Plasma IGF-I Levels Research Articles

Establishment of time-resolved fluoroimmunoassays for detection of growth hormone and insulin-like growth factor I in rainbow trout plasma

The GH/IGF-I axis influences many aspects of salmonid life history and is involved in a variety of physiological processes that are related to somatic growth (e.g., reproduction, smoltification, and the response to fasting and stress). As such, fisheries studies utilize GH/IGF-I axis components as indicators of growth and metabolic status. This study established time-resolved fluoroimmunoassays (TR-FIAs) for rainbow trout plasma GH and IGF-I using commercially available reagents. For the GH TR-FIA, the ED80 and ED20 were 0.6 and 28.1 ng/mL, the minimum detection limit was 0.2 ng/mL, and the intra- and inter-assay coefficients of variation (%CV) were 4.1% and 13.4%, respectively. Ethanol remaining from acid-ethanol cryoprecipitation (AEC) of plasma samples to remove IGF binding proteins reduced binding and increased variability in the IGF-I TR-FIA. Drying down and reconstituting extracted samples restored binding and reduced variability. The extraction efficiency of IGF-I standards through AEC, drying down, and reconstitution did not vary over the working range of the assay. For the IGF-I TR-FIA, the ED80 and ED20 were 0.2 and 6.5 ng/mL, the minimum detection limit was 0.03 ng/mL, and the intra- and inter-assay %CV were 3.0% and 6.5%, respectively. Biological validation was provided by GH injection and fasting studies in rainbow trout. Intraperitoneal injection with bovine GH increased plasma IGF-I levels. Four weeks of fasting decreased body weight, increased plasma GH levels, and decreased plasma IGF-I levels. The GH and IGF-I TR-FIAs established herein provide a cost-comparable, non-radioisotopic method for quantifying salmonid plasma GH and IGF-I using commercially available reagents.

The effects of dietary heat-killed probiotics bacteria additives in low-fishmeal feed on growth performance, immune responses, and intestinal morphology in juvenile olive flounder Paralichthys olivaceus

Fishmeal is an important source of protein in the fish diet, but its supply is unstable due to environmental pollution and overfishing of anchovy and herring. In addition, the disease outbreak of fish has been increased, and the abuse of antibiotics and vaccines has been becoming a problem for residual substances. Therefore, studies that address diets with reduced fishmeal content and additives that can increase efficiency and replace antibiotics are needed. Hence, in this study, the probiotics bacteria Bacillus sp. SJ-10 (BSJ-10) and Lactobacillus plantarum (LP) were heat-killed (HK) used as additives in a low-fishmeal diet. The two bacteria with a 45 % fishmeal diet were added at a concentration of 3.34 × 108 CFU/mL, and both of probiotics bacteria were mixed and added to the same concentration in order to produce the diet for HK BSJ-10 (HKBSJ-10), HK LP (HK-LP), and MIX (HKBSJ-10 + HK-LP) groups. We raised four replicates of juvenile olive flounder for 8 weeks. In the HKBSJ-10 group, the plasma insulin, GH, and IGF-I level were higher than the other groups (P < 0.05). Similarly, intramuscular IGF-I activity and signaling pathway were higher in HKBSJ-10 (P < 0.05). The innate immunity lysosome activity was higher in the HKBSJ-10 and MIX groups (P < 0.05), even cholecystokinin manifestation, intestinal wall thickness, and the density of the intestinal folds more evolved in the HKBSJ-10 group. Therefore, the HKBSJ-10 additive could be advanced in growth-related endocrine, innate immunity, and intestinal morphology, positively affecting a low-fishmeal diet for juvenile olive flounder.

