Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The realtionship between growth rate and the metabolic activity of certain liver enzymes was studied using two strains of White Plymouth Rock chickens which had been selected in divergent directions for eight-week body weight. The activities of hexokinase, glucokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, citrate synthase, glycogen synthetase, glutamate dehydrogenase and aspartate transaminase were measured at 4, 8 and 20 weeks of age. The mean percentage rate of growth of the birds selected for high eight-week body weight exceeded that of the birds selected for low eight-week body weight only during the early growth period. Thereafter, and until sexual maturity, the low-line birds grew at a faster rate, relative to body size. The mature body weight of the high-line birds exceeded that of the low-line birds by a factor of approximately 1.5. A close similarity was noted between the metabolic activity of certain liver enzymes and the growth rate (relative to body size) of the birds studied. At four and eight weeks of age, the faster-growing birds (whether high- or low-line) generally exhibited a greater capacity for glucose phosphorylation and glycolysis, but a poorer capacity for glycogen synthesis, than the slower-growing birds. At twenty weeks, growth rate and metabolic activity were similar in both strains.
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PMID:Activity of certain liver enzymes in fast- and slow-growing lines of chickens. 118 17

Twenty-four male (12 obese and 12 lean) and 21 female (11 obese and 10 lean) SHR/N-cp rats were fed a diet containing either 54% sucrose or starch for periods of 3-4 months. Rats were killed after a 14-16 h fast and liver enzyme activities were determined in both sex groups. Liver glucose-6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), malic enzyme (ME), phosphofructokinase (PFK), glucokinase (GK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (per total liver capacity) were significantly affected by phenotype (obese > lean). Arginase and ornithine transcarbamylase levels were analysed only in male rats and were found to be elevated in obese rats as compared to lean littermates. Some of the above changes in enzyme levels were exaggerated by sucrose feeding but not the changes in FBPase, PEPCK, ME and GK (in both sexes) plus AST, arginase and arginine synthase activities in male rats and ALT levels in female rats. Results from SHR/N-cp rats published in this paper were compared to results obtained from LA/N-cp rats published previously. Comparison of the non-diabetic obese LA/N-cp with the diabetic obese SHR/N-cp male shows a greater excess in lipogenic capacity of the liver in the LA/N-cp male rat. The SHR/N-cp obese female also shows a greater liver lipogenic capacity as compared with the obese male SHR/N-cp rat. The results suggest that an adaptation of excessive lipogenesis in the liver of obese rats may be an anti-diabetogenic adaptation resulting in increased glucose conversion to lipids, thus reducing blood glucose levels.
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PMID:Adaptation in enzyme (metabolic) pathways to obesity, carbohydrate diet and to the occurrence of NIDDM in male and female SHR/N-cp rats. 133 Sep 56

A co-culture system of cerebellar granule cells (glutamatergic neurons) and hepatocytes has been developed. Petri dishes divided in halves by a temporary septum were coated with poly-L-lysine and cerebellar granule cells plated in one of the compartments. Five days later hepatocytes were plated in the other compartment and after 2 days the septum was removed and the two cell types shared the same culture medium for a period of 5 days. During this period of time cultures of neurons and hepatocytes kept separately or in co-culture exhibited identical characteristics with regard to activities of pyruvate kinase and glucokinase (hepatocytes), aspartate aminotransferase (neurons) as well as evoked transmitter release (neurons) and content of cytochrome P-450 (hepatocytes). The results show that it is possible to maintain neurons and hepatocytes in co-culture sharing the same culture medium for a prolonged period of time. Such a system may serve as a pharmacological model to study interactions between liver and brain cells with regard to neuroactive drugs.
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PMID:Characterization of a co-culture system of neurons and hepatocytes. 256 Aug 19

