scholarly journals Effect of rhIL-6 infusion on GH→IGF-I axis mediators in humans

2006 ◽  
Vol 291 (6) ◽  
pp. R1663-R1668 ◽  
Author(s):  
Dan Nemet ◽  
Alon Eliakim ◽  
Frank Zaldivar ◽  
Dan M. Cooper

Exercise leads to simultaneous increases in mediators signaling apparently antagonistic functional responses such as growth factors and inflammatory mediators. The aim of the present study was to demonstrate the physiological effect of IL-6 on circulating components of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis. Twelve men (ages 26 ± 2 yr) were divided into two groups ( n = 6 in each group), receiving either albumin or recombinant human (rh) IL-6 infusion. IL-6 was infused via an antecubital vein, and a contralateral antecubital vein was used for blood sampling. The IL-6 dose was chosen to reach plasma levels of IL-6 characteristic of intense exercise (5 μg/h, for 3 h, resulting in plasma levels of 100 pg/ml). Blood samples for GH, GH binding protein, IGF-I, and IGF binding protein (IGFBP)-1 and -3 were collected at baseline, 30 min, and 1, 2, 3, 4, 5, and 8 h after the beginning of the rhIL-6 infusion. IL-6 levels increased only in the rhIL-6-infused group ( P < 0.0005) and returned to baseline after the infusion was stopped. IL-6 infusion led to a significant increase in GH, peaking 1 h after the beginning of infusion ( P < 0.001). A decrease in total IGF-I levels was noted only in the rhIL-6-infused group ( P < 0.027). An initial decrease in IGFBP-1 levels was noted in both groups during infusion ( P < 0.03). Following the initial decrease, there was a significant increase in IGFBP-1 levels only in the IL-6-infused participants, peaking at 2 after the infusion cessation ( P < 0.001). IL-6 infusion had no effect on GH binding protein, IGFBP-3, and acid-labile subunit levels. rhIL-6 levels similar to the levels found after strenuous exercise induced a typical exercise-associated GH→IGF-I axis response (increase GH, decreased IGF-I, and elevated IGFBP-1). The results suggest that IL-6 plays a role in the GH→IGF-I response to intense exercise.

1998 ◽  
Vol 156 (3) ◽  
pp. 519-527 ◽  
Author(s):  
JC Divino Filho ◽  
SJ Hazel ◽  
P Furst ◽  
J Bergstrom ◽  
K Hall

Elevated insulin-like growth factor binding protein (IGFBP) levels, including IGFBP-1, occur in renal failure, and may contribute towards reduced IGF bioactivity in uraemia. The reduced IGF bioactivity may, in turn, contribute towards the disturbances in protein metabolism present in renal failure. In this study, the relationships between intra- and extracellular amino acid (AA) levels and IGF-I and/or IGFBP-1 levels were studied in 30 adult patients (aged 24-70 years) on haemodialysis who had no clinical signs of malnutrition. Blood samples (n = 30) and muscle biopsies (n = 13) were collected for determination of free AA in erythrocytes (RBC), plasma and muscle by reverse-phase HPLC while IGFBP-1, IGF-I and insulin plasma levels were determined by radioimmunoassay The patients on haemodialysis had elevated glutamate concentrations in RBC and plasma compared with healthy controls (524 +/- 26 vs 448 +/- 17 mumol/l, P < 0.05 and 45 +/- 4 vs 32 +/- 4 mumol/l, P < 0.01 respectively), although glutamate levels in muscle were within the normal range. The mean IGF-I level was slightly increased (s.d. score +0.74 +/- 0.30) but insulin levels were within the normal range. IGFBP-1 levels, which were inversely correlated to insulin (r = -0.40, P < 0.02), were elevated threefold compared with controls. No plasma AA level displayed a significant correlation with IGF-I, IGFBP-1 or insulin levels. However, glutamate concentrations in RBC were positively correlated to IGFBP-1 (r = 0.51, P < 0.01) and inversely correlated to IGF-I (r = -0.46. P < 0.01), although unrelated to insulin. Muscle glutamate, which was inversely related to RBC glutamate, displayed an opposite pattern with an inverse relation to IGFBP-1 levels (r = - 0.73, P < 0.01) and a positive correlation to IGF-I levels (r = 0.64, P < 0.02). Glutamate was the only AA to display an inverse correlation between RBC and muscle (r = -0.65, P < 0.02, n = 12). These findings lead us to propose that, in uraemia, the elevated IGFBP-I levels, which reduce the bioavailability of IGFs, are linked to glutamate uptake in muscle, resulting in accumulation of RBC glutamate. Whether there is a causal relationship or the correlation is due to some common regulator is not clarified in the present study.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Yuhan Tang ◽  
Juan Li ◽  
Chao Gao ◽  
Yanyan Xu ◽  
Yanyan Li ◽  
...  

