Plasma Concentrations Of Insulin-like Growth Factor Research Articles

Feeding a DHA-enriched diet increases skeletal muscle protein synthesis in growing pigs: association with increased skeletal muscle insulin action and local mRNA expression of insulin-like growth factor 1

Dietary n-3 PUFA have been demonstrated to promote muscle growth in growing animals. In the present study, fractional protein synthesis rates (FSR) in the skeletal muscle of growing pigs fed a DHA-enriched (DE) diet (DE treatment) or a soyabean oil (SO) diet (SO treatment) were evaluated in the fed and feed-deprived states. Feeding-induced increases in muscle FSR, as well as the activation of the mammalian target of rapamycin and protein kinase B, were higher in the DE treatment as indicated by the positive interaction between diet and feeding. In the fed state, the activation of eIF4E-binding protein 1 in the skeletal muscle of pigs on the DE diet was higher than that in pigs on the SO diet (P<0·05). Feeding the DE diet increased muscle insulin-like growth factor 1 (IGF-1) expression (P<0·05) and insulin action (as demonstrated by increased insulin receptor (IR) phosphorylation, P<0·05), resulting in increased IR substrate 1 activation in the fed state. However, no difference in plasma IGF-1 concentration or hepatic IGF-1 expression between the two treatments was associated. The increased IGF-1 expression in the DE treatment was associated with increased mRNA expression of the signal transducer and activator of transcription 5A and decreased mRNA expression of protein tyrosine phosphatase, non-receptor type 3 in skeletal muscle. Moreover, mRNA expression of protein tyrosine phosphatase, non-receptor type 1 (PTPN1), the activation of PTPN1 and the activation of NF-κB in muscle were significantly lower in the DE treatment (P<0·05). The results of the present study suggest that feeding a DE diet increased feeding-induced muscle protein synthesis in growing pigs, and muscle IGF-1 expression and insulin action were involved in this action.

Quantification of insulin-like growth factor-1 in dried blood spots for detection of growth hormone abuse in sport

There is significant evidence that athletes are using recombinant human growth hormone (rhGH) to enhance performance, and its use is banned by the World Anti-Doping Agency and professional sports leagues. Insulin-like growth factor-1 (IGF-1) is the primary mediator of growth hormone action and is used as a biomarker for the detection of rhGH abuse. The current biomarker-based method requires collection and expedited shipment of venous blood which is costly and may decrease the number of tests performed. Measurement of GH biomarkers in dried blood spots (DBS) would considerably simplify sample collection and shipping methods to allow testing of a greater number of samples regardless of location. A method was developed to quantify intact IGF-1 protein in DBS by liquid chromatography-tandem mass spectrometry. A step-wise acid-acetonitrile extraction was optimized to achieve a sensitive assay with a lower limit of quantification of 50 ng/mL. IGF-1 remained stable at room temperature for up to 8 days, which would allow shipment of DBS cards at ambient temperature. In a comparison between plasma concentrations of IGF-1 and concentrations measured from venous and finger prick DBS, there was good correlation and agreement, r(2) of 0.8551 and accuracy of 86-113 % for venous DBS and r(2) of 0.9586 and accuracy of 89-122 % for finger prick DBS. The method is intended for use as a rapid screening method for IGF-1 to be used in the biomarker method of rhGH abuse detection.

Temporal Changes in Plasma Concentration of Leptin, IGF-1, Insulin and Metabolites Under Extended Fasting and Re-Feeding Conditions in Growing Lambs