The early stages of insulin-dependent diabetes mellitus are characterized by a selective inability to secrete insulin in response to glucose, coupled to a better response to nonnutrient secretagogues. The deficient glucose response may be a result of the autoimmune process directed toward the beta-cells. Interleukin-1 (IL-1) has been suggested to be one possible mediator of immunological damage of the beta-cells. In the present study we characterized the sensitivity of beta-cells to different secretagogues after human recombinant IL-1 beta (rIL-1 beta) exposure. Furthermore, experiments were performed to clarify the biochemical mechanisms behind the defective insulin response observed in these islets. Rat pancreatic islets were isolated and kept in tissue culture (medium RPMI-1640 plus 10% calf serum) for 5 days. The islets were subsequently exposed to 60 pM human recombinant IL-1 beta during 48 h in the same culture conditions as above and examined immediately after IL-1 exposure. The rIL-1 beta-treated islets showed a marked reduction of glucose-stimulated insulin release. Stimulation with arginine plus different glucose concentrations, and leucine plus glutamine partially counteracted the rIL-1 beta-induced reduction of insulin release. The activities of the glycolytic enzymes hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in control and IL-1-exposed islets. Treatment with IL-1 also did not impair the activities of NADH+- and NADPH+-dependent glutamate dehydrogenase, glutamate-aspartate transaminase, glutamate-alanine transaminase, citrate synthase, and NAD+-linked isocitrate dehydrogenase. The oxidation of D-[6-14C]glucose and L-[U-14C]leucine were decreased by 50% in IL-1-treated islets. Furthermore, there was a significant decrease in the ratios of [2-14C]pyruvate oxidation/[1-14C]pyruvate decarboxylation and L-[U-14C]leucine oxidation/L-[1-14C]leucine decarboxylation, indicating that IL-1 decreases the proportion of generated acetyl-coenzyme-A residues undergoing oxidation. However, in the presence of IL-1 there was a significant increase in L-[U-14C]glutamate oxidation. These combined observations suggest that exposure to IL-1 induces a preferential decrease in glucose-mediated insulin release and mitochondrial glucose metabolism. This mitochondrial dysfunction seems to reflect an impairment in proximal steps of the Krebs cycle. It is conceivable that the IL-1-induced suppression and shift in islet metabolism can be an explanation for the beta-cell insensitivity to glucose observed in the early phases of human and experimental insulin-dependent diabetes mellitus.
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PMID:Differential sensitivity to beta-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1 beta. 266 6

We recently described a preferential reduction of the secretory response to nutrient secretagogues (glucose; leucine plus glutamine) in islets maintained in culture after in vitro exposure to streptozotocin (SZ). The present study is an attempt to further clarify the biochemical mechanisms behind this defective insulin response. Mouse pancreatic islets were collagenase isolated and, after 4-5 days in culture, exposed during 30 min at 37 C to 1.8 mM SZ or vehicle alone (controls). The islets were subsequently cultured for 7 days in medium RPMI 1640 plus 10% calf serum, before the enzymatic and metabolic studies were performed. The activities of the glycolytic enzymes, hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in the control and SZ-exposed islets. The relative amount of cytosolic and mitochondria-bound hexokinase was also unaffected by SZ. However, there was a 30-40% decrease in the activity of NAD+- and NADP+-dependent glutamate dehydrogenase and glutamate-aspartate transaminase in the SZ-treated islets. This coincided with a 40% decrease in L-[U-14C]glutamine oxidation in the SZ-treated islets. The D-glucose catabolism was further examined in the presence of D-[5-3H] and D-[6-14C] glucose. There was no difference between control and SZ islets in terms of glucose utilization at either 1.7 or 16.7 mM glucose. The oxidation of D-[6-14C]glucose was nevertheless decreased by more than 50% in SZ islets incubated at 16.7 mM (but not 1.7 mM) glucose. Altogether, these converging observations suggest a perturbation of distal regulatory processes, apparently at the mitochondrial level, in the D-glucose and L-glutamine catabolism of SZ-exposed islets. Whether this reflects a primary action of SZ on the islet mitochondria, or an inhibitory effect of SZ on the synthesis of mitochondrial enzymes, as a result of nuclear DNA damage, remains to be elucidated.
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PMID:Defective catabolism of D-glucose and L-glutamine in mouse pancreatic islets maintained in culture after streptozotocin exposure. 296 23

The effects of a high fat diet (30% (w/w) corn oil) on chronic streptozotocin-diabetic rats were investigated at the whole body level and at the enzyme level. The diet caused significant decreases in the extent of polydipsia (66% decrease), polyphagia (49%), polyuria (67%) and glycosuria (70%). The activities of selected hepatic enzymes from the glycolytic, gluconeogenic, ureogenic and lipogenic clusters were determined. The fat diet caused significant decreases (range: 47 to 54%) in the activity of the ureogenic enzymes carbamyl phosphate synthetase, ornithine transcarbamylase and arginase; had no effect on the glycolytic enzymes glucokinase, hexokinase and pyruvate kinase; partially decreased the diabetes-induced elevated activities of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase (63% decrease), serine dehydratase (90%), alanine aminotransferase (31%) and aspartate aminotransferase (65%), and partially reversed the activity of one lipogenic enzyme, ATP citrate lyase.
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PMID:The effects of a high fat diet on chronic streptozotocin-diabetic rats. 692 68

The serum glucose concentration, HbAc1, fructoseamine, the activity of AST, ALT, amylase, glycogen content and glucokinase activity in rat hepatocytes were examined in streptozotocin-diabetic rats during long-term orthovanadate and vanadyl sulphate treatment. The improvement of this parameters were demonstrated after oral orthovanadate and vanadyl sulphate administration. However, insulin-mimetic properties of vanadyl sulphate were more marked in comparison with orthovanadate. LD-50 and cytotoxicity analysis in isolated hepatocytes showed that vanadyl sulphate was less toxic than orthovanadate.
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PMID:[Comparative characteristics of vanadium-containing compounds, possessing insulin-like effects]. 1088 36

