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)

Insulin resistance in skeletal muscle is associated with 1) relative increases in the proportion of glycolytic and fast-twitch muscle fibers and decreases in the proportion of more oxidative fibers and 2) a higher proportion of the saturated fatty acids in membrane structural lipids. Exercise is known to improve insulin action. The aims of the current studies were 1) to investigate the relationship between muscle fiber type and membrane fatty acid composition and 2) to determine how voluntary exercise might influence both variables. In sedentary Wistar rats in experiment 1, increased amounts of unsaturated fatty acids were found in the more oxidative insulin-sensitive red quadriceps and soleus muscles, whereas reduced levels of polyunsaturated fatty acids were found in primarily glycolytic white quadriceps muscles. In experiment 2, voluntary running-wheel exercise by adult female rats over 45 days resulted in reduced proportions of type IIb fibers (P = 0.01) and increased proportions of type IIa/IIx fibers (P = 0.03) in extensor digitorum longus muscle. The magnitude of these changes was related to the distance run (r = -0.73, P = 0.04; r = 0.79, P = 0.02, respectively). Exercise significantly increased oxidative capacity, as assessed by the proportion of intensely NADH-stained fibers (P = 0.0004) and citrate synthase (P = 0.003) and hexokinase (P = 0.04) activities. Citrate synthase activity was also increased by exercise in soleus muscle, where, as expected, no fiber type changes were detected. No significant differences in the fatty acid profile of soleus and extensor digitorum longus were found between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationships between muscle membrane lipids, fiber type, and enzyme activities in sedentary and exercised rats. 750 5

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

We evaluated training adaptations by 18 baboons (Papio cynocephalus anubis) to low and moderate quadrupedal walking exercise on a motorized treadmill. Moderate training produced 47% increases in lactate threshold, 63% increases in muscle citrate synthetase activity, increases in percentage of Type IIc muscle fibers, and reduced plasma insulin concentrations. Low training produced only reduced plasma insulin concentrations. Only results indicate that the baboon response to exercise training was similar to that of Homo sapiens, and dependent on exercise intensity.
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PMID:Training adaptations of baboons to light and moderate treadmill exercise. 760 80

The purpose of the present investigation was to determine the relationship between skeletal muscle characteristics, adiposity, and in vivo insulin action. Percutaneous muscle biopsies of the vastus lateralis (VL) and gastrocnemius (G) muscles were obtained from twenty-two sedentary male subjects. Insulin sensitivity (SI) and glucose effectiveness (SG) were determined from minimal model analysis, and indexes of regional and overall adiposity were obtained. SI was positively related to the citrate synthase activity from the VL (r = 0.50, P < 0.01) but unrelated to the citrate synthase activity from the G (r = 0.28). Similarly, SI was inversely related to the percentage of type IIb fibers in the VL (r = -0.47, P < 0.01) but unrelated to the percentage of type IIb fibers in the G (r = 0.06). SG was unrelated to fiber type, oxidative capacity, or adiposity. These data suggest that oxidative capacity and other characteristics related to VL skeletal muscle fiber type are determinants of in vivo insulin action but that this relationship cannot be extended to all muscle groups. Finally, neither skeletal muscle characteristics nor adiposity appears to be a determinant of SG in sedentary males.
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PMID:The insulin action-fiber type relationship in humans is muscle group specific. 763 70

Visceral obesity is strongly associated with insulin resistance. One potential cause is increased availability of FFA. Alternatively, it has been proposed that there is impaired oxidation of lipid in individuals at risk for obesity. The extent to which either concept involves skeletal muscle is uncertain. To examine these opposing hypotheses, 17 healthy lean and obese premenopausal women, among whom cross-sectional area of visceral fat ranged from 18 to 180 cm2, participated in leg balance studies for measurement of FFA and glucose utilization during basal and insulin-stimulated conditions. A metabolic profile of skeletal muscle, based on enzyme activity, was determined in vastus lateralis muscle obtained by percutaneous biopsy. Visceral fat content was negatively correlated with insulin sensitivity (rates of leg glucose uptake and storage), but insulin resistance was not caused by glucose-FFA competition. During hyperinsulinemia, neither leg FFA uptake nor oxidation was increased in women with visceral obesity. During fasting conditions, however, rates of FFA uptake across the leg were negatively correlated with visceral adiposity as were activities of muscle carnitine palmitoyl transferase and citrate synthase. In summary, visceral adiposity is clearly associated with skeletal muscle insulin resistance but this is not due to glucose-FFA substrate competition. Instead, women with visceral obesity have reduced postabsorptive FFA utilization by muscle.
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PMID:Skeletal muscle utilization of free fatty acids in women with visceral obesity. 770 45

