IGF-I Levels Research Articles

Usefullness of a Combined Evaluation of the Serum Adiponectin Level and Insulin Growth Factor 1 to Predict the Early Stage of Nonalcoholic Steatohepatitis

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western industrialised countries and affects around 25% of the European population. The prevalence of NAFLD is increasing in parallel with the global increase in obesity and type 2 diabetes mellitus (T2DM). Aim of the Work To investigate the role of adiponectin and IGF1 in the diagnosis of NASH. Patients and Methods The present study included 60 patients who attending the outpatient clinic of Ain Shams University hospital, they age ranges from thirty to sixty years. Results It was found that highly significant decrease in Adiponectin and IGF-1 levels, in NASH group; compared to NAFLD control group (p < 0.01 respectively) a This data is similar to many studies done before in NAFLD and NASH patients. Our study also shows that; AST, ALT, total and direct bilirubin, had a highly significant negative correlation with IGF-1 and Adiponectin level (p < 0.01 respectively). This go with many studies who found a significant inverse correlation between IGF-I levels and liver enzymes, indicating that lower IGF-I levels in NAFLD are related to parenchymal dysfunction. With proven evidence that low circulating IGF-I levels correlate with the degree of liver dysfunction. Conclusion Serum adiponectin and insulin growth factor 1 are lower in patients with NASH compared to NAFLD patients which reflect the protective effect of both of adiponectin and IGF1 against the development of NASH.

Evaluation of the Effect of Glycemic Control on Insulin-Like Growth Factor 1 and Growth in a Sample of Pre-Pubertal Egyptian Children with Type 1 Diabetes Mellitus

Abstract Background Pre-Pubertal children with type 1 diabetes mellitus are shorter than their non- diabetic peers. We aimed to evaluate the role of HbAlc and IGF-1 in this phenomenon. Methods This study was a cross sectional study conducted on 80 prepubertal Egyptian children, divided into 30 Males and 30 Females with T1DM and 20 age matched controls (10 Males and 10 Females), the participants were recruited from the Outpatient Clinic of the Pediatric Department of Ain Shams University Hospitals and the National Institute of Diabetes and Endocrinology in Cairo, Egypt during the period from July 2018 to January 2019. Anthropometric measures including height and weight were obtained and used to calculate the height and weight percentiles using the CDC calculators. HbA1c as well as IGF-1 levels were tested. Results The mean age (years) of the participants was (9.781 ± 2.23) for male patients, (9.126 ± 2.199) for female patients and (8.437 ± 2.034) for controls. The height and weight percentiles (%) were found to be lower in the children with T1DM when compared to the disease-free controls with median values of 14.50 (IQR 27.98) in male patients, 17.95 (IQR 29.18) in female patients and 87 (IQR 20.58) in the controls. A negative correlation between serum IGF-1(ng/ml) and HbA1c (%) as well as height and weight percentiles (%), was found with (P = 0.014, 0.009 and 0.05 respectively). Serum IGF-1 levels were also found to be significantly lower in patients (P < 0.001) with a mean value of (77.60 ± 69.377) in male patients and (64.0 ± 29.402) in female patients and (201.0 ± 102.798) in the disease-free controls. HbA1c (%) was also found to be negatively correlated with height percentile (P = 0.012). Conclusion Serum IGF-1 levels (ng/ml) as well as growth are negatively affected in pre-pubertal children with T1DM in relation to the glycemic control.

Loss of Dact2 alleviates cisplatin-induced nephrotoxicity through regulation of the Igfl-MAPK pathway axis.

Wnt signaling is a principal pathway regulating the essential activities of cell proliferation. Here, we investigated the effect of Wnt/β-catenin signaling on in vivo drug-induced renal injury through the deletion of Dact2, a Wnt antagonist, and deciphered the underlying mechanism. Wild-type (WT) and Dact2 knockout (KO) mice were administered a single intraperitoneal injection of cisplatin to induce renal injury. The injury was alleviated in Dact2 KO mice, which showed lower levels of blood urea nitrogen and creatinine. RNA sequencing revealed 194 differentially expressed genes (DEGs) between WT and Dact2 KO mouse kidney before cisplatin treatment. Among them, higher levels of Igf1, one of the Wnt target genes responsible for "Positive regulation of cell proliferation" in KO mice, were confirmed along with the induction of Ki67 expression. In RNA-seq analysis comparing WT and Dact2 KO mice after cisplatin treatment, genes related to "Apoptosis" and "Activation of mitogen-activated protein kinase (MAPK) activity" were among the downregulated DEGs in KO mice. These results were corroborated in western blotting of proteins related to apoptosis and proapoptotic MAPK pathway; the expression of which was found to be lower in cisplatin-treated KO mice. Importantly, β-catenin was found to directly bind to and regulate the transcription of Igf1, leading to the alleviation of cisplatin-induced cytotoxicity by the Wnt agonist, CHIR-99021. In addition, Igf1 knockdown accelerated cisplatin-induced cytotoxicity, accompanied by the MAPK upregulation. Our findings suggest that Dact2 knockout could protect cisplatin-induced nephrotoxicity by inhibiting apoptosis, possibly through the regulation of the Igf1-MAPK axis associated with Wnt/β-catenin signaling.

