Changes In Insulin-like Growth Factor Research Articles

Dynamic changes in insulin-like growth factor binding protein expression occur between embryonic and early post-hatch development in broiler chickens

Somatotropic gene expression has been altered by genetic selection, and developmental changes in insulin-like growth factor (IGF) and IGF binding protein (IGFBP) expression may contribute to rapid growth and muscle accretion in commercial broilers. The objective of this study was to evaluate changes in somatotropic axis activity between embryonic day (e) 12 and post-hatch day (d) 21. Liver and breast muscle (pectoralis major) were collected to measure gene expression, and blood was collected post-hatch to measure circulating IGFs. Liver IGF1 rose rapidly post-hatch and, in muscle, IGF1 exhibited a dynamic expression pattern. Levels decreased from e14 to e20, returned to e14 levels at d3, decreased again at d10, and stayed low thereafter. In both tissues, mRNA levels of several IGFBPs changed between embryogenesis and post-hatch. Liver IGFBP2 increased between e12 and e20, returned to e12 levels on d1, and remained low. Conversely, liver IGFBP4 expression was greater post-hatch than during embryogenesis. Expression of select IGFBPs was depressed in liver during the peri-hatch period. Liver IGFBP1, IGFBP3, IGFBP5, and IGFBP7 mRNA levels all decreased around this time and returned to embryonic levels by d3. In breast muscle, expression of both IGFBP2 and IGFBP4 was reduced after hatch. Circulating insulin-like growth factor IGF1 and IGF2 levels did not change between hatch and d21. These data suggest that post-hatch IGF effects are likely modulated by target tissue IGFR1 and IGFBP expression rather than changes in circulating hormone levels, with promotion or restriction of IGF-receptor binding regulating growth. Downregulation of several IGFBPs synthesized in the liver may facilitate the metabolic transition from utilizing yolk lipids to dietary carbohydrates. Several IGFBPs produced in breast muscle appear to have growth-promotive effects during embryogenesis but restrict growth of this tissue after hatch, as their post-hatch downregulation could facilitate local IGF signaling. These developmental gene expression patterns suggest that somatotropic hormonal signaling regulating growth and muscle accretion might be controlled through differential actions of IGFBPs and provide a basis for future functional studies.

A protocol for a proof-of-concept randomized control trial testing increased protein quantity and quality in ready-to-use therapeutic food in improving linear growth among 6-23-month-old children with severe wasting in Malawi.

Ready-to-use therapeutic foods (RUTFs) have successfully promoted recovery from severe wasting and increased treatment coverage. However, RUTFs do not sufficiently improve linear growth, leaving many survivors of severe wasting at risk of persistent stunting, which is associated with high mortality risk, poor child development and non-communicable diseases in adulthood. High protein quantity and quality can stimulate linear growth. The trial aims to assess whether higher-protein-RUTF leads to higher concentrations of markers of linear growth compared to standard RUTF among 6-23 months old children with severe wasting. We designed a higher protein quantity and quality RUTF for a proof-of-concept (PoC) double-blind randomized controlled trial. The primary outcome is a change in insulin-like growth factor-1 (IGF-1), a hormone positively associated with linear growth after four weeks of treatment. Secondary outcomes include changes in ponderal and linear growth and in body composition from baseline to eight weeks later; plasma amino acid profile at four weeks; acceptability and safety. These findings will help in informing the potential impact of increased protein in RUTF on linear growth when treating severe wasting towards conducting a larger clinical trial. The trial has been registered on clinicaltrial.gov (NCT05737472).

Compensatory Growth Is Accompanied by Changes in Insulin-Like Growth Factor 1 but Not Markers of Cellular Aging in a Long-Lived Seabird.

AbstractDeveloping organisms often plastically modify growth in response to environmental circumstances, which may be adaptive but is expected to entail long-term costs. However, the mechanisms that mediate these growth adjustments and any associated costs are less well understood. In vertebrates, one mechanism that may be important in this context is the highly conserved signaling factor insulin-like growth factor 1 (IGF-1), which is frequently positively related to postnatal growth and negatively related to longevity. To test this idea, we exposed captive Franklin's gulls (Leucophaeus pipixcan) to a physiologically relevant nutritional stressor by restricting food availability during postnatal development and examined the effects on growth, IGF-1, and two potential biomarkers of cellular and organismal aging (oxidative stress and telomeres). During food restriction, experimental chicks gained body mass more slowly and had lower IGF-1 levels than controls. Following food restriction, experimental chicks underwent compensatory growth, which was accompanied by an increase in IGF-1 levels. Interestingly, however, there were no significant effects of the experimental treatment or of variation in IGF-1 levels on oxidative stress or telomeres. These findings suggest that IGF-1 is responsive to changes in resource availability but is not associated with increased markers of cellular aging during development in this relatively long-lived species.

