RESUMEN
AIM: The aim of this study was to provide a more extensive evaluation of the effects of chronic aerobic exercise on various components of the insulin signalling cascade in normal rodent skeletal muscle because of the limited body of literature that exists in this area of investigation. METHODS: Male Sprague-Dawley rats were assigned to either control (n = 7) or chronic aerobic exercise (n = 7) groups. Aerobic exercise animals were run 3 day week(1) for 45 min on a motor-driven treadmill (32 m min(1), 15% grade) for a 12 week period. Following the training period, all animals were subjected to hind limb perfusion in the presence of 500 microU mL(1) insulin to determine what effect chronic aerobic training had on various components of the insulin signalling cascade, c-Cbl protein concentration and c-Cbl phosphorylation. RESULTS: Twelve weeks of aerobic training did not alter skeletal muscle Akt 1/2 protein concentration, Akt Ser 473 phosphorylation, Akt Thr 308 phosphorylation, Akt 1 activity, aPKC-zeta protein concentration, aPKC-lambda protein concentration or c-Cbl protein concentration. In contrast, chronic aerobic exercise increased insulin-stimulated phosphatidylinositol 3-kinase, Akt 2 kinase and aPKC-zeta/lambda kinase activities, as well as c-Cbl tyrosine phosphorylation, in a fibre type specific response to aerobic training. In addition, chronic aerobic exercise enhanced insulin-stimulated plasma membrane glucose transporter 4 (GLUT4) protein concentration. CONCLUSION: Collectively, these findings suggest that chronic aerobic exercise enhances components of both the classical and novel insulin signalling cascades in normal rodent skeletal muscle, which may contribute to an increased insulin-stimulated plasma membrane GLUT4 protein concentration.
Asunto(s)
Aerobiosis/fisiología , Insulina/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/fisiología , Condicionamiento Físico Animal/fisiología , 3-O-Metilglucosa/metabolismo , Animales , Transporte Biológico/fisiología , Transportador de Glucosa de Tipo 4 , Proteínas Sustrato del Receptor de Insulina , Masculino , Proteínas de Transporte de Monosacáridos/sangre , Proteínas Musculares/sangre , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfoproteínas/metabolismo , Fosforilación , Proteína Quinasa C/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Ratas , Ratas Sprague-Dawley , Transducción de Señal/fisiologíaRESUMEN
The aim of this investigation was to determine if resistance training exercise improved glucose uptake and transport in rodent skeletal muscle. Sprague-Dawley rats were assigned to one of the three groups: control (CON), resistance trained (RT) and aerobic exercise trained (AT). Resistance trained rats were placed in a rodent squat apparatus and performed three sets of 10 repetitions at 75% of their one repetition maximum 3 days week-1 for 12 weeks. Aerobic exercise training consisted of running the rats 3 days week-1 for 45 min over a 12-week period on a motor-driven treadmill (32 m min-1, 15% grade). Following the training period, all animals were subjected to hind limb perfusion in the presence of 500 microU mL-1 insulin. Hind limb glucose uptake was similar in the RT (9.91 +/- 0.7 micromol g-1 h-1) and AT (10.23 +/- 1.0 micromol g-1 h-1) animals and significantly greater than control (CON) (6.40 +/- 0.6 micromol g-1 h-1). Rates of 3-O-methyl-d-glucose transport in the RT animals were elevated in the muscles utilized for RT while in the AT animals rates of 3-O-methyl-d-glucose transport were increased in those muscles recruited for running. The increased rates of 3-O-methyl-d-glucose transport in the skeletal muscles of the resistance trained and aerobic exercise trained animals appeared to be, in part, because of an increased GLUT4 protein concentration. These findings suggest that both resistance or aerobic training exercise can improve insulin-stimulated skeletal muscle glucose uptake and transport, but the training adaptations are restricted to the muscles recruited for the exercise performance.
Asunto(s)
Glucosa/metabolismo , Proteínas Musculares , Músculo Esquelético/metabolismo , Condicionamiento Físico Animal/fisiología , 3-O-Metilglucosa/metabolismo , Aerobiosis/fisiología , Animales , Transporte Biológico/fisiología , Peso Corporal , Citrato (si)-Sintasa/metabolismo , Transportador de Glucosa de Tipo 4 , Glucógeno/análisis , Hexoquinasa/metabolismo , Masculino , Proteínas de Transporte de Monosacáridos/análisis , Músculo Esquelético/anatomía & histología , Ratas , Ratas Sprague-DawleyRESUMEN
A possible mechanism by which chronic clenbuterol treatment causes multiple physiological changes in skeletal muscle that leads to reduced insulin resistance in the obese Zucker rat (falfa) was investigated. Animals were gavaged with clenbuterol (CB) (0.8 mg x kg(-1) day(-1)), terbutaline (TB) (1.0 mg x kg(-1)day(-1)), or control (CT) vehicle for six weeks. Oral glucose tolerance and insulin responses were markedly improved in CB rats and impaired in TB rats. CB treatment caused a 24-34% gain in muscle mass in all muscle fiber types, and increases in 3-O-methyglucose transport (2-fold) and GLUT4 concentration (57%) in fast twitch glycolytic (FG) muscle. Oxidative capacity was reduced in both FG (47%) and fast twitch oxidative (FO) muscle (30%), but not in slow twitch oxidative (SO) muscle. Null model analysis for receptor occlusion demonstrated that most functional beta-adrenoceptors were lost in FO (82%) and FG (89%) fibers, but not in SO fibers. We propose that hypertrophy is the result of continuous direct activation of beta-adrenoceptors while loss in oxidative capacity may be the result of receptor down regulation. Improvements in insulin resistance may have been due, in part, to both increases in lean body mass and specific adaptations in FG muscle.
Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2 , Agonistas Adrenérgicos beta/farmacología , Clenbuterol/farmacología , Resistencia a la Insulina/fisiología , Proteínas Musculares , Músculos/efectos de los fármacos , 3-O-Metilglucosa/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Modelos Animales de Enfermedad , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Transportador de Glucosa de Tipo 4 , Proteínas de Transporte de Monosacáridos/metabolismo , Músculos/fisiología , Oxidación-Reducción/efectos de los fármacos , Ratas , Ratas Zucker , Receptores Adrenérgicos beta 2/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
In addition to suppressing appetite, leptin may also modulate insulin secretion and action. Leptin was administered here to insulin-resistant rats to determine its effects on secretagogue-stimulated insulin release, whole body glucose disposal, and insulin-stimulated skeletal muscle glucose uptake and transport. Male Wistar rats were fed either a normal (Con) or a high-fat (HF) diet for 3 or 6 mo. HF rats were then treated with either vehicle (HF), leptin (HF-Lep, 10 mg. kg(-1). day(-1) sc), or food restriction (HF-FR) for 12-15 days. Glucose tolerance and skeletal muscle glucose uptake and transport were significantly impaired in HF compared with Con. Whole body glucose tolerance and rates of insulin-stimulated skeletal muscle glucose uptake and transport in HF-Lep were similar to those of Con and greater than those of HF and HF-FR. The insulin secretory response to either glucose or tolbutamide (a pancreatic beta-cell secretagogue) was not significantly diminished in HF-Lep. Total and plasma membrane skeletal muscle GLUT-4 protein concentrations were similar in Con and HF-Lep and greater than those in HF and HF-FR. The findings suggest that chronic leptin administration reversed a high-fat diet-induced insulin-resistant state, without compromising insulin secretion.
Asunto(s)
Grasas de la Dieta/farmacología , Resistencia a la Insulina/fisiología , Leptina/farmacología , Proteínas Musculares , Músculo Esquelético/metabolismo , 3-O-Metilglucosa/farmacocinética , Animales , Glucemia/metabolismo , Índice de Masa Corporal , Dieta , Ingestión de Energía/fisiología , Técnica de Clampeo de la Glucosa , Prueba de Tolerancia a la Glucosa , Transportador de Glucosa de Tipo 4 , Glucógeno/metabolismo , Hiperinsulinismo/metabolismo , Hipoglucemiantes/farmacología , Insulina/sangre , Masculino , Proteínas de Transporte de Monosacáridos/metabolismo , Músculo Esquelético/efectos de los fármacos , Ratas , Ratas Wistar , Tolbutamida/farmacologíaRESUMEN
The effect of a carbohydrate-arginine supplement on postexercise muscle glycogen storage was investigated. Twelve well-trained cyclists rode for 2 hr on two separate occasions to deplete their muscle glycogen stores. At 0, 1, 2, and 3 hr after each exercise bout, the subjects ingested either a carbohydrate (CHO) supplement (1 g carbohydrate/kg body weight) or a carbohydrate-arginine (CHO/AA) supplement (1 g carbohydrate/kg body mass and 0.08 g arginine-hydrochloride/kg body weight). No difference in rate of glycogen storage was found between the CHO/AA and CHO treatments, although significance was approached. There were also no differences in plasma glucose, insulin, or blood lactate responses between treatments. Postexercise carbohydrate oxidation during the CHO/AA treatment was significantly reduced compared to the CHO treatment. These results suggest that the addition of arginine to a CHO supplement reduces the rate of CHO oxidation postexercise and therefore may increase the availability of glucose for muscle glycogen storage during recovery.