Oestrogen treatment restores dentate gyrus development in premature newborns by IGF1 regulation.

Prematurely-born infants cared for in the neonatal units suffer from memory and learning deficits. Prematurity diminishes neurogenesis and synaptogenesis in the hippocampal dentate gyrus (DG). This dysmaturation of neurons is attributed to elevated PSD95, NMDR2A, and IGF1 levels. Since oestrogen treatment plays key roles in the development and plasticity of DG, we hypothesized that 17β-estradiol (E2) treatment would ameliorate neurogenesis and synaptogenesis in the DG, reversing cognitive deficits in premature newborns. Additionally, E2-induced recovery would be mediated by IGF1 signalling. These hypotheses were tested in a rabbit model of prematurity and nonmaternal care, in which premature kits were gavage-fed and reared by laboratory personnel. We compared E2- and vehicle-treated preterm kits for morphological, molecular, and behavioural parameters. We also treated kits with oestrogen degrader, RAD1901, and assessed IGF1 signalling. We found that E2 treatment increased the number of Tbr2+ and DCX+ neuronal progenitors and increased the density of glutamatergic synapses in the DG. E2 treatment restored PSD95 and NMDAR2A levels and cognitive function in preterm kits. Transcriptomic analyses showed that E2 treatment contributed to recovery by influencing interactions between IGF1R and neurodegenerative, as well as glutamatergic genes. ERα expression was reduced on completion of E2 treatment at D7, followed by D30 elevation. E2-induced fluctuation in ERα levels was associated with a reciprocal elevation in IGF1/2 expression at D7 and reduction at D30. ERα degradation by RAD1901 treatment enhanced IGF1 levels, suggesting ERα inhibits IGF1 expression. E2 treatment alleviates the prematurity-induced maldevelopment of DG and cognitive dysfunctions by regulating ERα and IGF1 levels.

Pharmacological blockade of the interleukin-1 receptor suppressed Escherichia coli lipopolysaccharide-induced neuroinflammation in preterm fetal sheep

Intraamniotic inflammation is associated with preterm birth, especially in cases occurring before 32 weeks' gestation, and is causally linked with an increased risk for neonatal mortality and morbidity. Targeted anti-inflammatory interventions may assist in improving the outcomes for pregnancies impacted by intrauterine inflammation. Interleukin-1 is a central upstream mediator of inflammation. Accordingly, interleukin-1 is a promising candidate target for intervention therapies and has been targeted previously using the interleukin-1 receptor antagonist, anakinra. Recent studies have shown that the novel, noncompetitive, allosteric interleukin-1 receptor inhibitor, rytvela, partially resolved inflammation associated with preterm birth and fetal injury. In this study, we used a preterm sheep model of chorioamnionitis to investigate the anti-inflammatory efficacy of rytvela and anakinra, administered in the amniotic fluid in the setting of intraamniotic Escherichia coli lipopolysaccharide exposure. We hypothesized that both rytvela and anakinra would reduce lipopolysaccharide-induced intrauterine inflammation and protect the fetal brain. Ewes with a singleton fetus at 105 days of gestation (term is ∼150 days) were randomized to one of the following groups: (1) intraamniotic injections of 2 mL saline at time=0 and time=24 hours as a negative control group (saline group, n=12); (2) intraamniotic injection of 10 mg Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 2 mL saline at time=0 hours and time=24 hours as an inflammation positive control group (lipopolysaccharide group, n=11); (3) intraamniotic injection of Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 2.5 mg rytvela at time=0 hours and time=24 hours to test the anti-inflammatory efficacy of rytvela (lipopolysaccharide + rytvela group, n=10); or (4) intraamniotic injection of Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 100 mg anakinra at time=0 hours and time=24 hours to test the anti-inflammatory efficacy of anakinra (lipopolysaccharide + anakinra group, n=12). Amniotic fluid was sampled at time 0, 24, and 48 hours (ie, at each intervention and at delivery). Fetal umbilical cord blood was collected at delivery for differential blood counts and chemical studies. Inflammation was characterized by the analysis of fetal tissue cytokine and chemokine levels using quantitative polymerase chain reaction, enzyme-linked inmmunosorbent assay, and histology. The primary study outcome of interest was the assessment of anakinra and rytvela brain-protective effects in the setting of Escherichia coli lipopolysaccharide-induced intrauterine inflammation. Secondary outcomes of interest were to assess protection from fetal and intrauterine (ie, amniotic fluid, chorioamnion) inflammation. Intraamniotic administration of lipopolysaccharide caused inflammation of the fetal lung, brain, and chorioamnionitis in preterm fetal sheep. Relative to treatment with saline only in the setting of lipopolysaccharide exposure, intraamniotic administration of both rytvela and anakinra both significantly prevented periventricular white matter injury, microglial activation, and histologic chorioamnionitis. Anakinra showed additional efficacy in inhibiting fetal lung myeloperoxidase activity, but its use was associated with metabolic acidaemia and reduced fetal plasma insulin-like growth factor-1 levels at delivery. Intraamniotic administration of rytvela or anakinra significantly inhibited fetal brain inflammation and chorioamnionitis in preterm fetal sheep exposed to intraamniotic lipopolysaccharide. In addition, anakinra treatment was associated with potential negative impacts on the developing fetus.

