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Circulating cell free DNA response to exhaustive exercise in average trained men with type I diabetes mellitus.

ABSTRACT: It is believed that neutrophils extracellular traps (NETs) formation is responsible for the increase in cf DNA after exercise. Since T1DM is accompanied by enhanced NETs generation, we compared exercise-induced increase in cf DNA in 14 men with T1DM and 11 healthy controls and analyzed its association with exercise load. Subjects performed a treadmill run to exhaustion at speed corresponding to 70% of their personal VO2max. Blood was collected before and just after exercise for determination of plasma cf nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) by real-time PCR, blood cell count and metabolic markers. Exercise resulted in the increase in median cf n-DNA from 3.9 ng/mL to 21.0 ng/mL in T1DM group and from 3.3 ng/mL to 28.9 ng/mL in controls. Median exercise-induced increment (?) in cf n-DNA did not differ significantly in both groups (17.8 ng/mL vs. 22.1 ng/mL, p?=?0.23), but this variable correlated with run distance (r?=?0.66), ? neutrophils (r?=?0.86), ? creatinine (r?=?0.65) and ? creatine kinase (r?=?0.77) only in controls. Pre- and post-exercise cf mt-DNA were not significantly different within and between groups. These suggest low usefulness of ? cf n-DNA as a marker of exercise intensity in T1DM men.

SUBMITTER: Walczak K

PROVIDER: S-EPMC7907132 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Circulating cell free DNA response to exhaustive exercise in average trained men with type I diabetes mellitus.

Walczak Konrad K Stawski Robert R Perdas Ewelina E Brzezinska Olga O Kosielski Piotr P Galczynski Szymon S Budlewski Tomasz T Padula Gianluca G Nowak Dariusz D

Scientific reports 20210225 1

It is believed that neutrophils extracellular traps (NETs) formation is responsible for the increase in cf DNA after exercise. Since T1DM is accompanied by enhanced NETs generation, we compared exercise-induced increase in cf DNA in 14 men with T1DM and 11 healthy controls and analyzed its association with exercise load. Subjects performed a treadmill run to exhaustion at speed corresponding to 70% of their personal VO2max. Blood was collected before and just after exercise for determination of ...[more]

PMID: 33633280

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Project description:Acute single strenuous exercise increases circulating cell free DNA (cf DNA). We tested whether three repeated bouts of exhaustive exercise induced the cf DNA response without development of tolerance in healthy men.Eleven average-trained men (age 34.0±5.2 years, body mass index 26.2±3.1 kg/m2, maximal oxygen consumption-VO2max 49.6±4.5 ml/kg*min) performed three treadmill exercise tests to exhaustion at speed corresponding to 70% VO2max separated by 72 hours of resting. Blood was collected before and after each bout of exercise for determination of cell free nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) by real-time PCR, selected markers of muscle damage, and blood cell count.Each bout induced the increase (p<0.05) in plasma cf n-DNA: from 3.4±1.4 to 38.5±27.5, from 4.1±3.3 to 48.5±26.2, and 3.1±1.6 to 53.8±39.9 ng/mL after the first, second, and third exercise, respectively. In a congruent way, cf mt-DNA rose significantly after the second (from 229±216 to 450±228*103 GE/mL) and third bout of exercise (from 173±120 to 462±314*103 GE/mL). Pre-exercise cf mt-DNA decreased (p<0.05) by 2-times (from 355±219 before the first bout to 173±120*103 GE/mL before the third bout) over the study period and were accompanied by significant increase in white blood cells, platelets, creatine kinase, creatinine and lactate after each bout. However, the exercise induced percentage increment of cf n-DNA was always many times higher than corresponding increments of the afore-mentioned markers at any occasion.Repeated bouts of exhaustive exercise induced remarkable increase in circulating cf n-DNA without signs of tolerance development. Baseline cf mt-DNA decreased in response to series of strenuous exercise. Since percentage increments of cf n-DNA in response to exercise were many times higher than those observed for other markers, measurement of circulating cf n-DNA could be a sensitive tool for monitoring acute exercise effects in human body.

