Serum IGF-I Research Articles

Association of GDF15 levels with body mass index and endocrine status in β-thalassaemia.

GDF15 has emerged as a stress-induced hormone, acting on the brain to reduce food intake and body weight while affecting neuroendocrine function. Very high GDF15 levels are found in thalassaemia, where growth, energy balance and neuroendocrine function are impaired. We examined the relationships between GDF15 and anthropometric measures and endocrine status in β-thalassaemia. Cross sectional study. All β-thalassaemia patients attending the thalassaemia unit of Colombo North Teaching Hospital for blood transfusions. Anthropometric data, appetite scores, circulating GDF15, IGF, thyroid and reproductive hormone levels in 103 β-thalassaemia patients were obtained. GDF15 levels were markedly elevated in thalassaemia patients (24.2-fold with β-thalassaemia major compared with healthy controls). Among patients with β-thalassaemia major, the relationship between GDF15 and body mass index (BMI) was curvilinear with all individuals with GDF15 levels above 24,000 pg/mL having a BMI below 20 kg/m2 . After adjustment for BMI, age and Tanner stage, serum IGF1 concentrations correlated negatively with GDF15 in all thalassaemia patients (β = -.027, p = .02). We found a significant positive relationship between GDF15 and gonadotropin (in both sexes) and testosterone (in males). GDF15 levels were markedly elevated in patients with β-thalassaemia and its association with BMI is consistent with the known effect of GDF15 to reduce body weight. The inverse association between GDF15 with IGF1 levels may reflect a neuroendocrine impact of GDF15 or an indirect effect via impaired nutritional state. The positive association with testosterone in males and gonadotropins in both sexes, was surprising and should prompt further GDF15 studies on the hypothalamic pituitary gonadal axis.

Rumen-Protected Lysine and Methionine Supplementation Reduced Protein Requirement of Holstein Bulls by Altering Nitrogen Metabolism in Liver.

The aim of this study was to investigate the effect of low-protein diets supplemented with rumen-protected lysine (RPLys) and methionine (RPMet) on growth performance, rumen fermentation, blood biochemical parameters, nitrogen metabolism, and gene expression related to N metabolism in the liver of Holstein bulls. Thirty-six healthy and disease-free Holstein bulls with a similar body weight (BW) (424 ± 15 kg, 13 months old) were selected. According to their BW, they were randomly divided into three groups with 12 bulls in each group in a completely randomized design. The control group (D1) was fed with a high-protein basal diet (CP13%), while bulls in two low-protein groups were supplied a diet with 11% crude protein and RPLys 34 g/d·head + RPMet 2 g/d·head (low protein with low RPAA, T2) or RPLys 55 g/d·head + RPMet 9 g/d·head (low protein with high RPAA, T3). At the end of the experiment, the feces and urine of dairy bulls were collected for three consecutive days. Blood and rumen fluid were collected before morning feeding, and liver samples were collected after slaughtering. The results showed that the average daily gain (ADG) of bulls in the T3 group was higher than those in D1 (p < 0.05). Compared with D1, a significantly higher nitrogen utilization rate (p < 0.05) and serum IGF-1 content (p < 0.05) were observed in both T2 and T3 groups; however, blood urea nitrogen (BUN) content was significantly lower in the T2 and T3 groups (p < 0.05). The content of acetic acid in the rumen of the T3 group was significantly higher than that of the D1 group. No significant differences were observed among the different groups (p > 0.05) in relation to the alpha diversity. Compared with D1, the relative abundance of Christensenellaceae_R-7_group in T3 was higher (p < 0.05), while that of Prevotellaceae _YAB2003_group and Succinivibrio were lower (p < 0.05). Compared with D1 and T2 group, the T3 group showed an expression of messenger ribonucleic acid (mRNA) that is associated with (CPS-1, ASS1, OTC, ARG) and (N-AGS, S6K1, eIF4B, mTORC1) in liver; moreover, the T3 group was significantly enhanced (p < 0.05). Overall, our results indicated that low dietary protein (11%) levels added with RPAA (RPLys 55 g/d +RPMet 9 g/d) can benefit the growth performance of Holstein bulls by reducing nitrogen excretion and enhancing nitrogen efficiency in the liver.