BackgroundA fall in plasma concentration of energy status related hormones (leptin, insulin-like growth factor-1 (IGF-1) and insulin) and body energy expenditure occurs in response to short term fasting. Nevertheless, the relations of the fasting-induced changes in energy related hormones and metabolites with fasting energy expenditure (FEE) under extended fasting condition have received little attention so far.ObjectivesIt is not clear how energy status related hormones coordinate to cope with feed deprivation under extended fasting time conditions and how quickly these hormones re-bound to fed-state values in response to re-feeding. Thus the objectives of this study were: 1) to determine the effects of extended fasting on plasma concentration of leptin, IGF-1, insulin, glucose, NEFA, 3-β-hydroxybutyrate (BOHB) and urea; and 2) to study the relations of energy status related hormones with FEE and substrate oxidations under extended fasting conditions.Materials and MethodsEighteen six-month-old growing lambs (9 females and 9 males) were fasted for three days. Blood samples were taken one hour before (-1H) and 48 and 72 hours after fasting (48H and 72H) and two hours after re-feeding (+2H) from jugular vein. During the last 22 hours of fasting, gas exchange (CO2 production and O2 consumption) were measured using an open-circuit indirect calorimeter. Respiratory quotient (RQ), FEE and relative proportions of oxidized protein, fat and carbohydrate were calculated.ResultsPlasma levels of leptin, insulin, IGF-1 and glucose decreased but NEFA and urea levels increased within 48H of fasting. Concentration of insulin significantly increased with extended fasting while leptin and IGF-1 levels remained constant. Glucose was the only blood variable that showed a quick re-bound within two hours after re-feeding. Leptin and IGF-1 showed significant positive relations with glucose and BOHB but negative relations with NEFA and Urea. Carbohydrate, fat and proteins contributed to 17%, 61% and 22% of FEE respectively in three-day-fasted lambs. FEE was negatively correlated with insulin and NEFA concentrations in plasma.ConclusionsEven though plasma levels of leptin and IGF-1 decreased and remained constant under extended fasting, neither leptin nor IGF1 re-bounded to fed-status values within two hours after re-feeding. Under extended fasting condition, firstly an insulin resistance develops and secondly, a fall in FEE through a switch from carbohydrate- to fat-based metabolism occurs and there is an evident negative correlation between FEE and plasma concentration of NEFA.

S73 Circulating Regulators of Acute Muscle Wasting in the Critically Ill: GDF-15 a Potential Novel Driver of Acute Muscle Wasting

IntroductionAcute muscle wasting in the critically ill manifesting as intensive care unit acquired paresis (ICUAP) is common, and causes significant morbidity and mortality. The pathological mechanisms underlying ICUAP are poorly...

Supplemental feeding with glycerol or propylene glycol of dairy cows in early lactation—Effects on metabolic status, body condition, and milk yield

The objective of this field study was to evaluate the effect of supplemental feeding with glycerol or propylene glycol to dairy cows in early lactation on metabolic status, body condition and milk yield. In total, 673 newly calved cows from 12 commercial Swedish dairy herds were randomized to daily supplementation with 450g of glycerol (GLY), 300g of propylene glycol (PG), or nothing (control, CON). Supplements were fed twice daily from 0 to 21 d in milk (DIM) as a top dress on concentrates. For each cow, data on parity, breed, calving date, monthly test-day milk yield, and cases of diseases were collected. Blood samples were taken at approximately 2, 5, and 8 wk postpartum (pp) and analyzed for glucose, β-hydroxybutyrate (BHBA), nonesterified fatty acids (NEFA), and insulin. Samples taken within 3 wk pp were also analyzed for insulin-like growth factor 1 (IGF-1). Measurements of body condition score (BCS) and heart girth (HG) were obtained at approximately 2 and 5 wk pp and at time of first insemination. The effects of supplemental feeding with GLY or PG on the plasma concentrations of glucose, NEFA, BHBA, insulin, and IGF-1, and BCS, HG, and occurrence of disease were analyzed. No differences in BCS or HG or in plasma concentrations of glucose, BHBA, NEFA, or IGF-1 were found between the control group and any of the treatment groups. Cows in the GLY group had lower plasma insulin concentrations during DIM 0 to 63 compared with group CON, but no difference in insulin was found between the PG group and the CON group. Cows supplemented with GLY had a higher milk yield (kg of milk and kg of energy-corrected milk) during the first 90 DIM. Cows in the PG group tended to yield more milk during the same period. No differences in the occurrence of diseases were seen between the groups. In conclusion, supplementation with GLY in early lactation did increase milk yield without a subsequent decrease of metabolic status, and supplementation with PG tended to do the same.

