Differences In Insulin-like Growth Factor-1 Levels Research Articles

Association between serum insulin-like growth factor 1 levels and the improvements of cognitive impairments in a subgroup of schizophrenia: Preliminary findings

BackgroundNumerous studies have implicated abnormal insulin-like growth factor 1 (IGF-1) in the pathophysiology of schizophrenia, but findings have been inconsistent. MethodsWe conducted a meta-analysis to compare IGF-1 levels in schizophrenia patients with healthy controls and explored factors contributing to variability between estimates. In an independent sample (58 chronic schizophrenia patients and 30 healthy controls), we investigated differences in IGF-1 levels among schizophrenia subgroups with distinct cognitive profiles, identified using k-means clustering based on five cognitive domains from The Repeatable Battery for the Assessment of Neuropsychological Status. Associations between serum IGF-1 levels and clinical and neurocognitive improvements were also examined. ResultsThe meta-analysis revealed significantly lower serum IGF-1 levels in schizophrenia patients compared to healthy controls, albeit with high heterogeneity. Medication status, BMI, and severity of negative symptoms were identified as potential contributors to this heterogeneity. In our independent study, antipsychotic treatment led to a significant increase in IGF-1 levels, and lower pre-treatment serum IGF-1 levels correlated with greater improvement in cognitive deficits, particularly in a subgroup with more severe cognitive symptoms. ConclusionsOur findings support the “IGF-1 deficiency hypothesis” in the pathogenesis of schizophrenia. Further research is crucial to elucidate the role of IGF-1 in the cognitive impairments associated with schizophrenia.

The Role of Insulin-Like Growth Factor 1 in Delirium: A Systematic Review and Meta-Analysis

Background: The relationship between delirium and low levels of insulin-like growth factor 1 (IGF-1) is contradictory and uncertain. We hypothesised that low levels of IGF-1 are a predisposing factor for delirium in medical and abdominal surgical cohorts, in contrast to other surgical cohorts. Aims: Systematic review and meta-analysis investigating the association between peripheral levels of IGF-1 and delirium in medical and surgical patients to explore if there are distinct patterns of associations by using subgroup meta-analysis. Methods: PubMed, Scopus, CINAHL, Cochrane, and Embase databases were searched. Inclusion criteria were prospective studies in medical and surgical populations and available data. The following were collected: the setting (surgical/medical), the type (orthopaedic surgery, abdominal, cardiovascular, or medical), the number of participants, mean age, the number of delirious patients, scale/criteria for delirium, IGF-1 levels, and MMSE. Results: Thirteen studies were included and analysed. Low levels of IGF-1 are significantly associated with delirium in abdominal surgical samples and medical samples but not in the other surgical samples. Age, cognition, and the setting (medical vs. surgical) do not have any significant effect on the differences in IGF-1 levels between those with and without delirium. Discussion: Delirium in acute medical and abdominal surgery is triggered by low IGF-1 which may reflect chronic conditions like frailty/cachexia/sarcopenia, while in other surgeries perhaps from an inflammatory process. Conclusions: Low peripheral levels of IGF-1 are a predisposing factor for delirium only in acute medical and abdominal surgery. More studies are needed to confirm and to explore further this finding.

CALORIC RESTRICTION INCREASES OVARIAN FOXO3A EXPRESSION IN A MOUSE MODEL OF DELAYED AGING: IMPLICATIONS FOR REPRODUCTIVE LONGEVITY

