RESUMEN
Exercise facilitates cerebral lactate uptake, likely by increasing arterial lactate concentration and hence the diffusion gradient across the blood-brain barrier. However, nonspecific ß-adrenergic blockade by propranolol has previously reduced the arterio-jugular venous lactate difference (AVLac) during exercise, suggesting ß-adrenergic control of cerebral lactate uptake. Alternatively, we hypothesized that propranolol reduces cerebral lactate uptake by decreasing arterial lactate concentration. To test that hypothesis, we evaluated cerebral lactate uptake taking changes in arterial concentration into account. Nine healthy males performed incremental cycling exercises to exhaustion with and without intravenous propranolol (18.7 ± 1.9 mg). Lactate concentration was determined in arterial and internal jugular venous blood at the end of each workload. To take changes in arterial lactate into account, we calculated the fractional extraction (FELac) defined as AVLac divided by the arterial lactate concentration. Arterial lactate concentration was reduced by propranolol at any workload (P < 0.05), reaching 14 ± 3 and 11 ± 3 mmol·l-1 during maximal exercise without and with propranolol, respectively. Although AVLac and FELac increased during exercise (both P < 0.05), they were both unaffected by propranolol at any workload (P = 0.68 and P = 0.26) or for any given arterial lactate concentration (P = 0.78 and P = 0.22). These findings support that while propranolol may reduce cerebral lactate uptake, this effect reflects the propranolol-induced reduction in arterial lactate concentration and not inhibition of a ß-adrenergic mechanism within the brain. We hence conclude that cerebral lactate uptake during exercise is directly driven by the increasing arterial concentration with work rate.NEW & NOTEWORTHY During exercise the brain consumes lactate as a substitute for glucose. Propranolol has previously attenuated this cerebral lactate uptake, suggesting a ß-adrenergic transport mechanism. However, in the present study, we demonstrate that the fractional extraction of arterial lactate by the brain is unaffected by propranolol throughout incremental exercise to exhaustion. We conclude that cerebral lactate uptake during exercise is passively driven by the increasing arterial concentration, rather than by a ß-adrenergic mechanism within the brain.
Asunto(s)
Antagonistas Adrenérgicos beta , Ácido Láctico , Ciclismo , Ejercicio Físico , Humanos , Masculino , PropranololRESUMEN
OBJECTIVES: Optimized concurrent training regimes are warranted in physical training of military-, law enforcement- and rescue-personnel. This study investigated if four 15-min endurance training sessions weekly improve aerobic capacity and performance more than one 60-min endurance session weekly during the initial phase of a Basic Military Training program. DESIGN: A randomized training intervention study with functional and physiological tests before and after the intervention. METHODS: Military conscripts (n=290) were randomly allocated to three groups completing 9 weeks training. Weekly training consisted of four endurance and four strength training sessions lasting 15min each ('Micro-training': MIC); one strength and one endurance session lasting 60min each ('Classical-training': CLA) or two 60min sessions of standard military training ('Control-training': CON). RESULTS: Both 12-min (â¼7-10%) and shuttle run performance (â¼35-42%) improved (P≤0.001) similarly in all groups. Likewise, functional 2-min maximal repetition exercise capacity increased (P≤0.05) similarly in all groups (Lunges â¼17-24 %; PushUp â¼10-20%; AbdominalFlexionsâ¼21-23%). Peak oxygen uptake changes depended on group (P≤0.05) with increases (P≤0.01) in MIC (7±7%, n=23) and CON (12±18%, n=17) and no changes in CLA. Maximal m. vastus lateralis citrate synthase activity decreased 14±26% (P≤0.001, n=18) in CLA. Likewise, maximal m. vastus lateralis 3-hydroxyacyl-CoA dehydrogenase activity decreased 8±17% in MIC (n=28) and 14±24% in CLA (n=18). CONCLUSIONS: Four 15-min endurance training sessions weekly improves running performance and strength-endurance similarly to one 60min session. Peak oxygen uptake only increases with more than one endurance session weekly and leg muscle oxidative capacity appears reduced after basic military training.