Comparison of growth response and adverse reaction according to growth hormone dosing strategy for children with short stature: LG Growth Study

ObjectiveGrowth hormone (GH) dosage in children is conventionally determined either by body weight (BW) or body surface area (BSA). However, there is no consensus on the calculation method for proper GH treatment dose. We aimed to compare growth response and adverse reactions between BW- and BSA-based GH treatment doses for children with short statures. DesignData from 2284 GH-treated children were analyzed. Distributions of BW- and BSA-based GH treatment doses and their association with growth response parameters, including changes in height, height standard deviation score (SDS), body mass index (BMI), and safety parameters, such as changes in insulin-like growth factor (IGF)-I SDS and adverse events, were investigated. ResultsThe mean BW-based doses were close to the recommended dose's upper limit in participants with GH deficiency and idiopathic short stature, while they were below the recommended dose in patients with Turner syndrome (TS). As age and BW increased, BW-based dose decreased, whereas BSA-based dose increased. Gain in height SDS was positively associated with BW-based dose in the TS group and negatively associated with BW in all groups. Despite having a lower BW-based dose, the overweight/obese groups had a higher BSA-based dose and higher frequencies of children with high IGF-I and adverse events than those of the normal-BMI group. ConclusionsIn children of older age or with high BW, BW-based doses can be overdosed in terms of BSA. and BW-based dose positively correlated with height gain only in the TS group. BSA-based doses represent an alternative dosing strategy in children who are overweight/obese.

GLP-1 Receptor Agonists Induce Growth Hormone Secretion in Healthy Volunteers.

Growth hormone (GH) is an essential regulator of growth, body composition and fuel metabolism and, consequently, GH secretion is under the feedback control of numerous nutritional and endocrine mediators. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to exert pleiotropic effects, including stimulation of the activity of the hypothalamic-pituitary-adrenal axis. As GLP-1RAs exert multiple metabolic effects, we hypothesised that they may also affect the secretion of GH and examined the effect of a short-acting and a long-acting GLP-1 RA on GH secretion. This is a post hoc analysis of data from clinical trials. Two separate single-group open-label clinical trials were carried out in the ambulatory care setting with a duration of 1 and 21days, respectively. Healthy adult male and female volunteers with no chronic illnesses or use of daily medicines were recruited for the study. The two interventions were: study 1, single dose of 10µg exenatide administered subcutaneously (s.c.); study 2, 0.6mg liraglutide administered s.c. once daily for 21days. Administration of a single dose of exenatide (study 1) caused a clear increase in GH levels, peaking between 60 and 120min post-administration. There was also a small but statistically significant decrease in luteinising hormone and testosterone levels 120min after exenatide dosing. Administration of the long-acting GLP-1RA liraglutide daily for 21 days (study 2) elicited an increase in GH levels with no change in insulin-like growth factor-1 (IGF-1) concentrations after 3weeks of treatment. The results show that the administration of GLP-1RAs may elicit an increase in growth hormone levels. GLP-1 signalling may be a novel mechanism of regulation of GH secretion. This finding needs to be replicated in the placebo-controlled trial. NCT02089256 and NCT03160261.

Insulin-like growth factors and their transporter proteins in the liver of rats with experimental diabetes, adenocarcinoma of the uterine corpus, and their combination

Aim. To investigate the content of insulin-like growth factor (IGF)-1, IGF-2, and their transporter proteins IGFBP-1 and IGFBP in the liver of rats with experimental diabetes, Guerin’s carcinoma, and their combination.Materials and methods. The experiment was carried out on 64 white outbred rats of both sexes, which were divided into 4 groups of 8 animals each: group 1 – intact animals, group 2 – animals with experimental diabetes, group 3 – animals with subcutaneously inoculated Guerin’s carcinoma, group 4 – animals with experimental diabetes and subcutaneously inoculated Guerin’s carcinoma. In the study, biochemical and statistical analyses and enzyme immunoassays were performed.Results. In the liver of the outbred rats, sex specificity in the content of insulin-like growth factors and IGFBP-1 was established: the levels of IGF-1, IGF-2, and IGFBP-1 in males were lower than in females. It was shown that the development of diabetes mellitus and the growth of Guerin’s carcinoma led to changes in the sex-specific components in the rat liver.Conclusion. The growth of Guerin’s carcinoma and the progression of diabetes mellitus cause multidirectional changes in IGF and IGFBP levels in the liver of females and unidirectional changes in the liver of males. Following the growth of Guerin’s carcinoma against the background of diabetes mellitus, sex-specific differences in the content of the studied parameters were minimized. It was shown that diabetes mellitus changed the metabolic profile of the liver in the animals of both sexes.