Project description:Exhaustive exercise can cause a transient depression of immune function. Data indicate significant effects of immune activation cascades on the biochemistry of monoamines and amino acids such as tryptophan. Tryptophan can be metabolized through different pathways, a major route being the kynurenine pathway, which is often systemically up-regulated when the immune response is activated. The present study was undertaken to examine the effect of exhaustive aerobic exercise on biomarkers of immune activation and tryptophan metabolism in trained athletes. After a standardized breakfast 2 h prior to exercise, 33 trained athletes (17 women, 16 men) performed an incremental cycle ergometer exercise test at 60 rpm until exhaustion. After a 20 min rest phase, the participants performed a 20 min maximal time-trial on a cycle ergometer (RBM Cyclus 2, Germany). During the test, cyclists were strongly encouraged to choose a maximal pedalling rate that could be maintained for the respective test duration. Serum concentrations of amino acids tryptophan, kynurenine, phenylalanine, and tyrosine were determined by HPLC and immune system biomarker neopterin by ELISA at rest and immediately post exercise. Intense exercise was associated with a strong increase in neopterin concentrations (p<0.001), indicating increased immune activation following intense exercise. Exhaustive exercise significantly reduced tryptophan concentrations by 12% (p<0.001) and increased kynurenine levels by 6% (p = 0.022). Also phenylalanine to tyrosine ratios were lower after exercise as compared with baseline (p<0.001). The kynurenine to tryptophan ratio correlated with neopterin (r = 0.560, p<0.01). Thus, increased tryptophan catabolism by indoleamine 2,3-dioxygenase appears likely. Peak oxygen uptake correlated with baseline tryptophan and kynurenine concentrations (r = 0.562 and r = 0.511, respectively, both p<0.01). Findings demonstrate that exhaustive aerobic exercise is associated with increased immune activation and alterations in monoamine metabolism in trained athletes which may play a role in the regulation of mood and cognitive processes.

Project description:Exercise has multi-systemic benefits and attenuates the physiological impairments associated with aging. Emerging evidence suggests that circulating exosomes mediate some of the beneficial effects of exercise via the transfer of microRNAs between tissues. However, the impact of regular exercise and acute exercise on circulating exosomal microRNAs (exomiRs) in older populations remains unknown. In the present study, we analyzed circulating exomiR expression in endurance-trained elderly men (n = 5) and age-matched sedentary males (n = 5) at baseline (Pre), immediately after a forty minute bout of aerobic exercise on a cycle ergometer (Post), and three hours after this acute exercise (3hPost). Following the isolation and enrichment of exosomes from plasma, exosome-enriched preparations were characterized and exomiR levels were determined by sequencing. The effect of regular exercise on circulating exomiRs was assessed by comparing the baseline expression levels in the trained and sedentary groups. The effect of acute exercise was determined by comparing baseline and post-training expression levels in each group. Regular exercise resulted in significantly increased baseline expression of three exomiRs (miR-486-5p, miR-215-5p, miR-941) and decreased expression of one exomiR (miR-151b). Acute exercise altered circulating exomiR expression in both groups. However, exomiRs regulated by acute exercise in the trained group (7 miRNAs at Post and 8 at 3hPost) were distinct from those in the sedentary group (9 at Post and 4 at 3hPost). Pathway analysis prediction and reported target validation experiments revealed that the majority of exercise-regulated exomiRs are targeting genes that are related to IGF-1 signaling, a pathway involved in exercise-induced muscle and cardiac hypertrophy. The immediately post-acute exercise exomiR signature in the trained group correlates with activation of IGF-1 signaling, whereas in the sedentary group it is associated with inhibition of IGF-1 signaling. While further validation is needed, including measurements of IGF-1/IGF-1 signaling in blood or skeletal muscle, our results suggest that training status may counteract age-related anabolic resistance by modulating circulating exomiR profiles both at baseline and in response to acute exercise.