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Entrenamiento Aeróbico/métodos , Tolerancia al Ejercicio/fisiología , Personal Militar , Entrenamiento de Fuerza/métodos , Carrera/fisiología , 3-Hidroxiacil-CoA Deshidrogenasa/metabolismo , Colesterol/sangre , Citrato (si)-Sintasa/metabolismo , Femenino , Humanos , Masculino , Consumo de Oxígeno/fisiología , Músculo Cuádriceps/metabolismo , Factores de TiempoRESUMEN
OBJECTIVES: Military-, rescue- and law-enforcement personnel require a high physical capacity including muscular strength. The present study hypothesized that 9 weeks of volume matched concurrent short frequent training sessions increases strength more efficiently than less frequent longer training sessions. DESIGN: A randomized training intervention study with functional and physiological tests before and after the intervention. METHODS: Military conscripts (n=290) were assigned to micro-training (four 15-min strength and four 15-min endurance bouts weekly); classical-training (one 60-min strength and one 60-min endurance training session weekly) or a control-group (two 60-min standard military physical training sessions weekly). RESULTS: There were no group difference between micro-training and classical-training in measures of strength. Standing long jump remained similar while shotput performance was reduced (P≤0.001) in all three groups. Pull-up performance increased (P≤0.001) in micro-training (7.4±4.6 vs. 8.5±4.0 repetitions, n=59) and classical-training (5.7±4.1 vs. 7.1±4.2 repetitions, n=50). Knee extensor MVC increased (P≤0.01) in all groups (micro-training, n=30, 11.5±8.9%; classical-training, n=24, 8.3±11.5% and control, n=19, 7.5±11.8%) while elbow flexor and hand grip MVC remained similar. Micro-training increased (P≤0.05) type IIa percentage from 32.5±11.0% to 37.6±12.3% (n=20) and control-group increased (P≤0.01) type IIax from 4.4±3.0% to 11.6±7.9% (n=8). In control-group type I, fiber size increased (P≤0.05) from 5121±959µm to 6481±2084µm (n=5). Satellite cell content remained similar in all groups. CONCLUSIONS: Weekly distribution of low-volume concurrent training completed as either eight 15-min bouts or two 60-min sessions of which 50% was strength training did not impact strength gains in a real-world setting.
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Entrenamiento Aeróbico/métodos , Personal Militar , Fuerza Muscular/fisiología , Entrenamiento de Fuerza/métodos , Femenino , Voluntarios Sanos , Humanos , Masculino , Adulto JovenRESUMEN
Erythropoietin (EPO) is expressed in human brain tissue, but its exact role is unknown. EPO may improve the efficiency of oxidative metabolism and has neuroprotective properties against hypoxic injuries in animal models. We aimed to investigate the effect of recombinant human EPO (rHuEPO) administration on healthy cerebral metabolism in humans during normoxia and during metabolic stress by inhalation of 10% O2 hypoxic air. Twenty-four healthy men participated in a two-arm double-blind placebo-controlled trial. rHuEPO was administered as a low dose (5,000 IU) over 4 wk ( n = 12) or as a high dose (500 IU·kg body wt-1·day-1) for three consecutive days ( n = 12). Global cerebral blood flow (CBF) and metabolic rate of glucose (CMRglc) were measured with positron emission tomography. CBF, metabolic rate of oxygen ([Formula: see text]), and cerebral lactate concentration were measured by magnetic resonance imaging and spectroscopy. Low-dose treatment increased hemoglobin and was associated with a near-significant decrease in CBF during baseline normoxia. High-dose treatment caused no change in CBF. Neither treatment had an effect on normoxia CMRglc, [Formula: see text], or lactate concentration or an effect on the cerebral metabolic response to inhalation of hypoxic air. In conclusion, the study found no evidence for a direct effect of rHuEPO on cerebral metabolism. NEW & NOTEWORTHY We demonstrate with magnetic resonance imaging and positron emission tomography that administration of erythropoietin does not have a substantial direct effect on healthy human resting cerebral blood flow or effect on cerebral glucose and oxygen metabolism. Also, administration of erythropoietin did not have a direct effect on the metabolic response to acute hypoxic stress in healthy humans, and a suggested neuroprotective effect from erythropoietin is therefore likely not a direct effect of erythropoietin on cerebral metabolism.