Features of changes in insulin-like growth factor-1 in patients with coronary heart disease in combination with type 2 diabetes mellitus

The purpose of the study was to study the level of insulin-like growth factor-1 in the blood of patients with coronary heart disease with type 2 diabetes mellitus, in patients with coronary heart disease without type 2 diabetes mellitus and in almost healthy individuals. Materials and methods. We examined 73 patients (30 men, 43 women) with coronary heart disease aged 49 to 75 years (mean age –58.3 ± 1.8). All patients were treated in the therapeutic department of the prof. А. А. Shalimov Kharkiv Municipal Clinical Hospital No. 2. Examination of patients was performed using clinical, laboratory and instrumental methods. All patients had ischemic heart disease in the form of stable angina pectoris of I – II functional classes, I functional class was diagnosed in 27 patients, II – in 46 patients. From the group of examined patients in 36 patients the disease was accompanied by concomitant type 2 diabetes mellitus (group 1). Mild diabetes was detected in 15 people, moderate – in 21 patients. 37 patients did not have diabetes mellitus (group 2). Diagnosis of diabetes was based on the criteria of the World Diabetes Federation. The control group consisted of 20 people of the same age, who according to the results of clinical and additional studies were found to be practically healthy. Determination of insulin-like growth factor-1 and insulin levels in the blood was performed by enzyme-linked immunosorbent assay on a «Humareader photometer-analyzer». DRG kits (USA) were used to study the level of insulin-like growth factor-1. Results and discussion. It was found that patients with coronary heart disease with concomitant type 2 diabetes had higher levels in serum triglycerides (p <0.05) and very low density lipoprotein cholesterol (p <0.05) compared with patients with coronary heart disease without diabetes. Patients with coronary heart disease and concomitant type 2 diabetes showed a statistically significant increase in blood insulin levels compared with patients with coronary heart disease without diabetes. The results of the analysis of insulin-like growth factor-1 showed that the content of insulin-like growth factor-1 in the blood of patients with coronary heart disease and type 2 diabetes was probably lower compared with patients with coronary heart disease without diabetes and with practically healthy individuals (p <0.01). At the same time, the levels of insulin-like growth factor-1 in almost healthy individuals and patients with coronary heart disease without type 2 diabetes did not differ significantly. Conclusion. In patients with coronary heart disease with type 2 diabetes the level of insulin-like growth factor-1 is probably lower than in patients with coronary heart disease without diabetes and almost healthy individuals. Given the antiapoptotic, antiatherosclerotic, anabolic properties of this growth factor, it can be argued that the development of relative insulin-like growth factor-1 deficiency in the combination of coronary heart disease with type 2 diabetes causes a significant increase in the risk of cardiovascular complications in this category of patients

Changes in Insulin-Like Growth Factor 1 and Quadriceps Muscle Size in Follicular Stage Compared to Luteal Stage in Adaptation to Resistance Training in Young Women

Background and Objectives Menstrual cycle may affect the training of strength and muscle size. The aim of the present study was to determine the effect of exercise volume distribution in the 2 follicular and luteal phases of the menstrual cycle on serum Insulin-like Growth Factor 1 (IGF-1) and muscle mass in women. Methods in this semi experimental study’ 20 amenorrheic women with a mean age of 22±5 years, without contraceptive use and a history of eight weeks of resistance training were selected. Each subject had 8 training sessions on one leg in the first 14 days of menstruation and 2 training sessions on the second 14 days of menstruation (training in the follicular period) and the other leg had 2 training sessions on the first 14 days of menstruation and 8 training sessions on the second 14 days of menstruation (training in the luteal period). The training protocol was consist of unilateral leg extension. Results the quadriceps Muscle diameter (according to pretest size) in follicular training (FT) (0.67±0.34 (cm)) was higher than luteal training(LT) (0.46, 0.41 cm) (P=0.012). Also, insulin-like growth factor increased in both groups (13%) regardless of the type of exercise schedule (P> 0.001). Conclusion According to this study it is recommended that follicular based training may cause more muscle hypertrophy and maximum strength than luteal based training in young amenorrheic women who do not take birth control pills.