The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS) and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min) resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw). Intense exercise and thapsigargin- (Tg-) induced ERS (glucose-regulated protein 78, GRP78) and inflammatory cytokines levels (IL-6 and TNF-α) were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K) induction, Ca2+restoration, and blockade of the activities of Jun N-terminal kinase (JNK), activating transcription factor 6 (ATF6) and especially NF-κB (p65 and p50 nuclear translocation). A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor), AEBSF (ATF6 inhibitor), and especially PDTC (NF-κB inhibitor) enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals.


1996 ◽  
Vol 80 (3) ◽  
pp. 760-764 ◽  
Author(s):  
H. Koistinen ◽  
R. Koistinen ◽  
L. Selenius ◽  
Q. Ylikorkala ◽  
M. Seppala

Acute physical exercise increases growth hormone (GH) secretion, and GH regulates the expression of insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP) 3. IGFBP-1 is a local modulator of IGF activity with rapid dynamic regulation that is downregulated by insulin. The IGF system mediates the metabolic actions of GH, and possibly it regulates glucose metabolism. We hypothesize that strenuous exercise causes changes in the IGF system. We studied the effects of the marathon run on the circulating levels of IGF-I, IGFBP-1, IGFBP-3, and insulin in 23 participants. Immediately after the run, the most striking change was an 11.6-fold median increase in serum IGFBP-1 level (from 63.7 +/- 50.5 to 736 +/- 408 micrograms/l; P < 0.001). Because the insulin level remained unchanged, the elevation of serum IGFBP-1 level cannot be explained by changes in insulin. One day after the run, the IGFBP-1 level had returned to baseline. The physiological role of this increment could be the inhibition of hypoglycemic effects of IGF-I and/or regulation of glucose availability to the muscles. The changes in IGF-I and IGFBP-3 levels were less dramatic: the IGF-I and IGFBP-3 levels were lower 1 and 3 days after the run. This report provides an important basis for authentic effects of strenuous exercise on the IGF-system.


2021 ◽  
Vol 8 ◽  
Author(s):  
Marion Charton ◽  
Gäelle Kervio ◽  
David Matelot ◽  
Thibault Lachard ◽  
Elena Galli ◽  
...  

Background: Echocardiographic signs of exercise-induced cardiac fatigue (EICF) have been described after strenuous endurance exercise. Nevertheless, few data are available on the effects of repeated strenuous exercise, especially when associated with other constraints as sleep deprivation or mental stress which occur during military selection boot camps. Furthermore, we aimed to study the influence of experience and training level on potential EICF signs.Methods: Two groups of trained soldiers were included, elite soldiers from the French Navy Special Forces (elite; n = 20) and non-elite officer cadets from a French military academy (non-elite; n = 38). All underwent echocardiography before and immediately after exposure to several days of uninterrupted intense exercise during their selection boot camps. Changes in myocardial morphology and function of the 4 cardiac chambers were assessed.Results: Exercise-induced decrease in right and left atrial and ventricular functions were demonstrated with 2D-strain parameters in both groups. Indeed, both atrial reservoir strain, RV and LV longitudinal strain and LV global constructive work were altered. Increase in LV mechanical dispersion assessed by 2D-strain and alteration of conventional parameters of diastolic function (increase in E/e' and decrease in e') were solely observed in the non-elite group. Conventional parameters of LV and RV systolic function (LVEF, RVFAC, TAPSE, s mitral, and tricuspid waves) were not modified.Conclusions: Alterations of myocardial functions are observed in soldiers after uninterrupted prolonged intense exercise performed during selection boot camps. These alterations occur both in elite and non-elite soldiers. 2D-strain is more sensitive to detect EICF than conventional echocardiographic parameters.


