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1.
Med Sci Sports Exerc ; 49(9): 1859-1867, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28398944

RESUMO

INTRODUCTION: To counteract the winter activity deficit, we set out to analyze cardiorespiratory and metabolic responses of two high-intensity training (HIT) protocols during alpine skiing (AS), cross-country skiing (XCS), and indoor cycling (IC) and the effects of sex, age, and fitness level in this comparison. METHODS: Nineteen healthy subjects (two age and fitness groups, both sexes) performed AS, XCS, and IC with measurements of oxygen uptake (V˙O2), energy expenditure (EE), HR, lactate, blood glucose and rate of perceived exertion, determined during 4 min of continuous HIT (HITc: 90% HRmax for XCS and IC or short turn skiing during AS) or 10-min intermittent HIT [HITint: 5 × 1 min high intensity (>90% HRmax or short turn skiing), 1 min active recovery]. RESULTS: During all three exercise modes and irrespective of HIT protocols, sex, age, and fitness, participants were able to reach exercise intensities >90% HRmax and >84% V˙O2max. In all exercise modes 10-min of HITint with a 10-min postexercise O2 consumption phase resulted in greater mean EE per minute compared to 4-min HITc with 10 min postexercise O2 consumption. When applying the same HIT loading and recovery pattern to all three exercise modes, EE during approximately 1:15 h of AS was equivalent to about 1:00 h of either XCS or IC. CONCLUSIONS: Across all exercise modes and HIT protocols, high cardiorespiratory and metabolic responses were achieved regardless of age, sex, or fitness. EE during AS can be maximized by choosing the skiing mode "short turn skiing" in combination with an HITint to prolong the duration of continuous high-intensity loading during each descent. Therefore, all exercise modes and both HIT protocols are applicable and feasible in a broad spectrum of healthy subjects.


Assuntos
Aptidão Cardiorrespiratória/fisiologia , Temperatura Baixa , Metabolismo Energético/fisiologia , Treinamento Intervalado de Alta Intensidade , Estações do Ano , Esqui/fisiologia , Adulto , Fatores Etários , Ciclismo/fisiologia , Glicemia/metabolismo , Feminino , Frequência Cardíaca/fisiologia , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Percepção/fisiologia , Esforço Físico/fisiologia , Aptidão Física/fisiologia , Fatores Sexuais
2.
J Sports Sci Med ; 15(1): 184-95, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26957942

RESUMO

Since physical inactivity especially prevails during winter months, we set out to identify outdoor alternatives to indoor cycling (IC) by comparing the metabolic and cardiorespiratory responses during alpine skiing (AS), cross-country skiing (XCS) and IC and analyse the effects of sex, age and fitness level in this comparison. Twenty one healthy subjects performed alpine skiing (AS), cross-country skiing (XCS), and IC. Oxygen uptake (VO2), total energy expenditure (EE), heart rate (HR), lactate, blood glucose and rate of perceived exertion (RPE) were determined during three 4-min stages of low, moderate and high intensity. During XCS and IC VO2max and EE were higher than during AS. At least 2½ hours of AS are necessary to reach the same EE as during one hour of XCS or IC. HR, VO2, lactate, and RPEarms were highest during XCS, whereas RPEwhole-body was similar and RPElegs lower than during AS and IC, respectively. Weight adjusted VO2 and EE were higher in men than in women while fitness level had no effect. Male, fit and young participants were able to increase their EE and VO2 values more pronounced. Both AS and XCS can be individually tailored to serve as alternatives to IC and may thus help to overcome the winter activity deficit. XCS was found to be the most effective activity for generating a high EE and VO2 while AS was the most demanding activity for the legs. Key pointsDuring cross-country skiing and indoor cycling VO2max and energy expenditure were higher than during alpine skiingApproximately 2½ hours of alpine skiing are necessary to reach the same energy expenditure of one hour of cross-country skiing or indoor cycling.Alpine skiing and cross-country skiing can be individually tailored to serve as sports alternatives in winter to activity deficit.By applying different skiing modes as parallel ski steering, carving long radii and short turn skiing, metabolic and cardiorespiratory response can be increased during alpine skiing.Male, fit and young participants were able to increase their energy expenditure and VO2 more pronounced with an increase in intensity compared with their counterparts.