Prospects Of Using Resveratrol For Cognitive Impairment Correction In Patients With Type II Diabetes Mellitus

Our goal was to study the effectiveness of resveratrol in correcting cognitive impairments and in normalization of neurotrophin levels in patients with type II diabetes mellitus. Material and Methods ― In a randomized placebo-controlled trial, 100 patients with a verified diagnosis of type II diabetes mellitus took part, who were subsequently placed into two groups: the treatment group of 50 patients taking a polyphenol therapeutic drug in addition to standard therapy, and the comparison group of 50 indivuduals taking a placebo medication in addition to standard therapy. The control group consisted of 30 individuals belonging to the health group I sensu RF Ministry of Healthcare. Treatment efficacy was assessed using the Montreal Cognitive Assessment (MoCA) scale. The concentrations of insulin-like growth factor 1 (IFR-1), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in blood plasma were analyzed before and after treatment completion (10 weeks later). Results ― Before starting treatment, patients exhibited an increase in the level of IFR-1 and a decrease in the content of neurotrophic factors (BDNF and NGF) in their blood plasma. In patients receiving resveratrol in addition to standard treatment, changes in IFR-1, BDNF and NGF in blood plasma were more noticeable relative to the comparison group and approached the values of the control group. According to the MoCA scale, more pronounced dynamics of cognitive functions was observed in patients of the treatment group. Conclusion ― The high efficiency of the polyphenol therapeutic drug resveratrol in the correction of cognitive impairments in patients with type II diabetes mellitus was established. The use of resveratrol promoted the normalization of the levels of IFR-1 and neurotrophic factors in the blood plasma: in the treatment group, a more pronounced statistically significant decrease in the concentration of IFR-1, along with an increase in BDNF and NGF levels, were observed relative to the control group. The clinically significant effect of resveratrol was in the reduction of cognitive deficit symptoms, which was confirmed by the data of dynamic monitoring on the MoCA scale: in treatment group, there was a statistically significant improvements of optical and spatial functions, attention, abstract thinking, and fulfilling delayed reproduction task; in the comparison group, there was a statistically significant improvement solely of completing delayed reproduction task.

Effect of Progressive Resistance Training on Circulating Adipogenesis-, Myogenesis-, and Inflammation-Related microRNAs in Healthy Older Adults: An Exploratory Study

Background: Functional and physiological adaptations induced by resistance training have been extensively studied in older adults. However, microRNA (miRNA) as the novel regulator in protective effects remains poorly understood. Objective: The purpose of an exploratory study was to analyze the response of a panel of circulating miRNAs to adaptations mediated by resistance training. Methods: Ten healthy older adults (age: 67.6 ± 2.2 years, 7 women and 3 men) without previous experience in resistance training were recruited. Blood samples were collected at baseline and after a 12-week resistance training. Next-generation sequencing was used to determine circulating miRNA responses to chronic resistance training. Results: After the 12-week training, physical functions including grip strength, lower body strength and endurance, and walking capacity were improved in the older adults, while the serum levels of leptin (from 18.1 ± 20.0 to 14.9 ± 17.6 ng/mL, p = 0.029) and tumor necrosis factor alpha (TNFα; from 4.4 ± 0.6 to 4.0 ± 0.6 pg/mL, p < 0.001) were significantly decreased. In addition, adipogenesis-related miRNAs (miR-103a-3p, -103b, -143-5p, -146b-3p, -146b-5p, -17-5p, -181a-2-3p, -181b-5p, -199a-5p, -204-3p, and -378c), anti-adipogenesis-related miRNAs (miR-155-3p, -448, and -363-3p), myogenesis-related miRNAs (miR-125b-1-3p, -128-3p, -133a-3p, 155-3p, -181a-2-3p, -181b-5p, -199a-5p, -223-3p, and -499a-5p), and inflammation-related miRNAs (miR-146b-3p, -146b-5p, -155-3p, -181a-2-3p, and -181b-5p) were changed significantly in the older adults after training (fold change >2, p < 0.05). The log₂ fold change of miRNA-125-1-3p was inversely correlated with delta walking time (R = –0.685, p = 0.029) and change in insulin-like growth factor 1 (R = –0.644, p = 0.044). Conclusions: Our results can help explain the link between specific circulating miRNAs and beneficial effects of resistance training on functional and physiological adaptations in older adults.

Effects of Seasonal Vitamin D3 Supplementation on Strength, Power, and Body Composition in College Swimmers.