Ovarian hormonal and reproductive function are dependent on the primordial follicle pool. The exit of follicles from the primordial follicle pool is the critical event that depletes the ovarian reserve; therefore, an understanding of the mechanisms that regulate the primordial pool is critical for the development of interventions to prolong the reproductive lifespan. Moderate caloric restriction (CR) without malnutrition has been shown to increase ovarian reserve and prolong the reproductive lifespan in mouse models; however, the mechanism by which it does so remains under investigation. The aim of this study was to evaluate the nutritional triggers, specifically the contribution of amino acid composition during CR, as well as the molecular mechanisms, by which CR impacts ovarian reserve during physiologic aging in mice. Twenty-six 9-month-old female C57BL/6 mice were divided into 4 groups: (1) ad libitum feeding, (2) 40% caloric restriction (CR), (3) 40% CR + non-essential glycine amino acid supplementation (CR + Gly), and (4) 40% CR + sulfur amino acid supplementation (CR + SAA). CR was continued for 12 weeks. Following CR, the ovarian reserve was quantified. Formalin-fixed ovaries were sectioned and stained with hematoxylin and eosin for primordial follicle counts. Quantitative polymerase chain reaction (qPCR) was used to quantify levels of ovarian expression of forkhead box protein O3A (FOXO3A), an important suppressor of follicular activation, growth hormone receptor (GHR), and insulin-like growth factor-1 (IGF-1). Primordial follicle counts increased in the 40% CR (53 vs 41, p = 0.7) and CR + Gly supplementation groups (82 vs 41, p = 0.029) compared to the ad-lib fed group. There was no increase in primordial follicles in the CR + SAA group (44 vs 41, p = 0.99). The relative expression of FOXO3A was increased by 10-fold in the CR group (p = 0.3) and 20-fold in the CR + Gly group compared to the ad lib group (p = 0.016). There was no increase in FOXO3A expression in the CR + SAA group. Relative GHR expression was decreased 4-fold in the CR + Gly compared to the ad-lib-fed animals (p = 0.07). There was no difference in IGF-1 levels between the CR + Gly group and controls; however, levels of IGF-1 in the CR + SAA group increased dramatically by 100-fold (p = 0.001). CR (40%) with Gly supplementation significantly increases ovarian reserve in a mouse model of physiologic aging. The improvement in ovarian reserve appears to be mediated by an increase in the expression of FOXO3A, an important suppressor of follicular activation. Consistent with observations that GHR knockout mice have a larger ovarian reserve, the CR + Gly group also showed a decrease in GHR expression.

The alteration of IGF-1 levels and relationship between IGF-1 levels and growth velocity during GnRH analogue therapy

Background Some studies have examined the effect of gonadal suppression on insulin-like growth factor-1 (IGF-1) levels and the growth velocity (GV) with conflicting results. Methods Forty-four girls treated with gonadotropin-releasing hormone analogue (GnRHa) for central precocious puberty (CPP) were included in the study. IGF-1 levels were examined at the beginning and after 12 months of treatment. Results IGF-1 and IGF-1 standard deviation score (SDS) according to chronological age (CA-IGF-1 SDS) at diagnosis were positively correlated with chronological age (CA), anthropometric measurements, stage of puberty, bone age (BA), BA-CA, follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, uterus length, endometrium thickness and ovarian volume (OV) at diagnosis (p < 0.05). There was no significant difference in IGF-1 levels after treatment. However, there was a negative correlation between ΔIGF-1 SDS and IGF-1 level, CA-IGF-1 SDS and BA-IGF-1 SDS at diagnosis (p < 0.05). There was no correlation between GV and IGF-1, ΔIGF-1. GV was negatively correlated with basal LH level at diagnosis (p = 0.008, r = -0.397). Peak LH levels of the patients who had GV-SDS < 0 were more suppressive than those of the patients who had GV-SDS > 0 after 12 months of treatment. Conclusions It was determined that the IGF-1 level and CA-IGF-1 SDS at baseline were correlated with more advanced pubertal stage prior to treatment. Initiation of treatment with a relatively high level of IGF-1 increased the risk of a decrease in the IGF-1 level. Likewise, the initiation of treatment with a relatively high LH level may increase the risk of low GV, but low GV was not related to the IGF-1 level. Increased sex steroid suppression may increase the risk of low GV.