4.
ScientificWorldJournal ; 2014: 145747, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25431775

RESUMO

The effects of varying recovery modes and the influence of preexercise sodium bicarbonate and carbohydrate ingestion on repeated high intensity performance, acid-base response, and recovery were analyzed in 12 well-trained males. They completed three repeated high intensity running bouts to exhaustion with intervening recovery periods of 25 min under the following conditions: sodium bicarbonate, active recovery (BIC); carbohydrate ingestion, active recovery (CHO); placebo ingestion, active recovery (ACTIVE); placebo ingestion, passive recovery (PASSIVE). Blood lactate (BLa), blood gases, heart rate, and time to exhaustion were collected. The three high intensity bouts had a duration of 138 ± 9, 124 ± 6, and 121 ± 6 s demonstrating a decrease from bout 1 to bout 3. Supplementation strategy had no effect on performance in the first bout, even with differences in pH and bicarbonate (HCO3(-)). Repeated sprint performance was not affected by supplementation strategy when compared to ACTIVE, while PASSIVE resulted in a more pronounced decrease in performance compared with all other interventions. BIC led to greater BLa, pH, and HCO3(-) values compared with all other interventions, while for PASSIVE the opposite was found. BLa recovery was lowest in PASSIVE; recovery in pH, and HCO3(-) was lower in PASSIVE and higher in BIC.


Assuntos
Desempenho Atlético/fisiologia , Bicarbonatos/administração & dosagem , Carboidratos da Dieta/administração & dosagem , Suplementos Nutricionais , Resistência Física/fisiologia , Adulto , Carboidratos/administração & dosagem , Humanos , Masculino , Resistência Física/efeitos dos fármacos , Esforço Físico/efeitos dos fármacos , Esforço Físico/fisiologia , Corrida/fisiologia , Fatores de Tempo
5.
Nagoya J Med Sci ; 72(3-4): 129-37, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20942267

RESUMO

The present study was conducted to investigate the effect of daily passive exercise using a horseback riding machine (Joba) on insulin sensitivity and resting metabolism in middle-aged, diabetic patients. Participants were 24 type 2 diabetes mellitus patients aged 59 +/- 8 years (mean +/- SD; range from 43 to 75 years of age). Patients were randomly divided into control (normal lifestyle) and Joba exercise groups. The latter group was instructed to perform one 30-min session of Joba riding per day, 7 times per week, for 3 months. Compared with baseline values, serum immunoreactive insulin (IRI) concentrations decreased and HOMA-IR was improved by Joba training. In addition, exercise duration per day significantly correlated (r = -0.65) with changes in serum IRI, and 3-month mechanical horseback riding significantly increased the resting metabolic rate of the patients. These results suggest that daily Joba passive exercise is potentially useful as a means to improve insulin sensitivity and resting metabolism in diabetic patients. The Joba fitness equipment can prove especially useful as an alternative exercise therapy for aged individuals incapable of performing independent exercise or for those who suffer from knee-joint disorders.


Assuntos
Metabolismo Basal/fisiologia , Diabetes Mellitus Tipo 2 , Terapia Assistida por Cavalos/métodos , Exercício Físico/fisiologia , Resistência à Insulina/fisiologia , Adulto , Idoso , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/terapia , Terapia Assistida por Cavalos/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Metabolism ; 58(10): 1489-95, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19586643

RESUMO

The mitochondrial branched-chain alpha-keto acid dehydrogenase complex (BCKDC) is responsible for the committed step in branched-chain amino acid catabolism. In the present study, we examined BCKDC regulation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats both before (8 weeks of age) and after (25 weeks of age) the onset of type 2 diabetes mellitus. Long-Evans Tokushima Otsuka (LETO) rats were used as controls. Plasma branched-chain amino acid and branched-chain alpha-keto acid concentrations were significantly increased in young and middle-aged OLETF rats. Although the hepatic complex was nearly 100% active in all animals, total BCKDC activity and protein abundance of E1alpha, E1beta, and E2 subunits were markedly lower in OLETF than in LETO rats at 8 and 25 weeks of age. In addition, hepatic BCKDC activity and protein amounts were significantly decreased in LETO rats aged 25 weeks than in LETO rats aged 8 weeks. In skeletal muscle, E1beta and E2 proteins were significantly reduced, whereas E1alpha tended to increase in OLETF rats. Taken together, these results suggest that (1) whole-body branched-chain alpha-keto acid oxidation capacity is extremely reduced in OLETF rats independently of diabetes development, (2) the aging process decreases BCKDC activity and protein abundance in the liver of normal rats, and (3) differential posttranscriptional regulation for the subunits of BCKDC may exist in skeletal muscle.