Case Study, Plant-Based Diet and Igf-1 Modulation in Her2-positive Breast Cancer

Abstract Objectives Breast cancer is the most common type of cancer in women worldwide and is therefore a field of research that has gained particular relevance. Stimulation of insulin-like factor-1 (IGF-1) would increase breast cancer risk and promote relapse. Here we present a case study of a woman with HER2-positive breast cancer that, after chemotherapy and radiotherapy, followed a Healthful Predominantly Plant-based Diet. This work aimed to investigate IGF-1 plasma levels modulation through this eating pattern. Methods For 210 days, diet was based on regular consumption of whole grains, fruits, vegetables, nuts and seeds, legumes, and olive oil as a source of monounsaturated fat, while reducing intake of less healthy plant foods as well as other animal foods. Blood markers including IGF-1, Glycemia, Total Cholesterol, and also Body Mass Index were assessed at baseline and after 210 days. Results At baseline IGF-1 was 21 nmol/L and decreased to 16.3 nmol/L, Glycemia was 80 mg/dL and increased to 85 mg/dL, Total Cholesterol was 155 mg/dL and increased to 161 mg/dL, and BMI was 21.7 kg/m2 decreased to 20.6 kg/m2, after 210 days. A decrease of 22.4% in IGF-1 and an increase of 6.3% in Glycemia were noted in plasma levels of this 49 years old woman. Conclusions Predominantly Healthful Plant-based Diet seems to modulate IGF-1 and Glycemia plasma levels in a woman diagnosed with HER2-positive breast cancer. Future research should explore mechanistic pathways through which plant-based diets may confirm these results on IGF-1 levels and to clear whether a Predominantly Healthful Plant-Based Diet might be clinically useful in HER2-positive breast cancer. Funding Sources No funding sources.

Long-term feeding of a maintenance ration affects the release of Igf-1 and leptin, and delays maturation in a male teleost fish, Dicentrarchus labrax L.

Male European sea bass were used to investigate the effects of long-term exposure (14 months) to a maintenance ration on body weight gain, muscle lipid content and maturity. To this end, a group of animals were fed to visual satiety (CT), whereas a second group (EX) was provided an amount of feed each month equal to 0.35% of the CT group's biomass. To determine how energy balance affects metabolic factors, the circulating levels of Igf-1 and leptin and changes in mRNA levels of igf-1, igf-2 and igf-3 in the gonad were analyzed. Feed restriction impacted fish growth, and the specific growth rate was higher in the CT group than in the EX group. Moreover, the condition factor decreased over time in the EX group. Muscle lipid content, HSI, MFI and GSI also decreased in the EX group, which displayed increased apoptosis and low spermatogonial proliferation. Consequently, fish exposed to the maintenance ration showed lower rates of spermiation and delayed testicular development. Overall, fish in the EX group exhibited lower plasma levels of Igf-1 and leptin than those of the CT group. Of note, both plasma and expression levels of igf-1 in September and mRNA levels of igf-2 and igf-3 in February decreased significantly in the EX group, coinciding with the beginning of gametogenesis and full spermiation in this species, respectively. These results indicate that fish under a maintenance ration apparently use stored energy to support at least a basal metabolism and preserve their reproduction, although growth is disrupted. In this line, we suggest that leptin might act as a permissive factor for reproductive function, while Igf-1 might control spermatogenesis in sea bass.

Evaluation of the high intensity interval training with and without flaxseed oil on the plasma level of IGF-1 after in male rats

Background: IGF-1 is an anabolic hormone that is effective in cell metabolism and growth. Flaxseeds contain unsaturated fatty acids and are useful. Previous studies have shown that physical activity and natural substances affect hormonal levels. Thus the present study aimed to investigate the effect of 10 weeks of high intensity interval training (HIIT) with and without flaxseed oil on plasma IGF-1 level in male rats. Methods: 20 adult male Wistar rats were present in study. Animals randomly divided into four groups (five in each group) including control- saline (CS), training- saline (TS), control- flaxseed oil (CO), and training- flaxseed oil (TO) groups. The training groups performed HIIT (10 weeks, five sessions per week, 90–95% VO2 max) on a rodent treadmill. The supplementation groups also received flaxseed oil supplement (300 mg/kg). The rats were sacrificed five days after the last training session. The plasma was collected, and plasma IGF-1 lever evaluated by ELISA method. Results: Training increased the level of the plasma IGF-1 than non-training groups (P=0.009). The level of plasma IGF-1 was higher in the flaxseed oil-supplemented groups than the saline-treated groups. (P=0.002). The interaction between training and supplementation also led to an increase in plasma IGF-1 level than training or supplement alone (P=0.001). Conclusion: HIIT and flaxseed oil consumption can increase the IGF-1 in body.

IGF-1 Child-Turcotte-Pugh score as a predictor of overall survival to therapy in CTP-A, BCLC stage C patients with advanced hepatocellular carcinoma.

