Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.3.3.1 (citrate synthase)
4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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)
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PMID:Muscle glucose transport, GLUT-4 content, and degree of exercise training in obese Zucker rats. 144 11

The interrelationships among glucose uptake, GLUT-4 protein, and citrate synthase activity in insulin-resistant skeletal muscle were investigated. Female obese (fa/fa) Zucker rats were randomly assigned to treadmill training, ingestion of the selective beta 2-adrenergic agonist clenbuterol, or sedentary control groups. After 7-8 wk of treatment, hindlimbs were perfused to determine maximal insulin-stimulated (10 mU/ml) 2-[3H]deoxy-D-glucose (2-DG) uptake. Exercise training significantly enhanced 2-DG uptake and GLUT-4 protein in red gastrocnemius and plantaris. Alternatively, 2-DG uptake was not altered in soleus after exercise training despite a 52% increase in GLUT-4 protein. The increases in GLUT-4 protein in red gastrocnemius, plantaris, and soleus of the trained rats were accompanied by increases in citrate synthase activity. In contrast to exercise training, clenbuterol administration decreased citrate synthase activity in red and white gastrocnemius, yet had no effect on GLUT-4 protein levels or maximal insulin-stimulated 2-DG uptake. Clenbuterol treatment did, however, increase citrate synthase activity and GLUT-4 protein in soleus. These findings indicate that total GLUT-4 protein largely determines the maximal rate of insulin-stimulated glucose uptake in fast-twitch muscle, whereas in slow-twitch muscle it does not. In addition, the results demonstrate that coordination of proteins governing glucose uptake and disposal may be disrupted in a fiber type-specific manner. Overall, the findings raise important questions as to whether regulation of proteins governing glucose uptake and disposal differs significantly among fiber types.
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PMID:Fiber type-specific effects of clenbuterol and exercise training on insulin-resistant muscle. 755 15

The purpose of this study was to determine the interactive effects of 10-12 wk of streptozotocin-induced diabetes (65 mg/kg) and moderate-intensity exercise training on total myocardial GLUT-4 and GLUT-1 proteins. Sprague-Dawley rats (n = 52) were randomly divided into sedentary control (SC), exercise-trained control (ETC), sedentary diabetic (SD), and exercise-trained control (ETD) groups. Diabetes (SD), and exercise-trained diabetic (ETD) groups. Diabetes resulted in a 70% reduction in myocardial GLUT-4 (28.3+/- 3.1 and 94.6 +/- 3.4% for SD and SC, respectively; P < 0.0001) and an 18.5% decrease in GLUT-1 (62.5 +/- 4.7 and 76.8 +/- 4.5% for SD and SC, respectively; P = 0.06). Exercise training increased citrate synthase activity in the medial and long heads of the triceps brachii in both groups (P < 0.001). Fasting blood glucose improved with training in diabetic animals (348 +/- 27 and 569 +/- 28 mg/dl for ETD and SD, respectively; P < 0.05). The diabetes-induced reduction in GLUT-4 was attenuated with exercise training (46.8 +/- 9.3% for ETD; P < 0.02 compared with SD). In contrast, training resulted in a further 25% decrease compared with SD in GLUT-1 in ETD (46.8 +/- 9.3%; P < 0.03 compared with SD). Exercise training had no effect on either GLUT-4 (87.2 +/- 4.0%) or GLUT-1 (75.4 +/- 5.1%) in ETC. GLUT-4 inversely correlated (r = -0.81; P < or = 0.001) with fasting blood glucose. In conclusion, diabetes resulted in a 70% reduction in myocardial GLUT-4 and an 18% decrease in GLUT-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exercise training attenuates the reduction in myocardial GLUT-4 in diabetic rats. 771 47