Older male Fischer 344 (F344) rats do not maintain core temperature as well as do older females during cold exposure. To elucidate factors contributing to the decreased thermoregulatory ability of older males, the metabolic potentials of interscapular brown adipose tissue (IBAT) and skeletal muscle were evaluated at rest (26 degrees C) and during 4 h of cold (6 degrees C) in male and female F344 rats, aged 6, 12, and 26 mo. Compared with 26-mo-old females, cold-exposed 26-mo-old males exhibited a greater drop in core temperature and lower amounts of IBAT mitochondrial uncoupling protein (UCP) and IBAT thyroxine 5'-deiodinase (T5'D) activity. Unlike females, 26-mo-old males showed no cold-induced increase in total IBAT UCP or T5'D activity. In contrast, plasma norepinephrine was higher in cold-exposed 26-mo-old males vs. females, whereas plasma insulin and thyroxine did not differ with gender. Skeletal muscle oxidative capacity (measured by citrate synthase activity) and carbohydrate availability (measured by muscle glycogen and plasma glucose levels) did not differ between the 26-mo-old males and females. Our data suggest that altered regulation of IBAT UCP levels during cold exposure of aged rats, due at least in part to attenuated cold-induced IBAT T5'D activity, contributes to the gender difference in thermoregulatory ability of older males vs. females.
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PMID:Effects of age and gender on brown fat and skeletal muscle metabolic responses to cold in F344 rats. 773 4

The effects of regular exercise training on the onset and/or severity of hyperglycemia were studied in female diabetes-prone Biobreeding/Worcester (DP BB/Wor) rats. At 38-39 d of age, animals were weight-matched and randomly assigned to exercise-trained (T) and untrained (Unt) groups. The T rats exercised on a rodent treadmill at a moderate workload, 5 successive days with the 6th day being one of rest. Training lasted 5-11 wk until rats became moribund. Red gastrocnemius muscle citrate synthase activity was significantly higher in T (54.2 +/- 4.7 mumol.g-1.min-1) compared with Unt (42.9 +/- 5.1). No significant difference was found between the T and Unt groups in the following: age at onset of hyperglycemia (T = 82.9 +/- 8.7 d; Unt = 82.0 +/- 13.5 d, mean +/- SD), ultimate level of hyperglycemia, age of death (T = 89.9 +/- 9.2 d; Unt = 89.4 +/- 13.9 d), number of days between onset of hyperglycemia and death, or body weights at the onset of hyperglycemia. No significant difference was found between groups in pancreatic insulin concentration (microgram.g-1 of protein), T = 0.22 +/- 0.04; Unt = 0.20 +/- 0.34. These data suggest that a program of regular exercise training may not delay the onset and/or reduce the severity of hyperglycemia in the DP BB/Wor rat. Regular exercise training had no beneficial or detrimental effect on pancreatic beta-cell destruction.
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PMID:Effect of exercise training on the onset of type I diabetes in the BB/Wor rat. 780 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

The effect of alloxan-induced diabetes on CuZn- and Mn-superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) activities, as well as the content of thiobarbituric acid reactive substances (TBARs) were examined in rat lymphoid organs (mesenteric lymph nodes (MLN), thymus and spleen) and, for comparison, red and white muscle fibres. The capacity for generation of reduced equivalents was also evaluated by measuring the activities of glucose-6-phosphate dehydrogenase (pentose-phosphate pathway-cytosol) and citrate synthase (Krebs cycle-mitochondria). Diabetes raised the capacity for the generation of reducing equivalents in the lymphoid organs: in the mitochondria of the thymus and spleen and in the cytosol of the mesenteric lymph nodes and thymus. In muscles, diabetes reduced CuZn-SOD activity in soleus and raised the activity in gastrocnemius, and depressed the activities of catalase in soleus and of glutathione peroxidase in both soleus and gastrocnemius. In relation to the lymphoid organs, the spleen showed a decrease in the antioxidant enzyme activities (except for glutathione peroxidase), whereas the thymus showed an increased level (except for Mn-SOD), and the MLN presented a reduction in Mn-SOD and catalase activities and an increase in GPX activity caused by diabetes. The content of TBARs in the tissues followed the changes in GPX activity inversely: i.e. a decrease in the lymphoid organs (except in the spleen) and an increase in the muscles of diabetic rats compared with the control group. All these changes found in diabetic rats were reversed by insulin treatment and were not modified by the normalization of glycaemia.
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PMID:Superoxide dismutase, catalase and glutathione peroxidase activities in the lymphoid organs of diabetic rats. 796 75


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