488 Background: Child-Turcotte-Pugh (CTP) A is the standard population for active HCC therapy. The IGF-CTP score, comprises levels of type 1 insulin-like growth factor (IGF-1), bilirubin, INR, and albumin, significantly improved the prediction of overall survival (OS) in recently published studies. Our current study aimed to investigate the accuracy of the IGF-CTP score in predicting OS in HCC Child-Pugh A patients (pts) treated with local and/or systemic therapies (tx). The overall hypothesis is that the IGF-CTP score can further distinguish CP-A pts in terms of overall survival, PFS. Methods: Between 2014 and 2018, a total of 274 pts with new advanced HCC BCLC stage who had available baseline plasma IGF-1 level were retrospectively enrolled. Clinicopathologic features and treatment history were collected. We calculated IGF-CTP scores, used Kaplan-Meier method and log rank test to estimate and compare time to event outcomes between subgroups of patients. Results: 198 pts were CTP Class A, 209 patient underwent systemic tx, 65 underwent local tx [see table]; 161 were re-classified as IGF-CTP-A with a median OS of 16.09 months (95% CI = 13.06 to 23.29 months) (p &lt;0.0001), whereas 37 patients were reclassified as intermediate risk (IGF-CTP-B) and had significantly shorter OS of 10.66 months (95% CI = 5.49 to 26.51) (p &lt;0.0001). Conclusions: The results of this study support our biologically-driven hypothesis that IGF-CTP score is predictive of overall survival to therapy in advanced HCC treated with local and/or systemic therapy. Among HCC pts with CTP-A class, some are reclassified as IGF-CP-B/C and were found to have significantly poorer prognosis in terms of shorter OS. Future validation of the predictive ability of our IGF-1 score may lead to adopting it as a stratification tool in clinical trials as well as to predict HCC outcome and guide therapy decision in routine practice. [Table: see text]

Feeding forage or concentrates early in life influences rumen fermentation, metabolic response, immune function and growth of Wagyu × Friesian calves

Context Early life nutrition of calves influences their performance later in life. There is limited literature demonstrating the effects of rearing dairy calves in early life on milk with either exclusively forage or concentrate starter diets on metabolic and immune function and post-weaning growth and body composition on a pasture only diet. Aim This study evaluated the effects of feeding Wagyu × Holstein Friesian calves a forage starter (FS) or a concentrate starter (CS) for the first 14 weeks of rearing on rumen fermentation, blood metabolites, immune function, growth and body composition to Week 41. Methods Group-housed calves (Wagyu × Friesian, 10 calves per group, three groups per treatment) were fed milk (2 L per calf twice daily) until Week 7, then transitioned to once a day milk feeding until weaning by Week 9, with ad libitum access to either FS or CS. All calves were transferred to graze ryegrass pastures a week after transitioning to once daily milk feeding, with starter feeds removed gradually by Week 14. Thereafter, calves were reared together on pasture until Week 41. Results Solid feed intake was lower in FS than CS calves during the first 7 weeks. Total short chain fatty acids were lower, but acetate to propionate ratio and rumen pH were higher in FS than CS calves at Week 7, with no differences observed at Week 12 or 30. Plasma β-hydroxybutyrate an indicator of ketogenic ability of the rumen in developing calves was higher in FS vs CS calves at weaning. Further, FS calves had lower concentrations of circulating non-esterified fatty acids compared with CS calves at weaning. Compared with CS calves, FS calves grew slower for the first 14 weeks which was associated with lower plasma IGF-1 levels. However, FS calves had greater average daily gain after 14 weeks when on pasture and had similar plasma IGF-1 at 30 weeks and similar body weight and body composition (muscle and subcutaneous fat deposition) by Week 41 compared to CS calves. Conclusions These results indicate that offering a FS starter has better prepared calves for weaning onto pasture and potentially improved utilisation of forage post-weaning to achieve similar muscle and fat deposition and overall liveweight in both groups by 41 weeks. Implications Dairy beef calves can be successfully reared using forage as the only solid feed source without affecting their growth performance on pasture until 10 months of age. Rearing calves using forage will contribute to reducing the usage of concentrate feeds in pastoral dairy-beef production systems and provide an opportunity to fulfil the market requirements and standards for grain-free beef production.

Modifications of Own Mothers' Milk Fortification Protocol Affect Early Plasma IGF-I and Ghrelin Levels in Preterm Infants. A Randomized Clinical Trial.