LncRNA MIR4435-2HG suppression regulates macrophage M1/M2 polarization and reduces intestinal inflammation in mice with ulcerative colitis

ObjectiveTo explore the effect and potential mechanism of LncRNA MIR4435-2HG on macrophage polarization and intestinal inflammation in ulcerative colitis (UC).MethodsRAW264.7 macrophage cells stimulated with lipopolysaccharide (LPS) were co-cultured with Caco-2 cells to establish an inflammatory model of UC in vitro. Balb/c mice were orally administered dextran sulfate sodium (DSS) to establish an in vivo UC model. Flow cytometry and immunohistochemical (IHC) analyses were performed to assess the levels of surface phenotype markers. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) were performed to measure the levels of inflammatory cytokines. Western blotting was used to analyze expression of the tight junction protein zona occludens 1 (ZO-1) and the key proteins of the JAK1/STAT1 signaling pathway (Janus kinase-1(JAK1), p-JAK1, signal transducer and activator of transcription 1 (STAT1), p-STAT1.ResultsIn in vitro experiments, we found that inhibition of MIR4435-2HG was able to decrease the levels of CD68, iNOS, IL-6, and TEER, and increase the levels of CD206, Arg-1, IGF-1, and ZO-1. Meanwhile, inhibition of MIR4435-2HG significantly suppressed the levels of p- JAK1 and p- STAT1. In addition, we further demonstrated by in vivo experiments that inhibition of MIR4435-2HG significantly attenuated intestinal inflammation in mice, as evidenced by increased body weight, increased colon length and weight, decreased fecal scores, hemorrhagic scores, and DAI scores, and amelioration of colonic injury, and decreased inflammatory factors.ConclusionsMIR4435-2HG suppression inhibits macrophage M1 polarization while promoting M2 polarization, thereby alleviating intestinal inflammation in mice with ulcerative colitis through JAK1/STAT1 signaling.

Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Utility of Noninvasive Scores in Patients With Acromegaly.

Nonalcoholic fatty liver disease (NAFLD) is a metabolical disorder and can lead to liver fibrosis. Because it is commonly seen, several noninvasive scores (NS) have been validated to identify high-risk patients. Patients with NAFLD have been shown to have higher serum angiopoietin-like protein-8 (ANGPTL-8) levels. The risk of NAFLD is known insufficiently in acromegaly. Moreover, the utility of the NS and the link between NAFLD and ANGPTL-8 in acromegaly is unknown. Thirty-two patients with acromegaly (n = 15, active [AA] and n = 17, controlled acromegaly [CA]) and 19 healthy controls were included. Magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) was used to evaluate hepatic steatosis, and magnetic resonance elastography to evaluate liver stiffness measurement. ANGPTL-8 levels were measured with ELISA. Median liver MRI-PDFF and NAFLD prevalence in AA were lower than in CA (P = .026 and P < .001, respectively). Median magnetic resonance elastography-liver stiffness measurement were similar across groups. Of the NS, visceral adiposity index, fatty liver index, hepatic steatosis index, and triglyceride-glucose index (TyG) all showed positive correlation with the liver MRI-PDFF in the control group. However, only TyG significantly correlated with liver fat in the AA and CA groups. There was no correlation between traditional NAFLD risk factors (body mass index, waist circumference, C-reactive protein, homeostasis model assessment for insulin resistance, visceral adipose tissue) and liver MRI-PDFF in the AA and CA. Patients with acromegaly with NAFLD had lower GH, IGF-1, and ANGPTL-8 levels than in those without NAFLD (P = .025, P = .011, and P = .036, respectively). Active acromegaly may protect from NAFLD because of high GH. In patients with acromegaly, NAFLD risk cannot be explained with classical risk factors; hence, additional risk factors must be identified. TyG is the best score to evaluate NAFLD risk. Lower ANGPTL-8 in patients with acromegaly and NAFLD implies this hormone may be raised because of insulin resistance rather than being a cause for NAFLD.