Asunto(s)
Arginina/administración & dosificación , Carbohidratos de la Dieta/administración & dosificación , Suplementos Dietéticos , Ejercicio Físico/fisiología , Glucógeno/metabolismo , Músculo Esquelético/metabolismo , Adulto , Ciclismo , Glucemia/metabolismo , Humanos , Insulina/sangre , Cinética , Ácido Láctico/metabolismo , Masculino , Consumo de Oxígeno , Polisacáridos/administración & dosificaciónRESUMEN
Ten physically active, untrained, college-aged males (26.4 +/- 5. 8 years old) received creatine (CR, 5 g creatine monohydrate + 3 g dextrose) and placebo (PLA, 7 g dextrose) supplementation four times per day for 5 days in a double-blind, randomized, balanced, crossover design. Performance was assessed during maximal and three repeated submaximal bouts of isometric knee extension and handgrip exercise. CR supplementation significantly increased (p <.05) maximal isometric strength during knee extension but not during handgrip exercise. CR supplementation increased time to fatigue during each of the three bouts of submaximal knee extension and handgrip exercise when compared to the PLA trials. These findings suggest that CR supplementation can increase maximal strength and time to fatigue during isometric exercise. However, the improvements in maximal isometric strength following CR supplementation appear to be restricted to movements performed with a large muscle mass.
Asunto(s)
Creatina/administración & dosificación , Suplementos Dietéticos , Contracción Isométrica/efectos de los fármacos , Fatiga Muscular/efectos de los fármacos , Músculo Esquelético/fisiología , Adulto , Estudios Cruzados , Método Doble Ciego , Fuerza de la Mano , Humanos , Masculino , Músculo Esquelético/efectos de los fármacos , Placebos , Factores de TiempoRESUMEN
Leptin, the product of the ob gene, has been shown to reduce fat mass, food intake, hyperglycemia, and hyperinsulinemia and to increase whole-body glucose disposal. However, it is unknown if leptin improves insulin action in skeletal muscle. Therefore, the purpose of this investigation was to determine if chronic leptin administration increases insulin-stimulated skeletal muscle glucose uptake and transport. Sixty-nine female Sprague-Dawley rats (240 to 250 g) were randomly assigned to one of three groups: (1) control, (2) pair-fed, and (3) leptin. All animals were subcutaneously implanted with miniosmotic pumps that delivered 0.5 mg leptin/kg/d to the leptin animals and vehicle to the control and pair-fed animals for 14 days. Following this 14-day period, all animals were subjected to hindlimb perfusion to determine the rates of skeletal muscle glucose uptake and 3-O-methyl-D-glucose (3-MG) transport under basal, submaximal (500 microU/mL), and maximal (10,000 microU/mL) insulin concentrations. Chronic leptin treatment significantly increased (P < .05) the rate of glucose uptake across the hindlimb by 27%, 32%, and 47% under basal, submaximal, and maximal insulin, respectively, compared with the control and pair-fed condition. However, when the submaximal rate of glucose uptake was expressed as a percentage of maximal insulin-stimulated glucose uptake, no differences existed among the groups, indicating that leptin treatment does not increase insulin sensitivity. Rates of 3-MG transport in the soleus, plantaris, and white and red portions of the gastrocnemius (WG and RG) were significantly increased (P < .05) in leptin animals under all perfusion conditions. 3-MG transport was not different between control and pair-fed animals. Collectively, these findings suggest that improvements in insulin-stimulated skeletal muscle glucose uptake and transport following chronic leptin treatment result from increased insulin responsiveness.
Asunto(s)
Glucosa/metabolismo , Insulina/farmacología , Músculo Esquelético/metabolismo , Proteínas/farmacología , 3-O-Metilglucosa/farmacocinética , Animales , Transporte Biológico , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Miembro Posterior/efectos de los fármacos , Leptina , Músculo Esquelético/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Thirty-two female Sprague-Dawley rats were assigned to one of four groups: control (CON); exercise training (TR); exercise training + clenbuterol treatment (0.8 mg kg body wt(-1) d(-1)) (TR + CL) or exercise training + clenbuterol treatment + 2% beta-guanidinoproprionic acid diet (TR + CL + beta) to examine whether alterations in the high energy phosphate state of the muscle mediates exercise training-induced increases in skeletal muscle GLUT4 protein concentration and citrate synthase activity. Exercise training consisted of running the rats 5 d week(-1) for 8 weeks on a motor-driven treadmill (32 m min(-1), 15% grade). Gastrocnemius GLUT4 protein concentration and citrate synthase activity were significantly elevated in the TR animals, but these adaptations were attenuated in the TR + CL animals. Providing beta-GPA in combination with clenbuterol enabled training to elevate GLUT4 protein concentration and citrate synthase activity, with the increase in GLUT4 being greater than that observed for the TR animals. Skeletal muscle ATP levels were reduced in the TR + CL + beta animals while ATP levels in the TR + CL animals were significantly elevated compared with CON. An acute 40-min bout of electrical stimulation of the sciatic nerve was found to lower skeletal muscle ATP levels by approximately 50% and elevate cAMP levels in all groups. No difference in post-contraction cAMP levels were observed among groups. However, post-contraction ATP levels in the TR + CL animals were significantly greater than the other groups. Collectively, these findings suggest that exercise training-induced increases in skeletal muscle GLUT4 protein concentration and citrate synthase activity are initiated in response to a reduction in the skeletal muscle ATP concentration.