Assuntos
3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/metabolismo , Diabetes Mellitus Tipo 2/enzimologia , Fígado/enzimologia , Envelhecimento/metabolismo , Aminoácidos de Cadeia Ramificada/sangue , Animais , Western Blotting , Eletroforese em Gel de Poliacrilamida , Músculo Esquelético/enzimologia , Músculo Esquelético/metabolismo , Ratos , Ratos Endogâmicos OLETF , Triglicerídeos/sangue , Aumento de Peso/fisiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-19163450

RESUMO

A new type of 'Passive Exercise Equipment' has been developed, which can induce muscular contraction of the functional muscles around knee joint. Not only user s who are not eager to exercise but also patients with both type 2 diabetes and knee joint osteoarthritis can perform exercise just by following our equipment's motion while sitting on it. In order to reduce knee joint pain, the equipment has three types of original functions. Our experiments, using the equipment, shows that (1) from a subjective evaluation by persons with knee joint osteoarthritis, knee joint pain was smaller than that of walking on a flat surface area, (2) glucose uptake was significantly enhanced from the Euglycemic Clamp study for both young healthy persons and elder persons with type 2 diabetes, and (3) 12 weeks training using the equipment has improved the rating of the knee joint osteoarthritis.


Assuntos
Terapia por Exercício/instrumentação , Contração Isotônica/fisiologia , Articulação do Joelho/fisiopatologia , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Osteoartrite do Joelho/fisiopatologia , Fenômenos Biomecânicos , Diabetes Mellitus Tipo 2/terapia , Eletromiografia/métodos , Desenho de Equipamento , Terapia por Exercício/métodos , Glucose/metabolismo , Humanos , Osteoartrite do Joelho/reabilitação , Medição da Dor , Amplitude de Movimento Articular/fisiologia , Fatores de Tempo
8.
Exp Biol Med (Maywood) ; 232(10): 1330-7, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17959846

RESUMO

It is well known that exercise training, including voluntary running (VR), improves insulin resistance. However, the effect of VR on insulin resistance induced by high salt intake is unclear. The aim of this study was to determine whether VR would improve the glucose utilization in normal male Sprague-Dawley rats fed a high-salt diet (HSD) on 2-week early prevention and 1-week midway intervention protocols. In vivo glucose utilization was measured by euglycemic clamp technique. Further analyses of the possible changes in insulin signaling occurring in skeletal muscle were performed by Western blot and reverse transcription polymerase chain reaction (RT-PCR). The glucose infusion rates (GIRs) after 2 weeks of HSD feeding were decreased (HSD vs. control: 21.5 +/- 0.8 vs. 27 +/- 0.5 mg/kg body wt/min; P < 0.05), and improved by 2 weeks VR to 30.5 +/- 1.5 mg/kg body wt/min. Additionally, the GIRs after 3 weeks of HSD feeding were decreased (HSD vs. control: 20.0 +/- 0.3 vs. 26.5 +/- 0.6 mg/kg body wt/min; P < 0.05), and they also improved by the third week of VR (28.5 +/- 0.7 mg/ kg body wt/min vs. sedentary; P < 0.01). There were no differences in skeletal muscle for the total mass of insulin receptor-beta (IR-beta), IR substrate-1 (IRS-1), Akt, and glucose transporter 4 (GLUT4) in any of the groups of 2 weeks of HSD loading control and VR. VR did not regulate the enhanced tyrosine phosphorylation of IR-beta and IRS-1 by 2 weeks of HSD feeding. However, the enhanced serine phosphorylation of Akt and the tyrosine phosphorylation of GLUT4 were significantly inhibited by the early VR. HSD also impaired GLUT4 content in the plasma membrane and mRNA expression, but the decreases were improved by 2 weeks of VR. These results suggest that early voluntary exercise would prevent the development of insulin resistance induced by an HSD due in part by enhancing the impaired GLUT4 translocation and mRNA expression in skeletal muscle.