Effects of insulin-like growth factor-1 on the proliferation and apoptosis of stallion testicular cells under normal and heat stress culture conditions

This study investigated the effect of heat stress on stallion testicular cells (TCs) and the effect of insulin-like growth factor (IGF)−1 on TC viability, proliferation, and apoptosis, including different stages of germ cells. TCs were divided into control or treatment groups with 0.01, 0.1, 1, 10, and 100 ng/mL of recombinant human IGF-1 (rhIGF-1) for 24 h at 34 °C and 37 °C. The population and viability were measured before and after treatment. The effects of rhIGF-1 on TC viability, proliferation, and apoptosis were determined using RT-qPCR. Proliferating cell nuclear antigen (PCNA) and marker of proliferation Ki-67 (MKI-67) were used as proliferation markers. Myeloid leukemia-1 (MCL-1) was used as an antiapoptotic marker. BCL2 antagonist/killer-1 (BAK-1) was used as a proapoptotic marker. The relative abundance of mRNA transcript of undifferentiated cell transcription factor 1 (UTF-1), protein gene product 9.5 (PGP9.5), and deleted in azoospermia-like (DAZL), was measured for spermatogenesis progression. TCs treated with 1 ng/mL rhIGF-1 at 34 °C exhibited the highest viability. Significant upregulation of the relative abundance of mRNA transcript of PCNA, MKI-67, and MCL-1 was observed in treated TCs compared with untreated TCs; however, BAK-1 was significantly downregulated in treated TCs. Germ cells treated with 1 ng/mL rhIGF-1 exhibited the highest relative abundance of mRNA transcript of UTF-1 and DAZL, whereas TCs exposed to 0.1 ng/mL showed the highest PGP9.5 level. These data confirm that heat stress in stallions decreases TC viability. These findings may help identify a basal IGF-1 level for TC proliferation and apoptosis during heat stress-induced testicular degeneration in stallions.

The metabolic effects of resumption of a high fat diet after weight loss are sex dependent in mice

Dietary restriction is a frequent strategy for weight loss, but adherence is difficult and returning to poor dietary habits can result in more weight gain than that previously lost. How weight loss due to unrestricted intake of a healthy diet affects the response to resumption of poor dietary habits is less studied. Moreover, whether this response differs between the sexes and if the insulin-like growth factor (IGF) system, sex dependent and involved in metabolic control, participates is unknown. Mice received rodent chow (6% Kcal from fat) or a high-fat diet (HFD, 62% Kcal from fat) for 4 months, chow for 3 months plus 1 month of HFD, or HFD for 2 months, chow for 1 month then HFD for 1 month. Males and females gained weight on HFD and lost weight when returned to chow at different rates (p < 0.001), but weight gain after resumption of HFD intake was not affected by previous weight loss in either sex. Glucose metabolism was more affected by HFD, as well as the re-exposure to HFD after weight loss, in males. This was associated with increases in hypothalamic mRNA levels of IGF2 (p < 0.01) and IGF binding protein (IGFBP) 2 (p < 0.05), factors involved in glucose metabolism, again only in males. Likewise, IGF2 increased IGFBP2 mRNA levels only in hypothalamic astrocytes from males (p < 0.05). In conclusion, the metabolic responses to dietary changes were less severe and more delayed in females and the IGF system might be involved in some of the sex specific observations.

Use of the WINROP Screening Algorithm for the Prediction of Retinopathy of Prematurity (ROP): A Hospital-Based Study

