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)

1. Thinness at birth is associated with insulin resistance in adult life and an apparent delay in activation of glycolysis/glycogenolysis in exercising skeletal muscle. As developmental abnormalities of skeletal muscle histology or metabolism may explain this association we examined muscle histology, biochemistry and blood flow in a group of 27 adult women whose birth details were known. 2. Subjects were examined by near-infrared spectroscopy to determine forearm muscle oxygen supply, and by muscle biopsy and forearm plethysmography. Those with a ponderal index at birth < 23 kg/m3 were insulin resistant (assessed by the short insulin-tolerance test-mean rate constants for glucose disappearance = 4.14 compared with 4.83%/min, P = 0.045) and had significantly more rapid muscle reoxygenation than the remainder of the subjects (13 compared with 22 s, P = 0.004). 3. Thinness at birth did not influence muscle capillary density, muscle glycogen content, glycogen synthase activity, citrate synthase activity or resting forearm blood flow. 4. Insulin resistance seen after fetal malnutrition was not associated with abnormal muscle histology, resting muscle blood flow, mitochondrial volume or glycogen content. 5. The increase in muscle reoxygenation rate in adult subjects who were thin at birth could occur to promote oxidative ATP synthesis in compensation for the delay in activation of glycolysis/glycogenolysis. It suggests altered regulation rather than structure of the muscle microcirculation. These changes appear to antedate the structural and biochemical changes seen in muscle from patients with established diabetes.
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PMID:Fetal growth and insulin resistance in adult life: role of skeletal muscle morphology. 909 10

The effects of exercise training on maximal glucose transport activity and cell surface GLUT-4 were examined in rat epitrochlearis muscle. Five days of swim training (2 x 3 h/day) produce a significant increase in citrate synthase activity (24.5 +/- 0.6 vs. 20.1 +/- 0.7 micromol x min(-1) x g(-1)), GLUT-4 content (22.9 +/- 0.8 vs. 17.4 +/- 0.4% GLUT-4 standard), and glycogen levels (54.3 +/- 9.4 vs. 28.6 +/- 9.4 micromol/g). Maximally, insulin-stimulated glucose transport activity and cell surface GLUT-4 are increased by 55 (1.50 +/- 0.11 vs. 0.97 +/- 0.10 micromol x ml(-1) x 20 min(-1)) and 48% [12.0 +/- 0.8 vs. 8.1 +/- 0.9 disintegrations x min(-1) (dpm) x mg(-1)], respectively, in exercise-trained epitrochlearis muscles. In contrast, hypoxia-stimulated glucose transport activity and cell surface GLUT-4 are reduced by 38 (0.78 +/- 0.08 vs.1.25 +/- 0.14 micromol x ml(-1) x 20 min(-1)) and 40% (5.7 +/- 0.9 vs. 9.4 +/- 1.2 dpm/mg), respectively, in exercise-trained epitrochlearis muscles. These results demonstrate that changes in insulin- and hypoxia-stimulated glucose transport activity after exercise training are fully accounted for by the appearance of cell surface GLUT-4 and support the concept of two intracellular pools of GLUT-4. Finally, we propose that high levels of muscle glycogen with exercise training may contribute to the decrease in hypoxia-stimulated glucose transport activity.
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PMID:Effects of exercise training on glucose transport and cell surface GLUT-4 in isolated rat epitrochlearis muscle. 912 41