Assuntos
Resistência à Insulina/fisiologia , Atividade Motora/fisiologia , Músculo Esquelético/fisiologia , Corrida , Animais , Peso Corporal , Ingestão de Líquidos , Ingestão de Energia , Glucose/metabolismo , Transportador de Glucose Tipo 4/genética , Masculino , Fosforilação , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Cloreto de Sódio na Dieta , Água
9.
Diabetes Res Clin Pract ; 77 Suppl 1: S87-91, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17498834

RESUMO

Evidence-based medicine (EBM) has come to be regarded as essential in all fields of medical sciences and practical medicine. In the field of diabetes and exercise, among the epidemiological studies of physical exercise, recent mega-trials such as the Diabetes Prevention Program (DPP) in the U.S. have shown that lifestyle intervention programs involving diet and/or exercise reduce the progression of impaired glucose tolerance (IGT) to type 2 diabetes. In studies examining the endocrinological and metabolic effects of exercise, it has been demonstrated that physical exercise promotes the utilization of blood glucose and free fatty acids in muscles and lowers blood glucose levels in well-controlled diabetic patients. Long-term, mild, regular jogging increases the action of insulin in both carbohydrate and lipid metabolism without influencing body mass index or maximal oxygen uptake. A significant correlation has been observed between delta MCR (Deltainsulin sensitivity) and the average number of steps performed in a day. Our recent data suggested that the improved effectiveness of insulin that occurs as a result of physical exercise is attributable, at least in part, to increases in GLUT4 protein, IRS1 and PI3-kinase protein in skeletal muscle. As a prescription for exercise, aerobic exercise of mild to moderate intensity, including walking and jogging, 10-30 min a day, 3-5 days a week, is recommended. Resistance training of mild intensity with the use of light dumbbells and stretch cords should be combined in elderly individuals who have decreased muscle strength. An active lifestyle is essential in the management of diabetes, which is one of typical lifestyle-related diseases.


Assuntos
Diabetes Mellitus/reabilitação , Exercício Físico , Síndrome Metabólica/reabilitação , Aptidão Física , Diabetes Mellitus/prevenção & controle , Diabetes Mellitus/terapia , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/reabilitação , Diabetes Mellitus Tipo 2/terapia , Metabolismo Energético , Medicina Baseada em Evidências , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Síndrome Metabólica/prevenção & controle , Síndrome Metabólica/terapia
10.
Metabolism ; 55(3): 317-23, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16483874

RESUMO

The activity of the pyruvate dehydrogenase complex (PDC) is regulated by covalent modification of its E1 component, which is catalyzed by specific pyruvate dehydrogenase kinases (PDKs) and phosphatases. In the liver, PDK2 and PDK4 are the most abundant PDK isoforms, which are responsible for inactivation of PDC when glucose availability is scarce in the body. In the present study, regulatory mechanisms of hepatic PDC were examined before and after the onset of type 2 diabetes mellitus in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, using Long-Evans Tokushima Otsuka (LETO) rats as controls. Plasma glucose and insulin concentrations were at normal levels in rats aged 8 weeks, but were significantly higher in OLETF than in LETO rats aged 25 weeks, indicating insulin resistance in OLETF rats. Plasma free fatty acids (FFAs) were 1.6-fold concentrated, and the liver PDC activity was significantly lower in OLETF than in LETO rats at both ages, suggesting suppression of pyruvate oxidative decarboxylation in OLETF rats before and after the onset of diabetes. Pyruvate dehydrogenase kinase activity and abundance of PDK2 and PDK4 proteins, as well as mRNAs, were greater in OLETF rats at both ages. These results suggest that persistently elevated levels of circulating free fatty acid in normal and diabetic OLETF rats play an important role in stimulating PDK2 and PDK4 expression in liver.