Background: Retinopathy of prematurity (ROP) may be the blinding disease that affects the retina of neonates. WINROP utilizes the rate of postnatal weight increase as a replication of IGF-1 or uses weight increase and IGF-1 levels together as highly analytical markers for those infants at increased risk for the development of proliferative ROP. So this study was undertaken to find out the sensitivity and specificity of this algorithm concerning international screening guidelines to predict retinopathy of prematurity. Material &amp; Methods: A prospective cross-sectional study was carried out in the Department of Neonatology, Bangladesh Shishu Hospital &amp; Institute from January 2017 to December 2018. A total of 50 neonates (N=50) with proper documentation following the inclusion and exclusion criteria were confirmed as the study population. Informed written consent was obtained from all the parents or guardians after they were thoroughly briefed about the nature and purpose of the study. Data were processed and analyzed using statistical package for social sciences (SPSS-22 version) software (SPSS Inc., Chicago, IL, USA). The ethical review board of the Bangladesh Institute of Child Health approved the protocol of this study. Results: The mean gestational age was 29±1.17 weeks in ROP-positive cases and 31.79±0.51 weeks in ROP-negative cases. The mean weight was 1121.9±94.34 grams in ROP-positive cases and 1302.7±139.72 grams in ROP-negative cases. It was observed that the majority 92.3% of the ROP positive cases had weight gain ≤10gm/kg/day for 4 weeks but 87.5% of the ROP negative cases had weight gain &gt;10gm/kg/day. The validity test of WINROP for the prediction of retinopathy has a sensitivity of 92.3%, specificity of 87.5%, and positive predictive value of 88.9% and negative predictive value of 91.3%. Low-grade ROP – In zone II or III and stage 1. High-grade ROP – In zone I and stage 2 or more and plus disease. Conclusion: Retinopathy of prematurity (ROP) is a severe eye infection that can affect premature neonates. In this study, WINROP predicted 92.3% sensitivity and 88.9% positive predictive value in comparison to the gold standard screening method for detecting ROP within 2 weeks of birth.

Changing presentation of acromegaly in half a century: a single-center experience.

Investigate the changes in the characteristics of presentation, in patients with acromegaly over a period of approximately half a century. The medical records of patients diagnosed with acromegaly between 1980 and 2023 were retrospectively reviewed. The collected data were examined to assess any changes observed over the years and a comparison was made between the characteristics of patients diagnosed in the last decade and those diagnosed in previous years. A total of 570 patients were included in the study, 210 (37%) patients were diagnosed in the last decade. Patients diagnosed before 2014 had longer symptom duration before diagnosis, advanced age, larger pituitary adenomas, higher incidence of cavernous sinus invasion, and higher GH and IGF-1 levels than those diagnosed last decade (p < 0.05, for all). Furthermore, the patients diagnosed before 2014 had a lower rate of surgical remission (p < 0.001), and a higher prevalence of comorbidities such as diabetes, hypertension, colon polyps, and thyroid cancer at the time of diagnosis (p < 0.05, for all). There may be a trend for earlier detection of patients with acromegaly.

Alterations of materno-placento-fetal glucose homeostasis after a single course of antenatal betamethasone

IntroductionIntrauterine growth impairment is associated with long-term metabolic changes (perinatal programming). We recently demonstrated that antenatal betamethasone (BET) decreased head circumference in term born females. Since glucose is the main energy source for fetal growth, BET-induced changes in maternal glucose homeostasis, a reduced transplacental glucose transfer or an altered fetal glucose utilization may be linked with the observed growth impairment. Methods86 pregnant women exposed to BET (single course, <34 + 0 weeks of gestation (wks)) were compared to 92 gestational-age/sex-matched controls. Glucose, insulin, leptin, insulin-like growth factors (IGF-1, IGF-2) and their binding proteins (IGFBP-1, IGFBP-3) were measured in maternal and umbilical cord blood samples. Homeostasis Model Assessment (HOMA-IR) was calculated. Placental glucose transporter 1 and 3 (GLUT1, GLUT3) protein levels were determined. Statistics were performed for overall and subgroup analysis (gestational age, sex). ResultsAfter BET maternal HOMA-IR was elevated, IGFBP-1 reduced. In female pregnancies, glucose levels ≥37 + 0 wks and IGF-1 levels <37 + 0 wks were tendentially increased. Placental GLUT1 and GLUT3 protein levels were not significantly altered. Fetal umbilical venous glucose levels ≥37 + 0 wks were increased. HOMA-IR tended to be elevated in females. DiscussionGrowth impairment after BET appears neither caused by maternal nor fetal hypoglycemia nor changes of GLUT1 and GLUT3 total protein levels. Nonetheless, glucose homeostasis of mothers and daughters was altered even beyond the BET time frame (hyperglycemia, enhanced insulin resistance). Despite glucose supply was sufficient, an anabolic effect was apparently absent. Overall, our results highlight the relevance of adequate glucose management after BET and peripartum.

Zinc-nanoparticles alleviate the ovarian damage induced by bacterial lipopolysaccharide (LPS) in pregnant rats and their fetuses