The present study was undertaken to examine the effect of 10 days of detraining levels of GLUT-4 protein expression and citrate synthase (CS) activity in the vastus lateralis of trained men. During the course of normal training, seven endurance-trained (T) men and eight age- and weight-matched active but untrained (UT) men underwent an oral glucose tolerance test (OGTT) after an overnight fast. Muscle samples were obtained from the vastus lateralis by needle biopsy for measurement of GLUT-4 protein and CS activity. The tests were repeated on six of the T subjects after 10 days of detraining (DT men). The area under the insulin response curve during OGTT was lower in T men than in DT and UT men (22.4 +/- 2.8, 32.1 +/- 5.9, and 39.9 +/- 4.7 x 10(-3) pmol.l-1.min-1, respectively; P < 0.05). There were no differences between groups in the glucose responses to OGTT. GLUT-4 protein levels and CS activity were higher in T men than in DT and UT men (GLUT-4: 4.37 +/- 0.40, 2.92 +/- 0.53, and 1.71 +/- 0.22 arbitrary standard units and CS: 47.12 +/- 4.75, 33.63 +/- 3.98, and 24.51 +/- 2.97 mumol.min-1.g-1, respectively; both P < 0.05). Muscle GLUT-4 protein content was correlated with CS activity in all three groups (r = 0.64, 0.68, and 0.96 for UT, T, and DT men, respectively). These results suggest that muscle GLUT-4 protein content and oxidative capacity undergo parallel adaptations after detraining in previously well-trained men.
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PMID:Effect of detraining on GLUT-4 protein in human skeletal muscle. 783 61

The present study examined the relationship between total skeletal muscle GLUT-4 protein level and glucose uptake during exercise. Eight active non-endurance-trained men cycled at 72 +/- 1% peak pulmonary oxygen consumption for 40 min, with rates of glucose appearance and disappearance (Rd) determined by utilizing a primed continuous infusion of [3-3H]glucose commencing 2 h before exercise. Muscle glycogen content and utilization, citrate synthase activity, and total GLUT-4 protein were measured on muscle biopsy samples obtained from the vastus lateralis. A direct relationship existed between preexercise muscle glycogen content and glycogen utilization during exercise (r = 0.76, P < 0.05). Citrate synthase activity and glucose Rd at the end of exercise averaged 21.9 +/- 3.0 mumol.min-1.g-1 and 27.3 +/- 2.5 mumol.kg-1.min-1, respectively. There was a direct correlation between citrate synthase activity and GLUT-4 protein (r = 0.78, P < 0.05); however, at the end of exercise, glucose Rd was inversely related to both GLUT-4 (r = -0.89, P < 0.01) and citrate synthase activity (r = -0.72, P < 0.05). Plasma insulin, which decreased during exercise, was not related to glucose Rd. In conclusion, glucose uptake during 40 min of exercise at 72% peak pulmonary oxygen consumption was inversely related to the total muscle GLUT-4 protein level. This suggests that factors other than the total GLUT-4 protein level are important in the regulation of glucose uptake during exercise.
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PMID:Skeletal muscle GLUT-4 and glucose uptake during exercise in humans. 783 67

Glucose transporter (GLUT-4) protein, hexokinase, and citrate synthase (proteins involved in oxidative energy production from blood glucose catabolism) increase in response to chronically elevated neuromuscular activity. It is currently unclear whether these proteins increase in a coordinated manner in response to this stimulus. Therefore, voluntary wheel running (WR) was used to chronically overload the fast-twitch rat plantaris muscle and the myocardium, and the early time courses of adaptative responses of GLUT-4 protein and the activities of hexokinase and citrate synthase were characterized and compared. Plantaris hexokinase activity increased 51% after just 1 wk of WR, whereas GLUT-4 and citrate synthase were increased by 51 and 40%, respectively, only after 2 wk of WR. All three variables remained comparably elevated (+50-64%) through 4 wk of WR. Despite the overload of the myocardium with this protocol, no substantial elevations in these variables were observed. These findings are consistent with a coordinated upregulation of GLUT-4 and citrate synthase in the fast-twitch plantaris, but not in the myocardium, in response to this increased neuromuscular activity. Regulation of hexokinase in fast-twitch muscle appears to be uncoupled from regulation of GLUT-4 and citrate synthase, as increases in the former are detectable well before increases in the latter.
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PMID:Adaptive responses of GLUT-4 and citrate synthase in fast-twitch muscle of voluntary running rats. 784 Mar 12