The purpose of this study was to evaluate the impact of fall season vitamin D3 supplementation on strength/power, body composition, and anabolic hormones in swimmers with optimal vitamin D status at summer's end. Male and female National Collegiate Athletic Association Division I swimmers (N = 19) with optimal 25-hydroxyvitamin D [25(OH)D] randomly received 5,000IU of vitamin D3 (VITD) or placebo (PLA) daily for 12 weeks while participating in swimming and strength and conditioning training (August-November). Before and after the intervention, the participants underwent blood sampling for analysis of serum 25(OH)D, parathyroid hormone, total testosterone, free testosterone, sex hormone-binding globulin, and insulin-like growth factor 1, dual-energy X-ray absorptiometry, and strength/power testing (bench press, squat, dead lift, standing broad jump, vertical jump, and dips and pull-ups). Sex was used as a covariate for analyses. The 25(OH)D was decreased by 44% in PLA (p < .05) and increased by 8% in VITD over the 12 weeks. Fat-free mass increased in VITD (56.4-59.1kg; p < .05), but not PLA (59.4-59.7kg; p < .01). Significant Group × Time interaction effects were observed for dead lift (F = 21.577, p < .01) and vertical jump (F = 11.219, p < .01), but no other strength/power tests. Total testosterone decreased similarly in both groups, but free testosterone decreased and sex hormone-binding globulin increased only in PLA (p < .01). There were no group differences or changes in insulin-like growth factor 1 with the intervention. The findings suggest that vitamin D supplementation is an efficacious strategy to maintain 25(OH)D during the fall season training and to enhance some aspects of strength/power and fat-free mass in swimmers. Further research on the relationship between vitamin D and anabolic hormones is needed.

The Aberrant Expression of MicroRNA-125a-5p/IGF2BP3 Axis in Advanced Gastric Cancer and Its Clinical Relevance.

RNA-binding proteins have been associated with cancer development. The overexpression of a well-known RNA-binding protein, insulin-like growth factor 2 messenger RNA–binding protein 3, has been identified as an indicator of poor prognosis in patients with various types of cancer. Although gastric cancer is a relatively frequent and potentially fatal malignancy, the mechanism by which insulin-like growth factor 2 messenger RNA–binding protein 3 regulates the development of this cancer remains unclear. This study aimed to investigate the role and regulatory mechanism of insulin-like growth factor 2 messenger RNA–binding protein 3 in gastric cancer. An analysis of IGF2BP3 expression patterns reported in 4 public gastric cancer–related microarray data sets from the Gene Expression Omnibus and The Cancer Genome Atlas-Stomach Adenocarcinoma revealed strong expression of this gene in gastric cancer tissues. Insulin-like growth factor 2 messenger RNA–binding protein 3 expression in gastric cancer was further confirmed via quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively, in an in-house gastric cancer cohort (n = 30), and the association of insulin-like growth factor 2 messenger RNA–binding protein 3 expression with clinical parameters and prognosis was analyzed. Notably, stronger IGF2BP3 expression significantly correlated with poor prognosis, and significant changes in insulin-like growth factor 2 messenger RNA–binding protein 3 expression were only confirmed in patients with advanced-stage gastric cancer in an independent cohort. The effects of insulin-like growth factor 2 messenger RNA–binding protein 3 on cell proliferation were confirmed through in vitro experiments involving the HGC-27 gastric cancer cell line. MicroR-125a-5p, a candidate microRNA that target on insulin-like growth factor 2 messenger RNA–binding protein 3, decreased in advanced-stage gastric cancer. Upregulation of microR-125a-5p inhibited insulin-like growth factor 2 messenger RNA–binding protein 3, and dual-luciferase report assay indicated that microR-125a-5p inhibited the translation of IGF2BP3 by directly targeting the 3′ untranslated region. These results indicate that the microR-125a-5p/insulin-like growth factor 2 messenger RNA–binding protein 3 axis contributes to the oncogenesis of advanced gastric cancer.

Evaluation of Safety and Efficacy of Growth Hormone Therapy by IGF-1 Z Score in Children with Short Stature.