Lipopolysaccharide (LPS) is an endotoxin derived from the cell wall of Gram-negative bacteria. LPS exposure during early gestation is associated with adverse effects on the placenta as well as on developmental outcomes, including embryonic resorption, fetal death, congenital teratogenesis, and fetal growth retardation. This work aimed to explore the adverse effects of LPS injected at an early stage of gestation on the gonads of pregnant rats and the ovaries of their pups and the role of zinc nanoparticles (Zn-NPs) against these adverse effects. Twenty-four pregnant rats were used in this study. They were divided at gestation day 4 into four groups (n = 6): control, Zn-NPs (20 mg/kg orally from gestation day E14 till the end of weaning), LPS (50 µg/kg at gestation days E7 and E9), and LPS + Zn-NPs group. The body weight and placenta weight were recorded at gestational day 16. At postnatal day 21 (weaning), the mothers rats and their offspring were sacrificed and immediately dissected to remove the ovaries and uteri from the mothers and the ovaries from their offspring for subsequent biochemical, histological, and immunohistochemical investigations. The obtained results revealed that LPS exposure during early gestation caused severe histopathological alterations in the placenta, uterus, and ovaries of mothers, as well as in the ovaries of their pups. Also, the uterine and ovarian sections displayed a positive reaction for caspase-3 antibody and a negative reaction for Bcl-2 antibody, which reflects the apoptotic effect of LPS. Additionally, remarkable reductions in the levels of antioxidants (superoxide dismutase and catalase) and significant increases in malondialdehyde (MDA) levels were recorded in the serum of LPS-treated mothers and in the ovarian tissues of their offspring. Further biochemical analysis of the ovarian tissues from LPS-maternally treated offspring showed a significant increase in the levels of caspase-3, TNF-α, and TGF-β1, but a significant decrease in the level of IGF-1. On the other hand, treatment of mothers with Zn-NPs from day 14 of gestation until the weaning day (21st day postnatal) successfully ameliorated most of the deleterious histopathological, immunohistochemical, and biochemical changes induced by LPS.Graphical abstract

Acute Physiological Effects of Drop Set on IGF and GH in the Quadriceps Femoris Among Males in Kakamega County, Kenya

Background: Resistance training (RT) for muscle growth (hypertrophy training – HT) theoretically optimizes the mechanical tension placed on the working muscle, which may be key to activating hypertrophic mechanisms. After prolonged HT, specialized weightlifting techniques like drop set training (DS) – or lifting progressively reduced loads without recovery – may help overcome plateaus in strength and re-stimulate hypertrophy, but physiological evidence to potentially support this hypothesis or the efficacy of implementing an acute drop set protocol in comparison to maintaining a standard hypertrophy training program is lacking. Objective: This objective of this study was to assess the levels of plasma growth hormone, and IGF during drop set and concentric exercises. Methods: The study used a randomized controlled, counterbalanced, repeated measures design. A repeated measures design was used to minimize the inter-individual variability of the hypertrophic response to resistance training. Thirty young males participated in a randomized, counterbalanced, within-subjects design, a DS protocol (4 sets, 4 loads/set, 75-30% 1RM, minimal recovery between loads, 3-minute recovery intervals between sets) and, separated by at least 7 days, a HT protocol (4 sets, 75% 1RM, 3-minute recovery intervals between sets). Data was analyzed using a 2 (Training Type: DS, HT, levels of quadriceps muscle hypertrophy) ´ 2 (Time: pre-exercise, post-exercise) repeated measures ANOVA to test the differences in concentrations of IGF-1 and GH during DS and HT at the specified time points. Results: The study found that there was a significant difference in IGF 1 levels before and after the exercise for both groups (Drop set and concentric exercise), with a p-value of .007. The interaction effect between the within-subjects factor (IGF 1 pre and post) and group was also significant. The results showed that there was a significant difference in GH levels before and after the exercise for both groups (Drop set and concentric exercise), with a p-value of &lt; .001. For the Drop set group, GH pre was also significantly lower than GH post. It can be concluded that both the drop set and concentric exercise techniques have an impact on the levels of IGF 1, and GH in the quadriceps femoris. The study recommends that physical trainers and fitness professionals should consider using the Drop set exercise technique in their training programs for clients who are looking to improve their performance.

Effects of dietary leucine on growth, antioxidant capacity, immune response, and inflammation in juvenile yellow catfish Pelteobagrus fulvidraco.

The experiment was conducted to investigate the effects of dietary leucine on growth, antioxidant capacity, immune response, and inflammation in juvenile yellow catfish. Five diets were formulated to contain five dietary leucine levels: 12.00 (control), 19.00, 26.00, 33.00, and 40.00gkg-1. Each diet was randomly assigned to triplicate groups of 30 juvenile fish (5.02 ± 0.15g) twice daily to apparent satiation for 56days. Weight gain rate, specific growth rate, and activities of liver superoxide dismutase, glutathione peroxidase, and serum lysozyme, as well as immunoglobulin M content, significantly increased with increase in dietary leucine levels up to 26.00gkg-1, but those values decreased significantly with a further increase in dietary leucine. On the contrary, the lowest malondialdehyde content was found in 26.00 and 33.00gkg-1 leucine groups. The expression levels of IGF 1 and MYF 5 genes in muscle were significantly upregulated with increase in dietary leucine levels up to 26.00gkg-1, but the expression of MSTN level showed the opposite trend. The lowest expression levels of IL 8 and TNFɑ genes in the liver were found in 26.00gkg-1 leucine groups. The quadratic regression analysis on weight gain, specific growth rate, and feed conversion ratio against dietary leucine levels indicated that the optimal dietary leucine requirement was estimated to be 26.84-27.00gkg-1of the dry diet.