Existe-t-il une relation entre la dose d'hormone de croissance et d'éventuelles complications tumorales ou cardiovasculaires ?

Growth hormone (GH) affects protein (anabolism), lipid (lipolysis) and carbohydrate (hyperglycemia) metabolism and stimulates hepatic synthesis of insulin-like growth factor 1 (IGF1). IGF1 is believed to act as a postnatal growth factor. In addition to its effects on growth, IGF1 affects cell proliferation, differentiation and survival, and has anabolic effects on proteins, and also lipogenic and glucose-lowering effects. The increasing availability of biosynthetic pituitary GH has made it feasible to treat GH-deficient children and adults, and patients of short stature due to a variety of other causes (Turner's syndrome, anomalies of SHOX, intrauterine growth retardation (IUGR), chronic renal failure, Prader-Willi syndrome, or idiopathic short stature). The therapeutic dose has been increased in some situations in which the response is inadequate, particularly in patients with certain conditions such as IUGR. However, it has been reported that cancers and cardiovascular diseases are associated with high plasma concentrations of GH and IGF1, particularly in patients with acromegaly but also in large epidemiological studies of apparently healthy populations. These findings raise questions as to the safety of GH treatment. Some long-term follow-up studies have shown an increase in the risk of some kinds of cancer or cerebrovascular disease, but these findings have not been replicated by others. The results of these studies remain debatable, due to their small sample sizes, methodological weaknesses, nonexhaustive data collection and problems involved in comparing these patients with an appropriate control group. Finally, GH and IGF1 deficiencies are themselves associated with an increased risk of cardiovascular diseases, as is small stature/low weight at birth (due to IUGR). Recent studies have demonstrated a higher risk of cardiovascular disease in patients with both low and high plasma concentrations of GH and IGF1, these risks disappearing at average values. These findings suggest that the GH dose should be adjusted during treatment to ensure that plasma IGF1 concentrations remain within the physiological range.

Pre-weaning growth of red deer calves is not determined by ability of hinds to produce milk

Three experiments were carried out to determine whether growth of suckling red deer calves is determined by the potential of their mothers to produce milk. In the first experiment red deer hinds (n = 10, calves 6 weeks old) were treated either with bovine somatotrophin (bST, 54 mg s.c. injected every 2 weeks for 8 weeks then 108 mg every 2 weeks for a further 8 weeks) or saline. There was no effect of bST treatment on calf or hind liveweight, calf liveweight gain or body condition score of hinds. The second experiment used red and red-wapiti crossbred deer calves (n = 8–11) suckled by red deer dams that had been treated with bST or had received excipient only for 12 weeks from when the calves were 5 weeks old. Calf liveweight was affected by genotype (wapiti-red crossbreds were heavier than their red counterparts) but there was no effect of bST treatment of the hinds on calf growth in either of the genotypes. Although bST treatment of the suckled hinds elevated their plasma insulin-like growth factor-1 concentration it had no effect on milk yield. A third experiment ruled out the possibility that bST ingested by calves in milk from treated hinds would have had any influence on growth of calves in the other experiments. From these results it is concluded that the inherent demand from suckling calves, rather than the ability of adequately nourished hinds to produce milk, determines growth rate of red deer calves from birth to weaning.

Insulin-like growth factor 1 receptor polymorphism rs2229765 and circulating interleukin-6 level affect male longevity in a population-based prospective study (Treviso Longeva− TRELONG)

Insulin-like growth factor 1 (IGF-1) signaling modulation has been associated with increased lifespan in model organisms, while high levels of circulating interleukin-6 (IL-6) are a marker of disability and mortality. In the prospective, population-based “Treviso Longeva”− TRELONG Study from Italy (n = 668, age range 70–105.5 years at baseline, followed for seven years) we investigated the effects of survival on the IGF-1 receptor (IGF-1R) gene polymorphism rs2229765, the IL-6 gene promoter polymorphism rs1800795, and plasma concentrations of IGF-1 and IL-6, alone or in combination. We found a sex-dependent effect for the IGF-1R rs2229765 polymorphism, as male carriers of the homozygous A/A genotype survived longer, while the IL-6 rs1800795 genotype did not influence overall or sex-specific longevity. Higher IL-6 levels were more detrimental for survival among males than females, while IGF-1 had no dose–response effect. These findings sustain the hypothesis that sex-specific longevity relies on detectable differences in genetic and biochemical parameters between males and females.

