodents demonstrated a 35% increase in functional recovery (stimulated grip strength) compared to untreated rodents, with no differences observed between the different concentrations of IGF-1 that were evaluated. Median nerve histomorphometry demonstrated a significantly greater total number of axons at each concentration of IGF-1 compared to untreated rodents (p<0.0001). IGF-1 treated rodents also demonstrated a greater percentage of reinnervation of neuromuscular junctions by 17% (from 14% to 31%). In addition, the IGF-1 treated non-human primate demonstrated a 31% increase in functional recovery compared to the untreated animal (N=1 per group).Conclusion:The IGF-1 NP/NHC delivery system provided sustained delivery for over 42 days in rodents and NHP. IGF-1 improves motor functional recovery by enhancing axonal regeneration and neuromuscular junction reinnervation while limiting denervation-induced muscle and Schwann cell atrophy in rodents. Our NHP pilot study has established a used pre-clinical model with robust functional analysis that will serve as a platform for a formal NHP study prior to clinical testing. The components of the NP-NHC delivery system are already used in FDA approved formulations, which will facilitate clinical translation.

Changes in Growth Performance and Ileal Microbiota Composition by Xylanase Supplementation in Broilers Fed Wheat-Based Diets.

Xylanase exerts key roles in improving growth performance and intestinal health of broilers fed wheat-based diets. However, knowledge is limited regarding effects of xylanase supplementation on ileal microbiota in broilers. A total of 128 one-day-old broilers (initial BW 48.03 ± 0.33 g) were selected to investigate effects of xylanase (AT-xynA) on growth performance, ileal morphology, microbiota composition, immune response, antioxidant capacity, and endocrine peptide levels in broilers. Broilers were randomly allotted into two dietary treatments (n = 8), namely, a wheat-soybean basal diet and a basal diet with 4,000 U/kg AT-xynA (XY). On days 7, 14, 21, and 42, broilers were weighted and ileal tissues were sampled. Ileal digesta samples were collected for analyzing microbiota composition on days 21 and 42. The results showed that AT-xynA could improve average daily weight gain and average daily feed intake, and there were interactions between diet and age of broilers (p < 0.05). On days 21 and 42, xylanase supplementation decreased ileal microbiota α-diversity, and the relative abundance of potentially pathogenic microbiota, such as phylum Proteobacteria, family Moraxellaceae and Staphylococcaceae, genus Staphylococcus, Pseudomonas, Streptococcus, and Enterococcus, increased the abundance of Lactobacillus (p < 0.05). Moreover, the reduction in acetate concentration and abundance of short-chain fatty acid-producing bacteria was also observed in broilers from XY group (p < 0.05). AT-xynA increased ileal villus height, glucagon-like peptide-1, and insulin-like growth factor-1 concentrations and decreased interleukin-1β, interleukin-6, tumor necrosis factor-α, and malondialdehyde content in broilers, and these positive effects on intestinal health were greater in young broilers. In conclusion, xylanase supplementation to wheat-based diets could improve ileal intestinal morphology and immune function, and alleviate excess fermentation of bacteria, which may be related to changes of intestinal microbiota. In addition, the positive effects of xylanase on intestinal health were more pronounced in young broilers, thus contributing to subsequent improvement in growth performance of broilers.

Circulating Insulin and IGF-1 and Frequency of Food Consumption during Pregnancy as Predictors of Birth Weight and Length.

The aim of the study was to assess the relationships between maternal insulin and insulin-like growth factor-1 (IGF-1) concentration and food consumption frequency and the birth parameters of the newborn. A total of 157 mother-newborn pairs participated in the study. The study showed that more frequent consumption of sweet and salty snacks as well as fruit and fruit or vegetable juices may promote greater weight gain in pregnancy and higher newborn birth weight. A significantly higher insulin concentration was found among overweight women according to body mass index (BMI), and a significantly lower concentration of IGF-1 was demonstrated among women ≥35 years of age. There was no significant correlation between the concentration of insulin and IGF-1 in the mother’s blood plasma and the birth weight and length of the newborn. A significant relationship was only found between the concentration of IGF-1 in the mother’s blood and the Ponderal index of the newborn. A woman’s eating habits during pregnancy have a significant impact on the mother’s health and on the proper growth and development of the foetus.

Serum insulin-like growth factor-1 as a marker of improved liver function and surgical outcome in dogs with congenital extrahepatic portosystemic shunts