This study aims to explore the safety and efficacy of growth hormone (GH) therapy by retrospectively analyzing the changes of insulin-like growth factor-1 (IGF-1) Z-scores in children with short stature after treatment with GH. The etiology of 104 children with short stature was classified according to the GH stimulation test and IGF-1 levels: (1) growth hormone deficiency (GHD); (2) mild growth hormone deficiency (M-GHD); (3) idiopathic short stature (ISS); (4) GH insensitivity syndrome (GHIS). In addition, all patients were treated with recombinant human growth hormone (rhGH) for 12months, and the growth rate (Gv), height, body mass, bone age, height standard deviation scores (HtSDS), IGF-1 and adverse reactions were compared among these three groups before and after treatment. The height, body mass, Gv and HtSDS were significantly higher in each group compared with those before treatment. Furthermore, the Z-score of IGF-1 significantly increased after 1month of GH treatment and was positively correlated with the dosage of GH. Moreover, the difference in standard deviation score was significantly positively correlated with the increase in standard deviation score of IGF-1. The detection of the GH-IGF-1 axis function can be carried out for the etiologic diagnosis of short stature. IGF-1 increased after rhGH treatment, and IGF-1 level was correlated to the time of therapy and dosage of GH. IGF-1-based GH dosing targeted to age- and gender-adjusted means may save medical costs and offer a more dose-sparing and potentially safer mode of therapy compared with traditional weight-based dosing.

The Role of Serum Levels of Insulin-Like Growth Factor-1 and Brain-Derived Neurotrophic Factor in Predicting Recovery in Stroke

Background: Despite the neurotrophins like brain-derived neurotrophic factor and insulin-like growth factor-1 are thought to have important role in neurorehabilitation, the factors that affect these biomarkers are not well known. Objectives: We aimed to investigate the effect of maximal aerobic exercise on serum neurotrophins levels in patients with chronic stroke and to investigate the factors that affect their resting and exercise-associated levels. Patients and Methods: Potential factors of resting and exercise-related serum neurotrophins levels were studied among 35 patients with chronic stroke. Resting brain derived neurotrophic factor, resting insulin-like growth factor, exercisedependent change brain derived neurotrophic factor, and exercise- dependent change in insulin-like growth factor were studied using demographic, disease burden, and cardiometabolic factors. Results: Brain-derived neurotrophic factor did not change after exercise (p = 0.38) while insulin-like growth factor decreased (p = 0.001). Higher resting brain-derived neurotrophic factor was determined by greater lower extremity impairment (p = 0.004, r2 = 0.23). The greater response of brain-derived neurotrophic factor to exercise was determined by higher fluid intelligence (p = 0.01, r2 = 0.18). Resting insulin-like growth factor-1 was not changed by all of the studied factors. Conclusion: Resting and percent change in brain-derived neurotrophic factor were associated with cognitive and physical recovery after chronic stroke. On the other hands, insulin-like growth factor-1 was not useful in chronic stroke. Interestingly, fluid intelligence was positively associated with exercise-related rise in brain-derived neurotrophic factor.

Features of changes in insulin-like growth factor-1 in patients with chemoresistant pulmonary tuberculosis who are on palliative treatment

One of the causes of death of patients with pulmonary tuberculosis is cachexia. In the available literature, there are no data on the study of changes in the significate of insulin-like growth factor-1 (IGF-1) in patients with chemo-resistant pulmonary tuberculosis (CRTB) with a body mass deficit. The purpose of the work is to determine the level of IGF-1 in the serum of patients with CRHT of the lungs who are under palliative treatment, and to establish the features of its change depending on the body mass index (BMI). Materials and methods . The main group of follow-up consisted of 52 patients with CRTB of lungs, who are on palliative treatment (mean age 39.4 ± 1.8 years). The comparison group included 29 patients who receive anti-mycobacterial therapy for category 4 in accordance with the profile of drug resistance, the average age was 41.3 ± 1.8 years. The difference in P 18.1 kg/m 2 and 1.7 times than in the comparison group. It was established that, in patients with CRTB, who got the palliative care, a decrease in the level of IGF-1 in serum was significantly directly dependent on a decrease in BMI: in main group 1 (r = 0.91; P = 0.001) and in main group 2 (r = 0.97; P = 0.001). Conclusions . In patients with CRTB of the lungs who got palliative treatment, a significant decrease in the serum IGF-1 level of 1.4 times is determined compared to patients with CRTB of the lungs who receive antimycobacterial therapy. At the same time, in patients CRTB of the lungs, who got palliative care and had a body mass index of ≤18.1 kg/m 2 , the level of serum IGF-1 is significantly lower by 1.9 times compared with patients with a body mass index of >18.1 kg/m 2 . In patients CRTB, who got palliative care, a decrease in serum IGF-1 levels reliably depends on a decrease in body mass index. Significate of serum IGF-1 can be used as an early marker of the increase and progression of cachexia.

