259 resultados para Glycogen phosphorylase
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation. This work reports on the crystallographic study of the complex of human PNP-immucillin-H (HsPNP-ImmH) solved at 2.6 Angstrom resolution using synchrotron radiation. Immucillin-H (ImmH) inhibits the growth of malignant T-cell lines in the presence of deoxyguanosine without affecting non-T-cell tumor lines. ImmH inhibits activated normal human T cells after antigenic stimulation in vitro. These biological effects of ImmH suggest that this agent may have utility in the treatment of certain human diseases characterized by abnormal T-cell growth or activation. This is the first structural report of human PNP complexed with immucillin-H. The comparison of the complex HsPNP-ImmH with recent crystallographic structures of human PNP explains the high specificity of immucillin-H for human PNP. (C) 2003 Elsevier B.V. All rights reserved.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Physical exercises have been recommended in the prevention of non-insulin dependent diabetes mellitus (NIDDM), but the mechanisms involved in this intervention are not yet fully understood. Experimental models offer the opportunity for the study of this matter. The present study was designed to analyze the diabetes evolution in rats submitted to neonatal treatment with alloxan with the objective of verifying the suitability of the model to future studies with exercises. For this, newly born rats (6 days old) received intraperitoneal alloxan (A = 200 mg/kg of body weight). Rats injected with vehicle (citrate buffer) were used as controls (C). The fasting blood glucose level (mg/dL) was higher in the alloxan group at the day 28 (C=47.25 +/- 5.08; A=54.51 +/- 7.03) but not at the 60 day of age (C=69.18 +/- 8.31; A=66.81 +/- 6.08). The alloxan group presented higher blood glucose level during glucose tolerance test (GTT) (mg/dL. 120 min) in relation to the control group both at day 28 (C=16908.9 +/- 1078.8; A=21737,7 +/- 1106.4) and at day 60 (C=11463.45 +/- 655.30; A=15282.21 +/- 1221.84). Insulinaemia during GTT (ng/mL.120 min) was lower at day 28 (C=158.67 +/- 33.34; A=123.90 +/- 19.80), but presented no difference at day 60 (C=118.83 +/- 26.02; A=97.8 +/- 10.88). At day 60, the glycogen concentration in the soleus muscle (mg/100mg) was lower in the alloxan group (0.3 +/- 0.13) in relation to the control group (0.5 +/- 0.07). No difference was observed between groups in relation to (mu mol/g.h): Glucose Uptake (C = 5.8 +/- 0.63; A = 5.2 +/- 0.73); Glucose Oxidation (C= 4.3 +/- 1.13; A= 3.9 +/- 0.44); Glycogen Synthesis (C= 0.8 +/- 0.18; A= 0.7 +/- 0.18) and Lactate Production (C= 3.8 +/- 0.8; A= 3.8 0.7) by the isolated soleus muscle. The glucose-stimulated insulin secretion (16.7mM) by the isolated islets (ng/5 islets. h) of the alloxan group was lower (14.3 +/- 4.7) than the control group (32.0 +/- 7.9). Thus, we may conclude that this neonatal diabetes induction model gathers interesting characteristics and may be useful for further studies on the role of the exercise in the diabetes mellitus appearance.
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To investigate the influence of short-term physical training on IGF-I concentrations in diabetic rats, male wistar rats were distributed into four groups: sedentary control, trained control, sedentary diabetic and trained diabetic. Diabetes was induced by Alloxan (32 mg/kg b.w.) and training protocol consisted of swimming 1 h/day, 5 days/week, during 4 weeks, supporting 5% b.w. At the end of this period, rats were sacrificed and blood was collected for determinations of serum glucose, insulin, albumin, IGF-I and hematocrit. Liver samples were used to determine glycogen, protein, DNA and IGF-I concentrations. Diabetes reduced insulin and IGF-I concentrations in blood and liver protein, ratio protein/DNA and IGF-I concentrations in liver and increased glycemia. Physical training reduced serum glucose and recovered hepatic glycogen stores in diabetic rats and reduced serum and liver IGF-I concentrations. In conclusion, short-term physical training improved the metabolic conditions of diabetic rats, despite of impairing liver and blood IGF-I concentrations.