Assuntos
Ácidos Graxos/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/enzimologia , Proteínas Quinases/genética , Fatores Etários , Animais , Diabetes Mellitus Tipo 2 , Ácidos Graxos/sangue , Resistência à Insulina , Proteínas Serina-Treonina Quinases , Piruvato Desidrogenase Quinase de Transferência de Acetil , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos OLETF , Regulação para Cima/efeitos dos fármacos
11.
Diabetes Res Clin Pract ; 71(2): 124-30, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16105705

RESUMO

The present study was undertaken to analyze the acute and chronic effects of exercise on insulin sensitivity in elder diabetic patients using a horseback riding therapeutic equipment (Joba). The acute effects of exercise were examined by means of a single session of Joba riding that lasted for 30 min. The average glucose infusion rates (GIR) before and during exercise were regarded as an index of the insulin action in peripheral tissues by the euglycemic clamp. The chronic effects of exercise were studied by training the elder diabetic patients for 12 weeks using the Joba apparatus. The insulin sensitivity was determined pre- and post-training by a 90 min euglycemic clamp. In the acute study, average GIR during exercise was significantly higher than pre-exercise (7.8+/-0.4 versus 5.2+/-0.3 mg kg(-1)min(-1), P<0.01) and average GIR during recovery decreased to almost the same levels of pre-exercise (5.0+/-0.4 mg kg(-1)min(-1); P<0.01). The 12-week training resulted in a significant increase in the steady-state GIR (from 5.2+/-0.3 to 7.4+/-0.8 mg kg(-1)min(-1); P<0.05). The steady-state GIR after 12 weeks of detraining returned to pre-training levels (5.3+/-0.5 mg kg(-1)min(-1); P<0.05). In elder diabetic patients, mechanical horseback riding enhances the insulin-induced glucose uptake.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Exercício Físico , Idoso , Animais , Índice de Massa Corporal , Tamanho Corporal , Diabetes Mellitus Tipo 2/sangue , Feminino , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , Cavalos , Humanos , Pessoa de Meia-Idade
12.
Biosci Biotechnol Biochem ; 69(10): 1819-23, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16244429

RESUMO

We examined the effects of ingesting a non-sugar chocolate containing polydextrose and lactitol in place of sucrose and lactose on the concentrations of plasma glucose and serum insulin and triglyceride in humans. A regular chocolate was used as the control. A crossover study was employed, and the subjects each ingested 46 g of the control or non-sugar chocolate in the experiments. Alterations in the blood components were monitored for a period of 150 min after ingestion. The control chocolate elevated the concentrations of plasma glucose and serum insulin, with the peak occurring 30 min after ingestion, but the non-sugar chocolate had a very minor effect. The serum triglyceride concentration gradually increased after ingesting the control chocolate, but was only slightly elevated 150 min after ingesting the non-sugar chocolate. An animal study also showed an attenuated response of serum triglyceride to the administration of a fat emulsion containing polydextrose and lactitol, suggesting that the triglyceride transit through the gut was promoted by these compounds. These results suggest that, compared to regular chocolate, fat absorption in the gut was less after ingesting the non-sugar chocolate, presumably resulting in less effect on body fat deposition.


Assuntos
Cacau/química , Glucanos/farmacocinética , Álcoois Açúcares/farmacocinética , Edulcorantes/farmacocinética , Triglicerídeos/sangue , Adulto , Animais , Glicemia , Cacau/metabolismo , Glucanos/administração & dosagem , Glucanos/farmacologia , Humanos , Insulina/sangue , Absorção Intestinal , Intestino Delgado/metabolismo , Masculino , Farmacocinética , Ratos , Álcoois Açúcares/administração & dosagem , Álcoois Açúcares/farmacologia , Edulcorantes/administração & dosagem , Edulcorantes/farmacologia
13.
Hepatol Res ; 30S: 3-8, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15607132

RESUMO

Significant evidence of the pharmacological and physiological effects of branched-chain amino acids (BCAA) has accumulated, attracting the interest of not only clinicians but also basic medical researchers. We summarize here the characteristic features of BCAA catabolism, focusing on the initial two enzymes in the pathway, branched-chain aminotransferase and branched-chain alpha-keto acid dehydrogenase complex. In addition, we describe a unique characteristic of the valine catabolic pathway. Finally, we present evidence obtained in animal studies that indicates that BCAA treatment may be appropriate for liver cirrhosis, but not acute liver failure.

