Serum Insulin-like Growth Factor-1 Levels Research Articles

Dipeptidyl peptidase-4 inhibitors reduced long-term cardiovascular risk in diabetic patients after percutaneous coronary intervention via insulin-like growth factor-1 axis

Dipeptidyl-peptidase-4 inhibitors (DPP4i) have been the most used antidiabetic medications worldwide due to their good safety profiles and tolerability with a low risk of hypoglycemia, however, large cardiovascular outcome trials (CVOTs) have not shown any significant the prognostic superiority. On the contrary, since observational studies have suggested the effects of DPP4i are enhanced some populations, such as Asians and those who without overweight, their prognostic benefit is still under debate. The aim of this study was thus to assess the prognostic impact of DPP4i in patients with both diabetes and coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) through the insulin-like growth factor-1 (IGF-1) axis, a substrate of DPP4. This single-center analysis involved consecutive Japanese diabetic patients who underwent PCI for the first time between 2008 and 2018 (n = 885). Primary and secondary endpoints were set as cardiovascular (CV) death and the composite of CV death, non-fatal myocardial infarction and ischemic stroke (3P-MACE). Serum levels of IGF-1 and its main binding protein (insulin-like growth factor binding protein-3: IGFBP-3) were measured. In consequences, unadjusted Kaplan–Meier analyses revealed reduced incidences of CV-death and 3P-MACE by DPP4i, which was particularly enhanced in patients who were not overweight (BMI ≤ 25). Multivariate Cox hazard analyses consistently indicated reduced risks of CV death by DPP4i at PCI (hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.16–0.82, p = 0.01) and 3P-MACE (HR 0.47, 95% CI 0.25–0.84, p = 0.01), respectively. Moreover, elevated IGF-1 activity indicated by the IGF-1/IGFBP-3 ratio was associated with decreased risks of both endpoints and it was significantly higher in patients with DPP4i (p < 0.0001). In conclusion, the findings of the present study indicate beneficial effects of DPP4i to improve outcomes in Japanese diabetic patients following PCI, which might be mediated by DPP4–IGF-1 axis.

Analysis of Insulin-like growth factor-1 serum levels and promoter (rs12579108) polymorphism in the children with autism spectrum disorders

ObjectivesAutism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by a deficit in social behaviors and nonverbal interactions such as reduced eye contact and facial expression. Changes in growth factors expression including Insulin-like growth factors (IGFs) have been shown in ASD. This project aimed to study the association of IGF-1 (rs12579108) promoter polymorphism and its serum concentration with ASD. MethodsDNA was extracted from blood samples of 200 ASD children and 198 healthy controls and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and IGF-1 serum concentration was measured by ELISA. ResultsThe results showed that the prevalence of AA, CA, and CC genotypes were 2%, 61%, 37% in controls and 4%, 31%, and 65% in ASD patients, respectively (P = 0.0005). The prevalence of A and C alleles in the controls were 33% and 67% and in ASD patients were 19% and 81%, respectively (P = 0.001). We have also showed that serum IGF-1 concentration in ASD and control groups was 31.45 ± 9.84 and 54.62 ± 11.63 ng/ml, respectively (P = 0.001). Our results also showed that AA genotype is significantly related to decreased serum IGF-1 concentrations in ASD (CC, CA and AA serum levels were 50.22 ± 12.68, 33.55 ± 9.13 and 22.55 ± 7.26 and in controls were 77.88 ± 17.14, 54.77 ± 15.31 and 31.33 ± 9.91 ng/ml, respectively). ConclusionIt is concluded that there is a significant association between IGF-1 (rs12579108) promoter polymorphism and its serum concentration with ASD. We also suggest that AA genotype is linked to lower IGF-1 serum levels and may play as risk factor for ASD.

Chemotherapy of Capecitabine plus Temozolomide for Refractory Pituitary Adenoma after Tumor Resection and Its Impact on Serum Prolactin, IGF-1, and Growth Hormone.