We determined the effect of dietary starch on growth performance and feed utilization in European sea bass juveniles. Data on the dietary regulation of key hepatic enzymes of the glycolytic, gluconeogenic, lipogenic and amino acid metabolic pathways (hexokinase, HK; glucokinase, GK; pyruvate kinase, PK; fructose-1,6-bisphosphatase, FBPase; glucose-6-phosphatase, G6Pase; glucose-6-phosphate dehydrogenase, G6PD; alanine aminotransferase, ALAT; aspartate aminotransferase, ASAT and glutamate dehydrogenase, GDH) were also measured. Five isonitrogenous (48% crude protein) and isolipidic (14% crude lipids) diets were formulated to contain 10% normal starch (diet NS10), 10% waxy starch (diet WS10), 20% normal starch (diet NS20), 20% waxy starch (diet WS20) or no starch (control diet). Another diet was formulated with no carbohydrate, and contained 68% crude protein and 14% crude lipids (diet HP). Each experimental diet was fed to triplicate groups of 30 fish (initial weight: 23.3 g) on an equivalent feeding scheme for 12 weeks. The best growth performance and feed efficiency were achieved with fish fed the HP diet. Neither the level nor the nature of starch had measurable effects on growth performance of sea bass juveniles. Digestibility of starch was higher with waxy starch and decreased with increasing levels of starch in the diet. Whole-body composition and plasma metabolites, mainly glycemia, were not affected by the level and nature of the dietary starch. Data on enzyme activities suggest that dietary carbohydrates significantly improve protein utilization associated with increased glycolytic enzyme activities (GK and PK), as well as decreased gluconeogenic (FBPase) and amino acid catabolic (GDH) enzyme activities. The nature of dietary carbohydrates tested had little influence on performance criteria.
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PMID:Effect of normal and waxy maize starch on growth, food utilization and hepatic glucose metabolism in European sea bass (Dicentrarchus labrax) juveniles. 1634 62

While salicylates (non-steroidal anti-inflammatory drugs) have been detected in the aquatic environment, few studies have focused on the mechanism of action of these pharmaceuticals on aquatic organisms. We reported previously that salicylate disrupted the acute trophic hormone-stimulated corticosteroidogenesis in rainbow trout (Oncorhynchus mykiss) interrenal tissue in vitro. Here, we tested the hypothesis that this drug will inhibit the adaptive plasma cortisol response and the associated metabolic response to an acute stressor in trout. Fish were fed salicylate-laced feed (100 mg/kg body weight) for 3 days, subjected to an acute (5 min) handling disturbance and sampled 1, 4 and 24 h after the stressor exposure. Salicylate treatment attenuated the stressor-induced plasma cortisol but not glucose or lactate elevations. The disruption of cortisol response corresponded with a significant reduction in transcript levels of the steroidogenic acute regulatory protein (StAR), but not peripheral-type benzodiazepine receptor, cytochrome P450 side-chain cleavage or 11beta-hydroxylase. Salicylate did not modify the stressor-induced elevation of brain glucocorticoid receptor (GR) protein expression, while liver GR protein content was reduced. Salicylate impact on liver metabolic capacity involved depressed liver glycogen content, whereas no significant changes in liver hexokinase, glucokinase, lactate dehydrogenase, pyruvate kinase, phosphoenolpyruvate carboxykinase, aspartate aminotransferase and alanine aminotransferase activities were observed. Taken together, salicylate impairs the stressor-mediated plasma cortisol response and the associated liver metabolic capacity in trout. The mode of action of salicylate involves disruption of StAR and liver GR, two key proteins critical for cortisol production and target tissue responsiveness to this steroid, respectively.
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PMID:Salicylate impacts the physiological responses to an acute handling disturbance in rainbow trout. 1788 47

Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound 3-hydroxymethyl xylitol (3-HMX) has been isolated and its optimum dose has been determined in a short duration study and patented. In the present study, the long-term effect of 3-HMX in type 2 diabetic rats has been investigated. An optimum dose of 3-HMX (40 mg/kg body weight) was orally administered for 45 days to streptozotocin-diabetic rats for the assessment of glucose, insulin, hemoglobin (Hb), glycated hemoglobin (HbA(1c)), hepatic glycogen, and activities of carbohydrate metabolizing enzymes, such as glucokinase, glucose 6-phosphatase, fructose 1,6-bisphosphatase and glucose-6-phosphate dehydrogenase and hepatic marker enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gammaglutamyl transferase (GGT) in normal and streptozotocin-diabetic rats. 3-HMX at 40 mg dose produced similar effects on all biochemical parameters studied as that of glibenclamide, a standard drug. Histological study of pancreas also confirmed the biochemical findings. These results indicate that 3-hydroxymethyl xylitol, the compound from C. esculenta, possesses antihyperglycemic effect on long-term treatment also.
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PMID:A novel compound from Casearia esculenta (Roxb.) root and its effect on carbohydrate metabolism in streptozotocin-diabetic rats. 1863 65


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