Correlation of serum IGF-1, AGEs and their receptors with the risk of colorectal cancer in patients with type 2 diabetes mellitus.

According to epidemiological evidence, people with type 2 diabetes mellitus have a higher risk of developing colorectal cancer. To examine the relationship between colorectal cancer (CRC) and serum levels of IGF-1, IGF-1R, AGEs,RAGE and sRAGE in patients with type 2 diabetes. By using RNA-Seq data of CRC patients from The Cancer Genome Atlas (TCGA) database, we divided the patients into normal group(58 patients)and tumor group(446 patients), and analyzed the expression and prognostic value analysis of IGF-1,IGF1R and RAGE. Cox regression and the Kaplan-Meier method were used to determine the predictive value of target gene on clinical outcomes in CRC patients. In order to further combine CRC with diabetes research,one hundred forty-eight patients hospitalized in the Second Hospital of Harbin Medical University from July 2021 to July 2022 were enrolled and divided into CA and control groups. There were 106 patients in the CA group, including 75 patients with CRC and 31 patients with CRC+T2DM; the control group comprised 42 patients with T2DM. Circulating levels of IGF-1, IGF-1R, AGEs, RAGE, and sRAGE in the serum of the patients were measured using Enzyme-Linked Immunosorbnent Assay(ELISA) kits, and other clinical parameters were also measured during hospitalization. Statistical methods used were χ² test, independent samples t-test and Pearson correlation analysis were. Finally, we controlled for confounding factors and used logistic multi-factor regression analysis. Bioinformatics analysis showed that IGF-1, IGF1R and RAGE were highly expressed in CRC patients, and the patients with high expression also showed significantly lower overall survival rate. Through Cox regression analysis, IGF-1 can be used as an independent influencing factor of CRC. In the ELISA experiment, serum AGE, RAGE, IGF-1, and IGF-1R levels were higher in the CRC and CRC+T2DM groups than in the T2DM group, but the serum sRAGE concentrations in these groups were lower than those in the T2DM group (P < 0.05). Serum AGE, RAGE, sRAGE, IGF1, and IGF1R levels were higher in the CRC+T2DM group than in the CRC group (P < 0.05). In CRC+T2DM patients, serum AGEs were correlated with age (p = 0.027), and the serum AGE levels in these groups were positively correlated with RAGE and IGF-1 levels (p < 0.001) and negatively correlated with sRAGE and IGF-1R levels (p < 0.001). After correcting for confounding factors based on logistic multiple regression analysis, the effects of age, serum IGF-1 and IGF-1R on the development of CRC in patients with T2DM were statistically significant (p<0.05). Serum IGF-1 and IGF-1R levels independently influenced the development of CRC in patients with T2DM. Furthermore, IGF-1 and IGF-1R were correlated with AGEs in CRC patients who also had T2DM, suggesting that AGEs may influence the development of CRC in T2DM patients. These findings suggest that we may be able to lower the risk of CRC in the clinic by regulating AGEs through the regulation of blood glucose levels, which will affect IGF-1 and its receptors.

Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.

Outcomes of Management of Pituitary Adenoma by Use of Octreotide Injections Preoperatively

Objective: This study explored the effects of octreotide injections in patients with pituitary adenoma pre-operatively.&#x0D; Material and Methods: A quasi-observational study was conducted on 12 patients in the Neurosurgery department of the Punjab Institute of Neurosciences (PINS) with a diagnosis of pituitary adenoma. To determine the size of the tumor, we did an MRI brain with pituitary protocol and after octreotide medication. The mode of diagnosis was clinical status, MRI brain, and biopsy of the tumor. We gave 14 short-acting octreotide injections to all patients before surgery and monitored their clinical and serum IGF levels. After the completion of 14 injections of octreotide, we planned surgery for the complete excision of the tumor. We performed IGF level 2 weeks after surgery. Then, we gave long-acting octreotide injections to all patients after every 28 days.&#x0D; Results: The mean age was 43 years. 67% of patients were male and 33% of patients were female. 92% of patients presented with decreased vision. 17% of patients presented to us with complete loss of vision. In 17% of patients, the vision of the patients improved. Serum IGF levels significantly decreased after short-acting octreotide, surgical excision, and long-acting octreotide therapy.&#x0D; Conclusion: With the use of octreotide therapy clinical status and outcomes of management of pituitary adenoma improve.