Objective To investigate the efficiency of capecitabine (CAP) plus temozolomide (TEM) in refractory pituitary adenoma after tumor resection and its impact on serum prolactin (PRL), insulin-like growth factor 1 (IGF-1), and growth hormone (GH) levels. Methods From January 2017 to January 2020, 80 patients assessed for eligibility receiving transsphenoidal tumor resection for refractory pituitary adenoma in the Department of Neurosurgery of our hospital were recruited. They were randomly distributed at a ratio of 1 : 1 via the random number table method to receive either bromocriptine and TEM (control group) or bromocriptine plus combination chemotherapy of TEM and CAP (study group). The two groups were compared in terms of clinical efficacy and serum levels of PRL, IGF-1, and GH. Results The objective response rate (ORR) was 87.50% and 67.50% in the study group and the control group, respectively (P=0.032). Before treatment, two groups had similar levels of PRL, IGF-1, and GH. After treatment, PRL levels in the study group were lower than that in the control group (278.35 ± 39.25 versus 326.35 ± 42.45, P < 0.001). Compared with the control group, IGF-1 levels in the study group were also lower (311.78 ± 28.82 versus 364.35 ± 31.35, P < 0.001). The study group presented markedly lower levels of thyroid-stimulating hormone (TSH) and higher serum levels of free thyroxine-4 (FT-4) and adrenocorticotropic hormone (ACTH) versus the control group (P < 0.05). The incidence of adverse events was comparable between the study group (30.0%) and the control group (22.5%) (P > 0.05). All eligible patients had similar progression-free survival (PFS) after chemotherapy. Conclusion For patients with refractory pituitary adenoma, the combination chemotherapy of CAP and TEM significantly improves clinical outcomes and corrects hormonal disturbances, with a good safety profile, but its long-term efficacy requires further investigation.

Alterations in the fecal microbiota and serum metabolome in unstable angina pectoris patients.

Unstable angina pectoris (UAP) is a type of Coronary artery disease (CAD) characterized by a series of angina symptoms. Insulin-like growth factor 1 (IGF-1) system may be related to CAD. However, the correlation between the IGF-1 system, metabolism, and gut microbiota has not been studied. In the present study, we investigated the alterations of serum IGF-1 system, metabolomics, and gut microbiota in patients with UAP. Serum and stool samples from healthy volunteers and UAP patients were collected. Serum metabolomics, PAPP-A, IGF-1, IGFBP-4, STC2, hs-CRP, TNF-α, and IL-6 were detected in serum samples by LC-MS, and commercial ELISA kits, respectively. Fecal short-chain fatty acids (SCFAs) were measured by gas chromatography. 16S rDNA was used to measure the changes of the gut microbiota. The correlation of the above indicators was analyzed. There were 24 upregulated and 31 downregulated metabolites in the serum of UAP patients compared to those in the controls. Pathway analysis showed that these metabolites were enriched in pathways including linoleic acid metabolism, amino acid metabolism, starch metabolism, sucrose metabolism, and citrate cycle (TCA cycle), etc. Additionally, the UAP patients had lower fecal levels of 2-hydroxyisobutyric acid and succinic acid. 16S rDNA sequencing results showed that the relative abundances of Bacteroidetes, Synergistetes, Lactobacillaceae, Burkholderiaceae, Synergistaceae, and Subdoligranulum were significantly higher in the UAP patients than the healthy subjects. Moreover, the UAP patients had lower serum IGF-1, IGFBP-4, and STC2 and higher serum inflammatory cytokines (hs-CRP, TNF-α, and IL-6) levels than the healthy controls. Furthermore, there was a strong correlation between serum amino acids and IL-6, which played an important role in the development of UAP. These results indicated that the UAP patients had decreased serum IGF-1 level and imbalanced amino acids metabolism, which may be caused by the altered gut microbiota. It may provide a new therapeutic strategy for unstable angina pectoris.

Growth Hormone and Thyroid Function in Children With Attention Deficit Hyperactivity Disorder Undergoing Drug Therapy.