Mediation of vertebrate life historiesviainsulin‐like growth factor‐1

Life-history traits describe parameters associated with growth, size, survival, and reproduction. Life-history variation is a hallmark of biological diversity, yet researchers commonly observe that one of the major axes of life-history variation after controlling for body size involves trade-offs among growth, reproduction, and longevity. This persistent pattern of covariation among these specific traits has engendered a search for shared mechanisms that could constrain or facilitate production of variation in life-history strategies. Endocrine traits are one candidate mechanism that may underlie the integration of life history and other phenotypic traits. However, the vast majority of this research has been on the effects of steroid hormones such as glucocorticoids and androgens on life-history trade-offs. Here we propose an expansion of the focus on glucocorticoids and gonadal hormones and review the potential role of insulin-like growth factor-1 (IGF-1) in shaping the adaptive integration of multiple life-history traits. IGF-1 is a polypeptide metabolic hormone largely produced by the liver. We summarize a vast array of research demonstrating that IGF-1 levels are susceptible to environmental variation and that IGF-1 can have potent stimulatory effects on somatic growth and reproduction but decrease lifespan. We review the few studies in natural populations that have measured plasma IGF-1 concentrations and its associations with life-history traits or other characteristics of the organism or its environment. We focus on two case studies that found support for the hypothesis that IGF-1 mediates adaptive divergence in suites of life-history traits in response to varying ecological conditions or artificial selection. We also examine what we view as potentially fruitful avenues of research on this topic, which until now has been rarely investigated by evolutionary ecologists. We discuss how IGF-1 may facilitate adaptive plasticity in life-history strategies in response to early environmental conditions and also how selection on loci controlling IGF-1 signaling may mediate population divergence and eventual speciation. After consideration of the interactions among androgens, glucocorticoids, and IGF-1 we suggest that IGF-1 be considered a suitable candidate mechanism for mediating life-history traits. Finally, we discuss what we can learn about IGF-1 from studies in free-ranging animals. The voluminous literature in laboratory and domesticated animals documenting relationships among IGF-1, growth, reproduction, and lifespan demonstrates the potential for a number of new research questions to be asked in free-ranging animals. Examining how IGF-1 mediates life-history traits in free-ranging animals could lead to great insight into the mechanisms that influence life-history variation.

Long-Term Ethanol Consumption Promotes Hepatic Tumorigenesis but Impairs Normal Hepatocyte Proliferation in Rats

Chronic and excessive alcohol consumption has been related to an increased risk of several cancers, including that of the liver; however, studies in animal models have yet to conclusively determine whether ethanol acts as a tumor promoter in hepatic tumorigenesis. We examined whether prolonged alcohol consumption could act as a hepatic tumor promoter after initiation by diethylnitrosamine (DEN) in a rat model. Male Sprague-Dawley rats were injected with 20 mg DEN/kg body weight 1 wk before introduction of either an ethanol liquid diet or an isoenergic control liquid diet. Hepatic pathological lesions, hepatocyte proliferation, apoptosis, PPARα and PPARγ, and plasma insulin-like growth factor 1 (IGF-1) levels were assessed after 6 and 10 mo. Mean body and liver weights, plasma IGF-1 concentration, hepatic expressions of proliferating cellular nuclear antigen and Ki-67, and cyclin D1 in ethanol-fed rats were all significantly lower after 10 mo of treatment compared with control rats. In addition, levels of hepatic PPARγ protein, not PPARα, were significantly higher in the ethanol-fed rats after prolonged treatment. Although ethanol feeding also resulted in significantly fewer altered hepatic foci, hepatocellular adenoma was detected in ethanol-fed rats at 10 mo, but not in control rats given the same dose of DEN. Together, these results indicate that chronic, excessive ethanol consumption impairs normal hepatocyte proliferation, which is associated with reduced IGF-1 levels, but promotes hepatic carcinogenesis.