Emerging Role of IGF-1 in Prostate Cancer: A Promising Biomarker and Therapeutic Target.

Prostate cancer (PCa) is a highly heterogeneous disease driven by gene alterations and microenvironmental influences. Not only enhanced serum IGF-1 but also the activation of IGF-1R and its downstream signaling components has been increasingly recognized to have a vital driving role in the development of PCa. A better understanding of IGF-1/IGF-1R activity and regulation has therefore emerged as an important subject of PCa research. IGF-1/IGF-1R signaling affects diverse biological processes in cancer cells, including promoting survival and renewal, inducing migration and spread, and promoting resistance to radiation and castration. Consequently, inhibitory reagents targeting IGF-1/IGF-1R have been developed to limit cancer development. Multiple agents targeting IGF-1/IGF-1R signaling have shown effects against tumor growth in tumor xenograft models, but further verification of their effectiveness in PCa patients in clinical trials is still needed. Combining androgen deprivation therapy or cytotoxic chemotherapeutics with IGF-1R antagonists based on reliable predictive biomarkers and developing and applying novel agents may provide more desirable outcomes. This review will summarize the contribution of IGF-1 signaling to the development of PCa and highlight the relevance of this signaling axis in potential strategies for cancer therapy.

Disturbance of suprachiasmatic nucleus function improves cardiac repair after myocardial infarction by IGF2-mediated macrophage transition.

Suprachiasmatic nucleus (SCN) in mammals functions as the master circadian pacemaker that coordinates temporal organization of physiological processes with the environmental light/dark cycles. But the causative links between SCN and cardiovascular diseases, specifically the reparative responses after myocardial infarction (MI), remain largely unknown. In this study we disrupted mouse SCN function to investigate the role of SCN in cardiac dysfunction post-MI. Bilateral ablation of the SCN (SCNx) was generated in mice by electrical lesion; myocardial infarction was induced via ligation of the mid-left anterior descending artery (LAD); cardiac function was assessed using echocardiography. We showed that SCN ablation significantly alleviated MI-induced cardiac dysfunction and cardiac fibrosis, and promoted angiogenesis. RNA sequencing revealed differentially expressed genes in the heart of SCNx mice from D0 to D3 post-MI, which were functionally associated with the inflammatory response and cytokine-cytokine receptor interaction. Notably, the expression levels of insulin-like growth factor 2 (Igf2) in the heart and serum IGF2 concentration were significantly elevated in SCNx mice on D3 post-MI. Stimulation of murine peritoneal macrophages in vitro with serum isolated from SCNx mice on D3 post-MI accelerated the transition of anti-inflammatory macrophages, while antibody-mediated neutralization of IGF2 receptor blocked the macrophage transition toward the anti-inflammatory phenotype in vitro as well as the corresponding cardioprotective effects observed in SCNx mice post-MI. In addition, disruption of mouse SCN function by exposure to a desynchronizing condition (constant light) caused similar protective effects accompanied by elevated IGF2 expression on D3 post-MI. Finally, mice deficient in the circadian core clock genes (Ckm-cre; Bmal1f/f mice or Per1/2 double knockout) did not lead to increased serum IGF2 concentration and showed no protective roles inpost-MI, suggesting that the cardioprotective effect observed in this study was mediated particularly by the SCN itself, but not by self-sustained molecular clock. Together, we demonstrate that inhibition of SCN function promotes Igf2 expression, which leads to macrophage transition and improves cardiac repair post-MI.

MRL/MpJ Mice Resist to Age-Related and Long-Term Ovariectomy-Induced Bone Loss: Implications for Bone Regeneration and Repair.