Asunto(s)
Adenosina Trifosfato/metabolismo , Citrato (si)-Sintasa/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas Musculares , Músculo Esquelético/metabolismo , Condicionamiento Físico Animal/fisiología , Adenilil Ciclasas/metabolismo , Animales , Clenbuterol/farmacología , AMP Cíclico/metabolismo , Dieta , Estimulación Eléctrica , Femenino , Transportador de Glucosa de Tipo 4 , Guanidinas/farmacología , Músculo Esquelético/efectos de los fármacos , Propionatos/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
The present study investigated whether alterations in the muscle high energy phosphate state initiates the contraction-induced increase in skeletal muscle GLUT4 protein concentration. Sprague-Dawley rats were provided either a normal or a 2% beta-guanidinoproprionic acid (beta-GPA) diet for 8 weeks and then the gastrocnemius of one hind limb was subjected to 0, 14 or 28 days of chronic (24 h day-1) low-frequency electrical stimulation (10 Hz). The beta-GPA diet, in the absence of electrical stimulation, significantly reduced ATP, creatine phosphate, creatine and inorganic phosphate and elevated GLUT4 protein concentration by 60% without altering adenylate cyclase activity or cAMP concentration. Following 14 days of electrical stimulation, GLUT4 protein concentration was elevated above non-stimulated muscle in both groups but was significantly more elevated in the beta-GPA group. Concurrent with this greater rise in GLUT4 protein concentration was a greater decline in the high energy phosphates and a greater rise in cAMP. After 28 days of electrical stimulation, GLUT4 protein concentration and cAMP stabilized and was not different between diet treatments. However, the high energy phosphates were significantly higher in the normal diet rats as opposed to the beta-GPA rats. These findings therefore suggest that a reduction in cellular energy supply initiates the contraction-induced increase in muscle GLUT4 protein concentration, but that a rise in cAMP may potentiate this effect.
Asunto(s)
Guanidinas/farmacología , Proteínas de Transporte de Monosacáridos/metabolismo , Músculo Esquelético/fisiología , Propionatos/farmacología , Adenosina Trifosfato/metabolismo , Adenilil Ciclasas/metabolismo , Animales , Peso Corporal/fisiología , AMP Cíclico/metabolismo , Dieta , Estimulación Eléctrica , Femenino , Transportador de Glucosa de Tipo 4 , Proteínas Musculares/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Tamaño de los Órganos/fisiología , Fosfatos/metabolismo , Fosfocreatina/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
This investigation used a model of increased skeletal muscle contractile activity to evaluate whether the adenylate cyclase-adenosine 3',5'-cyclic monophosphate (cAMP) pathway and/or the high-energy phosphate state of the muscle might be temporally related to the contraction-induced increase in skeletal muscle GLUT-4 protein concentration. Plantaris and gastrocnemius muscles of Sprague-Dawley rats were subjected to 3, 7, 14, or 28 days of chronic low-frequency electrical stimulation (10 Hz, 24 h/day). GLUT-4 protein concentration was slightly reduced after 3 days of electrical stimulation, similar to control values at 7 days and significantly elevated above control at 14 days (53%, P < 0.05) and 28 days (338%, P < 0.05) of stimulation. ATP, creatine phosphate, creatine, and P, were inversely related to GLUT-4 protein concentration. Adenylate cyclase activity increased with electrical stimulation and was significantly related to the increased GLUT-4 protein. cAMP was significantly increased at 14 days of stimulation and remained elevated through 28 days. These results demonstrate that both the adenylate cyclase-cAMP pathway and the high-energy phosphate state of the muscle are temporally related to elevations in skeletal muscle GLUT-4 protein concentration in response to chronic low-frequency electrical stimulation and, as such, suggest that both may comprise a component of the intracellular signal that regulates the contraction-induced increase in skeletal muscle GLUT-4 protein concentration.