Selective Insulin-like Growth Factor Resistance Associated with Heart Hemorrhages and Poor Prognosis in a Novel Preclinical Model of the Hematopoietic Acute Radiation Syndrome.

Although bone marrow aplasia has been considered for the past decades as the major contributor of radiation-induced blood disorders, cytopenias alone are insufficient to explain differences in the prevalence of bleeding. In this study, the minipig was used as a novel preclinical model of hematopoietic acute radiation syndrome to assess if factors other than platelet counts correlated with bleeding and survival. We sought to determine whether radiation affected the insulin-like growth factor-1 (IGF-1) pathway, a growth hormone with cardiovascular and radioprotective features. Gottingen and Sinclair minipigs were exposed to ionizing radiation at hematopoietic doses. The smaller Gottingen minipig strain was more sensitive to radiation; differences in IGF-1 levels were minimal, suggesting that increased sensitivity could depend on weak response to the hormone. Radiation caused IGF-1 selective resistance by inhibiting the anti-inflammatory anti-oxidative stress IRS/PI3K/Akt but not the pro-inflammatory MAPK kinase pathway, shifting IGF-1 signaling towards a pro-oxidant, pro-inflammatory environment. Selective IGF-1 resistance associated with hemorrhages in the heart, poor prognosis, increase in C-reactive protein and NADPH oxidase 2, uncoupling of endothelial nitric oxide synthase, inhibition of nitric oxide (NO) synthesis and imbalance between the vasodilator NO and the vasoconstrictor endothelin-1 molecules. Selective IGF-1 resistance is a novel mechanism of radiation injury, associated with a vicious cycle amplifying reactive oxygen species-induced damage, inflammation and endothelial dysfunction. In the presence of thrombocytopenia, selective inhibition of IGF-1 cardioprotective function may contribute to the development of hemostatic disorders. This finding may be particularly relevant for individuals with low IGF-1 activity, such as the elderly or those with cardiometabolic dysfunctions.

Reduced utility of serum IGF-1 levels in predicting retinopathy of prematurity reflects maternal ethnicity

AimsTo validate known risk factors and identify a threshold level for serum insulin-like growth factor 1 (IGF-1) in the development of severe retinopathy of prematurity (ROP) in an ethnically diverse...

P129 – 2792: Level of insulin-like growth factor-1 (IGF-1) on full term infant following massage stimulation

Objective To determine if effect of massage stimulation increase insulin-like growth factor-1 (IGF-1) on full term infant. Methods Experimental study, randomized control trial, conducted at the Teaching Hospital in Central Java Indonesia. Forty infants aged 1 month were divided into 2 groups of study, control group (20 subject) and massage group (20 subject). IGF-1 levels were the serum collected on Days 1 and 30, were analyzed by ELISA. Paired T test was used to analyze differences in the levels of IGF-1 before and after the study. Independent test T test was used to analyze differences in IGF-1 levels between the 2 groups. Levels of IGF-1 were analyzed further using the ROC to determine the optimal cut off point. Results Levels of IGF-1 in control group increased 20.90±8.25 ng/ml. In the massage group level of IGF-1 increased 52.87±26.04 ng/ml. There are significant differences in the levels of IGF-1 in both groups before and after the study (p Conclusion Massage stimulation in full term infant showed significant differences in the levels of IGF-1 during 30-day.

Expression of estrogen receptors in non-malignant mammary tissue modifies the association between insulin-like growth factor 1 and breast cancer risk