Osteoporosis and age-related bone loss increase bone fracture risk and impair bone healing. The need for identifying new factors to prevent or treat bone loss is critical. Previously, we reported that young MRL/MpJ mice have superior bone microarchitecture and biomechanical properties as compared to wild-type (WT) mice. In this study, MRL/MpJ mice were tested for resistance to age-related and long-term ovariectomy-induced bone loss to uncover potential beneficial factors for bone regeneration and repair. Bone tissues collected from 14-month-old MRL/MpJ and C57BL/6J (WT) mice were analyzed using micro-CT, histology, and immunohistochemistry, and serum protein markers were characterized using ELISAs or multiplex assays. Furthermore, 4-month-old MRL/MpJ and WT mice were subjected to ovariectomy (OV) or sham surgery and bone loss was monitored continuously using micro-CT at 1, 2, 4, and 6 months (M) after surgery with histology and immunohistochemistry performed at 6 M post-surgery. Sera were collected for biomarker detection using ELISA and multiplex assays at 6 M after surgery. Our results indicated that MRL/MpJ mice maintained better bone microarchitecture and higher bone mass than WT mice during aging and long-term ovariectomy. This resistance of bone loss observed in MRL/MpJ mice correlated with the maintenance of higher OSX+ osteoprogenitor cell pools, higher activation of the pSMAD5 signaling pathway, more PCNA+ cells, and a lower number of osteoclasts. Systemically, lower serum RANKL and DKK1 with higher serum IGF1 and OPG in MRL/MpJ mice relative to WT mice may also contribute to the maintenance of higher bone microarchitecture during aging and less severe bone loss after long-term ovariectomy. These findings may be used to develop therapeutic approaches to maintain bone mass and improve bone regeneration and repair due to injury, disease, and aging.

Mechanism of autophagy mediated by IGF-1 signaling pathway in the neurotoxicity of lead in pubertal rats

Lead can damage neuron synapses in the hippocampus and cause synaptic plasticity losses, and learning, memory, and intelligence impairments. Previous studies have focused on the functional and structural plasticity of hippocampal synapses; however, the specific molecular mechanisms behind such impairments are not fully understood. This study aimed to elucidate the molecular mechanisms of cognitive impairment in rats following chronic lead exposure and mitigate or prevent lead toxicity in the central nervous system. We found that lead exposure caused significant damage to rat nervous systems, that is, compared with the control group, the lead treatment group had more autophagosomes in their hippocampal neurons; lower serum and hippocampal IGF-1 levels; lower hippocampal IGF-1, IGF-1R, PI3K, Akt, and mTOR gene expression; and upregulated hippocampal autophagy-associated proteins levels. Brain stereotactic technology was used to conduct autophagy inhibitor in vivo intervention experiments, and the results of these experiments suggest that the autophagy inhibitor DC661 inhibited lead-exposure-induced autophagy and autophagy-related gene expression in the rat hippocampus, possibly through activation of the IGF-1 pathway. Overall, our findings suggest that lead might activate hippocampal autophagy through the IGF-1/PI3K/Akt/mTOR signaling pathway. Therefore, this study provides a novel molecular mechanism underlying developmental toxicity in pubertal rats induced by lead exposure and provides a new target for anticipation and reversal of such neurotoxicity.

Dietary Intake, Serum Hormone Concentrations, Amenorrhea and Bone Mineral Density of Physique Athletes and Active Gym Enthusiasts.