14.
J Nutr ; 134(10): 2628-33, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15465758

RESUMO

A diurnal rhythm occurs in the activity state of branched-chain alpha-keto acid dehydrogenase complex (BCKDC) in female but not male rats. We attempted to determine the role played by ovarian hormones in this difference in enzyme regulation. A series of experiments examined the effects of the 4-d estrous cycle, ovariectomy, and replacement of female sex steroids on the catabolism of BCAAs. A proestrous decrease in the activity state of the complex corresponded to an increase in the plasma 17beta-estradiol level. Withdrawal of gonadal steroids by ovariectomy resulted in an increase in the activity state of BCKDC and a decrease in the activity of the branched-chain alpha-keto acid dehydrogenase kinase (BDK). However, 17beta-estradiol reversed these effects, resulting in an increase in the BDK activity, thereby decreasing the activity of the complex. Progesterone administration was ineffective. The changes in the percentage of active BCKDC caused by 17beta-estradiol withdrawal and replacement resulted from changes in the amount of BDK protein associated with the complex and therefore its activity. Thus, the marked diurnal variation in the activity state of BCKDC exhibited by female rats involves estrogenic control of BDK activity. We hypothesize that the 17beta-estradiol-controlled feeding pattern produces these variations in BCKDC activity. This may function in female rats to conserve essential amino acids for protein synthesis.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Estradiol/fisiologia , Proteínas Quinases/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Estradiol/sangue , Estradiol/farmacologia , Feminino , Fígado/efeitos dos fármacos , Fígado/enzimologia , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia , Ratos , Ratos Sprague-Dawley
15.
Life Sci ; 75(17): 2117-30, 2004 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-15312755

RESUMO

The pyruvate dehydrogenase complex (PDC) catalyzes the irreversible oxidative decarboxylation of pyruvate in mitochondria. The PDC activity is regulated by a phosphorylation/dephosphorylation cycle catalyzed by specific kinases (PDK) and phosphatases (PDP). In this study, the regulatory mechanisms of PDC were examined in skeletal muscle of the spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rat before and after the onset of diabetes. The Long-Evans Tokushima Otsuka (LETO) rat was used as control. Plasma glucose and insulin concentrations were at normal levels in both groups at 8 weeks of age but were significantly higher in OLETF than in LETO rats at 25 weeks of age (1.2-fold for glucose and 15-fold for insulin), indicating development of diabetes in the former. Plasma free fatty acids were 1.6-fold concentrated and the skeletal muscle PDC activity state was significantly lower in OLETF than in LETO rats at both ages, suggesting suppression of pyruvate oxidation in OLETF rats even before the onset of diabetes. The PDK activity and the abundance of the PDK isoform 4 protein as well as mRNA were greater in OLETF rats at both ages. Conversely, the abundance of the PDP isoform 1 protein and mRNA was less in OLETF than in LETO rats at both ages. These results suggest that concomitant greater PDK4 and less PDP1 expression in skeletal muscle of OLETF rats before the onset of diabetes are responsible for the lowering of the PDC activity and may be related with the development of diabetes mellitus.


Assuntos
Diabetes Mellitus/metabolismo , Regulação para Baixo , Músculo Esquelético/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , RNA Mensageiro/metabolismo , Fatores Etários , Análise de Variância , Animais , Glicemia , Northern Blotting , Modelos Animais de Doenças , Eletroforese , Ácidos Graxos não Esterificados/sangue , Immunoblotting , Insulina/sangue , Análise dos Mínimos Quadrados , Proteínas Quinases/metabolismo , Piruvato Desidrogenase (Lipoamida)-Fosfatase/metabolismo , Radioimunoensaio , Ratos , Ratos Endogâmicos OLETF
16.
J Nutr ; 134(6 Suppl): 1583S-1587S, 2004 06.
Artigo em Inglês | MEDLINE | ID: mdl-15173434