Associations Between Insulin-Like Growth Factor-1 and Resting-State Functional Connectivity in Cognitively Unimpaired Midlife Adults.

Insulin-like growth factor (IGF)-1 plays an important role in Alzheimer's disease (AD) pathogenesis and increases disease risk. However, prior research examining IGF-1 levels and brain neural network activity is mixed. The present study investigated the relationship between IGF-1 levels and 21 neural networks, as measured by functional magnetic resonance imaging (fMRI) in 13,235 UK Biobank participants. Linear mixed models were used to regress IGF-1 against the intrinsic functional connectivity (i.e., degree of network activity) for each neural network. Interactions between IGF-1 and AD risk factors such as Apolipoprotein E4 (APOE4) genotype, sex, AD family history, and age were also tested. Higher IGF-1 was associated with more network activity in the right Executive Function neural network. IGF-1 interactions with APOE4 or sex implicated motor, primary/extrastriate visual, and executive function related neural networks. Neural network activity trends with increasing IGF-1 were different in different age groups. Higher IGF-1 levels relate to much more network activity in the Sensorimotor Network and Cerebellum Network in early-life participants (40-52 years old), compared with mid-life (52-59 years old) and late-life (59-70 years old) participants. These findings suggest that sex and APOE4 genotype may modify the relationship between IGF-1 and brain network activities related to visual, motor, and cognitive processing. Additionally, IGF-1 may have an age-dependent effect on neural network connectivity.

Cysteamine improves growth and the GH/IGF axis in gilthead sea bream (Sparus aurata): in vivo and in vitro approaches.

Aquaculture is the fastest-growing food production sector and nowadays provides more food than extractive fishing. Studies focused on the understanding of how teleost growth is regulated are essential to improve fish production. Cysteamine (CSH) is a novel feed additive that can improve growth through the modulation of the GH/IGF axis; however, the underlying mechanisms and the interaction between tissues are not well understood. This study aimed to investigate the effects of CSH inclusion in diets at 1.65 g/kg of feed for 9 weeks and 1.65 g/kg or 3.3 g/kg for 9 weeks more, on growth performance and the GH/IGF-1 axis in plasma, liver, stomach, and white muscle in gilthead sea bream (Sparus aurata) fingerlings (1.8 ± 0.03 g) and juveniles (14.46 ± 0.68 g). Additionally, the effects of CSH stimulation in primary cultured muscle cells for 4 days on cell viability and GH/IGF axis relative gene expression were evaluated. Results showed that CSH-1.65 improved growth performance by 16% and 26.7% after 9 and 18 weeks, respectively, while CSH-3.3 improved 32.3% after 18 weeks compared to control diet (0 g/kg). However, no significant differences were found between both experimental doses. CSH reduced the plasma levels of GH after 18 weeks and increased the IGF-1 ones after 9 and 18 weeks. Gene expression analysis revealed a significant upregulation of the ghr-1, different igf-1 splice variants, igf-2 and the downregulation of the igf-1ra and b, depending on the tissue and dose. Myocytes stimulated with 200 µM of CSH showed higher cell viability and mRNA levels of ghr1, igf-1b, igf-2 and igf-1rb compared to control (0 µM) in a similar way to white muscle. Overall, CSH improves growth and modulates the GH/IGF-1 axis in vivo and in vitro toward an anabolic status through different synergic ways, revealing CSH as a feasible candidate to be included in fish feed.

Can signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) be used as an indicator of endothelial dysfunction in acromegaly patients?

Acromegaly is closely related to increased oxidative stress and endothelial dysfunction (ED). This study aimed to evaluate, for the first time in the literature, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and endothelial nitric oxide synthase e(NOS) levels in the setting of acromegaly. A total of 56 acromegaly patients and a control group composed of 30 healthy volunteers were included in this study. In the postoperative follow-up, patients were grouped as active or in-remission according to their GH and IGF-1 levels in oral glucose stimulation test (OGST). After detailed physical examination of acromegaly patients and the control subjects, 8-hour fasting blood samples were collected to evaluate biochemical parameters including lipid profile, anterior pituitary hormones, and SCUBE-1 and e(NOS) levels. Inactive and active acromegaly was noted in 78.6% and 21.4% of patients, respectively. The median (min-max) SCUBE-1 levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (1.6(0.4-2.4) and 1.8(1.1-2.5) vs. 0.4(0.2-1.0) ng/mL, respectively, p < 0.001 for each). The median (min-max) e(NOS) levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (132.7 (26.8-602.9) and 137.3 (69.7-488.7) vs. 83.9 (16.4-218.7) pg/mL, p = 0.018 and p = 0.048, respectively). We have also detected positive correlations of e(NOS) with leukocyte (r = 0.307, p = 0.021) and neutrophil counts (r = 0.309, p = 0.021). Our study revealed for the first time in literature that SCUBE-1 levels, being a novel marker for ED, were significantly higher in acromegaly patients than in control subjects. When supported with clinical studies, SCUBE-1can be used as an early indicator of endothelial damage in acromegaly patients.