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O presente estudo visou avaliar a ingestão alimentar, ganho de peso e metabolismo muscular da glicose em ratos submetidos ao treinamento aeróbio durante recuperação de desnutrição protéica. Para isso, 60 ratos da linhagem Wistar, machos, foram separados nos grupos normoprotéico (NP) e hipoprotéico (HP), de acordo com a dieta NP (17% de proteína) ou HP (6% de proteína), respectivamente, recebida do desmame (21 dias) aos 90 dias de idade. Todos os animais passaram então, a receber a dieta NP e foram submetidos (treinado TRE) ou não (sedentário - SED) ao treinamento físico, que consistiu de corrida em esteira rolante, 25m/min, 50 minutos ao dia, cinco dias na semana, durante 30 dias, compondo os grupos NP-SED, NP-TRE, HP/NP-SED e HP/NP-TRE. Foi avaliado o metabolismo da glicose em fatias de músculo sóleo incubado em presença de insulina (100miU/L) e glicose (5,5mM, contendo [C14] glicose e [H³] 2-deoxiglicose). A ingestão alimentar diária (g/100g de peso corporal) do grupo HP/NP-TRE (24,39 ± 4,07) foi maior do que o grupo HP/NP-SED (21,62 ± 4,69). O ganho de peso (g) foi semelhante nos grupos HP/NP-TRE (203,80 ± 34,03) e HP/NP-SED (214,43 ± 30,54). Não houve diferença entre estes dois grupos quanto aos parâmetros: captação de glicose, oxidação de glicose e síntese de glicogênio pelo músculo sóleo. Desse modo, pudemos concluir que o treinamento aeróbio não teve impacto sobre a recuperação nutricional, visto que não houve diferenças metabólicas ou somáticas entre animais recuperados em presença ou ausência do treinamento.
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No presente estudo foram comparadas as respostas metabólicas agudas ao exercício em ratos alimentados com dieta padrão e à base de espirulina. Ratos Wistar jovens foram divididos em dois grupos de acordo com a dieta: controle (C) (dieta padrão) e espirulina (S) (dieta à base de espirulina). Ao final do período experimental (cinco semanas) os animais foram submetidos a uma sessão aguda de exercício de natação (20 minutos, suportando sobrecarga equivalente a 5% do peso corporal) para avaliação do lactato sanguíneo, glicose, insulina, proteínas, albumina e ácidos graxos livres (AGL) séricos. Amostras do músculo gastrocnêmio e fígado foram utilizadas para determinação dos teores de glicogênio e lipídeos. Ambos os grupos C e S apresentaram aumento da glicemia e dos AGL, queda da insulinemia e redução dos teores de glicogênio muscular e hepático pós-exercício. A lactacidemia durante o exercício foi superior no grupo S em relação ao C. Conclui-se que o padrão de respostas ao exercício agudo dos grupos C e S foi semelhante. Contudo, a proteína da dieta pareceu influenciar aspectos do metabolismo glicídico.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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To investigate the alterations of glucose homeostasis and variables of the insulin-like growth factor-I (IGF- 1) growth system in sedentary and trained diabetic (TD) rats, Wistar rats were divided into sedentary control (SC), trained control (TC), sedentary diabetic (SD), and TD groups. Diabetes was induced by Alloxan (35 mg kg(-1) b.w.). Training program consisted of swimming 5 days week(-1), 1 h day(-1), during 8 weeks. Rats were sacrificed and blood was collected for determinations of serum glucose, insulin, growth hormone (GH), IGF-1, and IGF binding protein-3(IGFBP-3). Muscle and liver were removed to evaluate glycogen content. Cerebellum was extracted to determinate IGF-1 content. Diabetes decreased serum GH, IGF-1, IGFBP-3, liver glycogen, and cerebellum IGF-1 peptide content in baseline condition. Physical training recovered liver glycogen and increased serum and cerebellum IGF-1 peptide in diabetic rats. Physical training induces important metabolic and hormonal alterations that are associated with an improvement in glucose homeostasis and serum and cerebellum IGF-1 concentrations. Copyright (C) 2009 John Wiley & Sons, Ltd.
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Aims: This study aims to investigate the influence of physical training on the immune system of diabetic rats. Materials and Methods: Adult male Wistar rats were distributed into Sedentary Control (SC), Trained Control (TC), Sedentary Diabetic (SD) and Trained Diabetic (TD) groups were used. Diabetes was induced by alloxan (32 mg/bw-i.v.). Training protocol consisted of swimming, at 32 18C, one hour/day, five days/week, supporting an overload equivalent to 5 of the body weight, during four weeks. At the end of the experiment the rats were sacrificed by decapitation and blood samples were collected for glucose, insulin, albumin, hematocrit determinations, total and differential leukocyte counting. Additionally, liver samples for glycogen analyses were obtained. Results: The results were analyzed by one way at a significance level of 5. Diabetes reduced blood insulin, liver glycogen stores and increased blood glucose and neutrophil count. Physical training restored glycemia, liver glycogen levels, neutrophils and lymphocytes count in diabetic rats. Conclusions: In summary, physical training was able to improve metabolic and immunological aspects in the experimental diabetic rats.