As the diet, hormones, amenorrhea, and bone mineral density (BMD) of physique athletes (PA) and gym enthusiasts (GE) are little-explored, we studied those in 69 females (50 PA, 19 GE) and 20 males (11 PA, 9 GE). Energy availability (EA, kcal·kgFFM−1·d−1 in DXA) in female and male PA was ~41.3 and ~37.2, and in GE ~39.4 and ~35.3, respectively. Low EA (LEA) was found in 10% and 26% of female PA and GE, respectively, and in 11% of male GE. In PA, daily protein intake (g/kg body mass) was ~2.9−3.0, whereas carbohydrate and fat intakes were ~3.6−4.3 and ~0.8−1.0, respectively. PA had higher protein and carbohydrate and lower fat intakes than GE (p < 0.05). Estradiol, testosterone, IGF-1, insulin, leptin, TSH, T4, T3, cortisol, or BMD did not differ between PA and GE. Serum IGF-1 and leptin were explained 6% and 7%, respectively, by EA. In non-users of hormonal contraceptives, amenorrhea was found only in PA (27%) and was associated with lower fat percentage, but not EA, BMD, or hormones. In conclusion, off-season dietary intakes, hormone levels, and BMD meet the recommendations in most of the PA and GE. Maintaining too-low body fat during the off-season may predispose to menstrual disturbances.

Umbilical cord serum insulin-like growth factor-1 levels of infants of diabetic mothers are correlated with diastolic dysfunction detected by tissue Doppler echocardiography.

To our knowledge, this is the first study to examine the relationship between cord serum IGF-1 levels and diastolic functions of IDMs assessed by TDI. A weak correlation was found between IGF-1 levels and IVS and LVPW thicknesses in M-Mode and LV e' and LV e'/a' parameters in TDI, revealing diastolic dysfunction in IDMs. • The umbilical cord blood serum IGF-1 level of IDMs is higher than in infants of healthy mothers. • Diastolic dysfunction is a well-studied and frequently observed consequence in IDMs. • This is the first study to examine the relationship between cord serum IGF-1 levels and diastolic functions of IDMs assessed by TDI. • A weak correlation was detected between the median cord serum IGF-1 level of IDMs and the median values of IVS, LVPW, LV e', LV a', LV e'/a' ratio.

Effects of supplementing narasin to Bos indicus heifers during late-gestation and lactation on development of the offspring.

This experiment evaluated the effects of supplementing narasin during late-gestation and lactation on productive and physiological responses of Bos indicus beef heifers and their offspring. Pregnant, nulliparous Nelore heifers (N = 88) that conceived under the same fixed-time artificial insemination protocol and to the same sire were used. Heifers were ranked by maternal ability genomic score, body weight (BW) and body condition score (BCS) and allocated to 44 drylot pens (2 heifers per pen; 10 × 25 m). Pens were ranked by these traits and alternatively assigned to receive (NAR) or not (CON) 0.260 mg of narasin/kg of heifer BW daily (Elanco Saúde Animal, São Paulo, Brazil). Narasin was mixed into a supplement offered at 0.30% of heifer BW from day 0 until heifers weaned their calves (day 316), whereas CON heifers received the same supplement without narasin addition. Heifers received Urochloa brizantha hay and water for ad libitum consumption (days 0 to 316) and calved between days 97 to 112 of the experiment. After calving, heifers and offspring had access to hay and supplement; hence, supplements and narasin were offered according to heifer + calf BW beginning on day 162. No treatment differences were detected (P ≥ 0.18) for heifer BW and BCS during the experiment, although BW loss from day 0 to calving was less (P = 0.04) in NAR compared to CON heifers. Hay intake during the experiment did not differ (P = 0.79) between treatments. Serum IGF-I concentrations were greater (P = 0.05) for NAR heifers on day 60 of the experiment and did not differ (P ≥ 0.28) between treatments 24 h and 30 d after calving (treatment × day interaction; P = 0.04). No treatment effects were detected (P ≥ 0.58) for calf birth BW. Serum concentrations of total protein 24 h after birth were greater (P = 0.04) in calves from NAR compared with CON heifers, and a tendency (P = 0.10) for a similar outcome was noted for serum IgG concentrations. Diarrhea incidence did not differ (P = 0.16) between treatments, although the number of total diarrhea cases per calf were greater (P = 0.03) in the CON offspring. Growth rate of calves from NAR heifers tended (P = 0.08) to be greater, resulting in heavier calves at weaning (P ≤ 0.04) compared with CON offspring. Collectively, these outcomes indicate narasin supplementation to beef heifers as a nutritional alternative to improve cow-calf productivity via developmental programming effects during gestation, as well as direct consumption by their nursing offspring.