Serum levels of insulin-like growth factor-1 and brain-derived neurotrophic factor as potential recovery biomarkers in stroke

ABSTRACTObjectives: Our objectives were: 1) to determine whether maximal aerobic exercise increased serum neurotrophins in chronic stroke and 2) to determine the factors that predict resting and exercise-dependent levels.Methods: We investigated the potential predictors of resting and exercise-dependent serum insulin-like growth factor-1 and brain-derived neurotrophic factor among 35 chronic stroke patients. Predictors from three domains (demographic, disease burden, and cardiometabolic) were entered into 4 separate stepwise linear regression models with outcome variables: resting insulin-like growth factor, resting brain-derived neurotrophic factor, exercise-dependent change in insulin-like growth factor, and exercise-dependent change brain-derived neurotrophic factor.Results: Insulin-like growth factor decreased after exercise (p = 0.001) while brain-derived neurotrophic factor did not change (p = 0.38). Greater lower extremity impairment predicted higher resting brain-derived neurotrophic factor (p = 0.004, r2 = 0.23). Higher fluid intelligence predicted greater brain-derived neurotrophic factor response to exercise (p = 0.01, r2 = 0.18). There were no significant predictors of resting or percent change insulin-like growth factor-1.Discussion: Biomarkers have the potential to characterize an individual’s potential for recovery from stroke. Neurotrophins such as insulin-like growth factor-1 and brain-derived neurotrophic factor are thought to be important in neurorehabilitation; however, the factors that modulate these biomarkers are not well understood. Resting brain-derived neurotrophic factor and percent change in brain-derived neurotrophic factor were related to physical and cognitive recovery in chronic stroke, albeit weakly. Insulin-like growth factor-1 was not an informative biomarker among chronic stroke patients. The novel finding that fluid intelligence positively correlated with exercise-induced change in brain-derived neurotrophic factor warrants further research.

Insulin-like growth factor-1 engaged in the mandibular condylar cartilage degeneration induced by experimental unilateral anterior crossbite

ObjectiveTo investigate the changes in insulin-like growth factor-1 (IGF-1) expression levels in the degenerative mandibular condylar cartilage. DesignThirty-six rats were divided into the unilateral anterior crossbite and control groups. The expression levels of IGF-1; IGF-1 receptor (IGF-1R); IGF-binding protein-3 and -5 (IGFBP-3 and -5); proliferating cell nuclear antigen (PCNA); aggrecan; type-I, -II, -VI, and -X collagen; tissue inhibitor of metalloproteinases-1 and -3 (TIMP-1 and -3); metalloproteinases of matrix metalloproteinases-3 and-13 (MMP-3 and -13); a disintegrin and metalloproteinase thrombospondin-4 and -5 (ADAMTS-4 and -5); alkaline phosphatase (ALP); β-glucuronidase; and N-acetyl-β-glucosaminidase in the mandibular condylar cartilage were assessed. ResultsThe protein expression levels of IGF-1and IGF-1R were increased from week 4 in the unilateral anterior crossbite group. The mRNA expression level of IGFBP-3 and -5 was upregulated from week 4 and week 2, respectively; that of IGFBP-3 was downregulated at week 8; and that of PCNA, type-II collagen, type-X collagen, aggrecan, TIMP-1, and TIMP-3 was downregulated, whereas that of MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, β-glucuronidase, and N-acetyl-β-glucosaminidase were upregulated from week 2. The positive area size of type-I collagen was increased and that of type VI collagen was decreased from week 2. The positive area size of type X collagen was increased at week 2 but decreased at week 8. The percentage of ALP-positive cells was increased from week 4. ConclusionsUnilateral anterior crossbite stimulated the multifarious expression of IGF-1 and IGFBP, which may be linked to chondrocyte proliferation and differentiation in the mandibular condylar cartilage that showed progressive degeneration.

Changes of insulin-like growth factor 1 axis in chronic kidney disease and its role in skeletal muscle atrophy