Whole body insulin responsiveness is higher in beef steers selected for increased muscling

The aim of this experiment was to evaluate the impact of selection for greater muscling on whole body insulin responsiveness in cattle, as reflected by greater uptake of glucose in response to constant insulin infusion and greater glucose disappearance following an intravenous glucose tolerance test. This study used 18-month-old steers from an Angus herd visually assessed and selected for divergence in muscling over 15 years. Eleven high-muscled (High), 10 low-muscled (Low) and 3 high-muscled steers, which were heterozygous for a myostatin polymorphism (HighHet), were infused with insulin using the hyperinsulineamic-euglyceamic clamp technique. Insulin was constantly infused at two levels, 0.6 μIU/kg per min and 6.0 μIU/kg per min. Glucose was concurrently infused to maintain euglyceamia and the steady state glucose infusion rate (SSGIR) indicated insulin responsiveness. An intravenous glucose tolerance test was also administered at 200 mg/kg live weight. Sixteen blood samples were collected from each animal between −30 and 130 min relative to the administration of intravenous glucose, plasma glucose and insulin concentration was determined in order to analyse insulin secretion and glucose disappearance. Insulin-like growth factor-1 (IGF-1) was also measured in basal plasma samples. At the low insulin infusion rate of 0.6 mU/kg per min, the SSGIR was 73% higher for the High muscling genotype animals when compared to the Low (P < 0.05). At the high insulin infusion rate of 6.0 mU/kg per min, these differences were proportionately less with the High and the HighHet genotypes having only 27% and 34% higher SSGIR (P < 0.05) than the Low-muscled genotype. The High-muscled cattle also had 30% higher plasma IGF-1 concentrations compared to the Low-muscled cattle. There was no effect of muscling genotype on basal insulin or basal glucose concentrations, glucose disappearance or insulin secretion following an intravenous glucose tolerance test. The increased whole body insulin responsiveness in combination with higher IGF-1 concentrations in the High-muscled steers is likely to initiate a greater level of protein synthesis, which may partially explain the increased muscle accretion in these animals.

Effect of Individualized Exercise Training Combined with Diet Restriction on Inflammatory Markers and IGF-1/IGFBP-3 in Obese Children

Aims: The present study was designed to examine the possible changes in body composition, insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3) and inflammatory markers of obese children in response to a 2-month program of exercise training combined with dietary restriction. Methods: Twenty-eight obese children (age 13.2 ± 0.7 years, body mass index 30.9 ± 1.3) were randomly assigned to a diet/training group or a control group and were tested two times: once before and once at the end of the experimental period. They performed a progressive cycle ergometer test at each visit. Substrate oxidation was evaluated by indirect calorimetry. Training was individualized at the point when fat oxidation was maximal (Lipox_max). Results: Diet/training induced a significant decrease in body weight and body fat (after vs. before, p < 0.01). Plasma concentrations of IGF-1, IGFBP-3 and inflammatory markers were significantly decreased after the completion of the program. The diet/training program resulted in an increase in VO_2maxACSM (24.6 ± 2.5 to 33.1 ± 3.1 ml/min/kg, p < 0.001) at the end of the intervention period. Conclu- sion: These data suggest that in the presence of weight loss, exercise training improves inflammatory markers and IGF-1 and IGFBP-3 levels in obese children.