Asunto(s)
Membranas Intracelulares/fisiología , Proteínas de Transporte de Monosacáridos/metabolismo , Contracción Muscular/fisiología , Proteínas Musculares , Músculo Esquelético/metabolismo , Transducción de Señal , Adenilil Ciclasas/metabolismo , Animales , Peso Corporal , AMP Cíclico/metabolismo , Metabolismo Energético , Femenino , Transportador de Glucosa de Tipo 4 , Músculo Esquelético/anatomía & histología , Tamaño de los Órganos , Concentración Osmolar , Fosfatos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Impaired skeletal muscle insulin receptor function is a feature of common forms of insulin resistance, including obesity and noninsulin-dependent diabetes mellitus. However, the extent to which this defect accounts for impaired muscle glucose disposal or altered in vivo glucose homeostasis remains to be established. We recently showed that transgenic mice that overexpress dominant-negative insulin receptors specifically in striated muscle have a severe defect in muscle insulin receptor-mediated signaling and modest hyperinsulinemia. Here we performed hindlimb perfusion studies to determine the impact of this defect on muscle glucose uptake and metabolism. Maximal rates of insulin-stimulated muscle 3-O-methylglucose transport were reduced by 32-40% in transgenic mice with proportional defects involving total hindlimb [14C]glucose uptake, lactate production, and muscle glycogen synthesis. To address the hypothesis that muscle insulin resistance could promote an increase in the accretion of body fat, carcass analysis was performed using two independent lines of transgenic mice. Although body weights were normal, transgenic mice had a 22-38% increase in body fat, with a reciprocal decrease (10-15%) in body protein. Mean gonadal fat pad weight was also increased in transgenic mice. Skeletal muscle histology and fiber type distribution were not affected. To determine whether muscle-specific insulin resistance was sufficient to cause impaired glucose tolerance, oral glucose tolerance tests were performed with 6-month-old transgenic and control mice. Fasting glucose levels were increased by 25%, and peak values were 22-40% higher in transgenic mice. Transgenic mice also had a 37% decrease in plasma lactate levels and modest increases in levels of plasma triglycerides and FFA (29% and 15%, respectively). We conclude that 1) severe defects in muscle insulin receptor function result in impaired insulin-stimulated glucose uptake and metabolism in this tissue; 2) muscle-specific insulin resistance can contribute to the development of obesity; and 3) a "pure" defect in insulin-mediated muscle glucose disposal is sufficient to result in impaired glucose tolerance and other features of the insulin resistance syndrome, including hyperinsulinemia and dyslipidemia.
Asunto(s)
Tejido Adiposo , Composición Corporal , Prueba de Tolerancia a la Glucosa , Hiperlipidemias/genética , Resistencia a la Insulina/genética , Músculo Esquelético/metabolismo , Tejido Adiposo/anatomía & histología , Animales , Ácidos Grasos no Esterificados/sangre , Femenino , Glucosa/metabolismo , Lactatos/sangre , Ácido Láctico , Masculino , Ratones , Ratones Transgénicos , Músculo Esquelético/anatomía & histología , Músculo Esquelético/efectos de los fármacos , Tamaño de los Órganos , Receptor de Insulina/fisiología , Triglicéridos/sangreRESUMEN
The aim of the present investigation was to determine whether the subcellular distribution and insulin-stimulated translocation of the GLUT4 isoform of the glucose transporter are affected when GLUT4 is overexpressed in mouse skeletal muscle, and if the overexpression of GLUT4 alters maximal insulin-stimulated glucose transport and metabolism. Rates of glucose transport and metabolism were assessed by hind-limb perfusion in GLUT4 transgenic (TG) mice and non-transgenic (NTG) controls. Glucose-transport activity was determined under basal (no insulin), submaximal (0.2 m-unit/ml) and maximal (10 m-units/ml) insulin conditions using a perfusate containing 8 mM 3-O-methyl-D-glucose. Glucose metabolism was quantified by perfusing the hind limbs for 25 min with a perfusate containing 8 mM glucose and 10 m-units/ml insulin. Under basal conditions, there was no difference in muscle glucose transport between TG (1.10 +/- 0.10 mumol/h per g; mean +/- S.E.M.) and NTG (0.93 +/- 0.16 mumol/h per g) mice. However, TG mice displayed significantly greater glucose-transport activity during submaximal (4.42 +/- 0.49 compared with 2.69 +/- 0.33 mumol/h per g) and maximal (11.68 +/- 1.13 compared with 7.53 +/- 0.80 mumol/h per g) insulin stimulation. Nevertheless, overexpression of the GLUT4 protein did not alter maximal rates of glucose metabolism. Membrane purification revealed that, under basal conditions, plasma-membrane (approximately 12-fold) and intracellular-membrane (approximately 4-fold) GLUT4 protein concentrations were greater in TG than NTG mice. Submaximal insulin stimulation did not increase plasma-membrane GLUT4 protein concentration whereas maximal insulin stimulation increased this protein in both NTG (4.1-fold) and TG (2.6-fold) mice. These results suggest that the increase in insulin-stimulated glucose transport following overexpression of the GLUT4 protein is limited by factors other than the plasma-membrane GLUT4 protein concentration. Furthermore, GLUT4 overexpression is not coupled to glucose-metabolic capacity.