Objective: To investigate the changes of insulin-like growth factor 1 (IGF-1) axis in chronic kidney disease (CKD) and its role in skeletal muscle atrophy. Methods: A total of 240 patients with CKD stage 1-5 (without dialysis treatment) were included between August 2016 and February 2017. Serum IGF-1 and IGF-1 binding protein-3 (IGFBP-3) were measured using chemiluminescence, and the influencing factors of serum IGF-1 and IGFBP-3 were analyzed. Besides, male Sprague-Dawley rats (200-250 g) were randomly assigned to the sham-operated control group (Control, n=15) and the 5/6 nephrectomy group (n=15) as CKD animal model. The expressions of local IGF-1 and IGF-1 receptor (IGF-1R) of skeletal muscles were evaluated at the level of transcription and protein by real-time PCR and Western blotting. Results: There was no significant correlation between changes of serum IGF-1 level and estimated glomerular filtration rate (eGFR) (r=-0.066, P=0.307). However, after multivariable adjustment, serum IGFBP-3 increased with decreasing of eGFR (r=-0.181, P=0.005) in adult CKD patients. In multivariate analysis, age, eGFR, serum cholesterol level and 24 h urinary protein quantification were independent factors of serum IGFBP-3 in patients with CKD (R2=0.243, P<0.001). Animal experiments showed that the expression of IGF-1 mRNA and protein decreased in skeletal muscles of CKD rats. Expressions of IGF-1R mRNA and protein were slightly reduced and phosphorylation of IGF-1R was severely impaired in skeletal muscles of CKD rats. Conclusions: IGF-1 levels seem to be independent of renal function, but IGFBP-3 levels increased with decreasing of eGFR, which may cause a low affinity of IGF-1 with IGF-1R in skeletal muscles. Low affinity of IGF-1 with IGF-1R, as well as the decreasing of IGF-1 synthesis could lead to disorders of IGF-1R phosphorylation, and thus cause atrophy of skeletal muscles.

Effects of Moxibustion on the Levels of Insulin-Like Growth Factor 1

Moxibustion (艾灸) is a traditional Chinese medicine therapy performed using Artemisia argyii. Zusanli (足三里, ST36) is an acupoint in the stomach meridian, long associated in ancient Chinese medical practices with the extension of life span when moxibustion is applied to it. The aim of this study was to investigate changes in insulin-like growth factor 1 (IGF-1) levels after application of moxibustion to ST36. Four healthy men and women participated in this 28-day trial and were randomly divided into 2 groups. Group A received moxibustion treatment from days 1 to 14, while group B received moxibustion treatment from days 15 to 28. Blood samples were taken 5 times during this study to measure serum IGF-1 (s-IGF-1) levels. The s-IGF-1 levels increased in both groups after 7 and 14 d of moxibustion therapy (group A: 11.02% [7 d] and 29.65% [14 d]; group B: 169.12% [7 d] and 274.85% [14 d]). After moxibustion therapy had been completed (day 14), s-IGF-1 levels continued to increase in group A (increases on day 21 and day 28 were 53.19% and 61.45%, respectively). There were no adverse events in either group. The s-IGF-1 levels were significantly raised in both groups after 7 and 14 d of moxibustion therapy. Moreover, once therapy had been completed, s-IGF-1 levels continued to increase in group A up to 14 d after the treatment.

The effect of pre- and post-operative physical activity on recovery after colorectal cancer surgery (PHYSSURG-C): study protocol for a randomised controlled trial

BackgroundSurgery for colorectal cancer is associated with a high risk of post-operative adverse events, re-operations and a prolonged post-operative recovery. Previously, the effect of prehabilitation (pre-operative physical activity) has been studied for different types of surgery, including colorectal surgery. However, the trials on colorectal surgery have been of limited methodological quality and size. The aim of this trial is to compare the effect of a combined pre- and post-operative intervention of moderate aerobic physical activity and inspiratory muscle training (IMT) with standard care on post-operative recovery after surgery for colorectal cancer.Methods/designWe are conducting a randomised, controlled, parallel-group, open-label, multi-centre trial with physical recovery within 4 weeks after cancer surgery as the primary endpoint. Some 640 patients planned for surgery for colorectal cancer will be enrolled. The intervention consists of pre- and post-operative physical activity with increased daily aerobic activity of moderate intensity as well as IMT. In the control group, patients will be advised to continue their normal daily exercise routine. The primary outcome is patient-reported physical recovery 4 weeks post-operatively. Secondary outcomes are length of sick leave, complication rate and severity, length of hospital stay, re-admittances, re-operations, post-operative mental recovery, quality of life and mortality, as well as changes in insulin-like growth factor 1 and insulin-like growth factor-binding protein 3, perception of pain and a health economic analysis.DiscussionAn increase in moderate-intensity aerobic physical activity is a safe, cheap and feasible intervention that would be possible to implement in standard care for patients with colorectal cancer. If shown to be effective, this lifestyle intervention could be a clinical parallel to pre-operative smoke cessation that has already been implemented with good clinical results.Trial registrationClinicalTrials.gov identifier: NCT02299596. Registered on 17 November 2014.