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Circulación Cerebrovascular/efectos de los fármacos , Cerebro/metabolismo , Eritropoyetina/administración & dosificación , Adulto , Cerebro/diagnóstico por imagen , Metabolismo Energético , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía de Emisión de PositronesRESUMEN
PURPOSE: To compare mean global cerebral blood flow (CBF) measured by phase-contrast mapping magnetic resonance imaging (PCM MRI) and by 15 O-H2 O positron emission tomography (PET) in healthy subjects. PCM MRI is increasingly being used to measure mean global CBF, but has not been validated in vivo against an accepted reference technique. MATERIALS AND METHODS: Same-day measurements of CBF by 15 O-H2 O PET and subsequently by PCM MRI were performed on 22 healthy young male volunteers. Global CBF by PET was determined by applying a one-tissue compartment model with measurement of the arterial input function. Flow was measured in the internal carotid and vertebral arteries by a noncardiac triggered PCM MRI sequence at 3T. The measured flow was normalized to total brain weight determined from a volume-segmented 3D T1 -weighted anatomical MR-scan. RESULTS: Mean CBF was 34.9 ± 3.4 mL/100 g/min measured by 15 O-H2 O PET and 57.0 ± 6.8 mL/100 g/min measured by PCM MRI. The measurements were highly correlated (P = 0.0008, R2 = 0.44), although values obtained by PCM MRI were higher compared to 15 O-H2 O PET (absolute and relative differences were 22.0 ± 5.2 mL/100 g/min and 63.4 ± 14.8%, respectively). CONCLUSION: This study confirms the use of PCM MRI for quantification of global CBF, but also that PCM MRI systematically yields higher values relative to 15 O-H2 O PET, probably related to methodological bias. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:692-699.
Asunto(s)
Velocidad del Flujo Sanguíneo/fisiología , Encéfalo/fisiología , Circulación Cerebrovascular/fisiología , Angiografía por Resonancia Magnética/métodos , Radioisótopos de Oxígeno , Oxígeno/sangre , Tomografía de Emisión de Positrones/métodos , Adolescente , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Imagen Multimodal/métodos , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Agua , Adulto JovenRESUMEN
The sensitivity of the adaptive model of the Athlete Biological Passport (ABP) and reticulocyte percentage (ret%) in detection of recombinant human erythropoietin (rHuEPO) misuse was evaluated using both a long-term normal dose and a brief high dose treatment regime. Sixteen subjects received either 65 IU rHuEPO × kg-1 every second day for two weeks (normal-dose), 390 IU rHuEPO × kg-1 on three consecutive days (high-dose), or frequent placebo treatment for 13 days in a randomized, placebo-controlled, double-blind crossover design. Blood variables were measured 4, 11, and 25 days following treatment initiation. The ABP based on haemoglobin concentration ([Hb]) and OFF-hr score ([Hb] - 60 × âret%) yielded atypical profiles following both normal-dose and high-dose treatment (0 %, 31 %, 13 % vs. 21 %, 33 %, 20 % at days 4, 11, and 25 after normal and high dose, respectively). Including ret% as a stand-alone marker for atypical blood profiles increased (P < 0.05) the sensitivity of the adaptive model at day 11 to 63 % and 67 % for normal-dose and high-dose rHuEPO administration, respectively. In conclusion, ~30 % of subjects injecting a normal-dose rHuEPO for two weeks or a high-dose rHuEPO for three days will present an atypical ABP profile. Including ret% as a stand-alone parameter improves the sensitivity two-fold. Copyright © 2015 John Wiley & Sons, Ltd.
Asunto(s)
Epoetina alfa/metabolismo , Eritropoyetina/sangre , Eritropoyetina/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Recuento de Reticulocitos/métodos , Atletas , Doping en los Deportes , Método Doble Ciego , Esquema de Medicación , Epoetina alfa/química , Eritropoyetina/administración & dosificación , Eritropoyetina/química , HumanosRESUMEN
The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% ([Formula: see text]), glutamate increased by 4.7% ([Formula: see text]) and creatine and phosphocreatine decreased by 15.2% (p[Formula: see text]). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia.