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)
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PMID:Effects of exercise training on muscle GLUT-4 protein content and translocation in obese Zucker rats. 821 51

The purpose of this study was to determine if 14 wk of exercise training would increase insulin-sensitive glucose transporter protein (GLUT-4) concentration in skeletal muscle of previously sedentary middle-aged men (47.2 +/- 1.3 yr; n = 13). Muscle samples (lateral gastrocnemius) and insulin action [insulin sensitivity index (ISI), minimal model] were obtained in the sedentary condition and 48 h after the final training bout. GLUT-4 protein concentration increased (P < 0.001, 2,629 +/- 331 to 4,140 +/- 391 absorbance units/100 micrograms protein) with exercise training by 1.8-fold. ISI increased by twofold (P < 0.05, 2.1 +/- 0.5 to 3.4 +/- 0.7 SI x 10(5) min/pM) with training. The percentage of GLUT-4 rich type IIa muscle fibers increased by approximately 10% (P < 0.01), which may have contributed to the elevation in transporter protein. GLUT-4 concentration and citrate synthase activity (1.7-fold, P < 0.001) also increased by similar increments. These findings indicate that GLUT-4 protein concentration is elevated in middle-aged individuals with exercise training.
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PMID:Exercise training increases GLUT-4 protein concentration in previously sedentary middle-aged men. 833 15

Feeding rats beta-guanidinopropionic acid (beta-GPA), a creatine analogue, results in depletion of creatine and phosphocreatine and induces increases in mitochondrial oxidative enzymes and hexokinase in skeletal muscle. Comparisons of different muscle types and studies of the adaptation to exercise suggest that 1) the levels of the insulin-responsive glucose transporter (GLUT-4), mitochondrial oxidative enzymes, and hexokinase may be coregulated and 2) GLUT-4 content can determine maximal glucose transport activity in muscle. To further evaluate these possibilities, we examined the effects of feeding rats 1% beta-GPA in their diet for 6 wk on muscle GLUT-4 expression and glucose transport activity. beta-GPA feeding induced 40-50% increases in cytochrome c concentration, citrate synthase activity, and hexokinase activity in plantaris muscle. GLUT-4 protein concentration was increased approximately 50% in plantaris and epitrochlearis muscles, while GLUT-4 mRNA was increased approximately 40% in plantaris muscles of beta-GPA-fed rats. Glucose transport activity maximally stimulated by insulin was increased in parallel with GLUT-4 protein concentration in the epitrochlearis. These results provide evidence that chronic creatine depletion increases GLUT-4 expression by pretranslational mechanisms. They support the hypothesis that the levels of mitochondrial enzymes, hexokinase, and GLUT-4 protein are coregulated in striated muscles. They also support the concept that the GLUT-4 content of a muscle determines its maximal glucose transport activity when the signaling pathways for glucose transport activation are intact.
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PMID:Adaptation of muscle to creatine depletion: effect on GLUT-4 glucose transporter expression. 843 Jul 63

The purpose of this study was to determine whether short-term training cessation resulted in reduced GLUT-4 protein levels. Endurance- (n = 12, ET) and strength-trained (n = 12) individuals (ST) were examined before and after 14 days of training withdrawal. GLUT-4 content was determined from muscle biopsy samples of the gastrocnemius in ET and the vastus lateralis in ST. Insulin sensitivity (oral glucose tolerance test) was significantly (P < 0.05) reduced in ET and ST with training cessation. GLUT-4 content was unaltered (P > 0.05) in both groups (92 and 100% of trained values for ET and ST, respectively). In ET, citrate synthase activity decreased significantly (P < 0.05) with training withdrawal (41.0 +/- 3.6 vs. 30.6 +/- 2.8 mumol.g-1.min-1); in ST no change was evident. The decrement in insulin sensitivity with the cessation of endurance- or resistance-oriented activity is therefore not associated with a reduction in GLUT-4 protein content. Muscle oxidative capacity and GLUT-4 content do not coincide with the removal of endurance training.
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PMID:Training cessation does not alter GLUT-4 protein levels in human skeletal muscle. 845 95


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