Insulin growth factor axis and cardio-renal risk in diabetic kidney disease: an analysis from the CREDENCE trial

BackgroundThe insulin-like growth factors (IGF) play a crucial role in regulating cellular proliferation, apoptosis, and key metabolic pathways. The ratio of IGF-1 to IGF binding protein-3 (IGFBP-3) is an important factor in determining IGF-1 bioactivity. We sought to investigate the association of IGF-1 and IGFBP-3 with cardio-renal outcomes among persons with type 2 diabetes.MethodsSamples were available from 2627 individuals with type 2 diabetes and chronic kidney disease that were randomized to receive canagliflozin or placebo and were followed up for incident cardio-renal events. Primary outcome was defined as a composite of end-stage kidney disease, doubling of the serum creatinine level, or renal/cardiovascular death. IGF-1 and IGFBP-3 were measured at baseline, Year-1 and Year-3. Elevated IGF-1 level was defined according to age-specific cutoffs. Cox proportional hazard regression was used to investigate the association between IGF-1 level, IGFBP-3, and the ratio of IGF-1/IGFBP-3 with clinical outcomes.ResultsElevated IGF-1 was associated with lower glomerular filtration rate at baseline. Treatment with canagliflozin did not significantly change IGF-1 and IGFBP-3 concentrations by 3 years (p-value > 0.05). In multivariable models, elevated IGF-1 (above vs below age-specific cutoffs) was associated with the primary composite outcome (incidence rate:17.8% vs. 12.7% with a hazard ratio [HR]: 1.52; 95% confidence interval CI 1.09–2.13;P: 0.01), renal composite outcome (HR: 1.65; 95% CI 1.14–2.41; P: 0.01), and all-cause mortality (HR: 1.52; 95% CI 1.00–2.32; P; 0.05). Elevations in log IGFBP-3 did not associate with any clinical outcomes. Increase in log IGF-1/IGFBP-3 ratio was also associated with a higher risk of the primary composite outcome (HR per unit increase: 1.57; 95% CI 1.09–2.26; P; 0.01).ConclusionsThese results further suggest potential importance of IGF biology in the risk for cardio-renal outcomes in type 2 diabetes. SGLT2 inhibition has no impact on the biology of IGF despite its significant influence on outcomes.Trial registration: CREDENCE; ClinicalTrials.gov Identifier: NCT02065791.

Effects of six weeks of aerobic training on the protein levels of Aβ-40 and IGF-1 in the hippocampus of diabetic rats

Background: Functional disorder of the nervous system is one of the consequences of type 2 diabetes. Aβ-40 and IGF-1 are probably involved in this mechanism. Therefore, the present study aimed to investigate the effect of aerobic training on Aβ-40 and IGF-1 proteins in the hippocampus of rats with type 2 diabetes. Materials and Methods: A total of 32 8-week-old male Wistar rats were placed in 4 groups: control (C), diabetes (D), diabetes training (DT), and training (T). Diabetes was induced by streptozotocin injection. The training was performed for six weeks. To measure proteins, the ELISA method was used, and a one-way ANOVA test was used for data analysis. Results: The amount of Aβ-40 in group D was different from that of DT, T, and C groups (P&lt;.05). The DT group displayed a significant difference from the C and T groups (P&lt;.05). Aβ-40 levels were not different between T and C groups (P=0.604). The amount of IGF-1 in the D group was lower compared to all groups (P=0.001). Nonetheless, the DT group had no difference from the C and T groups (P&gt;.05). The amount of IGF-1 in the T group was different only from the D group (P=0.001). The positive (Aβ-40) and negative (IGF-1) correlations were observed with blood glucose (P=0.001, r=0.850 and P=0.001, r=-0.814). Conclusion: Diabetes increases Aβ-40 and decreases IGF-1. Nevertheless, exercise moderates the effect of diabetes on them. Considering the appropriate duration of exercise and the correlation of these proteins with blood glucose, an increase in the intensity of aerobic training may further regulate the negative effect of diabetes on these two proteins.