Asunto(s)
Encéfalo/metabolismo , Metabolismo Energético/fisiología , Hipoxia/metabolismo , Adolescente , Adulto , Encéfalo/patología , Circulación Cerebrovascular/fisiología , Creatina/sangre , Ácido Glutámico/sangre , Homeostasis , Humanos , Ácido Láctico/sangre , Imagen por Resonancia Magnética/métodos , Masculino , Oxígeno/sangre , Perfusión , Adulto JovenRESUMEN
The membrane-assisted isoform immunoassay (MAIIA) quantitates erythropoietin (EPO) isoforms as percentages of migrated isoforms (PMI). We evaluated the effect of recombinant human EPO (rhEPO) on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13); high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13); or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3) % (mean (SD)). High-dose Epoetin beta decreased PMI on days 4 and 11 to 31.0 (4.2)% (p<0.00001) and 45.2 (7.3)% (p<0.00001). Low-dose Epoetin beta decreased PMI on days 4 and 11 to 46.0 (12.8)% (p<0.00001) and 46.1 (10.4)% (p<0.00001). In both rhEPO groups, PMI on day 25 was still decreased (high-dose Epoetin beta: 72.9 (19.4)% (p=0.029); low-dose Epoetin beta: 73.1 (17.8)% (p=0.039)). In conclusion, Epoetin beta leaves a footprint in the plasma-EPO isoform pattern. MAIIA can detect changes in EPO isoform distribution up til at least three weeks after administration of Epoetin beta even though the total EPO concentration has returned to normal.
Asunto(s)
Eritropoyetina/sangre , Isoformas de Proteínas/sangre , Proteínas Recombinantes/sangre , Adulto , Estudios Cruzados , Eritropoyetina/administración & dosificación , Eritropoyetina/genética , Humanos , Masculino , Isoformas de Proteínas/genética , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/genéticaRESUMEN
The local anaesthetic lidocaine is known to block voltage-gated Na(+) channels (VGSCs), although at high concentration it was also reported to block other ion channel currents as well as to alter lipid membranes. The aim of this study was to investigate whether the clinical regional anaesthetic action of lidocaine could be accounted for solely by the block of VGSCs or whether other mechanisms are also relevant. We tested the recovery of motor axon conduction and multiple measures of excitability by 'threshold-tracking' after ultrasound-guided distal median nerve regional anaesthesia in 13 healthy volunteers. Lidocaine caused rapid complete motor axon conduction block localized at the wrist. Within 3 h, the force of the abductor pollicis brevis muscle and median motor nerve conduction studies returned to normal. In contrast, the excitability of the motor axons at the wrist remained markedly impaired as indicated by a 7-fold shift of the stimulus-response curves to higher currents with partial recovery by 6 h and full recovery by 24 h. The strength-duration properties were abnormal with markedly increased rheobase and reduced strength-duration time constant. The changes in threshold during electrotonus, especially during depolarization, were markedly reduced. The recovery cycle showed increased refractoriness and reduced superexcitability. The excitability changes were only partly similar to those previously observed after poisoning with the VGSC blocker tetrodotoxin. Assuming an unaltered ion-channel gating, modelling indicated that, apart from up to a 4-fold reduction in the number of functioning VGSCs, lidocaine also caused a decrease of passive membrane resistance and an increase of capacitance. Our data suggest that the lidocaine effects, even at clinical 'sub-blocking' concentrations, could reflect, at least in part, a reversible structural impairment of the axolemma.