The aim was to investigate the effect of two own mother’s milk (OMM) fortification protocols on (a) IGF-I and ghrelin plasma levels at 35 post-conceptional weeks (PCW, T2) and whether this effect is maintained after elimination of the differences in OMM fortification, and (b) growth until 12 months corrected age. Forty-eight OMM-fed preterm infants (GA 24–32 weeks) were randomly allocated to the fixed-fortification (FF) group (n = 23) and the protein-targeting fortification (PTF) group (n = 25) targeting the recommended daily protein intake (PI). Plasma IGF-I and ghrelin were assessed at 35 (T2) and 40 (T3) PCW while growth was longitudinally assessed until 12 months corrected age. PTF group had lower IGF-I and higher ghrelin than FF group at T2, while receiving lower daily protein and energy amounts. PI correlated positively to T2-IGF-I and inversely to T3-ghrelin while energy intake (EI) correlated inversely to T2- and T3-ghrelin. Group and PI were independent predictors of adjusted T2-IGF-I, while group and EI were predictors of adjusted and T2-ghrelin. Growth parameter z-scores were comparable between groups up to 12 months corrected age. Modifications of OMM fortification have a transient effect on early plasma IGF-I and ghrelin levels in preterm infants in a way consistent with the previously recognized protein-energy/endocrine balance, indicating a potential programming effect.

The effects of Berberis vulgaris consumption on plasma levels of IGF-1, IGFBPs, PPAR-\u03b3 and the expression of angiogenic genes in women with benign breast disease: a randomized controlled clinical trial

BackgroundThe present study was designed to investigate the effects of Berberis vulgaris (BV) juice consumption on plasma levels of insulin-like growth factor (IGF-1), IGF-binding proteins (IGFBPs), and the expression of PPAR-γ, VEGF and HIF in women with benign breast disease.MethodsThis parallel design randomized, double-blind controlled clinical trial was conducted on 85 eligible patients diagnosed with benign breast disease. They were assigned randomly into either BV juice group (n = 44, BV juice: 480 ml/day) or placebo group (n = 41, BV placebo juice: 480 ml/day) for 8 weeks intervention. Participants, caregivers and those who assessed laboratory analyses were blinded to the assignments. Plasma levels of biomarkers were measured at baseline and after 8 weeks by ELISA. Quantitative real-time PCR was used to measure the fold change in the expression of each interested gene.ResultsThe compliance of participants was 95.2% and 40 available subjects analyzed in each group at last. Relative treatment (RT) effects for BV juice caused 16% fall in IGF-1 concentration and 37% reduction in the ratio of IGF-1/1GFBP1. Absolute treatment effect expressed 111 ng/ml increased mean differences of IGFBP-3 between BV group and placebo. Plasma level of PPAR-γ increased in both groups but it was not significant. Fold changes in the expressions of PPAR-γ, VEGF and HIF showed down-regulation in the intervention group compared to placebos (P < 0.05).ConclusionsThe BV juice intervention over 8 weeks was accompanied by acceptable efficacy and decreased plasma IGF-1, and IGF-1/IGFBP-1 ratio partly could be assigned to enhanced IGFBP-1 level in women with BBD. The intervention caused reductions in the expression levels of PPAR, VEGF, and HIF which are remarkable genomic changes to potentially prevent breast tumorigenesis.Trial registrationIRCT2012110511335N2. Registered 10 July 2013 (retrospectively registered).

Growth and Clinical Characteristics of Children with Floating-Harbor Syndrome: Analysis of Current Original Data and a Review of the Literature

Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by dysmorphic facial features, short stature, and expressive language delay. Objective: The aim of this study was to describe a cohort of patients with FHS and review the literature about the response to recombinant human growth hormone (rhGH) therapy. Methods: Anthropometric and laboratory data from 7 patients with FHS were described. The molecular diagnosis was established by multigene analysis. Moreover, we reviewed the literature concerning patients with FHS treated with rhGH. Results: All 7 patients were born small for gestational age. At first evaluation, 6 patients had a height standard deviation score (SDS) ≤–2 and 1 had short stature in relation to their target height. Bone age was usually delayed, which rapidly advanced during puberty. Nonspecific skeletal abnormalities were frequently noticed, and normal to elevated plasma IGF-I levels were observed in all except 1 patient with growth hormone deficiency. Information about 20 patients with FHS treated with rhGH was analyzed (4 from our cohort and 16 from the literature). The median height changes during the treatment period (approx. 2.9 years) were 1.1 SDS (range from –0.4 to 3.1). Nontreated patients had an adult height SDS of –4.1 ± 1.2 (n = 10) versus –2.6 ± 0.8 SDS (n = 7, p 0.012) for treated patients. Conclusion: We observed a laboratory profile compatible with IGF-1 insensitivity in some patients with FHS. Nevertheless, our study suggests that children with FHS may be considered as candidates for rhGH therapy. Further studies are necessary to establish the real benefit and safety of rhGH therapy in these patients.