The trends in hormone indices of children with attention deficit hyperactivity disorder (ADHD) who received long-term medication treatment remains controversial. This prospective study aimed to examine the changes in the growth hormone and thyroid hormone systems among children with ADHD undergoing various medication treatments. In total, 118 children who were diagnosed with ADHD and were drug-naive were observed naturalistically over 12 months. Of them, 22 did not receive any medication, while 39, 40, and 17 were treated with low doses of short-acting methylphenidate (MPH) (14 ± 6.7 mg/day), osmotic-release oral system (OROS) long-acting MPH (32 ± 9.6 mg/day), and atomoxetine (29.2 ± 9.7 mg/day), respectively. Blood samples were obtained at both the baseline and the endpoint (month 12) to measure serum levels of insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), prolactin, thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and free T4. Trends for IGF-1, IGFBP-3, prolactin, TSH, T3, T4, and free T4 levels were similar among the 4 groups. Changes in serum levels of IGF-1 were positively correlated with changes in height and weight of all the children with ADHD. However, patients who received MPH treatment had less body weight gain than the nonmedicated group. The ratio of MPH doses to body weight was inversely correlated with the increment in height. There were no changes in thyroid or growth hormones associated with the low doses of ADHD medications used in this study within 1 year's duration. Nonetheless, patients' growth and the appropriateness of drug dosage should be closely monitored.

Expression of vascular endothelial growth factor A (VEGFA), placental growth factor (PlGF) and insulin-like growth factor 1 (IGF-1) in serum from women undergoing frozen embryo transfer

VEGFA, PlGF and IGF-1 are three main angiogenic factors which play significant roles in embryo implantation. However, the relationship between serum expressions of VEGFA, PlGF and IGF-1 and pregnancy outcomes has not been fully illustrated. In this study, serum specimens were collected precisely on day 7 after the LH surge in a natural non-conception cycle from 38 infertile patients who underwent frozen embryo transfer (FET) treatment. ELISA was used to determine the concentrations of VEGFA, PlGF and IGF-1. Serum levels of VEGFA, PlGF and IGF-1 were compared between patients who conceived (n=25) and who did not (n=13). Correlation and linear regression analyses were used to investigate the correlations of serum angiogenic factors and β-hCG MoM levels in the pregnant group. The results demonstrated that no significant difference was found in serum VEGFA, PlGF or IGF-1 concentration between pregnant and non-pregnant women. Spearman correlation analysis revealed a positive correlation between IGF-1 concentration and β-hCG level in pregnant participants (rs = 0.490, p = 0.013). In conclusion, serum IGF-1 level correlated positively with β-hCG level in pregnant women, which may provide information on the prognostic value of IGF-1 in this group of women.

Effectiveness of Recombinant Human Growth Hormone Therapy for Children With Phelan-McDermid Syndrome: An Open-Label, Cross-Over, Preliminary Study.

BackgroundPhelan-McDermid syndrome (PMS), also known as the 22q13. 3 deletion syndrome, is a rare neurodevelopmental syndrome with approximately 2,800 patients reported worldwide. Previous pilot study demonstrated that IGF-1 could significantly improve in both social impairment and restrictive behaviors of the patients. However, most of the patients in the developing countries like China cannot afford the high cost of using IGF-1. Our research team speculated that rhGH might serve as a low-cost and more accessible treatment for PMS. Therefore, the purpose of this open-label, cross-over, pilot study was to further investigate the safety and efficiency of rhGH in patients with PMS.MethodsA total of six children with PMS were enrolled in in this open-label, cross-over, pilot study. The children were randomly divided into two different groups. Group A received placebo followed by rhGH, while group B was treated with rhGH first. Neuropsychological and behavior assessments of the patients were performed before the stage I of study and 3 months after the intervention of stage I. After a 4-week period of washout, these assessments were conducted again before the stage II of study and 3 months after the intervention of stage II. Serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding-protein (IGFBP)-3 were also evaluated monthly during the intervention phases of the pilot studyResultsCompared with the placebo, rhGH treatment significantly decreased subscale scores of GDS (P < 0.0085) and trended to improve the total scores of GDS (P < 0.05), while the total scores and subscale scores of SC-ABC significantly decreased (P < 0.0085) following 3-months rhGH treatment. The similar results were also observed in comparison with baseline. Compared with the baseline, the level of serum IGF-1 and IGFBP-3 increased significantly (P < 0.05) following 3-months rhGH treatment, while the placebo group had no significant impact on serum IGF-1 and IGFBP-3 (P > 0.05). One child developed skin allergy the day after the first rhGH treatment, which were resolved later.ConclusionsIn summary, this pilot study involving six PMS children patients reveals that rhGH has a positive treatment effect on PMS. These results encourage the undertaking of a large, randomized placebo-controlled trial to conclusively prove rhGH efficacy and tolerability in PMS, thereby promoting it as a low-cost, more accessible treatment for PMS, as compared to IGF-1.

Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in children with autism spectrum disorder.

To study the serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in children with autism spectrum disorder (ASD) and their association with the core symptoms of ASD. A total of 150 ASD children aged 2-7 years (ASD group) and 165 healthy children matched for age and sex (control group) who were recruited at the outpatient service of Chongqing Health Center for Women and Children were enrolled as subjects. Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the core symptoms of the ASD children. Chemiluminescence was used to measure the serum levels of IGF-1 and IGFBP-3 in both groups. The ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). The children with severe ASD had significantly lower serum levels of IGF-1 and IGFBP-3 than those with mild-to-moderate ASD (P<0.001). For the children aged 2-3 years, the ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). Boys had a significantly lower serum level of IGF-1 than girls in both ASD and control groups (P<0.05). The serum levels of IGF-1 and IGFBP-3 were negatively correlated with the total score of CARS (r=-0.32 and -0.40 respectively, P<0.001). The reduction in serum IGF-1 level in early childhood may be associated with the development of ASD, and the serum levels of IGF-1 and IGFBP-3 are associated with the core symptoms of ASD children.

Effect of Atomoxetine on Behavioral Difficulties and Growth Development of Primary School Children with Attention-Deficit/Hyperactivity Disorder: A Prospective Study.

(1) Objective: Atomoxetine is a selective norepinephrine reuptake inhibitor used to treat attention-deficit/hyperactivity disorder (ADHD) in children over six years old. Although it is common knowledge that primary school children with ADHD often present with difficulties in the morning prior to school and in the evening, these two periods, and the family interactions they involve, are often neglected in studies of ADHD. Questionnaire–Children with Difficulties (QCD) has been widely used in China to evaluate parents’ perceptions of ADHD and patients’ daily behaviors during different times. In the long term, the efficacy and safety of atomoxetine have been well established in previous studies. Still, the short-term effects of atomoxetine treatment on serum growth parameters, such as IGF-1, IGFBP-3, and thyroid function, are not well documented. Therefore, this study was the first one using the QCD to quantify the efficacy of atomoxetine treatment in the morning prior to school and in the evening, and has investigated the possible influence on the growth parameters of Chinese primary school children with ADHD. (2) Method: This prospective study was conducted at the Department of Pediatrics at the Affiliated Hospital of Jiangnan University from August 2019 to February 2021. Changes in the children’s behavior and core ADHD symptoms following treatment were assessed using three parent-reported questionnaires, including Children with Difficulties (QCD), the Swanson, Nolan, and Pelham IV scale (SNAP-IV), and the Conners’ parents rating scales (CPRS). The height, weight, and body mass index (BMI) were measured and corrected to reflect the standard deviations (SDS) in Chinese children based on age and gender. Serum growth parameters, such as insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP-3), and thyroid function, were also measured to assess the children’s growth development. Any adverse drug reactions were assessed every three weeks. (3) Result: Finally, 149 children were enrolled in this study, and they completed 12 weeks of atomoxetine treatment. The QCD results indicated that the atomoxetine treatment could significantly alleviate behavioral difficulties in primary children with ADHD, especially in the morning prior to school (p < 0.001, r = 0.66) and in the evening (p < 0.001, r = 0.73). A statically significant decrease in weight SDS (p < 0.05) was noted during treatment, but the effect size was slight (r = 0.09). The atomoxetine treatment had no significant impact on height SDS, BMI SDS, and serum growth parameters, such as the levels of IGF-1, IGFBP-3, and thyroid function. The SNAP-IV results showed a significant improvement in the core symptoms of ADHD, while the CPRS results indicated a significant improvement in controlling ADHD symptoms across two different domains, learning problems (r = 0.81) and hyperactivity (r = 0.86). No severe adverse reactions were observed in the course of treatment, and the most common adverse reactions were gastrointestinal symptoms. (4) Conclusions: Atomoxetine is an effective and safe treatment for primary school children with ADHD. In China, it may be an excellent choice to alleviate parenting stress and improve the condition of primary school children with ADHD. Moreover, our study indicated that the serum levels of IGF-1 and IGFBP-3 were within the normal range in newly diagnosed ADHD children, and atomoxetine will not affect the serum concentration of growth parameters, such as IGF-1, IGFBP-3, and thyroid function, in the short term. However, the treatment may reduce appetite, resulting in a reduction in the Children’s weight for a short period. Further observational studies to monitor the long-term effects of atomoxetine on primary school children are recommended.