Asunto(s)
Anestésicos Locales/farmacología , Axones/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Lidocaína/farmacología , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacología , Adulto , Anestesia Local , Axones/fisiología , Femenino , Humanos , Masculino , Modelos Neurológicos , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/fisiología , Músculo Esquelético/inervación , Conducción NerviosaRESUMEN
OBJECTIVE: In a recent study, we found that Greenlandic Inuit children had a more adverse metabolic profile than Danish children. Aerobic fitness and adiposity could only partly account for the differences. Therefore, we set out to evaluate and compare plasma leptin and adiponectin levels in Danish and Inuit children. METHODS: In total, 187 Inuit and 132 Danish children (5.7-17.1 years) had examinations of anthropometrics, body fat content, pubertal staging, fasting blood and aerobic fitness. RESULTS: Plasma leptin was higher in Danish boys [3,774 (4,741-3,005)] [pg/mL unadjusted geometric mean (95% CI)] compared to both northern [2,076 (2,525-1,706)] (p < 0.001) and southern (2,515 (3,137-2,016)) (p < 0.001) living Inuit boys and higher in Danish girls [6,988 (8,353-5,847)] compared to southern living Inuit girls [4,910 (6,370-3,785)] (p = 0.021) and tended to be higher compared to northern living Inuit girls [5,131 (6,444-4,085)] (p = 0.052). Plasma adiponectin was higher for both Danish boys [22,359 (2,573-19,428)] [ng/mL unadjusted geometric mean (95% CI)] and girls [26,609 (28,994-24,420)] compared to southern living Inuit boys [15,306 (18,406-12,728)] and girls [18,864 (22,640-15,717)] (both p < 0.001), respectively. All differences remained after adjustment for body fat percentage (BF%), aerobic fitness, age and puberty. The leptin/adiponectin ratio was higher in Danish boys and tended to be higher in Danish girls compared to northern living Inuit boys and girls, respectively. These differences were eliminated after adjustment for BF%, aerobic fitness, age and puberty. CONCLUSIONS: In contrast to our hypothesis, plasma leptin was higher in Danish children despite a more healthy metabolic profile compared to Inuit children. As expected, plasma adiponectin was lowest in Inuit children with the most adverse metabolic profile.
Asunto(s)
Adiponectina/sangre , Inuk , Leptina/sangre , Tejido Adiposo , Adolescente , Factores de Edad , Regiones Árticas/epidemiología , Niño , Preescolar , Dinamarca/epidemiología , Femenino , Groenlandia/epidemiología , Humanos , Masculino , Obesidad/sangre , Obesidad/etnología , Aptitud Física , Pubertad/fisiología , Factores SexualesRESUMEN
To elucidate the molecular mechanisms behind physical inactivity-induced insulin resistance in skeletal muscle, 12 young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies obtained before and after. In six of the subjects, muscle biopsies were taken from both legs before and after a 3-h hyperinsulinemic euglycemic clamp performed 3 h after a 45-min, one-legged exercise. Blood samples were obtained from one femoral artery and both femoral veins before and during the clamp. Glucose infusion rate and leg glucose extraction during the clamp were lower after than before bed rest. This bed rest-induced insulin resistance occurred together with reduced muscle GLUT4, hexokinase II, protein kinase B/Akt1, and Akt2 protein level, and a tendency for reduced 3-hydroxyacyl-CoA dehydrogenase activity. The ability of insulin to phosphorylate Akt and activate glycogen synthase (GS) was reduced with normal GS site 3 but abnormal GS site 2+2a phosphorylation after bed rest. Exercise enhanced insulin-stimulated leg glucose extraction both before and after bed rest, which was accompanied by higher GS activity in the prior-exercised leg than the rested leg. The present findings demonstrate that physical inactivity-induced insulin resistance in muscle is associated with lower content/activity of key proteins in glucose transport/phosphorylation and storage.
Asunto(s)
Reposo en Cama/efectos adversos , Transportador de Glucosa de Tipo 4/metabolismo , Glucógeno Sintasa/metabolismo , Resistencia a la Insulina/fisiología , Benzodiazepinonas , Glucemia , Proteínas Activadoras de GTPasa/genética , Proteínas Activadoras de GTPasa/metabolismo , Regulación de la Expresión Génica/fisiología , Glucosa/administración & dosificación , Transportador de Glucosa de Tipo 4/genética , Glucógeno/metabolismo , Glucógeno Sintasa/genética , Humanos , Insulina/metabolismo , Masculino , Músculo Esquelético/metabolismo , Palmitatos/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
To determine patient priority and degree of urgency with an objective high-quality evaluation, general Point of Care testing (POCT) was established as a novel facility in the emergency department at Holbæk Hospital, a laboratory that provides faster results for common lab tests. When evaluating response time from arrival of the patient to the time at which the test results are available, POCT is not a significantly better test method than ordinary test methods. This indicates that in order to benefit from POCT the time before taking blood samples should be reduced to a minimum. Overcrowding needs to be controlled in order to accomplish this.