Asunto(s)
Glucosa/farmacocinética , Proteínas de Transporte de Monosacáridos/metabolismo , Músculo Esquelético/metabolismo , Animales , Transporte Biológico , Membrana Celular/química , Membrana Celular/metabolismo , Glucosa/metabolismo , Humanos , Insulina/farmacología , Membranas Intracelulares/química , Membranas Intracelulares/metabolismo , Isomerismo , Proteínas de la Membrana/aislamiento & purificación , Proteínas de la Membrana/metabolismo , Ratones , Ratones Transgénicos , Músculo Esquelético/efectos de los fármacos , Estimulación Química , Fracciones Subcelulares/metabolismoRESUMEN
The aim of the present investigation was to examine the relationship between plasma potassium (K+) and ventilation (VE) during incremental and prolonged continuous exercise which varied between low and moderate intensity. Seven well-trained male cyclists who had a mean maximal aerobic power (VO2max) of 69.4 +/- 2.9 ml/kg/min were recruited to participate as subjects. The graded incremental exercise bout was composed of 3 min stages set to elicit 40, 50, 60, 70, 80 and 90% VO2max. The continuous variable intensity exercise consisted of 30 min of cycling at 45% VO2max and then 6 x 16 min periods which consisted of cycling for 8 min at 75% VO2max and 8 min at 45% VO2max. During prolonged continuous exercise, VE and plasma K+ changed in a coordinated manner between the low and moderate intensity exercise bouts with the responses during the moderate intensity intervals being significantly greater (p < 0.05) than the responses during the low intensity intervals. During the incremental exercise test, a strong positive relationship between VE and plasma K+ concentration was found for each subject. However, a positive relationship and slope was also found when the VE/K+ ratio was correlated with exercise intensity (r = 0.90-0.99). This indicates that with increasing exercise intensity, the rise in VE becomes increasingly greater than the rise in plasma K+. These findings suggest that the plasma K+ concentration contributes to but may not be the sole determinant of ventilatory regulation during exercise.
Asunto(s)
Ejercicio Físico/fisiología , Músculo Esquelético/fisiología , Potasio/sangre , Respiración/fisiología , Adulto , Humanos , Masculino , Contracción Muscular/fisiología , Consumo de Oxígeno/fisiologíaRESUMEN
The rates of muscle glucose uptake of lean and obese Zucker rats were assessed by hindlimb perfusion under basal conditions (no insulin), in the presence of a maximally stimulating concentration of insulin (10 mU/ml), and after muscle contraction elicited by electrical stimulation of the sciatic nerve. After perfusion, plasma and microsomal membranes were isolated from selected hindlimb muscles for determination of GLUT-4 protein distribution. Under basal conditions, rates of glucose uptake were similar for lean and obese rats despite plasma membranes from lean rats containing 82% more GLUT-4 protein than obese rats. Insulin stimulation resulted in significant increases in plasma membrane GLUT-4 protein concentration in lean but not obese rats. Glucose uptake of lean rats (35.3 +/- 4.7 mumol.h-1.g-1) in the presence of insulin was approximately fourfold greater than that of obese rats (8.8 +/- 1.3 mumol.h-1.g-1), but this difference in glucose uptake could not be completely accounted for by the difference in plasma membrane GLUT-4 protein concentration. Stimulation by contraction resulted in significant increases in plasma membrane GLUT-4 protein concentration in both lean and obese rats and similar rates of glucose uptake. These results suggest that the muscle insulin resistance of the obese Zucker rat is due to 1) a reduced plasma membrane GLUT-4 protein concentration, which results in part from an impairment in the insulin-stimulated GLUT-4 protein translocation process, and 2) a defect in the insulin-stimulated activation of this protein. However, contraction-stimulated glucose uptake, GLUT-4 protein translocation, and activation are normal in the obese Zucker rat.
Asunto(s)
Glucosa/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas Musculares , Músculos/metabolismo , Obesidad/metabolismo , 4-Nitrofenilfosfatasa/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , ATPasas Transportadoras de Calcio/metabolismo , Femenino , Transportador de Glucosa de Tipo 4 , Miembro Posterior , Insulina/farmacología , Contracción Muscular , Potasio/farmacología , Ratas , Ratas Zucker , Distribución TisularRESUMEN
The effect of electrically induced muscle contraction, insulin (10 m-units/ml) and electrically-induced muscle contraction in the presence of insulin on insulin-regulatable glucose-transporter (GLUT-4) protein distribution was studied in female Sprague-Dawley rats during hindlimb perfusion. Plasma-membrane cytochalasin B binding increased approximately 2-fold, whereas GLUT-4 protein concentration increased approximately 1.5-fold above control with contractions, insulin, or insulin + contraction. Microsomal-membrane cytochalasin B binding and GLUT-4 protein concentration decreased by approx. 30% with insulin or insulin + contraction, but did not significantly decrease with contraction alone. The rate of muscle glucose uptake was assessed by determining the rate of 2-deoxy[3H]glucose accumulation in the soleus, plantaris, and red and white portions of the gastrocnemius. Both contraction and insulin increased glucose uptake significantly and to the same degree in the muscles examined. Insulin + contraction increased glucose uptake above that of insulin or contraction alone, but this effect was only statistically significant in the soleus, plantaris and white gastrocnemius. The combined effects of insulin + contraction of glucose uptake were not fully additive in any of the muscles investigated. These results suggest that (1) insulin and muscle contraction are mobilizing two separate pools of GLUT-4 protein, and (2) the increase in skeletal-muscle glucose uptake due to insulin + contraction is not due to an increase in plasma-membrane GLUT-4 protein concentration above that observed for insulin or contraction alone.