Interrelationships among growth hormone, thyroid function, and endocrine-disrupting chemicals on the susceptibility to attention-deficit/hyperactivity disorder.

Abnormal growth hormones and thyroid function may be linked to pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Phthalates and bisphenol-A (BPA), two endocrine-disrupting chemicals (EDCs), may affect the human endocrine system. In this study, we aimed to perform a comprehensive investigation of whether growth hormone, thyroid function, and EDCs exhibited differential levels between ADHD patients and healthy controls. In total, 144 children with ADHD and 70 healthy control subjects were enrolled. Their endocrine systems were evaluated using the serum levels of insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (IGFBP-3), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and Free T4. The urinary levels of EDCs, including monoethyl phthalate (MEP), mono-methyl phthalate (MMP), monoethylhexyl phthalate (MEHP), mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), and BPA, were also examined. Patients with ADHD had lower IGF-1 levels than healthy controls (p = 0.003), but we observed no significant difference in IGFBP-3, TSH, T3, T4, or Free T4. Compared to the control group, patients with ADHD demonstrated higher MEHP levels (p = 0.043), MnBP (p = 0.033), and MBzP (p = 0.040). Furthermore, MEHP levels (p < 0.001) and BPA levels (p = 0.041) were negatively correlated with IGF-1 levels, while IGF-1 levels were negatively correlated with principal components consisting of ADHD clinical symptoms and neuropsychological performance variables. We suggest that MEHP exposure may be associated with decreased serum levels of IGF-1 and increased risk of ADHD. The mechanism underlying this association may be important for protecting children from environmental chemicals that adversely affect neurodevelopment.

Serum vascular endothelial growth factor, insulin-like growth factor-1 and aflibercept levels in retinopathy of prematurity.

To evaluate the serum levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) after intravitreal injection of aflibercept (IVA) and the transition of aflibercept into systemic circulation in infants with severe retinopathy of prematurity (ROP). Prospective study. This single-centered prospective cohort study included infants who received IVA for the treatment of type 1 ROP in zone I and posterior zone II. Blood samples were collected before IVA and at 1day and 1, 2, 4, and 8weeks after IVA. VEGF, IGF-1 and aflibercept levels were measured. Thirty eyes of 15 infants received IVA of 1mg/0.025mL. Serum VEGF levels decreased significantly at 1day and 1, 2, 4, and 8weeks after IVA compared with baseline (P < 0.05). Serum aflibercept levels decreased significantly 1, 2, 4, and 8weeks after IVA compared with the level at 1day after IVA (P < 0.05) and increased significantly at 1day, 1, 2, and 4weeks after IVA compared with the baseline level (P < 0.05). No significant difference was detected between serum IGF-1 levels any time in any infant (P > 0.05). Serum VEGF levels are suppressed for at least 8weeks, and aflibercept could be detected in the systemic circulation at 4weeks after injection. Clinicians should be cautious about changes in systemic VEGF levels and passage of the agent into systemic circulation after IVA in infants.