RESUMO

Branched-chain amino acids (BCAAs) are essential amino acids that can be oxidized in skeletal muscle. It is known that BCAA oxidation is promoted by exercise. The mechanism responsible for this phenomenon is attributed to activation of the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, which catalyzes the second-step reaction of the BCAA catabolic pathway and is the rate-limiting enzyme in the pathway. This enzyme complex is regulated by a phosphorylation-dephosphorylation cycle. The BCKDH kinase is responsible for inactivation of the complex by phosphorylation, and the activity of the kinase is inversely correlated with the activity state of the BCKDH complex, which suggests that the kinase is the primary regulator of the complex. We found recently that administration of ligands for peroxisome proliferator-activated receptor-alpha (PPARalpha) in rats caused activation of the hepatic BCKDH complex in association with a decrease in the kinase activity, which suggests that promotion of fatty acid oxidation upregulates the BCAA catabolism. Long-chain fatty acids are ligands for PPARalpha, and the fatty acid oxidation is promoted by several physiological conditions including exercise. These findings suggest that fatty acids may be one of the regulators of BCAA catabolism and that the BCAA requirement is increased by exercise. Furthermore, BCAA supplementation before and after exercise has beneficial effects for decreasing exercise-induced muscle damage and promoting muscle-protein synthesis; this suggests the possibility that BCAAs are a useful supplement in relation to exercise and sports.


Assuntos
Aminoácidos de Cadeia Ramificada/farmacologia , Suplementos Nutricionais , Atividade Motora/fisiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Aminoácidos de Cadeia Ramificada/efeitos adversos , Aminoácidos de Cadeia Ramificada/metabolismo , Animais , Exercício Físico/fisiologia , Humanos , Esportes
17.
J Hepatol ; 40(3): 439-45, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15123358

RESUMO

BACKGROUND/AIMS: Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex catalyses the committed step in the branched-chain amino acid (BCAA) catabolic pathway. In many cases of liver failure, the serum BCAAs/aromatic amino acids ratio (Fisher's ratio) decreases, and BCAAs have been administered to patients with liver failure to correct this ratio. We conducted an animal study to examine whether the effects on hepatic BCKDH complex differ between acute liver failure (ALF) and chronic liver failure (CLF). METHODS: ALF and CLF was induced in rats by a single high-dose injection and 21 weeks of repeated low-dose injections of carbon tetrachloride, respectively. Plasma BCAA and branched-chain alpha-keto acid (BCKA) levels, and activities and protein amounts of hepatic BCKDH complex and kinase were measured. RESULTS: ALF was characterized by elevated plasma BCAA and BCKA levels and decreased hepatic BCKDH activity. CLF was characterized by decreased plasma BCAA and BCKA levels and increased hepatic BCKDH activity. This increase in BCKDH activity in CLF was associated with the decreased BCKDH kinase, which is responsible for the BCKDH inactivation. CONCLUSIONS: The results obtained in the present study suggest that BCAA catabolism is suppressed in ALF and increased in CLF.


Assuntos
3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/metabolismo , Falência Hepática Aguda/enzimologia , Falência Hepática/enzimologia , Fígado/enzimologia , Músculo Esquelético/enzimologia , 3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/genética , Aminoácidos de Cadeia Ramificada/sangue , Animais , Tetracloreto de Carbono/administração & dosagem , Doença Crônica , Citrato (si)-Sintase/metabolismo , Relação Dose-Resposta a Droga , Esquema de Medicação , Isoenzimas/genética , Cetoácidos/sangue , Falência Hepática/sangue , Falência Hepática/induzido quimicamente , Falência Hepática Aguda/sangue , Falência Hepática Aguda/induzido quimicamente , Masculino , Proteínas Quinases/sangue , Proteínas Quinases/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
18.
Biochem Biophys Res Commun ; 313(2): 381-5, 2004 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-14684172

RESUMO

Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex catalyzes the committed step of the catabolism of branched-chain amino acids (BCAA). The liver cirrhosis chemically induced in rats raised the activity of hepatic BCKDH complex and decreased plasma BCAA and branched-chain alpha-keto acid concentrations, suggesting that the BCAA requirement is increased in liver cirrhosis. Since the effects of liver cirrhosis on the BCKDH complex in human liver are different from those in rat liver, further studies are needed to clarify the differences between rats and humans. In the valine catabolic pathway, crotonase and beta-hydroxyisobutyryl-CoA hydrolase are very important to regulate the toxic concentration of mitochondrial methacrylyl-CoA, which occurs in the middle part of valine pathway and highly reacts with free thiol compounds. Both enzyme activities in human and rat livers are very high compared to that of BCKDH complex. It has been found that both enzyme activities in human livers were significantly reduced by liver cirrhosis and hepatocellular carcinoma, suggesting a decrease in the capability to dispose methacrylyl-CoA. The findings described here suggest that alterations in hepatic enzyme activities in the BCAA catabolism are associated with liver failure.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Falência Hepática/enzimologia , 3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/metabolismo , Animais , Enoil-CoA Hidratase/metabolismo , Humanos , Complexos Multienzimáticos/metabolismo , Tioléster Hidrolases/metabolismo , Transaminases/metabolismo
19.
Evid Based Complement Alternat Med ; 1(3): 269-276, 2004 12.
Artigo em Inglês | MEDLINE | ID: mdl-15841260