Several studies have reported that the insulin-like growth factor 1 (IGF-1) is positively associated with estrogen receptor-positive [ER(+)] breast cancer risk, whereas there is little or no association with respect to ER(-) breast cancer. All comparisons of ER(+) breast cancer cases, however, have been made versus healthy controls, for whom there is no information about the ER expression in their mammary gland. In the context of a case-control investigation conducted in Athens, Greece, we studied 102 women with incident ERα(+) breast cancer and compared their IGF-1 blood levels with those of 178 ERα(+) and 83 ERα(-) women with benign breast disease (BBD) who underwent biopsies in the context of their standard medical care. Data were analysed using multiple logistic regression and controlling for potential confounding variables. ERα(+) breast cancer patients had higher IGF-1 levels compared with women with BBD [odds ratio (OR) 1.36, 95% confidence interval (CI): 0.95-1.94, per 1 standard deviation (SD) increase in IGF-1 levels]. When ERα status of women with BBD was taken into account, the difference in IGF-1 levels between ERα(+) breast cancer patients and women with BBD was clearly driven by the comparison with BBD women who were ERα(+) (OR = 1.95, 95% CI: 1.31-2.89 per 1 SD increase in IGF-1 levels), whereas there was essentially no association with IGF-1 levels when ERα(+) breast cancer patients were compared with ERα(-) BBD women. These contrasts were particularly evident among post/peri-menopausal women. We found evidence in support of an interaction of IGF-1 with the expression of ERα in the non-malignant mammary tissue in the context of breast cancer pathogenesis. This is in line with previous evidence suggesting that IGF-1 increases the risk of ER(+) breast cancer.

Relationships between IGF-1, schizophrenia, and treatment of metabolic syndrome

ObjectivesThe use of atypical antipsychotic drugs in patients with psychiatric illness may result in dyslipidemia, hypertension, glucose intolerance, and abdominal obesity, which are together referred to as metabolic syndrome (MS). To investigate any correlations among insulin-like growth factor-1 (IGF-1), schizophrenia, and MS, we examined the metabolic profiles of patients with schizophrenia taking atypical antipsychotics. DesignPatients with schizophrenia, their siblings, and controls participated in this study (N=50 in each group). The Structured Clinical Interview for DSM-IV Axis 1 Disorders (SCID I) and the Brief Psychiatric Rating Scale (BPRS) were administered to patients, and SCID I was administered to patients' siblings. We drew blood to measure IGF-1 levels and to determine the metabolic profiles of all participants; we also conducted anthropometric measurements. ResultsThere were no significant differences in IGF-1 levels between groups. By comparing IGF-1 levels with MS-related parameters, we found that IGF-1 levels were negatively correlated with triglyceride levels in the control group, and positively correlated with HDL levels in the patient group (Pearson's correlation: r=−0.291, P=0.04, and r=0.328, P=0.02, respectively). Compared to their siblings, patients with schizophrenia had a significantly different body mass index, waist circumference, and insulin resistance, and showed a trend toward a difference in glucose levels (ANOVA: P=0.004, P<0.0001, P=0.004, P=0.072, respectively). ConclusionA correlation between IGF-1 and MS may significantly influence future therapeutic strategies for MS. In order to determine the role of IGF-1 in schizophrenia, comprehensive longitudinal studies with first-episode drug-naive patients are needed.

Effects of acute stress on osmoregulation, feed intake, IGF-1, and cortisol in yearling steelhead trout ( Oncorhynchus mykiss) during seawater adaptation

Juvenile steelhead ( Oncorhynchus mykiss) acclimated to freshwater (FW) were subjected for 3 h to confinement stress in FW, and subsequently saltwater (SW, 25 ppt) was introduced to all tanks. Fish were sampled immediately after the stress treatment, and 1, 7, and 14 days after introduction of SW. Electrolytes, cortisol, glucose, and lactate showed the typical stress response expected after stress treatment in FW. Fish regained osmotic balance within 24 h. Glucose concentrations were increasing throughout the experiment and lactate levels stayed elevated during the time spent in SW. Insulin-like growth factor-1 (IGF-1) did not show an immediate response to stress but after transfer to SW we detected significantly higher concentrations for control fish at days 1 and 14. The differences in IGF-1 levels between stressed and control fish are not reflected in SW adaptability but positive correlations between IGF-1 and electrolyte levels in control fish may indicate its role for osmoregulation. Confinement stress did not impair feed intake subsequently in SW, but our results suggest that feed intake was suppressed by the change of the media from FW to SW.