Communication Pattern Changes Along With Declined IGF1 of Immune Cells in COVID-19 Patients During Disease Progression.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19) pandemic, represents a global crisis. Most patients developed mild/moderate symptoms, and the status of immune system varied in acute and regulatory stages. The crosstalk between immune cells and the dynamic changes of immune cell contact is rarely described. Here, we analyzed the features of immune response of paired peripheral blood mononuclear cell (PBMC) samples from the same patients during acute and regulatory stages. Consistent with previous reports, both myeloid and T cells turned less inflammatory and less activated at recovery phase. Additionally, the communication patterns of myeloid-T cell and T-B cell are obviously changed. The crosstalk analysis reveals that typical inflammatory cytokines and several chemokines are tightly correlated with the recovery of COVID-19. Intriguingly, the signal transduction of metabolic factor insulin-like growth factor 1 (IGF1) is altered at recovery phase. Furthermore, we confirmed that the serum levels of IGF1 and several inflammatory cytokines are apparently dampened after the negative conversion of SARS-CoV-2 RNA. Thus, these results reveal several potential detection and therapeutic targets that might be used for COVID-19 recovery.

Evaluation of Changes in Serum Insulin like Growth Factor-1 Levels with Growth Modulation via Twin Block TherapyA Prospective Clinical Study

Introduction: Serum insulin like growth factor is a pertinent growth regulator in bone and cartilage, therefore assessment of changes in serum Insulin like Growth Factor (IGF) levels in patients undergoing functional appliance therapy can act as valuable tool to understand the mode of action of functional appliances. Aim: To evaluate the changes in serum Insulin like Growth Factor-1 (IGF-1) levels in the patients undergoing twin block therapy and to establish IGF-1 as a biochemical marker produced in response to mechanical disturbance in the condylar region by twin block appliance. Materials and Methods: This prospective clinical trial was conducted in the Department of Orthodontics and Dentofacial Orthopedics, Postgraduate Institute of Dental Sciences, Rohtak, Haryana, India from May 2014 to November 2015. Total 27 patients included in study, divided into two groups, the test group which comprised of 15 patients treated with standard twin block appliance therapy and the control group which comprised of 12 patients not treated with the same. Serum samples were collected from test group and control group patients at four time intervals (pretreatment (T0), 1 month (T1), 3 months (T3) and 6 months (T6)) and subjected to EnzymeLinked Immunosorbent Assay (ELISA) to measure IGF-1 levels. The data thus obtained was subjected to statistical analysis using Statistical Package for the Social Sciences (SPSS) for windows 20.0. Intragroup differences were evaluated using paired t-test, while intergroup differences were evaluated using independent sample t-test. The p-value&lt;0.05 was considered as statistically significant. Results: The data was obtained from 11 patients (6 males and 5 females) in the test group and 10 patients (6 males and 4 females) in the control group after elimination of dropouts. Mean age of the test group subjects was 12.8±0.9 years and that of control group subjects was 13.1±0.9 years. The mean IGF-1 levels in the test group were 124.5 ng/mL (T0), 126.27 ng/mL (T1), 130.90 ng/mL (T3) and 135.54 ng/mL (T6). In the control group, 151.5 ng/mL (T0), 140.8 ng/mL (T1), 157.8 ng/mL (T3) and 120.2 ng/ mL (T6). In the test group, mean levels of serum IGF-1 did not change significantly when baseline levels were compared with the serum IGF-1 levels at T1 (0.467), T3 (0.729) and T6 (0.62) of functional appliance therapy, although an increase in IGF-1 levels was noted at each interval. Comparison of serum IGF-1 levels of test and control group showed no statistically significant difference between the groups at T0, T1, T3 and T6. Conclusion: Functional appliance therapy was not found to be associated with concomitant increase in serum IGF-1 levels.

FOXO Transcription Factors Are Required for Normal Somatotrope Function and Growth.