Project description:AIM:The aim of the study was to investigate pharmacokinetics of terbutaline after oral and inhaled administration in healthy trained male subjects in relation to doping control. METHODS:Twelve healthy well-trained young men (27 ±2 years; mean ± SE) underwent two pharmacokinetic trials that compared 10 mg oral terbutaline with 4 mg inhaled dry powder terbutaline. During each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption. Blood (0-4 h) and urine (0-24 h) samples were collected before and after administration of terbutaline. Samples were analyzed for concentrations of terbutaline by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). RESULTS:Pharmacokinetics differed between the two routes of administration. Serum Cmax and area under the serum concentration-time curve (AUC) were lower after oral administration compared to inhalation (Cmax: 4.2 ± 0.3 vs. 8.5 ± 0.7 ng/ml, P ? 0.001; AUC: 422 ± 22 vs. 1308 ± 119 ng/ml × min). Urine concentrations (sum of the free drug and the glucuronide) were lower after oral administration compared to inhalation 2 h (1100 ± 204 vs. 61 ± 10 ng/ml, P ? 0.05) and 4 h (734 ± 110 vs. 340 ± 48 ng/ml, P ? 0.001) following administration, whereas concentrations were higher for oral administration than inhalation 12 h following administration (190 ± 41 vs. 399 ± 108 ng/ml, P ? 0.05). Urine excretion rate was lower after oral administration than inhalation the first 2 h following administration (P ? 0.001). Systemic bioavailability ratio between the two routes of administration was 3.8:1 (inhaled: oral; P ? 0.001). CONCLUSION:Given the higher systemic bioavailability of inhaled terbutaline compared to oral, our results indicate that it is difficult to differentiate allowed inhaled use of terbutaline from prohibited oral ingestion based on urine concentrations in doping control analysis. However given the potential performance enhancing effect of high dose terbutaline, it is essential to establish a limit on the WADA doping list.

Project description:The purpose of this investigation was to compare changes in circulating lymphocyte subset cell counts between high-intensity interval exercise (HIIE), sprint interval exercise (SIE), and moderate-intensity continuous exercise (MICE). Recreationally active men (n = 11; age: 23 ± 4 yr; height: 179.9 ± 4.5 cm; body mass: 79.8 ± 8.7 kg; body fat %:12.6 ± 3.8%; V̇O2max: 46.6 ± 3.9 ml⋅kg-1⋅min-1) completed a maximal graded exercise test to determine maximal oxygen uptake (V̇O2max) and three duration-matched cycling trials (HIIE, SIE, and MICE) in a randomized, counterbalanced fashion. HIIE consisted of fifteen 90-s bouts at 85% V̇O2max interspersed with 90-s active recovery periods. SIE consisted of fifteen 20-s bouts at 130% maximal power and 160-s active recovery periods. MICE was a continuous bout at 65% V̇O2max. Total exercise duration was 53 min in all three trials, including warm-up and cool-down. Blood was collected before, immediately post, 30 min, 2 h, 6 h, and 24 h post-exercise. Changes in lymphocyte subset counts, and surface expression of various markers were analyzed via flow cytometry. Changes were assessed using mixed model regression analysis with an autoregressive first order repeated measures correction. Significant decreases were observed in absolute counts of CD56dim NK cells, CD19+ B cells, CD4+ T cells, and CD8+ T cells 30 min and 24-h post-exercise in all three trials. Despite resulting in greater total work and oxygen consumption, MICE elicited similar changes in lymphocyte subset counts and receptor expression compared to both SIE and HIIE. Similarly, while the two interval trials resulted in differing oxygen consumption and total work, no differences in the lymphocyte response were observed. Though both forms of exercise resulted in declines in circulating lymphocyte cell counts, neither exercise type provides an immune-related advantage when matched for duration.

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Circulating cell free DNA response to exhaustive exercise in average trained men with type I diabetes mellitus.

Publications

Circulating cell free DNA response to exhaustive exercise in average trained men with type I diabetes mellitus.

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