Insulin-like growth factor-1 short-period therapy improves cardiomyopathy stimulating cardiac progenitor cells survival in obese mice

Background and aimsCardiovascular diseases are the main cause of mortality in obesity. Despite advanced understanding, the mechanisms that regulate cardiac progenitor cells (CPC) survival in pathological conditions are not clear. Low IGF-1 plasma levels are correlated to obesity, cardiomyopathy and CPC death, so this work aimed to investigate IGF-1 therapeutic potential on cardiomyopathy and its relationship with the survival, proliferation and differentiation of CPC in Western diet-induced obesity. Methods and resultsMale Swiss mice were divided into control group (CG, n = 8), fed with standard diet; and obese group (OG, n = 16), fed with Western diet, for 12 weeks. At 11th week, OG was subdivided to receive a daily subcutaneous injection of human recombinant IGF-1 (100 μg.Kg−1) for seven consecutive days (OG + IGF1, n = 8). Results showed that IGF-1 therapy improved the metabolic parameters negatively impacted by western diet in OG, reaching levels similar to CG. OG + IGF-1 also demonstrated restored heart energetic metabolism, fibrosis resolution, decreased apoptosis level, restored cardiac gap junctions and intracellular calcium balance. Cardiomyopathy improvement was accompanied by increased CPC survival, proliferation and newly cardiomyocytes formation related to increased pAkt/Akt ratio. ConclusionThese results suggest that only one week of IGF-1 therapy has cardioprotective effects through Akt pathway upregulation, ensuring CPC survival and differentiation, contributing to heart failure rescue.

Low plasma levels of IGF-1 and IL-1RA with high plasma levels of IFN-γ as prognostic factor for mortality in hospitalized geriatric patients with delirium

Background: Delirium is common and serious problem with high morbidity and mortality, especially in geriatric patients. Decrease in the number of neuroprotective factors (IGF-I and IL-1RA) and increase in IFN-γ had been correlated with the incidence of delirium. This study aims to understand whether these markers can be used as predictors for mortality in geriatric patients with delirium in an effort to prevent the adverse events of delirium.Methods: In this observational analytic study with prospective cohort design carried out in the Geriatric Installation care room at Sanglah General Hospital in Denpasar in 2018, 76 samples were examined for their IGF-1, IL-1RA, IFN-γ plasma levels. Patients were then followed during their hospital stay until they were declared cured or died due to delirium or its complications. The relationship between each group and mortality rate were then analyzed using univariate, bivariate and multivariate analysis.Results: In this study, median was used as the cutoff point for IGF-1 levels [21.38 (0.00-91.07)], IL-1RA levels [2,491.48 (193,44-6720,13)] and IFN-γ [194.29 (0.00-2200.96)]. In multivariate analysis, low plasma levels of IGF-1 (HR= 4.12 [95% CI: 1,458 - 11,642, p=0.008]) and IL-1RA (HR=2.91 [95 % CI: 1.037 - 8.154, p= 0.043]) proved to be an independent factor in the occurrence of death in geriatric patients with delirium. However, IFN- γ failed to show any correlations.Conclusion: Both low plasma levels of IGF-1 and IL-1RA can be used as predictors for mortality in geriatric patients with delirium.

Effect of feeding level during the prepubertal phase on mammary gland development in female goat kids.

The experiment reported in this research communication aimed to determine the effects of post-weaning feeding level after early weaning on mammary parenchyma development in Alpine goats. Thirty Alpine female goat kids were weaned early (at around 9.8 kg and 32 d of age) and fed different levels of concentrate: Control (C, 730 g DM/d, n = 10), Low (L, 365 g DM/d, n = 10) or High (H, 1090 g DM/d, n = 10) until 235 d of age with ad libitum hay and water. Half of the goat kids were slaughtered before puberty (at around 208 d of age) and half at midgestation (at around 308 d of age and 70 d of gestation) for mammary parenchyma sampling. A histological analysis, Western blot and DNA quantification were performed. Blood samples were taken before puberty and at midgestation to determine plasma levels of IGF-I and prolactin. The mammary gland weights before puberty and at midgestation were positively and significantly associated with concentrate level. However, the organization of the mammary parenchyma and protein expression and quantity of DNA in the parenchyma were similar among the three groups. Before puberty, prolactin and IGF-I concentrations were significantly increased by the feeding level. In conclusion, feeding level after early weaning did not impact mammary parenchyma structure although it modified the weight of the mammary gland. The establishment of the mammary gland was not impacted by rearing management before puberty. Hence, increasing the feeding level during the rearing period could be an interesting way to increase the body development of goats without impairing mammary development whilst having a positive impact on reproductive parameters such as litter weight.