A super-agonist of growth hormone–releasing hormone causes rapid improvement of nutritional status in patients with chronic kidney disease

Chronic kidney disease is frequently associated with protein-energy wasting related to chronic inflammation and a resistance to anabolic hormones such as insulin and growth hormone (GH). In this study, we determined whether a new GH-releasing hormone super-agonist (AKL-0707) improved the anabolism and nutritional status of nondialyzed patients with stage 4-5 chronic kidney disease randomized to twice daily injections of the super-agonist or placebo. After 28 days, this treatment significantly increased 24-h GH secretion by almost 400%, without altering the frequency or rhythmicity of secretory bursts or fractional pulsatile GH release, and doubled the serum insulin-like growth factor-1 level. There was a significant change in the Subjective Global Assessment from 'mildly to moderately malnourished' to 'well-nourished' in 6 of 9 patients receiving AKL-0707 but in none of 10 placebo-treated patients. By dual-energy X-ray absorptiometry, both the mean fat-free mass and the body mineral content increased, but fat mass decreased, all significantly. In the AKL-0707-treated group, both serum urea and normalized protein equivalent of nitrogen appearance significantly decreased with no change in dietary protein intake, indicating a protein anabolic effect of treatment. Thus, our study shows that stimulation of endogenous GH secretion by AKL-0707 overcomes uremic catabolism of patients with advanced chronic kidney disease.

Activation of peroxisome proliferator-activated receptor-γ potentiates pro-inflammatory cytokine production, and adrenal and somatotropic changes of weaned pigs after Escherichia coli lipopolysaccharide challenge

Our previous study demonstrated mRNA and protein expression of peroxisome proliferator-activated receptor-g (PPAR-g) in the immune system of weaned pigs. In this report, to test the hypothesis that activation of PPAR-g in immune system modulates inflammatory response, and adrenal and somatotropic responses associated with immune challenge, we administered intraperitoneally PPAR-g agonist and/or antagonist in weaned pigs subjected to Escherichia coli lipopolysaccharide (LPS) challenge. Unexpectedly, we found that a single injection of the PPAR-g agonist rosiglitazone (given at 3 mg/kg body weight 30 min before LPS injection) failed to block pro-inflammatory cytokine production induced by LPS injection. Rather, plasma levels of tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6), mRNA abundance of TNF-a in thymus, spleen, mesenteric lymph node and peripheral white blood cells, mRNA abundance of IL-6 in thymus, protein levels of TNF-a in spleen and mesenteric lymph node, and protein levels of IL-6 in spleen and mesenteric lymph node, were elevated beyond the levels in control pigs injected with LPS. Furthermore, rosiglitazone potentiated the increase of plasma cortisol and prostaglandin E(2) concentrations, and the decrease of plasma insulin-like growth factor-1 concentration induced by LPS injection. Co-administration of the PPAR-g antagonist bisphenol A diglycidyl ether (given 30 mg/kg body weight) 30 min prior to treatment with rosiglitazone antagonized the effect of the PPAR-g agonist, indicating a PPAR-g-dependent effect. Our data indicate that ligand-induced activation of PPAR-g does not ameliorate but enhances pro-inflammatory cytokine production, and further potentiates the adrenal and somatotropic changes in weaned pigs subjected to E. coli LPS challenge, which suggests that PPAR-g activation may not be useful, but potentially harmful, in the treatment of immune challenge in livestock. Our results raise doubts about the prevalently accepted anti-inflammatory role for PPAR-g activation.

Impact of Growth Hormone (GH) Deficiency and GH Replacement upon Thymus Function in Adult Patients

BackgroundDespite age-related adipose involution, T cell generation in the thymus (thymopoiesis) is maintained beyond puberty in adults. In rodents, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and GH secretagogues reverse age-related changes in thymus cytoarchitecture and increase thymopoiesis. GH administration also enhances thymic mass and function in HIV-infected patients. Until now, thymic function has not been investigated in adult GH deficiency (AGHD). The objective of this clinical study was to evaluate thymic function in AGHD, as well as the repercussion upon thymopoiesis of GH treatment for restoration of GH/IGF-1 physiological levels.Methodology/Principal FindingsTwenty-two patients with documented AGHD were enrolled in this study. The following parameters were measured: plasma IGF-1 concentrations, signal-joint T-cell receptor excision circle (sjTREC) frequency, and sj/β TREC ratio. Analyses were performed at three time points: firstly on GH treatment at maintenance dose, secondly one month after GH withdrawal, and thirdly one month after GH resumption. After 1-month interruption of GH treatment, both plasma IGF-1 concentrations and sjTREC frequency were decreased (p<0.001). Decreases in IGF-1 and sjTREC levels were correlated (r = 0.61, p<0.01). There was also a decrease in intrathymic T cell proliferation as indicated by the reduced sj/β TREC ratio (p<0.01). One month after reintroduction of GH treatment, IGF-1 concentration and sjTREC frequency regained a level equivalent to the one before GH withdrawal. The sj/β TREC ratio also increased with GH resumption, but did not return to the level measured before GH withdrawal.ConclusionsIn patients with AGHD under GH treatment, GH withdrawal decreases thymic T cell output, as well as intrathymic T cell proliferation. These parameters of thymus function are completely or partially restored one month after GH resumption. These data indicate that the functional integrity of the somatotrope GH/IGF-1 axis is important for the maintenance of a normal thymus function in human adults.Trial RegistrationClinicalTrials.gov NTC00601419