Retracted: Levels of Serum IGF-1, HCY, and Plasma BNP in Patients with Chronic Congestive Heart Failure and Their Relationship with Cardiac Function and Short-Term Prognosis.

[This retracts the article DOI: 10.1155/2022/4118976.].

Predictors of postoperative remission of acromegaly. (Experience of the Burdenko Neurosurgical Center)

Treatment of acromegaly is still an unresolved problem. Overall postoperative remission rate ranges from 34 to 85%. These values are better for microadenomas (75-90%) and worse for macroadenomas (45-70%). Identification of predictors of acromegaly remission after surgical treatment is an urgent objective to improve the quality of medical care for these patients. To analyze postoperative freedom from acromegaly and predictors of remission. A retrospective single-center study included 227 patients with acromegaly who underwent resection of pituitary adenoma between August 2018 and August 2021. Remission (normalization of serum IGF-1) was achieved in 65 (55%) patients. Growth hormone and IGF-1 index decreased after surgery in all patients. Mean preoperative serum growth hormone was 12.45 [6.88, 29.85] ng/ml, early postoperative concentration - 1.54 [0.80, 3.38] ng/ml, in delayed period - 1.15 [0.57, 3.80] ng/ml. Mean IGF-1 index was 2.18 [1.69, 2.71], 1.47 [0.99, 1.90] and 0.99 [0.74, 1.43], respectively. Significant predictors of acromegaly remission after neurosurgical treatment were age, preoperative level of growth hormone, tumor size and location, growth hormone and IGF-1 index in early postoperative period and residual tumor after surgery. Multivariate analysis revealed a significant association of acromegaly remission with small tumor size, low postoperative level of growth hormone and no residual tumor within 3-6 month after surgery.

Desafiando la sarcopenia: investigando los impactos de un programa de ejercicio terapéutico, con un enfoque comparativo entre fuerza y aeróbico.

Scientific evidence supports the benefits of therapeutic exercise for people with sarcopenia disease. Despite this, the existing literature is limited, highlighting the need for further intervention to fully understand which type of exercise best supports. The present study aims to investigate the effects of a physiotherapeutic intervention programme using strength exercises compared to aerobic exercises in people affected with sarcopenia disease. The aim is to evaluate the influence of these interventions on muscle strength, muscle mass, physical performance and serum IGF-1 levels. We propose a physiotherapy protocol based on a controlled clinical trial for people diagnosed with sarcopenia in two groups: control and experimental, both of which will receive 20 intervention sessions, twice a week, with an approximate duration of 60 minutes per session. Several variables will be analysed, including socio-demographics, lifestyle habits, clinics, muscle strength, muscle mass, physical performance and serum IGF-1 levels.

Liver fibrosis is associated with impaired bone mineralization and microstructure in obese individuals with non-alcoholic fatty liver disease.

Chronic liver diseases are associated with increased bone fracture risk, mostly in end-stage disease and cirrhosis; besides, data in non-alcoholic fatty liver disease (NAFLD) are limited. Aim of this study was to investigate bone mineralization and microstructure in obese individuals with NAFLD in relation to the estimated liver fibrosis. For this cross-sectional investigation, we analyzed data from 1872 obese individuals (44.6 ± 14.1years, M/F: 389/1483; BMI: 38.3 ± 5.3kg/m2) referring to the Endocrinology outpatient clinics of Sapienza University, Rome, Italy. Participants underwent clinical work-up, Dual-Energy X-ray Absorptiometry for assessing bone mineral density (BMD) and microarchitecture (trabecular bone score, TBS). Liver fibrosis was estimated by Fibrosis Score 4 (FIB-4). Serum parathyroid hormone (PTH), 25(OH) vitamin D, osteocalcin and IGF-1 levels were measured. Obese individuals with osteopenia/osteoporosis had greater FIB-4 than those with normal BMD (p < 0.001). FIB-4 progressively increased in presence of degraded bone microarchitecture (p < 0.001) and negatively correlated with the serum osteocalcin (p < 0.001) and IGF-1 (p < 0.001), which were both reduced in presence of osteopenia/osteoporosis. FIB-4 predicted IGF-1 reduction in multivariable regression models adjusted for confounders (β: -0.18, p < 0.001). Higher FIB-4 predicted bone fragility with OR 3.8 (95%C.I:1.5-9.3); this association persisted significant after adjustment for sex, age, BMI, diabetes, smoking status and PTH at the multivariable logistic regression analysis (OR 1.91 (95%C.I:1.15-3.17), p < 0.01), with AUROC = 0.842 (95%C.I:0.795-0.890; p < 0.001). Our data indicate the presence of a tight relation between NAFLD-related liver fibrosis, lower bone mineral density and degraded microarchitecture in obese individuals, suggesting potential common pathways underlying liver and bone involvement in obesity and insulin resistance-associated disorders.