Oral bovine colostrum supplementation does not increase circulating insulin-like growth factor-1 concentration in healthy adults: results from short- and long-term administration studies

PurposeBovine colostrum is available in health food shops and as a sports food supplement and is rich in antibodies and growth factors including IGF-1. World Anti-Doping Agency advises athletes against taking colostrum for fear of causing increased plasma IGF-1. There are also concerns that colostrum may theoretically stimulate malignancy in organs which express IGF-1 receptors. We, therefore, determined changes in plasma IGF-1 levels in subjects taking colostrum or placebo for 1 day, 4 weeks, and 12 weeks.MethodsPlasma IGF1 levels were determined in healthy males (n = 16) who ingested 40 g bovine colostrum or placebo along with undertaking moderate exercise for total period of 4.5 h. Two further studies followed changes in IGF1 using double-blind, parallel group, placebo-controlled, randomized trials of colostrum or placebo (N = 10 per arm, 20 g/day for 4 weeks and N = 25 colostrum, N = 29 placebo arm 20 g/day for 12 weeks).ResultsBaseline IGF1 levels 130 ± 36 ng/ml. 4.5 h protocol showed no effect of colostrum on plasma IGF1 (ANOVA, treatment group: p = 0.400, group × time: p = 0.498, time p = 0.602). Similarly, no effect of colostrum ingestion was seen following 4 week (ANOVA, group: p = 0.584, group × time interaction: p = 0.083, time p = 0.243) or 12 week (ANOVA, group: p = 0.400, group × time interaction: p = 0.498, time p = 0.602) protocol.ConclusionsIngestion of standard recommended doses of colostrum does not increase IGF-1 levels in healthy adults, providing additional support for the safety profile of colostrum ingestion.

Skeletal Muscle Atrophy in Men with Chronic Alcoholic Myopathy (impairment to signal pathways)

The main effect of chronic alcoholic myopathy is atrophy of fast muscle fibers (18 years of alcohol abuse), followed by slow fibers (31 years of alcohol abuse); plasma IGF-1 levels decrease and muscle IRS-1 and p-p70S6k decrease, which is evidence for suppression of the functioning of the mTORC1 signal pathway and reductions in protein synthesis. Patients show increases in the expression of mRNA encoding HSP90/70, which can lead to increases in the protection of proteins from degradation. All patients showed increased expression of E3 ligase, which is evidence for an increase in the operation of the ubiquitin-proteasomal signal pathway for protein degradation.

SUN-321 Rare Case of Hypoglycemia Induced by IGF2 Secreted by an Ovarian Tumor

Introduction: Mesenchymal and epithelial tumors can produced un-cleaved IGF-2 molecules known as “big” IGF-2. These tumors are associated with elevated levels of IGF-2, which can mimic hypoglycemic events of insulin-producing islet-cell tumors by binding and activating insulin receptors. Typically plasma levels of insulin, IGF-1, and GH are low. “Big” IGF-2 molecular testing is not commercially available, however diagnosis of IGF-2 mediated hypoglycemia is based on low insulin and proinsulin in association with a IGF-2 to IGF-1 ratio >3. Clinical Case A 62 year old female with no significant past medical problems presented with 20 lb weight loss and a two month history documented symptomatic hypoglycemia episodes . Her PCP palpated a firm, non-painful mass occupying nearly her entire abdomen on physical exam. CT revealed a pelvic mass measuring 23.4 cm thought to originate from the ovary. Biopsy of the mass showed a well-differentiated neuroendocrine tumor grade 3, Ki 67 of 15%. Lab work by Endocrinology was significant for a serum glucose of 46 mg/dl, insulin <5 uIU/ml, C-peptide <1 ng/ml, cortisol 43 ug/dl, IGF-1 18 ng/ml, IGF-2 163 ng/ml (IGF1:IGF2: 9), pro-insulin 1.7 pmol/L, sulfonyl urea screen was negative, Ca 125: 230 U/ml, Ca 19-9: 7 U/ml, CEA <1 ng/ml, and chromogranin-A 598 ng/ml. Ga DOTATE scan revealed a 21 cm intra-abdominal mass with multiple peritoneal soft tissue implants consistent with a neuroendocrine tumor with peritoneal carcinomatosis. Due to persistent episodes of hypoglycemia, the patient was started on octretotide 200 mg q 8 hrs, Dexamethasone 1 mg q 3 hrs and parenteral nutrition. The patient was evaluated by surgery and deemed to inoperable due to multiple metastasis. She was then treated with cepecidobine and temozolomide with significant improvement in her glycemic control. A week later, the patient was able to be weaned off TPN and dexamethasone and was discharged home on oral diet. She was evaluated a month later as outpatient and had infrequent episodes of hypoglycemia. Conclusion This is the first case report of a patient with IGF-2 induced hypoglycemia treated with a combination of cepecidobine, temozolomide, and octreotide. While octreotide helped to improve her glycemic control by generally inhibiting hormonal secretion, likely of both IGF-2 and insulin production, final symptom relief and clinical stabilization occurred with the combination of capecitabine and temozolomide, which in vitro data has is synergistic for induction of apoptosis in neuroendocrine tumor cell lines .