A polymorphic variant of the insulin-like growth factor 1 (IGF-1) receptor correlates with male longevity in the Italian population: a genetic study and evaluation of circulating IGF-1 from the "Treviso Longeva (TRELONG)" study

BackgroundAn attenuation of the insulin-like growth factor 1 (IGF-1) signaling has been associated with elongation of the lifespan in simple metazoan organisms and in rodents. In humans, IGF-1 level has an age-related modulation with a lower concentration in the elderly, depending on hormonal and genetic factors affecting the IGF-1 receptor gene (IGF-1R).MethodsIn an elderly population from North-eastern Italy (n = 668 subjects, age range 70–106 years) we investigated the IGF-1R polymorphism G3174A (rs2229765) and the plasma concentration of free IGF-1. Frequency distributions were compared using χ2-test "Goodness of Fit" test, and means were compared by one-way analysis of variance (ANOVA); multiple regression analysis was performed using JMP7 for SAS software (SAS Institute, USA). The limit of significance for genetic and biochemical comparison was set at α = 0.05.ResultsMales showed an age-related increase in the A-allele of rs2229765 and a change in the plasma level of IGF-1, which dropped significantly after 85 years of age (85+ group). In the male 85+ group, A/A homozygous subjects had the lowest plasma IGF-1 level. We found no clear correlation between rs2229765 genotype and IGF-1 in the females.ConclusionThese findings confirm the importance of the rs2229765 minor allele as a genetic predisposing factor for longevity in Italy where a sex-specific pattern for IGF-1 attenuation with ageing was found.

Impact of Growth Hormone (GH) Deficiency and GH Replacement upon Thymus Function in Adult Patients (138.26)

Abstract Context: In rodents, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and GH secretagogues (such as ghrelin) reverse age-related changes in thymus cytoarchitecture and increase thymopoiesis. GH administration also enhances thymic mass and function in HIV-infected patients. Until now, thymic function has not been investigated in adult GH deficiency (AGHD). Objectives: The objective of this clinical study was to evaluate thymic function in AGHD, as well as the repercussion upon thymopoiesis of GH treatment for restoration of GH/IGF-1 physiological levels. Design: Twenty-two patients with documented AGHD were enrolled in this study. The following parameters were measured: plasma IGF-1 concentrations, signal-joint T-cell receptor excision circle (sjTREC) frequency, and sj/ß TREC ratio. Analyses were performed at three time points: firstly on GH treatment at maintenance dose, secondly one month after GH withdrawal, and thirdly one month after GH resumption. Results: After 1-month interruption of GH treatment, both plasma IGF-1 concentrations and sjTREC frequency were significantly decreased. Decreases in IGF-1 and sjTREC levels were significantly correlated. There was also a significant decrease in intrathymic T cell proliferation as indicated by the reduced sj/ß TREC ratio. One month after reintroduction of GH treatment, IGF-1 concentration and sjTREC frequency were restored at the level before arrest of GH treatment. The sj/ß TREC ratio also increased with GH resumption, but did not return to the level measured before GH withdrawal. Conclusions: In patients with AGHD under GH treatment, GH withdrawal decreases thymic T cell output, as well as intrathymic T cell proliferation. These parameters of thymopoiesis are completely or partially restored one month after GH resumption.