1982 ◽  
Vol 48 (02) ◽  
pp. 201-203 ◽  
Author(s):  
N A Marsh ◽  
P J Gaffney

SummaryThe effect of strenuous exercise on the fibrinolytic and coagulation mechanisms was examined in six healthy male subjects. Five min bicycle exercise at a work-rate of 800 to 1200 kpm. min−1 produced an abrupt increase in plasma plasminogen activator levels which disappeared after 90 min. However, there was no change in early or late fibrin degradation products nor was there a change in fibrinopeptide A levels or βthromboglobulin levels after exercise although activated partial thromboplastin times were significantly shortened. It is concluded that strenuous exercise does not produce any real increase in fibrinogen-fibrin conversion nor any real increase in the breakdown of these proteins. The role of exercise-induced release of plasminogen activator remains unclear, but probably helps to maintain plasma levels in a discontinuous manner concurrently with the continuous low-level secretion from the vascular wall. The shortening of partial thromboplastin time may be due to the raised levels of plasminogen activator changing the activation state of other coagulation factors.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 289
Author(s):  
Amelia Marti ◽  
Isabel Martínez ◽  
Ana Ojeda-Rodríguez ◽  
María Cristina Azcona-Sanjulian

Background: Elevated circulating plasma levels of both lipopolysaccharide-binding protein (LBP) and chemerin are reported in patients with obesity, but few studies are available on lifestyle intervention programs. We investigated the association of both LBP and chemerin plasma levels with metabolic syndrome (MetS) outcomes in a lifestyle intervention in children and adolescents with abdominal obesity Methods: Twenty-nine patients enrolled in a randomized controlled trial were selected. The lifestyle intervention with a 2-month intensive phase and a subsequent 10-month follow-up consisted of a moderate calorie-restricted diet, recommendations to increase physical activity levels, and nutritional education. Results: Weight loss was accompanied by a significant reduction in MetS prevalence (−43%; p = 0.009). Chemerin (p = 0.029) and LBP (p = 0.033) plasma levels were significantly reduced at 2 months and 12 months, respectively. At the end of intervention, MetS components were associated with both LBP (p = 0.017) and chemerin (p < 0.001) plasma levels. Conclusions: We describe for the first time a reduction in both LBP and chemerin plasma levels and its association with MetS risk factors after a lifestyle intervention program in children and adolescents with abdominal obesity. Therefore, LBP and chemerin plasma levels could be used as biomarkers for the progression of cardiovascular risk in pediatric populations.


Author(s):  
Mette Wærstad Hansen ◽  
Stein Ørn ◽  
Christine B. Erevik ◽  
Magnus Friestad Bjørkavoll-Bergseth ◽  
Øyvind Skadberg ◽  
...  

Abstract Background Dietary supplement use among recreational athletes is common, with the intention of reducing inflammation and improving recovery. We aimed to describe the relationship between omega-3 fatty acid supplement use and inflammation induced by strenuous exercise. Methods C-reactive protein (CRP) concentrations were measured in 1002 healthy recreational athletes before and 24 h after a 91-km bicycle race. The use of omega-3 fatty acid supplements was reported in 856 out of 1002 recreational athletes, and the association between supplement use and the exercise-induced CRP response was assessed. Results Two hundred seventy-four subjects reported regular use of omega-3 fatty acid supplements. One hundred seventy-three of these used cod liver oil (CLO). Regular users of omega-3 fatty acid supplements had significantly lower basal and exercise-induced CRP levels as compared to non-users (n = 348, p < 0.001). Compared to non-users, regular users had a 27% (95% confidence interval (CI): 14–40) reduction in Ln CRP response (unadjusted model, p < 0.001) and 16% (95% CI: 5–28, p = 0.006) reduction after adjusting for age, sex, race duration, body mass index, delta creatine kinase, MET hours per week, resting heart rate and higher education. CLO was the primary driver of this response with a 34% (95% CI: 19–49) reduction (unadjusted model, p < 0.001) compared to non-users. Corresponding numbers in the adjusted model were 24% (95% CI: 11–38, p < 0.001). Conclusion Basal CRP levels were reduced, and the exercise-induced CRP response was attenuated in healthy recreational cyclists who used omega-3 fatty acid supplements regularly. This effect was only present in regular users of CLO. Trial registration NCT02166216, registered June 18, 2014 – Retrospectively registered.


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