Effects of different photoperiod regimes on the smoltification and seawater adaptation of seawater-farmed rainbow trout (Oncorhynchus mykiss): Insights from Na+, K+–ATPase activity and transcription of osmoregulation and growth regulation genes

Photoperiod is thought to be the main zeitgeber that induces smoltification in salmonids. However, its effects on the smoltification of rainbow trout (Oncorhynchus mykiss) are not fully understood and no published data documents the effects of the photoperiod regime currently used commercially, continuous light (LL). The present study compared the effect of four different photoperiod regimes (i.e. advanced phase photoperiod (APP), delayed phase photoperiod (DPP), LL and simulated natural photoperiod (SNP)) on the smoltification and growth of juvenile rainbow trout during their freshwater phase of winter-spring and the following summer post smolt phase. Smoltification was evaluated by monitoring gill Na+,K+–ATPase (NKA) activity and transcription of NKA α-subunit isoforms 1a and 1b, and Na+,K+,2Cl‐cotransporter 1a. Growth was measured as specific growth rate of both length and weight, and through molecular growth proxies such as the levels of circulating insulin-like growth factor 1 (IGF-I) in plasma and transcription of igf-I, igf binding protein 1b (igfbp1b), growth hormone receptor 1 (ghr1) and cathepsin L (ctsl) in the liver. Results indicate that APP induces a longer smolt window and higher levels of plasma IGF-I in both freshwater and seawater (two months post transfer), while DPP led to a shorter smolt window, lower plasma IGF-I levels in freshwater and seawater, an earlier decrease in liver igf-I and ctsl transcription in freshwater (as seen by modelling over time) and lower specific growth rate in freshwater. The transcription analysis of osmoregulatory genes complemented NKA activity and allowed for the detection of a transient response to light and of differences between the osmoregulatory capacity of parr and desmolted fish. Furthermore, an upregulation of the liver transcription of igf-I, ghr1 and ctsl was found in all treatments during the smolt window, which corresponded to the periods with highest growth. Finally, both plasma IGF-I and liver igf-I in seawater were found to be significantly correlated to fish growth in seawater. However, our data did not show that plasma IGF-I prior to seawater transfer could be used as a reliable predictor of growth in seawater. Overall, and especially when compared with other salmonid species, photoperiod seems to be a weaker inducer of smoltification in rainbow trout, according to the parameters that were tested, suggesting that other environmental cues might be more important drivers of this process.

Effects of Adrenosterone, Testosterone, and 17β‐Estradiol on the Gene Expression of Insulin‐Like Growth‐Factor Binding Proteins (igfbps) in Atlantic Salmon Smolts

