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)

In the present study the effects of insulin, glucocorticoids and thyroid hormones on macrophage metabolism and function were investigated. The maximum activities of hexokinase, glucose-6-phosphate dehydrogenase, glutaminase and citrate synthase were determined in macrophages obtained from hormone-treated rats and those cultured for a period of 48 h in the presence of hormones. Macrophage phagocytosis was markedly inhibited by dexamethasone and thyroid hormones, remaining unchanged when insulin was added to the culture medium, however. The changes in the enzyme activities caused by hormone treatments of the rats were very similar to those found in culture. Insulin enhanced citrate synthase and hexokinase activities and diminished those of glutaminase and glucose-6-phosphate dehydrogenase. Dexamethasone had a similar effect except on glucose-6-phosphate dehydrogenase. The addition of thyroid hormones to the culture medium raised the activities of glutaminase and hexokinase and reduced that of citrate synthase. The results presented support the suggestion that the effects of insulin, glucocorticoids and thyroid hormones on immune and inflammatory responses could well be mediated through changes in macrophage metabolism.
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PMID:Effects of insulin, glucocorticoids and thyroid hormones on the activities of key enzymes of glycolysis, glutaminolysis, the pentose-phosphate pathway and the Krebs cycle in rat macrophages. 147 28

Insulin action was assessed in thighs of five healthy young males who had one knee immobilized for 7 days by a splint. The splint was not worn in bed. Subjects also used crutches to prevent weight bearing of the immobilized leg. Immobilization decreased the activity of citrate synthase and 3-OH-acyl-CoA-dehydrogenase in the vastus lateralis muscle by 9 and 14%, respectively, and thigh volume by 5%. After 7 days of immobilization, a two-step euglycemic hyperinsulinemic clamp procedure combined with arterial and bilateral femoral venous catheterization was performed. Insulin action on glucose uptake and tyrosine release of the thighs at mean plasma insulin concentrations of 67 (clamp step I) and 447 microU/ml (clamp step II) was decreased by immobilization, whereas immobilization did not affect insulin action on thigh exchange of free fatty acids, glycerol, O2, or potassium. Before and during the clamp step I, lactate release was significantly higher in the immobilized than in the control thigh. Seven days of one-legged immobilization causes local decreased insulin action on thigh glucose uptake and net protein degradation.
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PMID:Insulin action in human thighs after one-legged immobilization. 266 54

Muscle homogenates representing slow-twitch oxidative, fast-twitch oxidative-glycolytic, fast-twitch glycolytic, and mixed fiber types were prepared from normal, diabetic, and insulin-treated diabetic rats. Diabetes was induced by injection of 80 mg . kg-1 of streptozotocin. The activities of citrate synthase, succinate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase were employed as markers of oxidative potential, whereas phosphorylase, hexokinase, and phosphofructokinase activities were used as an indication of glycolytic capacity. Diabetes was associated with a general decrement in the activity of oxidative marker enzymes for all fiber types except the fast-twitch glycolytic fiber. In contrast, the fast-twitch glycolytic fibers demonstrated the greatest decline in glycolytic enzymatic activity. Insulin-treated animals, either trained or untrained, exhibited enzyme activities similar to their normal counterparts. Exercise training of diabetic rats mimicked the effect of insulin treatment and caused a near normalization of the activity of the marker enzymes. These findings suggest that the enzymatic potential of all skeletal muscle fiber types of diabetic rats may be normalized by exercise training even in the absence of significant amounts of insulin.
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PMID:Influence of training on skeletal muscle enzymatic adaptations in normal and diabetic rats. 293 94

Exercise has been shown to increase insulin sensitivity, and muscle is quantitatively the most important tissue of insulin action. Since the first step in insulin action is the binding to a membrane receptor, we postulated that exercise training would change insulin receptors in muscle and in this study we have investigated this hypothesis. Female rats initially weighing approximately 100 g were trained by treadmill running for 2 h/day, 6 days/wk for 4 wk at 25 m/min (0 grade). Insulin receptors from vastus intermedius muscles were solubilized by homogenizing in a buffer containing 1% Triton X-100 and then partially purified by passing the soluble extract over a wheat germ agglutinin column. The 4 wk training regimen resulted in a 65% increase in citrate synthase activity in red vastus lateralis muscle, indicating an adaptation to exercise. Insulin binding by the partially purified receptor preparation s was approximately doubled in muscle of trained rats at all insulin concentrations, suggesting an increase in the number of receptors. Training did not alter insulin receptor structure as evidenced by electrophoretic mobility under reducing and nonreducing conditions. Basal insulin receptor protein kinase activity was higher in trained than untrained animals and this was likely due to the greater number of receptors. However, insulin stimulation of the protein kinase activity was depressed by training. These results demonstrate that endurance training does alter receptor number and function in muscle and these changes may be important in increasing insulin sensitivity after exercise training.
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PMID:Insulin receptor binding and protein kinase activity in muscles of trained rats. 354 17