Changes in Serum Concentrations of Insulin-like Growth Factor-1 (IGF-1) during Different Methods of General Anesthesia

Background: IGFs (insulin-like growth factors) exert acute anabolic effects on protein and carbohydrate metabolism, and have a long-term impact on cell proliferation, differentiation, and apoptosis. The purpose of this study was to evaluate whether serum levels of IGF-1 were affected by the general anesthetics. Methods: Twenty patients, scheduled for a total abdominal hysterectomy were given either propofol (n = 10) or isoflurane (n = 10) general anesthesia. All patients were treated in a standardized manner in regard to surgical technique. Blood samples were taken before induction and at the time of peritoneal closure, postoperative 1 hour, and on postoperative days 2 and 5. Serum concentrations of IGF-1 were determined using an immunoradiometric assay. Results: IGF-1 levels decreased from the value before induction by 17.1% during surgery and 37.5% by day 5 in the propofol group. IGF-1 levels fell by 18.7% during surgery and returned to the preinduction level on day 5 after surgery in the isoflurane group. There were no differences in IGF-1 levels between the two groups with different methods of anesthesia. Conclusions: Our study suggests that general anesthesia with isoflurane is associated with a less effect in serum IGF-1 level than propofol. However, further experimental and clinical studies are needed to establish the definitive effect of general anesthetics on IGF.

Serum insulin-like growth factor-1 is not a useful marker of prostate cancer.

To determine whether the use of serum insulin-like growth factor 1 (IGF-1) levels is more efficient than serum prostate specific antigen (PSA) levels in predicting prostate cancer in patients undergoing prostatic biopsy. The study included 94 consecutive patients who required transrectal ultrasonography (TRUS)-guided biopsies of their prostate and who had blood samples taken before their biopsies. These samples were then analysed for IGF-1 and PSA concentrations. Six prostatic biopsies were taken from each patient; they were assessed and a diagnosis made of prostate cancer or no malignancy. Thirty-seven patients were found to have prostate cancer and 57 had no evidence of malignancy. There was no statistical difference in serum IGF-1 levels between these groups. The PSA level and age of the patients differed significantly between the groups (both P<0.001). There was no correlation between IGF-1 and PSA levels, and even when the age difference in the groups was considered, there was still no significant relationship between IGF-1 levels and the incidence of prostate cancer. In patients with a PSA level of 4-20 microg/L there was no statistically significant difference in IGF-1 levels between the groups. Serum IGF-1 as a tumour marker does not help to predict patients with prostate cancer. PSA level and even age were better predictors of the presence of prostate cancer than were serum IGF-1 levels.

INSULIN‐LIKE GROWTH FACTOR 1 AND BONE TURNOVER IN GLUCOCORTICOID‐TREATED AND CONTROL SUBJECTS

The role of the growth hormone-somatomedin axis in the genesis of steroid osteoporosis has been studied by measuring circulating insulin-like growth factor 1 (IGF-1) levels in asthmatic subjects either receiving or not receiving therapy with oral glucocorticoids. There was no difference in IGF-1 levels between the two groups (60.6 micrograms/l (95% confidence interval 47.3-77.8) in the control subjects vs 69.1 micrograms/l (49.3-96.9) in the steroid-treated group). IGF-1 declined with age in the control subjects but not in those taking steroids. When IGF-1 levels were correlated with biochemical indices of bone turnover, a significant relationship was found with urine hydroxyproline in the control subjects (r = 0.55, P less than 0.02) but not in those taking steroids. It is concluded that glucocorticoid therapy does not alter mean circulating levels of IGF-1 but that the growth hormone-somatomedin axis may influence bone turnover in normal subjects. Interference by glucocorticoids with the normal regulation of IGF-1 and its influence on bone turnover is suggested.