Asunto(s)
Servicio de Urgencia en Hospital , Pruebas Hematológicas , Sistemas de Atención de Punto , Dinamarca , Servicio de Urgencia en Hospital/normas , Pruebas Hematológicas/métodos , Pruebas Hematológicas/normas , Humanos , Admisión del Paciente , Sistemas de Atención de Punto/normas , Factores de TiempoRESUMEN
The aim was to test the hypothesis that 7 days of bed rest reduces mitochondrial number and expression and activity of oxidative proteins in human skeletal muscle but that exercise-induced intracellular signaling as well as mRNA and microRNA (miR) responses are maintained after bed rest. Twelve young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies taken before and after bed rest. In addition, muscle biopsies were obtained from six of the subjects prior to, immediately after, and 3 h after 45 min of one-legged knee extensor exercise performed before and after bed rest. Maximal oxygen uptake decreased by 4%, and exercise endurance decreased nonsignificantly, by 11%, by bed rest. Bed rest reduced skeletal muscle mitochondrial DNA/nuclear DNA content 15%, hexokinase II and sirtuin 1 protein content â¼45%, 3-hydroxyacyl-CoA dehydrogenase and citrate synthase activity â¼8%, and miR-1 and miR-133a content â¼10%. However, cytochrome c and vascular endothelial growth factor (VEGF) protein content as well as capillarization did not change significantly with bed rest. Acute exercise increased AMP-activated protein kinase phosphorylation, peroxisome proliferator activated receptor-γ coactivator-1α, and VEGF mRNA content in skeletal muscle before bed rest, but the responses were abolished after bed rest. The present findings indicate that only 7 days of physical inactivity reduces skeletal muscle metabolic capacity as well as abolishes exercise-induced adaptive gene responses, likely reflecting an interference with the ability of skeletal muscle to adapt to exercise.
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Ejercicio Físico/fisiología , Mitocondrias/metabolismo , Músculo Esquelético/metabolismo , ARN Mensajero/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Adulto , Reposo en Cama , Composición Corporal/fisiología , Citocromos c/genética , Citocromos c/metabolismo , Metabolismo Energético/genética , Humanos , Masculino , Mitocondrias/genética , Consumo de Oxígeno/genética , ARN Mensajero/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Recombinant human erythropoietin (rHuEPO) elevates haemoglobin concentration both by increasing red blood cell volume and by a decrease in plasma volume. This study delineates the association of rHuEPO-induced changes in blood volumes with changes in the reninaldosterone system and renal function. Sixteen healthy males were given rHuEPO for 28 days in doses raising the haematocrit to 48.3±4.1%.Renal clearance studieswith urine collections (N = 8) were done at baseline and at days 4, 11, 29 and 42. Glomerular filtration rate (GFR) was measured by 51Cr-EDTA.Renal clearance of lithium (CLi)was used as an index of proximal tubular outflow and to assess segmental renal tubular handling of sodium and water. rHuEPO-induced increases in haematocrit occurred from day 10 onwards and was caused by both an increase in red cell volume and a fall in plasma volume. Well before that (from day 2 and throughout the treatment time), rHuEPO decreased plasma levels of renin and aldosterone (N = 8) by 2133% (P < 0.05) and 1536% (P < 0.05), respectively. After cessation of rHuEPO, values returned to baseline. On days 11 and 29, CLi increased (P < 0.02) indicating a significant 1016% decrease in absolute proximal reabsorption of sodium and water (APR = GFR − CLi, P < 0.05). GFR decreased slightly, albeit significantly, on day 4 (P < 0.05). In conclusion, rHuEPO promptly, and before any changes in blood volumes and haematocrit can be detected, causes a down-regulation of the reninaldosterone system. The results are compatible with a rHuEPO-induced reduction in proximal reabsorption rate leading to activation of the tubuloglomerular feedback mechanism and a fall in GFR. Therefore, treatment with rHuEPO may result in suppression of endogenous EPO synthesis secondary to a decrease in intrarenal oxygen consumption.