Asunto(s)
Insulina/farmacología , Proteínas de Transporte de Monosacáridos/metabolismo , Contracción Muscular , Músculos/metabolismo , Animales , Estimulación Eléctrica , Femenino , Contracción Muscular/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
Effects of carbohydrate (CHO) supplementation on muscle glycogen utilization and endurance were evaluated in seven well-trained male cyclists during continuous cycling exercise that varied between low [45% maximal O2 uptake (VO2 max)] and moderate intensity (75% VO2 max). During each exercise bout the subjects received either artificially flavored placebo (P), 10% liquid CHO supplement (L; 3 x 18 g CHO/h), or solid CHO supplement (S; 2 x 25 g CHO/h). Muscle biopsies were taken from vastus lateralis during P and L trials immediately before exercise and after first (124 min) and second set (190 min) of intervals. Subjects then rode to fatigue at 80% VO2 max. Plasma glucose and insulin responses during L treatment reached levels of 6.7 +/- 0.7 mM and 70.6 +/- 17.2 microU/ml, respectively, and were significantly greater than those of P treatment (4.4 +/- 0.1 mM and 17.7 +/- 1.6 microU/ml) throughout the exercise bout. Plasma glucose and insulin responses of S treatment were intermediate to those of L and P treatments. Times to fatigue for S (223.9 +/- 3.5 min) and L (233.4 +/- 7.5 min) treatments did not differ but were significantly greater than that of P treatment (202.4 +/- 9.8 min). After the first 190 min of exercise, muscle glycogen was significantly greater during L (79 +/- 3.5 mumol/g wet wt) than during P treatment (58.5 +/- 7.2 mumol/g wet wt). Furthermore, differences in muscle glycogen concentrations between L and P treatments after 190 min of exercise and in time to fatigue for these treatments were positively related (r = 0.76, P < 0.05). These results suggest that CHO supplementation can enhance prolonged continuous variable-intensity exercise by reducing dependency on muscle glycogen as a fuel source.
Asunto(s)
Carbohidratos de la Dieta/farmacología , Ejercicio Físico/fisiología , Glucógeno/metabolismo , Músculos/metabolismo , Adulto , Ciclismo , Glucemia/metabolismo , Dióxido de Carbono/metabolismo , Ingestión de Líquidos/fisiología , Ergometría , Ácidos Grasos no Esterificados/sangre , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Humanos , Insulina/sangre , Lactatos/sangre , Ácido Láctico , Masculino , Músculos/efectos de los fármacos , Oxidación-Reducción , Consumo de Oxígeno/efectos de los fármacos , Pérdida de Peso/fisiologíaRESUMEN
The rates of muscle glucose uptake of trained (TR) and untrained (UT) obese Zucker rats were assessed by hindlimb perfusion under basal conditions (no insulin) in the presence of a maximally stimulating concentration of insulin (10 mU/ml) and after muscle contraction elicited by electrical stimulation of the sciatic nerve. Perfusate contained 28 mM glucose and 7.5 microCi/mmol of 2-deoxy-D-[3H]glucose. Muscle GLUT-4 concentration was determined by Western blot analysis and expressed as a percentage of a heart standard. The rates of insulin-stimulated glucose uptake were significantly higher in the plantaris, red gastrocnemius (RG), and white gastrocnemius (WG), but not the soleus or extensor digatorum longus (EDL) of TR compared with UT rats. After muscle contraction the rates of glucose uptake in the TR rats were significantly higher in the soleus, plantaris, and RG. TR rats had significantly higher GLUT-4 protein concentration and citrate synthase activity than the UT rats in the soleus, plantaris, RG, and WG. Basal plasma membrane GLUT-4 protein concentration of TR rats was 144% above UT rats (P < 0.01). Stimulation by insulin and contraction resulted in a significant increase in plasma membrane GLUT-4 protein concentration in UT rats only. However, plasma membrane GLUT-4 protein concentration in insulin- and contraction-stimulated TR rats remained 53% and 30% greater than that of UT rats, respectively (P < 0.05). Exercise training did not alter basal, insulin-, or contraction-stimulated GLUT-4 functional activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas Musculares , Músculos/metabolismo , Obesidad/metabolismo , Condicionamiento Físico Animal , 4-Nitrofenilfosfatasa/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , ATPasas Transportadoras de Calcio/metabolismo , Membrana Celular/metabolismo , Citrato (si)-Sintasa/metabolismo , Galactosiltransferasas/metabolismo , Glucosa/metabolismo , Transportador de Glucosa de Tipo 4 , Miembro Posterior , Insulina/farmacología , Contracción Muscular , Potasio/farmacología , Ratas , Ratas ZuckerRESUMEN
This study compared the effects of moderately intense exercise in hot and thermoneutral environments on muscle glycogen and carbohydrate utilization. Well-trained, heat acclimatized cyclists (n = 7) rode at 73.6 +/- 1.1% maximal oxygen consumption for 60 min in a thermoneutral room (23.5 +/- 0.6 degrees C, 52.7 +/- 2.9 relative humidity) or an environmental chamber (33.7 +/- 0.1 degrees C, 49.1 +/- 1.8% relative humidity). During each exercise bout, the subjects received 125 ml of water every 15 min. Muscle biopsies from the vastus lateralis were obtained prior to and following each exercise bout. Exercise in the heat significantly elevated rectal temperature and heart rate above and reduced body weight and plasma volume below that produced by exercise in a thermoneutral environment. Plasma glucose and blood lactate concentrations were similar between treatments prior to exercise, but increased to a greater concentration (p < 0.05) when exercise was performed in the heat. No differences between treatments were found for blood glycerol or free fatty acid concentrations, carbohydrate oxidation or muscle glycogen utilization. These results suggest that moderately intense exercise in the heat, as opposed to a thermoneutral environment, does not increase the rate of muscle glycogenolysis or carbohydrate oxidation in well conditioned, heat acclimatized subjects.