The purpose of this study was to assess the effects of voluntary wheel running on the expression of leptin mRNA in rats that are either sensitive (OM) or resistant (S5B/Pl) to diet-induced obesity. Male OM and S5B/Pl rats had ad libitum access to standard rodent diet and water. At 3-5 weeks of age, animals of both strains were randomly assigned to either an exercise or sedentary control group. The exercise groups had 24-h access to a running wheel, and they trained for 7 weeks. During weeks 1-4, animals in both OM and S5B/Pl exercise groups progressively increased their running. During weeks 5-7, S5B/Pl exercisers tended to run more than did OM (approximately 60 vs. 45 km/week), but by the end of the study both groups had an equally greater heart weight (mg/g body weight) and planteris citrate synthase activity than their sedentary controls. Oral glucose tolerance tests performed during the last week of training revealed that compared with their appropriate controls, insulin sensitivity was enhanced (P < 0.05) in OM but not in the S5B/Pl wheel-running groups. Inguinal, epididymal, and retroperitoneal fat pads weighed less in the running than in the nonrunning groups of both strains (P < 0.01). Additionally, exercised animals had an increased percentage of smaller cells (40-60 microm; P < 0.05) and a decreased percentage of larger cells (120-160 microm; P < 0.05) in the epididymal fat depot. Epididymal leptin mRNA measured by Northern blot analysis was reduced in the exercise-trained rats of both strains (P < 0.05). Furthermore, serum leptin was reduced in exercise-trained compared with the control animals of both strains. In comparison to S5B/Pl, control OM animals exhibited both a higher expression and higher circulating levels of leptin (P < 0.05). While serum leptin levels were decreased and food intake was increased in the exercise-trained animals of both strains (P < 0.05), the exact relationship between exercise, leptin, and food intake in this rat model of dietary obesity remains to be determined. Nonetheless, these results suggest that the expression and secretion of leptin can be influenced by exercise training and that these changes (i.e., reduced expression and secretion of protein) can occur independently of changes in whole-body insulin sensitivity and susceptibility to diet-induced obesity.
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PMID:Voluntary wheel running decreases adipose tissue mass and expression of leptin mRNA in Osborne-Mendel rats. 920 Jun 51

The insulin resistance of skeletal muscle in glucose-tolerant obese individuals is associated with reduced activity of oxidative enzymes and a disproportionate increase in activity of glycolytic enzymes. Because non-insulin-dependent diabetes mellitus (NIDDM) is a disorder characterized by even more severe insulin resistance of skeletal muscle and because many individuals with NIDDM are obese, the present study was undertaken to examine whether decreased oxidative and increased glycolytic enzyme activities are also present in NIDDM. Percutaneous biopsy of vatus lateralis muscle was obtained in eight lean (L) and eight obese (O) nondiabetic subjects and in eight obese NIDDM subjects and was assayed for marker enzymes of the glycolytic [phosphofructokinase, glyceraldehyde phosphate dehydrogenase, hexokinase (HK)] and oxidative pathways [citrate synthase (CS), cytochrome-c oxidase], as well as for a glycogenolytic enzyme (glycogen phosphorylase) and a marker of anaerobic ATP resynthesis (creatine kinase). Insulin sensitivity was measured by using the euglycemic clamp technique. Activity for glycolytic enzymes (phosphofructokinase, glyceraldehye phosphate dehydrogenase, HK) was highest in subjects with subjects with NIDDM, following the order of NIDDM > O > L, whereas maximum velocity for oxidative enzymes (CS, cytochrome-c oxidase) was lowest in subjects with NIDDM. The ratio between glycolytic and oxidative enzyme activities within skeletal muscle correlated negatively with insulin sensitivity. The HK/CS ratio had the strongest correlation (r = -0.60, P < 0.01) with insulin sensitivity. In summary, an imbalance between glycolytic and oxidative enzyme capacities is present in NIDDM subjects and is more severe than in obese or lean glucose-tolerant subjects. The altered ratio between glycolytic and oxidative enzyme activities found in skeletal muscle of individuals with NIDDM suggests that a dysregulation between mitochondrial oxidative capacity and capacity for glycolysis is an important component of the expression of insulin resistance.
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PMID:Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. 921 60

Skeletal muscle biopsies were performed on 12 healthy sedentary subjects and on 22 non-dyalized chronic renal failure patients (CRF) on a free diet and after overnight fasting. Parathormone, glucagon and insulin were determined at the same time of biopsies. CRF patients showed significantly low ATP and creatine phosphate levels. Regarding enzyme activities, a high hexokinase Vmax was found, while the pyruvate kinase activity was lower than in the control group. For the tricarboxylic acid cycle, citrate synthase, succinate dehydrogenase and malate dehydrogenase activities were higher; total NADH cytochrome c reductase activity was also high, while cytochrome oxidase activity was slightly lower. Both alanine aminotransferase and aspartate aminotransferase activities were considerably high in comparison with the control group. In conclusion, our study revealed a hypermetabolic TCA cycle, but impaired oxidative phosphorylation, which partly explained the reduced ATP concentration. Excessive protein intake and hormonal derangements may play a role in these metabolic changes.
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PMID:Altered muscle energy metabolism in post-absorptive patients with chronic renal failure. 924 94