Serum insulin-like growth factor-1 concentration (sIGF-1c) is reduced in various hepatopathies in humans and dogs. This work aimed to evaluate sIGF-1c in dogs before and after congenital extrahepatic portosystemic shunt (cEHPSS) attenuation, in relation to surgical outcome (closed vs. persistent shunting). Secondarily, it aimed to assess if sIGF-1c can discriminate between cEHPSS and portal vein hypoplasia (PVH) and finally compare sIGF-1c ratio (postoperative/preoperative sIGF-1c) to pre-prandial serum bile acids (preBA), post-prandial bile acids (postBA), bile acid stimulation test (BAST) and fasting ammonia (FA), regarding surgical outcome. Thirty-nine dogs were included: 15 with closed cEHPSS, 15 with persistent shunting and nine with PVH. Transplenic portal scintigraphy was used to classifiy surgical outcome.There was no significant difference in sIGF-1c between dogs with cEHPSS and those with PVH (P > 0.05). Postoperative sIGF-1c increased in all dogs (P < 0.001 and P = 0.023 for closed and persistent shunting, respectively) and the increase was more pronounced in closed cEHPSS than in persistent shunting (P = 0.006). Using an optimal sIGF-1c ratio cut-off of 2.23, the sensitivity was 93.3% and the specificity was 66.7% for differentiation between surgical outcomes. Serum pre-prandial bile acids, postBA BAST and FA had sensitivities of 80%, 86.7%, 86.7%, 60%; and specificities of 100%, 93.3%, 93.3%, 100%, respectively. There was a greater increase in sIGF-1c after shunt closure than during persistent shunting; nevertheless sIGF-1c ratio was inferior to advanced imaging to assess surgical outcome.

Insulin-Like Growth Factor 1 in the Preterm Rabbit Pup: Characterization of Cerebrovascular Maturation following Administration of Recombinant Human Insulin-Like Growth Factor 1/Insulin-Like Growth Factor 1-Binding Protein 3

Following preterm birth, serum levels of insulin-like growth factor 1 (IGF-1) decrease compared to corresponding in utero levels. A recent clinical trial indicated that supplementation with recombinant human (rh) IGF-1/rhIGF-binding protein 3 (rhIGF-1/rhIGFBP-3) prevents severe intraventricular hemorrhage (IVH) in extremely preterm infants. In a preterm rabbit pup model, we characterized endogenous serum and hepatic IGF-1, along with brain distribution of IGF-1 and IGF-1 receptor (IGF1R). We then evaluated the effects of rhIGF-1/rhIGFBP-3 on gene expression of regulators of cerebrovascular maturation and structure. Similar to preterm infants, serum IGF-1 concentrations decreased rapidly after preterm birth in the rabbit pup. Administration of rhIGF-1/rhIGFBP-3 restored in utero serum levels but was rapidly eliminated. Immunolabeled IGF1R was widely distributed in multiple brain regions, displaying an abundant density in the choroid plexus and sub-ependymal germinal zones. Increased IGF-1 immunoreactivity, distributed as IGF1R, was detected 4 h after rhIGF-1/rhIGFBP-3 administration. The rhIGF-1/rhIGFBP-3 treatment led to upregulation of choroid plexus genes involved in vascular maturation and structure, with corresponding protein translation for most of these genes. The preterm rabbit pup model is well suited for evaluation of IGF-1-based prevention of IVH. Administration of rhIGF-1/rhIGFBP-3 affects cerebrovascular maturation, suggesting a role for it in preventing preterm IVH.

The Involvement of Insulin-Like Growth Factor 1 and Nerve Growth Factor in Alzheimer's Disease-Like Pathology and Survival Role of the Mix of Embryonic Proteoglycans: Electrophysiological Fingerprint, Structural Changes and Regulatory Effects on Neurotrophins.

Alzheimer’s disease (AD)-associated neurodegeneration is triggered by different fragments of amyloid beta (Aβ). Among them, Aβ (25–35) fragment plays a critical role in the development of neurodegeneration—it reduces synaptic integrity by disruption of excitatory/inhibitory ratio across networks and alters the growth factors synthesis. Thus, in this study, we aimed to identify the involvement of neurotrophic factors—the insulin-like growth factor 1 (IGF-1) and nerve growth factor (NGF)—of AD-like neurodegeneration induced by Aβ (25–35). Taking into account our previous findings on the neuroprotective effects of the mix of proteoglycans of embryonic genesis (PEG), it was suggested to test its regulatory effect on IGF-1 and NGF levels. To evaluate the progress of neurodegeneration, in vivo electrophysiological investigation of synaptic activity disruption of the entorhinal cortex–hippocampus circuit at AD was performed and the potential recovery effects of PEG with relative structural changes were provided. To reveal the direct effects of PEG on brain functional activity, the electrophysiological pattern of the single cells from nucleus supraopticus, sensomotor cortex and hippocampus after acute injection of PEG was examined. Our results demonstrated that after i.c.v. injection of Aβ (25–35), the level of NGF decreased in cerebral cortex and hypothalamus, and, in contrast, increased in hippocampus, prompting its multidirectional role in case of brain damage. The concentration of IGF-1 significantly increased in all investigated brain structures. The administration of PEG balanced the growth factor levels accompanied by substantial restoration of neural tissue architecture and synaptic activity. Acute injection of PEG activated the hypothalamic nucleus supraopticus and hippocampal neurons. IGF-1 and NGF levels were found to be elevated in animals receiving PEG in an absence of amyloid exposure. We suggest that IGF-1 and NGF play a critical role in the development of AD. At the same time, it becomes clear that the neuroprotective effects of PEG are likely mediated via the regulation of neurotrophins.