Understanding the molecular mechanisms underlying pituitary organogenesis and function is essential for improving therapeutics and molecular diagnoses for hypopituitarism. We previously found that deletion of the forkhead factor, Foxo1, in the pituitary gland early in development delays somatotrope differentiation. While these mice grow normally, they have reduced growth hormone expression and free serum insulin-like growth factor-1 (IGF1) levels, suggesting a defect in somatotrope function. FOXO factors show functional redundancy in other tissues, so we deleted both Foxo1 and its closely related family member, Foxo3, from the primordial pituitary. We find that this results in a significant reduction in growth. Consistent with this, male and female mice in which both genes have been deleted in the pituitary gland (dKO) exhibit reduced pituitary growth hormone expression and serum IGF1 levels. Expression of the somatotrope differentiation factor, Neurod4, is reduced in these mice. This suggests a mechanism underlying proper somatotrope function is the regulation of Neurod4 expression by FOXO factors. Additionally, dKO mice have reduced Lhb expression and females also have reduced Fshb and Prl expression. These studies reveal FOXO transcription factors as important regulators of pituitary gland function.

Growth hormone, growth hormone receptor and insulin-like growth factor serum levels in patients with obesity and food addiction

Growth hormone, growth hormone receptor and insulin-like growth factor serum levels in patients with obesity and food addiction

The influence of Mediterranean diet in acne pathogenesis and the correlation with insulin-like growth factor-1 serum levels: implications and results

Acne is a chronic inflammatory disease of the pilosebaceous unit and its etiology is complex and multifactorial. The role of the diet in its pathogenesis is still debated. The purpose of this study was to assess the association between MD and IGF-1 in acne patients and, as secondary objective, the role of systemic treatment on IGF-1 serum levels, in accordance to the patients’ diet. This study included 35 patients aged 14-30 years affected by acne and treated in line with the EDF guidelines. Patients were divided into 2 groups based on a questionnaire score assessing the adherence to the Mediterranean diet: the Mediterranean Group (score ≥ 6) and the Western Group (score &lt; 5). IGF-1 serum levels were measured in all patients before and after treatment and then compared to healthy population. IGF-1 levels were higher in patients than in controls and in the Western group than in the Mediterranean group. We speculate that the Mediterranean diet can have a protective role in the pathogenesis of acne by acting on the systemic route of IGF-1.

The influence of Mediterranean diet in acne pathogenesis and the correlation with insulin-like growth factor-1 serum levels: Implications and results.

Acne is a chronic inflammatory disease of the pilosebaceous unit, and its etiology is complex and multifactorial. The role of the diet in its pathogenesis is still debated. The purpose of this study was to assess the association between MD and IGF-1 in acne patients and, as secondary objective, the role of systemic treatment on IGF-1 serum levels, in accordance with the patients’ diet. This study included 35 patients aged 14-30 years affected by acne and treated in line with the EDF guidelines. Patients were divided into 2 groups based on a questionnaire score assessing the adherence to the Mediterranean diet: the Mediterranean Group (score ≥6) and the Western Group (score< 5). IGF-1 serum levels were measured in all patients before and after treatment and then compared to healthy population. IGF-1 levels were higher in patients than in controls and in the Western group than in the Mediterranean group. We speculate that the Mediterranean diet can have a protective role in the pathogenesis of acne by acting on the systemic route of IGF-1.

Low bone mass in Noonan syndrome children correlates with decreased muscle mass and low IGF-1 levels.

Although musculoskeletal abnormalities have long been described in patients with Noonan syndrome (NS), only a few studies have investigated the bone status of these patients. The aim of this retrospective observational study was to describe the bone health of children with NS. Thirty-five patients with a genetically confirmed diagnosis of NS were enrolled. We analyzed the axial skeleton (lumbar spine) using dual energy X-ray absorptiometry and the appendicular skeleton (hand) with the BoneXpert system. Bone metabolism markers, including mineral homeostasis parameters, serum 25-hydroxy vitamin D (25-OHD) levels and markers of bone formation and resorption were also reported. Compared to the general population, axial and appendicular bone mass was significantly decreased in children with NS (p<0.0001). Serum 25-OHD levels were low in about half of the patients and were negatively correlated with age (r=-0.52; p<0.0001). Patients with NS exhibited reduced bone formation marker levels and increased bone resorption marker levels (p<0.0001). No gender difference or genotype-phenotype correlations were found for the different bone parameters. Muscle mass and, to a lesser extent, serum insulin-like growth factor 1 (IGF-1) levels were independent predictors of whole-body bone mineral content (p<0.0001 for both parameters; adjusted R2=0.97). In conclusion, bone mass is reduced in children with NS and correlates with decreased muscle mass and low serum IGF-1 levels. These data justify addressing all potential threats to bone health including sufficient calcium and vitamin D intake, regular physical exercise, and hormone replacement therapy.