The growth hormone (Gh)/insulin‐like growth‐factor (Igf) system is a key regulator of growth in teleost fishes, including salmonids. Igfs interact with a suite of binding proteins, termed Igf binding proteins (Igfbps), which modify their biological activities. Atlantic salmon (Salmo salar) express an expanded array of igfbp gene transcripts in liver, the primary site of Igfbp production. While gonadal steroids are known to impact the growth of fishes, there is little information on how androgens and estrogens affect the expression of various igfbps. In the current study, we characterized how 14‐day implants of adrenosterone (OA), testosterone (T) or 17β‐estradiol (E2) affected the Gh/Igf/Igfbp network in Atlantic salmon smolts. OA did not affect any of the parameters studied. There were no effects of T or E2 on body mass, plasma levels of Igf1, or hepatic igf1, igf2 or gh receptor mRNA levels. E2 stimulated hepatic estrogen receptor α mRNA levels by 17‐fold, while E2 and T stimulated hepatic vitellogenin mRNA levels by 140‐ and 19‐fold, respectively. Hepatic igfbp1b1 and igfbp4 mRNA levels were diminished by E2 but not T, whereas igfbp2a was diminished by T, but not E2. Alternatively, both T and E2 stimulated igfbp5a. igfbp2b2, igfbp5b2 and igfbp6b were not impacted by any of the tested steroids. Our findings suggest that steroid‐specific effects on the gene expression of various igfbps provide a means for gonadal steroids to modulate the Gh/Igf system.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cellular and molecular signatures of alcohol-induced myopathy in women.

Alcoholic myopathy is characterized by the reduction in cross-sectional area (CSA) of muscle fibers and impaired anabolic signaling. The goal of the current study was to investigate the causes and compare the changes in CSA and fiber type composition with the modifications of anabolic and catabolic signaling pathways at the early stages of chronic alcohol consumption in women. Skeletal muscle samples from 5 female patients with alcohol abuse (AL; 43 ± 5 yr old; alcohol abuse duration 5,6 ± 0,6 yr) were compared with the muscle from the control group of 8 healthy women (C; 35 ± 4 yr old). The average daily dose of alcohol consumption was 110 ± 10 ml of pure ethanol. In women patients, a significant decrease in CSA of type I and II muscle fibers, titin and nebulin content, plasma IGF-1 level and total IRS-1, p-Akt and p-4E-BP1 in vastus lateralis was found in comparison with the control group. The p-AMPK level was found to be increased versus the control group. In women patients with chronic alcoholic myopathy 1) both fast and slow muscle fibers are subjected to atrophy; 2) impairments in IGF-I-dependent signaling and pathways controlling translation initiation (AMPK/mTOR/4E-BP1), but not translation elongation, are observed; 3) the level of calpain-1 and ubiquitinated proteins increases, unlike E3 ligases content.

Relationships among maternal backfat depth, plasma adipokines and the birthweight of piglets

Adipose tissue produces hormones, such as leptin and adiponectin, that are key factors in energy metabolism. The aim of this study was to assess the endocrine role of the adipose tissue in controlling intrauterine growth, so we evaluated the relationships among maternal adiposity, leptin and adiponectin-pregnancy trends and foetal growth in 48 Large White x Landrace crossbreed sows. Two groups of sows were designated based on backfat (BF) depth at the end of the lactation phase: a Low Fat group (LF, 11.60 mm; n = 24) and a High Fat group (HF, 18.20 mm; n = 24). During the subsequent pregnancies, the same level of feed was provided to both groups. The BF values of the sows were recorded, and blood samples were collected to assess the concentrations of leptin and adiponectin at mating and during gestation. The weights and temperatures of piglets were recorded at farrowing and after 24 h, and their body mass index and ponderal index values were calculated at farrowing. Before the piglets suckled colostrum, blood samples were collected, and the leptin, adiponectin and IGF-1 plasma levels were analysed. The observed differences in backfat depth between the LF and HF groups at mating persisted during pregnancy, and a decrease in adiponectin and an increase in leptin plasma levels were observed throughout gestation in both groups. Plasma adiponectin was lower in the HF group than in the LF group, but plasma leptin did not differ significantly. Compared to HF sows, LF sows gave birth to lighter piglets (P = 0.014). In addition, the weights of 27% of the piglets in the LF group and 14% in the HF group fell within the first 25th percentile (weight ≤ 1 kg). A positive correlation between offspring weight and maternal adiposity at mating (r = 0.149; P = 0.020) and a negative correlation between offspring weight and adiponectin-leptin ratio at mating (r = −0.198; P = 0.022) were observed. The morphometric parameters (body mass index, ponderal index) and thermoregulatory abilities of the piglets were unaffected by maternal adiposity. In terms of haematology, differences were found in the IGF-1 level, which was lower in piglets born from LF than HF sows (P < 0.001). The knowledge gained from this study suggested that differences in maternal adiposity, which were due to individual variability and not feeding strategies, influence the plasma concentration of adipokines, thus affecting offspring weight.