Correlation of Bovine Dairy Igf-1 And the Neoplasia Development

Cow's milk and its derivatives are among the most consumed foods in the world being part of the daily diet of several people. However, its consumption is linked to factors that were associated with neoplastic development, such as IGF-1. IGF-1 acts by stimulating growth effects on most cells of the body via the IGF1R receptor. In this context, this work aimed to investigate studies that correlate these variables: IGF-1, cow's milk, and neoplasias. The results showed that IGF-1 in cow's milk may increase serum IGF-1 levels in humans from milk consumption. Also, we have shown it that some supplements such as choline and casein do not alter the amount of IGF-1, but when the cow undergoes recombinant bovine somatotropin treatment, there is a significant increase in circulating IGF-1. However, further studies are needed to explain the cause-and-effect relationship noted in this study.

Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease.

Obesity is a strong predictor for metabolic associated fatty liver disease (MAFLD), which has been associated with decreased insulin like growth factor 1 (IGF-1). In obesity, weight loss increases growth hormone secretion, but this is not unequivocally associated with increases in serum IGF-1 and IGF binding protein-3 (IGFBP-3). We studied the changes in the IGF axis in relation to weight loss and improvement in insulin resistance in children with or without MALFD after 10weeks of lifestyle intervention at a weight loss camp (WLC). We investigated 113 (66 females) Caucasian children with obesity, median age 12.4 (range 7.3-14.6) years, before and after 10weeks of lifestyle intervention at a WLC. We investigated children who was either MAFLD positive (n = 54) or negative (n = 59) before and after WLC. Children with MAFLD had lower baseline IGF-1 (249 ± 112 vs 278 ± 107µg/l, P = 0.048), whereas the IGF-1/IGFBP-3 molar ratio was similar to children without MAFLD (19.4 ± 6.6 vs. 21.8 ± 6.6%, P = 0.108). When all children were considered as one group, WLC decreased SDS-BMI and HOMA-IR (P < 0.001, both) and increased IGF-1 (264 ± 110 vs 285 ± 108µg/l, P < 0.001) and the IGF/IGFBP-3 molar ratio (20.7 ± 6.7 vs 22.4 ± 6.1%, P < 0.001). When categorized according to liver status, IGF-1 increased significantly in children with MAFLD (P = 0.008) and tended to increase in children without MAFLD (P = 0.052). Conclusions: Ten weeks of lifestyle intervention decreased insulin resistance and improved the IGF axis. We observed slight differences in the IGF axis in relation to MAFLD status. This suggests that the IGF axis is primarily influenced by insulin resistance rather than MAFLD status. What is New: •Weight loss decreases insulin resistance and subsequently increases the IGF axis in children with obesity. •Children with MAFLD had an aberration in the IGF axis compared to their MAFLD negative counter parts and the IGF axis was primarily influenced by the decreased BMI-SDS and insulin resistance, rather than MAFLD status. What is Known: • NAFLD has previously been associated with reduced serum IGF-1 concentrations. • Data on the impact of MAFLD and aberrations in the growth hormone and IGF axis and the effects of lifestyle interventions in children are limited.