Glucose, the most potent insulin secretagogue, stimulates insulin secretion by aerobic glycolysis, but other secretagogues stimulate insulin release exclusively by mitochondrial metabolism. It is well known that in the intact pancreatic beta-cell, either kind of secretagogue can induce oscillations in metabolism (e.g., glycolysis, ATP/ADP, NAD(P)/NAD(P)H ratios) that occur with a periodicity similar to oscillations in membrane electrical potential and insulin secretion. In this study, pancreatic islet cytosol or mitochondrial fractions were incubated in the presence of physiological concentrations of substrates. Repeated additions of physiological effectors caused oscillations in the activities of the three enzymes studied. Succinate dehydrogenase activity in islet mitochondrial extracts was made to oscillate by adding oxaloacetate (5 micromol/l) to inhibit the enzyme. The enzyme was reactivated by adding acetyl-CoA (3 micromol/l), which combines with oxaloacetate in the citrate synthase reaction and lowers the concentration of oxaloacetate, thus beginning another oscillation. Pyruvate kinase activity was made to oscillate by adding fructose bisphosphate (10 micromol/l). Fructose bisphosphate was degraded to triose phosphates fairly rapidly, and, as it was degraded, there was a parallel decrease in pyruvate kinase activity. The enzyme was reactivated and made to oscillate with subsequent additions of fructose bisphosphate. The mitochondrial glycerol phosphate dehydrogenase was made to oscillate by adding EGTA to chelate calcium, which activates the enzyme. When the concentration of free calcium was raised to >0.1 micromol/l by adding more calcium, the activity of the enzyme increased. Repeated additions of chelator and calcium caused the enzyme activity to oscillate. The results with these three enzymes and physiological concentrations of naturally occurring effectors raise the possibility that the activities of not only these enzymes but of numerous enzymes oscillate in vivo in response to levels of allosteric effectors and substrates. If this is the case, pacemaker activity may result from complex effects distributed across multiple regulatory sites in both the cytosol and mitochondria, rather than from a single enzyme acting as a primary pacemaker.
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PMID:Oscillations in activities of enzymes in pancreatic islet subcellular fractions induced by physiological concentrations of effectors. 939 86

Previous studies have shown that when exercise is stopped there is a rapid reversal of the training-induced adaptive increase in muscle glucose transport capacity. Endurance exercise training brings about an increase in GLUT-4 in skeletal muscle. The primary purpose of this study was to determine whether the rapid reversal of the increase in maximally insulin-stimulated glucose transport after cessation of training can be explained by a similarly rapid decrease in GLUT-4. A second purpose was to evaluate the possibility, suggested by previous studies, that the magnitude of the adaptive increase in muscle GLUT-4 decreases when exercise training is extended beyond a few days. We found that both GLUT-4 and maximally insulin-stimulated glucose transport were increased approximately twofold in epitrochlearis muscles of rats trained by swimming for 6 h/day for 5 days or 5 wk. GLUT-4 was 90% higher, citrate synthase activity was 23% higher, and hexokinase activity was 28% higher in triceps muscle of the 5-day trained animals compared with the controls. The increases in GLUT-4 protein and in insulin-stimulated glucose transport were completely reversed within 40 h after the last exercise bout, after both 5 days and 5 wk of training. In contrast, the increases in citrate synthase and hexokinase activities were unchanged 40 h after 5 days of exercise. These results support the conclusion that the rapid reversal of the increase in the insulin responsiveness of muscle glucose transport after cessation of training is explained by the short half-life of the GLUT-4 protein.
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PMID:Rapid reversal of adaptive increases in muscle GLUT-4 and glucose transport capacity after training cessation. 948 Sep 35

Twelve pairs of healthy sedentary males matched for their body mass index (BMI) with either a low insulin response (LIR; a stage of prediabetes) or a high (HIR; controls) to a standardized glucose infusion test (GIT) were studied in respect to their exercise capacities (W(OBLA), W(SL) and relative W(OBLA):W(OBLA) x W(SL)(-10 x 100), muscle fiber composition (%ST), muscle citrate synthase activity (CS), muscle ubiquinone (MUQ), MUQ over %ST (muscle quality index, MQI), and peripheral insulin sensitivity (PIS) as described with insulin-clamp techniques (SIGITmean). LIR and HIR displayed normal PIS and positive relationships versus exercise capacity. LIR's but not HIR's relative W(OBLA) was related to CS as earlier only documented in endurance athletes but at a lower level than in athletes. This pointed at a poor peripheral oxygen delivery in LIR. LIR's MQI decreased relative to HIR's the higher the muscle CS indicating radical related muscle trauma in LIR as in athletes. LIR representing prediabetes described muscle anomalies, which could represent prestages of the lesions observed in type-2 diabetes. They are claimed to be responsible for insulin-, glucose-, lipid-resistance, and peripheral circulatory resistance.
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PMID:Muscle metabolism and quality (MQI) in prediabetic sedentary man. 954 83