Comparison of the effects of open vs. closed skill exercise on the acute and chronic BDNF, IGF-1 and IL-6 response in older healthy adults

BackgroundAccumulating evidence shows that physical exercise has a positive effect on the release of neurotrophic factors and myokines. However, evidence regarding the optimal type of physical exercise for these release is still lacking. The aim of this study was to assess the acute and chronic effects of open-skill exercise (OSE) compared to closed-skill exercise (CSE) on serum and plasma levels of brain derived neurotrophic factor (BDNFS, BDNFP), and serum levels of insulin like growth factor 1 (IGF-1), and interleukin 6 (IL-6) in healthy older adults.MethodsTo investigate acute effects, thirty-eight participants were randomly assigned to either an intervention (badminton (aOSE) and bicycling (aCSE), n = 24, 65.83 ± 5.98 years) or control group (reading (CG), n = 14, 67.07 ± 2.37 years). Blood samples were taken immediately before and 5 min after each condition. During each condition, heart rate was monitored. The mean heart rate of aOSE and aCSE were equivalent (65 ± 5% of heart rate reserve). In a subsequent 12-week training-intervention, twenty-two participants were randomly assigned to either a sport-games (cOSE, n = 6, 64.50 ± 6.32) or a strength-endurance training (cCSE, n = 9, 64.89 ± 3.51) group to assess for chronic effects. Training intensity for both groups was adjusted to a subjective perceived exertion using the CR-10 scale (value 7). Blood samples were taken within one day after the training-intervention.ResultsBDNFS, BDNFP, IGF-1, and IL-6 levels increased after a single exercise session of 30 min. After 12 weeks of training BDNFS and IL-6 levels were elevated, whereas IGF-1 levels were reduced in both groups. However, only in the cOSE group these changes were significant. We could not find any significant differences between the exercise types.ConclusionOur results indicate that both exercise types are efficient to acutely increase BDNFS, BDNFP, IGF-1 and IL-6 serum levels in healthy older adults. Additionally, our results tend to support that OSE is more effective for improving basal BDNFS levels after 12 weeks of training.

Investigating whether serum IGF-1 and IGFBP-3 levels reflect the height outcome in prepubertal children upon rhGH therapy: LG growth study database.

Serum insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3) levels can be used to monitor the safety of recombinant human growth hormone (rhGH) therapy. In this study, we evaluated the changes in serum IGF-I and IGFBP-3 levels during rhGH therapy as a marker of height outcome in prepubertal children. Totally, 705 prepubertal children with short stature were enrolled from the LG Growth Study Database. Data for three groups of subjects were obtained as follows: Idiopathic GH deficiency (IGHD; n = 486); idiopathic short stature (n = 66); small for gestational age (n = 153). Serum IGF-I and IGFBP-3 levels at the baseline and after the 1st and 2nd year of rhGH therapy, as well as the Δheight standard deviation score (SDS), were obtained. Δheight SDS after the 1st and 2nd year of rhGH therapy had notably increased compared to that at the baseline for all three groups. IGF-I and IGFBP-3 levels in all three groups were significantly increased compared to those at the baseline (p <0.001). Δheight SDS was positively correlated with ΔIGF-1 SDS after the 1st year of therapy, ΔIGFBP-3 SDS after the 2nd year of therapy in the IGHD group, and ΔIGF-I SDS and ΔIGFBP-3 SDS after the 2nd year of therapy (p < 0.05), regardless of whether the height at the baseline was a covariate. The increase in IGF-I and IGFBP-3 levels during rhGH therapy was related to the growth response in children with IGHD. Therefore, it may be valuable to measure the change in serum IGF-I and IGFBP-3 levels, especially the latter, during rhGH treatment to predict the growth response upon long-term treatment.