Bovine somatotrophin stimulates milk production in red deer hinds

To determine its potential as a tool for studies of growth in suckling red deer calves, bovine somatotrophin (bST) was administered to lactating red deer hinds. The present study used twice-daily machine milking of bST-treated hinds (n = 10, 54 mg bST for 2 weeks then 108 mg for 1 week) and compared the milk yield with that of saline-treated controls (n = 9). Treatment with 54 mg bST tended to increase milk yield by ~16% and the 108-mg dose increased (P = 0.013) milk yield by ~32%. Both doses of bST increased (P &lt; 0.05 and P &lt; 0.001, respectively) plasma insulin-like growth factor-1 concentration but did not affect total solids or fat content of the milk, nor was there any effect on body condition score or liveweight of the hinds. This shows that milk production in red deer hinds is increased by administration of bST, which makes it a suitable experimental technique for investigating the lactational biology of red deer.

Ramadan Fasting and the GH/IGF-1 Axis of Trained Men during Submaximal Exercise

Aims: The aim of this study was to explore possible changes in body composition, blood glucose regulation, plasma growth hormone (GH), insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3), and insulin concentrations of trained athletes in response to the intermittent fasting and dehydration of Ramadan observance. Methods: Nine trained male rugby players (age 19 ± 2 years, height 1.78 ± 0.74 m) were tested 3 times: before Ramadan (C), at the end of the first week (R1), and during the fourth week (R2). They performed a progressive cycle ergometer test at each visit. The work rate was increased in 6-min stages corresponding to 20, 30, 40, 50 and 60% of &Wdot; max. Substrate oxidation was evaluated by indirect calorimetry. On each occasion, substrate and plasma hormone concentrations were measured at rest and at the end of the exercise. Results: Ramadan fasting induced a significant decrease in body mass and body fat (R2 vs. C, p < 0.001). Plasma concentrations of glucose, insulin, GH, IGF-1 and IGFBP-3 did not change significantly between C and R2, either at rest or following exercise. Conclusion: Ramadan fasting induces positive changes in body composition without disturbing glucose regulation or activity of the GH/IGF-1 system.

Effect of diet and ration on the relationship between plasma GH and IGF-1 concentrations in Arctic charr, Salvelinus alpinus (L.)

The purpose of the study was to investigate whether dietary ration or diet composition influence the relationship between plasma growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in Arctic charr (Salvelinus alpinus L.). The pattern of changes in plasma GH and IGF-1 concentrations was examined in fish fed at different ration levels (0%, 0.35% and 0.70% BW day−1) for 5 weeks, and in fish fed diets containing different lipid:crude protein (LCP) ratios. Ration level significantly affected plasma GH and IGF-1 concentrations; at 5 weeks the levels of both hormones in the food-deprived group were significantly lower than in fish fed the 0.70% BW day−1 ration. Also, plasma IGF-1 levels in fish of each ration treatment group were significantly correlated with individual final body weight; no such correlation was found for GH. To examine the effects of dietary LCP ratios, fish were fed for up to 18 weeks, with one of four formulated diets that had LCP ratios (dry matter basis) of 0.35 (Diet 1), 0.43 (Diet 2), 0.51 (Diet 3) or 0.59 (Diet 4), or a commercial diet (Diet 5) which had an LCP ratio of 0.38. Statistical differences in plasma GH and IGF-1 concentrations were found only after 18 weeks. Growth hormone was significantly lower in fish fed Diets 1 and 2 compared with Diets 3 and 5, and IGF-1 was significantly lower in fish fed Diet 1 compared with Diets 2 and 5. Significant correlations between plasma GH and IGF-1 concentrations were found only for fish fed Diets 1 and 5, suggesting that the influence of diet composition on the relationship between GH and IGF-1 varies with the dietary LCP ratio in this species. The decline in plasma IGF-1 concentrations during food deprivation is similar to that described in other species; however, the unexpected decrease in plasma GH during food deprivation in this study may represent a species-specific response.