Asunto(s)
Metabolismo de los Hidratos de Carbono , Ejercicio Físico/fisiología , Calor , Músculos/metabolismo , Aclimatación , Adulto , Ciclismo/fisiología , Glucemia/análisis , Temperatura Corporal/fisiología , Ácidos Grasos no Esterificados/sangre , Glucógeno/metabolismo , Frecuencia Cardíaca/fisiología , Humanos , Lactatos/sangre , Masculino , Intercambio Gaseoso PulmonarRESUMEN
The effects of high (HI)- and low (LI)-intensity exercise training were examined on insulin-stimulated 3-O-methyl-D-glucose (3-MG) transport and concentration of insulin-regulatable glucose transporter protein (GLUT-4) in the red (fast-twitch oxidative) and white (fast-twitch glycolytic) quadriceps of the obese Zucker rat. Sedentary obese (SED) and lean (LN) Zucker rats were used as controls. 3-MG transport was determined during hindlimb perfusion in the presence of 8 mM 3-MG, 2 mM mannitol, 0.3 mM pyruvate, and 0.5 mU/ml insulin. HI and LI rats displayed greater rates of red quadriceps 3-MG transport and GLUT-4 concentrations than SED rats. No significant differences in rates of 3-MG transport or GLUT-4 concentrations were observed in the red quadriceps of HI and LI rats. There were no differences found in the rates of 3-MG transport in the white quadriceps of HI, LI, and SED rats although the difference between the HI and SED rats approached significance (P < 0.07). The GLUT-4 concentration and citrate synthase activity of HI rats were significantly greater than SED rats. The 3-MG transport rates of LN rats were twofold greater than SED rats regardless of fiber type, but a difference in GLUT-4 content between the LN and SED rats was observed only in the white quadriceps. GLUT-4 content of the obese rats was significantly correlated with citrate synthase activity (r = 0.93) and 3-MG transport (r = 0.82).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Glucosa/farmacocinética , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas Musculares , Músculos/metabolismo , Condicionamiento Físico Animal , Esfuerzo Físico , 3-O-Metilglucosa , Animales , Transporte Biológico , Citrato (si)-Sintasa/metabolismo , Femenino , Transportador de Glucosa de Tipo 4 , Insulina/farmacología , Metilglucósidos/farmacocinética , Ratas , Ratas ZuckerRESUMEN
The rates of muscle glucose uptake of lean and obese Zucker rats were assessed via hindlimb perfusion under basal conditions (no insulin), in the presence of a maximal insulin concentration (10 mU/ml), and after electrically stimulated muscle contraction in the absence of insulin. The perfusate contained 28 mM glucose and 7.5 microCi/mmol of 2-deoxy-D-[3H-(G)]glucose. Glucose uptake rates in the soleus (slow-twitch oxidative fibers), red gastrocnemius (fast-twitch oxidative-glycolytic fibers), and white gastrocnemius (fast-twitch glycolytic fibers) under basal conditions and after electrically stimulated muscle contraction were not significantly different between the lean and obese rats. However, the rate of glucose uptake during insulin stimulation was significantly lower for obese than for lean rats in all three fiber types. Significant correlations were found for insulin-stimulated glucose uptake and glucose transporter protein isoform (GLUT-4) content of soleus, red gastrocnemius, and white gastrocnemius of lean (r = 0.79) and obese (r = 0.65) rats. In contrast, the relationships between contraction-stimulated glucose uptake and muscle GLUT-4 content of lean and obese rats were negligible because of inordinately low contraction-stimulated glucose uptakes by the solei. These results suggest that maximal skeletal muscle glucose uptake of obese Zucker rats is resistant to stimulation by insulin but not to contractile activity. In addition, the relationship between contraction-stimulated glucose uptake and GLUT-4 content appears to be fiber-type specific.