1. In epididymal adipose tissue synthesizing fatty acids from fructose in vitro, addition of insulin led to a moderate increase in fructose uptake, to a considerable increase in the flow of fructose carbon atoms to fatty acid, to a decrease in the steady-state concentration of lactate and pyruvate in the medium, and to net uptake of lactate and pyruvate from the medium. It is concluded that insulin accelerates a step in the span pyruvate-->fatty acid. 2. Mitochondria prepared from fat-cells exposed to insulin put out more citrate than non-insulin-treated controls under conditions where the oxaloacetate moiety of citrate was formed from pyruvate by pyruvate carboxylase and under conditions where it was formed from malate. This suggested that insulin treatment of fat-cells led to persistent activation of pyruvate dehydrogenase. 3. Insulin treatment of epididymal fat-pads in vitro increased the activity of pyruvate dehydrogenase measured in extracts of the tissue even in the absence of added substrate; the activities of pyruvate carboxylase, citrate synthase, glutamate dehydrogenase, acetyl-CoA carboxylase, NADP-malate dehydrogenase and NAD-malate dehydrogenase were not changed by insulin. 4. The effect of insulin on pyruvate dehydrogenase activity was inhibited by adrenaline, adrenocorticotrophic hormone and dibutyryl cyclic AMP (6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate). The effect of insulin was not reproduced by prostaglandin E(1), which like insulin may lower the tissue concentration of cyclic AMP (adenosine 3':5'-cyclic monophosphate) and inhibit lipolysis. 5. Adipose tissue pyruvate dehydrogenase in extracts of mitochondria is almost totally inactivated by incubation with ATP and can then be reactivated by incubation with 10mm-Mg(2+). In this respect its properties are similar to that of pyruvate dehydrogenase from heart and kidney where evidence has been given that inactivation and activation are catalysed by an ATP-dependent kinase and a Mg(2+)-dependent phosphatase. Evidence is given that insulin may act by increasing the proportion of active (dephosphorylated) pyruvate dehydrogenase. 6. Cyclic AMP could not be shown to influence the activity of pyruvate dehydrogenase in mitochondria under various conditions of incubation. 7. These results are discussed in relation to the control of fatty acid synthesis in adipose tissue and the role of cyclic AMP in mediating the effects of insulin on pyruvate dehydrogenase.
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PMID:Regulation of adipose tissue pyruvate dehydrogenase by insulin and other hormones. 515 98

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 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

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

Insulin- and contraction-stimulated skeletal muscle glucose transport is governed largely by the GLUT-4 isoform of the glucose transporter. Recently, it has been demonstrated that denervated muscle has decreased GLUT-4 protein content, suggesting that regulation of GLUT-4 protein is related to neuromuscular activity. However, until now the effects of the opposite situation, enhanced neuromuscular activity, could only be speculated on from exercise training studies. In the present investigation the effect of chronic low-frequency electrical stimulation (10 Hz, 8 h/day) on GLUT-4 protein content and citrate synthase activity was determined in the predominantly fast-twitch plantaris. Chronic electrical stimulation enhanced GLUT-4 protein content and citrate synthase activity in the muscles stimulated for 10-20 days. Electrical stimulation lasting 30-40 days resulted in no further enhancement of GLUT-4 protein content while citrate synthase activity continued to increase. Further prolongation of electrical stimulation (60-90 days) resulted in a plateauing of citrate synthase activity. The results suggest that increased neuromuscular activity can act independently of systemic changes to increase total GLUT-4 protein content. They also suggest that both GLUT-4 protein content and citrate synthase activity are positively related to increased neuromuscular activity but that their rates of increase differ substantially.
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PMID:Effect of chronic electrical stimulation on GLUT-4 protein content in fast-twitch muscle. 847 25

We have used an animal model of insulin resistance-the obese Zucker (fa/fa) rat-to test whether oral administration of the non-sulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor, trandolapril, alone or in combination with the Ca2+-channel blocker, verapamil, can induce a beneficial effect on insulin-stimulated glucose transport and metabolism in skeletal muscle. Insulin-stimulated 2-deoxyglucose (2-DG) uptake in the isolated epitrochlearis muscle was less than 50% as great in obese animals compared with lean (Fa/-) controls (P < .05), but was significantly improved in the obese group by both short-term (6 hours, +33%) and long-term (14 days,+70%) oral treatment with trandolapril. Verapamil treatment alone did not alter insulin-stimulated 2-DG uptake in muscle, but simultaneous administration of verapamil and trandolapril resulted in the most pronounced effect on insulin-stimulated 2-DG uptake (+106%). Long-term treatment with trandolapril alone and in combination with verapamil significantly increased muscle glycogen (+26% to 27%), glucose transporter GLUT-4 protein (+27% to 31%), and hexokinase activity (+21% to 49%), and decreased plasma insulin levels (-23% to -29%). Muscle citrate synthase activity was enhanced only when trandolapril and verapamil were administered in combination (+24%). We conclude that the long-acting, non-sulfhydryl-containing ACE inhibitor, trandolapril, alone and in combination with the Ca2+-channel blocker, verapamil, can significantly improve insulin-stimulated glucose transport activity in skeletal muscle of the insulin-resistant obese Zucker rat, and that this improvement is associated with favorable adaptive responses in GLUT-4 protein levels, glycogen storage, and activities of relevant intracellular enzymes of glucose catabolism.
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PMID:Effects of trandolapril and verapamil on glucose transport in insulin-resistant rat skeletal muscle. 862 94


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