Impaired muscle glucose phosphorylation to glucose-6-phosphate by hexokinases (HKs)-I and -II may contribute to insulin resistance in NIDDM and obesity. HK-II expression is regulated by insulin. We tested the hypothesis that basal and insulin-stimulated expression of HK-II is decreased in NIDDM and obese subjects. Skeletal muscle HK-I and HK-II activities were measured in seven lean and six obese normal subjects and eight patients with NIDDM before and at 3 and 5 h of a hyperinsulinemic (80 mU x m(-2) x min(-1)) euglycemic clamp. To assess whether changes in HK-II expression seen during a glucose clamp are likely to be physiologically relevant, we also measured HK-I and HK-II activity in 10 lean normal subjects before and after a high-carbohydrate meal. After an overnight fast, total HK, HK-I, and HK-II activities were similar in lean and obese control subjects; but HK-II was lower in NIDDM patients than in lean subjects (1.42 +/- 0.16 [SE] vs. 2.33 +/- 0.24 nmol x min(-1) x mg(-1) molecular weight, P < 0.05) and accounted for a lower proportion of total HK (33 +/- 3 vs. 47 +/- 3%, P < 0.025). HK-II (but not HK-I) activity increased during the clamp in lean and obese subjects by 34 and 36% after 3 h and by 14 and 22% after 5 h of hyperinsulinemia; no increase was found in the NIDDM patients. In the lean subjects, muscle HK-II activity also increased by 15% 4 h after the meal, from 2.47 +/- 0.19 basally to 2.86 +/- 0.28 nmol x min(-1) x mg(-1) protein (P < 0.05). During the clamps, muscle HK-II activity correlated with muscle citrate synthase activity in the normal subjects (r = 0.58, P < 0.05) but not in the NIDDM patients. A weak relationship was noted between muscle HK-II activity and glucose disposal rate at the end of the clamp when all three groups were combined (r = 0.49, P < 0.05). In summary, NIDDM patients have lower muscle HK-II activity basally and do not increase the activity of this enzyme in response to a 5-h insulin stimulus. This defect may contribute to their insulin resistance. In nondiabetic obese subjects, muscle HK-II expression and its regulation by insulin are normal.
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PMID:Regulation of skeletal muscle hexokinase II by insulin in nondiabetic and NIDDM subjects. 964 35

As muscle tissue constitutes a main target organ for glucose metabolism and is responsible for the development of insulin resistance, it seems plausible to elucidate the relationship between blood pressure and muscle morphology and metabolism. The association between blood pressure and capillarization/morphology of the vastus lateralis muscle and metabolic variables was evaluated in 24 perimenopausal obese women [body mass index (BMI) 34.9 +/- 1.1; waist-hip ratio (WHR) 0.90 +/- 0.02]. The muscle enzyme activity of lipoprotein lipase (LPL), citrate synthase and glycogen synthase was determined. There was a significant negative correlation between the percentage of type I fibres and relative fibre area of type I on the one hand and systolic and diastolic blood pressure on the other. There was a negative correlation between the capillary density (i.e. number of capillaries/muscle fibre) and a positive correlation between the diffusion distance (fibre area supplied by one capillary) and diastolic blood pressure. The activities of LPL and citrate synthase were positively correlated with the percentage of type I and negatively correlated with the percentage of type II muscle fibres. The activity of LPL was also negatively correlated with plasma glucose and the insulin/C-peptide ratio. The insulin/C-peptide ratio was positively correlated with the percentage of type II muscle fibres. In stepwise multiple regression analyses, 20-30% of the variation in systolic and diastolic blood pressure could be explained by the variables of muscle fibre distribution. Excluding muscle morphological variables from the regression model, the insulin/C-peptide ratio accounted for 13% of the variation in systolic and diastolic blood pressure. The results of the study show the close association between muscle morphology and blood pressure. It remains to be elucidated whether this association indicates a causal relationship.
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PMID:High blood pressure and muscle morphology/metabolism--causal relationship or only associated factors? 964 8


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