RESUMO

Previous studies have shown that the traditional herbal complex Gosha-jinki-gan (GJG) improves diabetic neuropathy and insulin resistance. The present study was undertaken to elucidate the molecular mechanisms related with the long-term effects of GJG administration on insulin action in vivo and the early steps of insulin signaling in skeletal muscle in streptozotocin (STZ) diabetes. Rats were randomized into five subgroups: (1) saline treated control, (2) GJG treated control, (3) 2-unit insulin + saline treated diabetic, (4) saline + GJG treated diabetic and (5) 2-unit insulin + GJG treated diabetic groups. After seven days of treatment, euglycemic clamp experiment at an insulin infusion rate of 6 mU/kg/min was performed in overnight fasted rats. Despite the 2-unit insulin treatment, the metabolic clearance rates of glucose (MCR, ml/kg/min) in diabetic rats were significantly lower compared with the controls (11.4 +/- 1.0 vs 44.1 +/- 1.5; P < 0.001), and were significantly improved by insulin combined with GJG or GJG alone (26 +/- 3.2 and 24.6 +/- 2.2, P < 0.01, respectively). The increased insulin receptor (IR)-beta protein content in skeletal muscle of diabetic rats was not affected by insulin combined with GJG administration. However, the decreased insulin receptor substrate-1 (IRS-1) protein content was significantly improved by treatment with GJG. Additionally, the increased tyrosine phosphorylation levels of IR-beta and IRS-1 were significantly inhibited in insulin combined with GJG treated diabetes. The present results suggest that the improvement of the impaired insulin sensitivity in STZ-diabetic rats by administration of GJG may be due, at least in part, to correction in the abnormal early steps of insulin signaling in skeletal muscle.

20.
Diabetes Res Clin Pract ; 62(3): 139-48, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14625128

RESUMO

Cinnamon has been shown to potentiate the insulin effect through upregulation of the glucose uptake in cultured adipocytes. In the present study, we evaluated the effect of the cinnamon extract on the insulin action in awaked rats by the euglycemic clamp and further analyzed possible changes in insulin signaling occurred in skeletal muscle. The rats were divided into saline and cinnamon extract (30 and 300 mg/kg BW-doses: C30 and C300) oral administration groups. After 3-weeks, cinnamon extract treated rats showed a significantly higher glucose infusion rate (GIR) at 3 mU/kg per min insulin infusions compared with controls (118 and 146% of controls for C30 and C300, respectively). At 30 mU/kg per min insulin infusions, the GIR in C300 rats was increased 17% over controls. There were no significant differences in insulin receptor (IR)-beta, IR substrate (IRS)-1, and phosphatidylinositol (PI) 3-kinase protein content between C300 rats and controls. However, the skeletal muscle insulin-stimulated IR-beta and the IRS-1 tyrosine phosphorylation levels in C300 rats were 18 and 33% higher, respectively, added to 41% higher IRS-1/PI 3-kinase association. These results suggest that the cinnamon extract would improve insulin action via increasing glucose uptake in vivo, at least in part through enhancing the insulin-signaling pathway in skeletal muscle.


Assuntos
Glicemia/metabolismo , Cinnamomum zeylanicum , Glucose/metabolismo , Insulina/fisiologia , Extratos Vegetais/farmacologia , Transdução de Sinais/fisiologia , Animais , Glicemia/efeitos dos fármacos , Peso Corporal , Relação Dose-Resposta a Droga , Ácidos Graxos não Esterificados/sangue , Técnica Clamp de Glucose , Insulina/sangue , Insulina/farmacologia , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
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