Zofenopril Treatment Efficacy on Survival, Endostatin and Insulin-Like Growth Factor-1 in Patients with Diabetes Mellitus Type 2 After Acute Myocardial Infarction

The aimto study zofenopril treatment effect on survival and endostatin and insulin-like growth factor-1 levels in patients with acute myocardial infarction with ST elevation (STEMI) with concomitant diabetes mellitus type 2(T2DM) in 6-month follow up. MethodsThe study was performed in 103 hospitalized patients with T2DM after myocardial infarction with ST elevation. Serum endostatin and IGF-1 levels were measured by enzyme-linked immunosorbent assay on the first day and 24-25 weeks. Two groups were analysed: the first one – treated with inclusion of zofenopril, and the second one –treatment with inclusion of enalapril with the same rest treatment. Cox proportional hazards regression analyses were used to estimate hazard ratios (HRs) and 95% Confident Intervals (CI). ResultsAs a result of a 6-month follow-up in a group of patients with complicated STEMI who received the recommended therapy with zofenopril, compared with another, similar in all parameters, group of patients who received therapy with enalapril, hazard ratio, 0.81; 95% CI, 0.61–0.95, p=0.041, after multivariable adjustment. There was a statistically significant increase of the IGF-1 level in patients who received zofenopril: first day 154.07 ± 11.15 ng / ml and at the end of follow-up 202.07 ± 12.22 ng / ml, p <0.001. ConclusionsTreatment with zofenopril compared to enalapril has significantly better survival effect in patients with T2DM after STEMI in 6 month follow up. The activation of angiogenesis proved by significant increase of IGF-1 level was more pronounced in the zofenopril group.

Impairment in insulin secretion without changes in insulin resistance explains hyperglycemia in patients with acromegaly treated with pasireotide LAR.

Pasireotide is a second-generation somatostatin receptor ligand (SRL) used for treating acromegaly. Its clinical use is limited by adverse effects on glucose homeostasis. The aim of this study was to evaluate longitudinal changes in beta-cell function and insulin sensitivity associated with pasireotide in patients not controlled by first-generation SRLs. We performed a retrospective study. The efficacy (growth hormone (GH)/insulin-like growth factor (IGF-1) concentrations; tumor size) and effect on glucose homeostasis were analyzed in 33 patients. Longitudinal data on oral glucose tolerance tests were available before, shortly (mean ± s.d., 6.1 ± 3.8 months) and long term (24.4 ± 11.1 months) after initiation of pasireotide in 14 patients. Insulin secretion (insulinogenic index; disposition index) and insulin sensitivity were calculated by validated indices. Pasireotide-induced diabetes occurred in 12 patients (36%). It was mediated by impaired insulin secretion, which occurred shortly after initiation of treatment and then remained stable on long term (insulinogenic index, median (min; max), 80 (12; 542) vs 16 (6.4; 101) vs 25 (3.7; 396) pmol/mmol, respectively; P = 0.028; disposition index, 1.45 (0.42; 4.88) vs 0.53 (0.17; 2.63) vs 0.60 (0.22; 1.71), respectively; P = 0.024). No significant changes in insulin sensitivity were observed, despite a marked reduction of GH/IGF-1 concentrations. Older age and a worse glycemic control at baseline were the strongest predictors for hyperglycemia and the need for antidiabetic treatment. Worsening of glycemic control during pasireotide therapy is caused by an impaired insulin secretion, whereas insulin sensitivity is not affected. These findings might be important for the choice of antidiabetic treatment for pasireotide-induced hyperglycemia. Pasireotide, a second-generation SRL used for treating acromegaly, may be associated with glucose metabolism impairment. In a retrospective study of 33 patients, we observed that treatment with pasireotide was associated with normalization of serum IGF-1 in almost 60% of patients, but one-third of patients developed diabetes. In the patients who stopped pasireotide because of hyperglycemia, HbA1c promptly decreased. Longitudinal data in 14 patients show that diabetes is mediated by impaired insulin secretion, which occurred shortly and then remained stable on long term, while no significant changes in insulin sensitivity were observed, despite a marked reduction of GH/IGF-1 concentrations. Older age and a worse glycemic control at baseline were the strongest predictors for hyperglycemia.