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Regulación hacia Abajo/efectos de los fármacos , Eritropoyetina/administración & dosificación , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/fisiología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Absorción/efectos de los fármacos , Absorción/fisiología , Adulto , Tamaño de la Célula/efectos de los fármacos , Regulación hacia Abajo/fisiología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Humanos , Inyecciones Subcutáneas , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Tasa de Depuración Metabólica/fisiología , Adulto JovenRESUMEN
CONTEXT: The GH/IGF-I axis has major impact on insulin sensitivity and insulin secretion. Recently a polymorphism in the GH receptor gene (GHR), a genomic deletion of exon 3 (GHRd3), has been linked to increased responsiveness to GH. OBJECTIVE: The objective of the present study was to evaluate the impact of the GHRd3 gene polymorphism on insulin sensitivity, insulin secretion, lipids, and IGF-I levels in healthy children and adolescents. DESIGN: This was cross-sectional and was part of the COPENHAGEN puberty study. SETTING: The study was conducted at a tertiary center for pediatric endocrinology. PARTICIPANTS: Participants included 142 healthy Caucasian subjects (65 boys) aged 8.5-16.1 yr. INTERVENTIONS: Standard 2-h oral glucose tolerance tests were preformed. GHR genotypes were determined by multiplex PCR. Main outcome measures were insulin sensitivity, insulin secretion, serum lipids, and IGF-I levels. RESULTS: Insulin secretion was higher in children and adolescents with a least one GHRd3 allele, even after adjustment for age, sex, pubertal stage, and insulin sensitivity (P = 0.018). Disposition index was higher in GHRd3-positive subjects (P = 0.026). In addition, the GHRd3 allele was associated with higher triglyceride (P = 0.028), but not IGF-I levels. CONCLUSION: The presence of at least one GHRd3 allele was associated with higher insulin secretion for a given degree of insulin sensitivity in healthy children and adolescents during puberty. In addition, the presence of the GHRd3 allele was associated with a higher disposition index. Thus, this common polymorphism in the GHR gene might play a role for pancreatic beta-cell compensatory capacity.
Asunto(s)
Glucosa/metabolismo , Factor I del Crecimiento Similar a la Insulina/análisis , Polimorfismo Genético , Pubertad/genética , Receptores de Somatotropina/genética , Triglicéridos/sangre , Adolescente , Alelos , Niño , Estudios Transversales , Exones , Femenino , Eliminación de Gen , Humanos , Insulina/metabolismo , Secreción de Insulina , Masculino , Pubertad/metabolismoRESUMEN
OBJECTIVE: Early puberty is associated with increased risk of subsequent cardiovascular disease. Low sex hormone-binding globulin (SHBG) levels are a feature of early puberty and of conditions associated with increased cardiovascular risk. The aim of the present study was to evaluate SHBG as a predictor of glucose metabolism and metabolic risk during puberty. RESEARCH DESIGN AND METHODS: This was a cross-sectional study on 132 healthy Caucasian children and adolescents evaluated by an oral glucose tolerance test, a dual-energy X-ray absorptiometry scan, direct oxygen uptake measurement during cycle ergometry, and fasting blood samples. RESULTS: SHBG levels declined with advancement of puberty in both boys (P < 0.001) and girls (P = 0.019). SHBG was significantly positively associated with insulin sensitivity in boys (P < 0.001) and girls (P < 0.001). In addition, SHBG was a strong predictor of insulin sensitivity (P = 0.001) and the only predictor of the disposition index (P = 0.031) after adjustment for puberty, fat mass, and aerobic fitness. SHBG was significantly negatively associated with metabolic risk (P = 0.032) and with hypersensitive C-reactive protein levels (P = 0.030) after adjustment for relevant confounders. CONCLUSIONS: SHBG was a strong predictor of insulin sensitivity and metabolic risk during puberty. Thus, we hypothesize that SHBG integrates the marked changes in glucose metabolism and body composition that occur during the pubertal transition.