Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthesis and release of alanine and glutamine were investigated with an intact rat epitrochlaris muscle preparation. This preparation will maintain on incubation for up to 6 hours, tissue levels of phosphocreatine, ATP, ADP, lactate, and pyruvate closely approximating those values observed in gastrocnemius muscles freeze-clamped in vivo. The epitrochlaris preparation releases amino acids in the same relative proportions and amounts as a perfused rat hindquarter preparation and human skeletal muscle. Since amino acids were released during incubation without observable changes in tissue amino acids levels, rates of alanine and glutamine release closely approximate net amino acid synthesis. Large increases in either glucose uptake or glycolysis in muscle were not accompanied by changes in either alanine or glutamine synthesis. Insulin increased muscle glucose uptake 4-fold, but was without effect on alanine and glutamine release. Inhibition of glycolysis by iodacetate did not decrease the rate of alanine synthesis. The rates of alanine and glutamine synthesis and release from muscle decreased significantly during prolonged incubation despite a constant rate of glucose uptake and pyruvate production. Alanine synthesis and release were decreased by aminooxyacetic acid, an inhibitor of alanine aminotransferase. This inhibition was accompanied by a compensatory increase in the release of other amino acids, such as aspartate, an amino acid which was not otherwise released in appreciable quantities by muscle. The release of alanine, pyruvate, glutamate, and glutamine were observed to be interrelated events, reflecting a probable near-equilibrium state of alanine aminotransferase in skeletal muscle. It is concluded that glucose metabolism and amino acid release are functionally independent processes in skeletal muscle. Alanine release reflects the de novo synthesis of the amino acid and does not arise from the selective proteolysis of an alanine-rich storage protein. It appears that the rate of alanine and glutamine synthesis in skeletal muscle is dependent upon the transformation and metabolism of amino acid precursors.
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PMID:Alanine and glutamine synthesis and release from skeletal muscle. I. Glycolysis and amino acid release. 124 58

The rapid weight decrease at the beginning of strict slimming regimens leads often to an inconsiderate shortening of these cures. Our long-term experience with a slimming regimen lasting 13 days based on diet (3.7 MJ) and 4 hours of supervised exercise of low to moderate intensity was omitted by the organizers. They shortened the cure to 8 days. We checked therefore a group of obese women on the first, eight and twelfth day in the course of this regimen. A statistically significant decrease of serum insulin, growth hormone, triiodothyronine and cholesterol was observed on the twelfth day. These trends were not significant on the eighth day. On the other hand, the step-test revealed on the eighth day a reduction of the heart rate during recovery. Nevertheless, a higher level of significance was obtained after 12 days. No significant response to the regimen was obtained in the case of blood glucose, thyroxine, cortisol, uric acid, AST and ALT. The advantages of the 12-day regimen are discussed--especially the decrease of insulinemia, because hyperinsulinemia is responsible for several complications of obesity. The importance of the decrease of cholesterolaemia and the modification of heart rate after a load was also stressed. These favourable effects are not depreciated by a smaller weight loss in the second week due to an enhanced protein synthesis, stimulated by exercise and supported by a decrease of T3 which protects the organism against energy deficit.
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PMID:Hormonal, metabolic and cardiovascular response to the duration of a combined slimming regimen. 180 33

The effects of epinephrine (E) and insulin infusions on the contents of tricarboxylic acid cycle intermediates (TCAI), adenine nucleotides and their catabolites, and amino acids in skeletal muscle have been investigated. Eight men were studied on two separate occasions: 1) during 120 min of euglycemic hyperinsulinemia (UH, approximately 5 mM; 40 mU.m-2.min-1) and 2) during UH while E was infused (UHE, 0.05 microgram.kg-1.min-1). Biopsies were taken from the quadriceps femoris muscle before and after each clamp. The sum of citrate, malate, and fumarate in muscle did not change significantly during UH (P greater than 0.05) but doubled during UHE (P less than 0.001). There were no significant changes in any of the adenine nucleotides, their catabolites (including inosine monophosphate), or aspartate during UH and UHE (P greater than 0.05); nor were there any significant changes in pyruvate or alanine contents during UH (P greater than 0.05). On the other hand, there were significant increases in pyruvate and alanine contents during UHE (P less than 0.01 and 0.05, respectively), suggesting that there was increased production of 2-oxoglutarate (a TCAI) via the alanine aminotransferase (ALT) reaction. It is concluded that E infusion increases the contents of TCAI in human skeletal muscle, and it is likely that at least part of the increase is attributable to increased flux through the ALT reaction.
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PMID:Epinephrine increases tricarboxylic acid cycle intermediates in human skeletal muscle. 200 96

To assess the validity of determining the origin of plasma lactate from the ratio of lactate and glucose specific activities (SA) during infusion of labeled glucose, normal subjects received infusions of [6-3H]- and [6-14C]glucose for 4 h after a 12 h fast, and, on another day, cold glucose labeled with both tracers during 4-6 h of hyperinsulinemia (approximately 650 microU/ml). Basally, less lactate was derived from plasma glucose when measured with [6-3H]glucose (27 +/- 2%) than with [6-14C]glucose (40 +/- 2%, P less than 0.001). Insulin did not increase the percent of lactate derived from plasma glucose when measured with [6-3H]glucose (29 +/- 2%) but did increase when measured with [6-14C]glucose (60 +/- 4%). The arterialized blood (A) [3H]lactate SA was 30-40% higher (P less than 0.01) than deep venous blood (V) [3H]lactate SA, whereas A and V [14C]lactate SA were similar. During conversion of alanine to lactate with glutamic-pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) in vitro, 32 +/- 2% of 3H in [3-3H]alanine was found in water and 68 +/- 2% in lactate. During infusion of [6-3H]- and [6-14C]glucose, the ratio of [14C]alanine to lactate SA (0.88 +/- 0.05) was less than the ratio of [3H]alanine to lactate SA (0.31 +/- 0.03, P less than 0.001). In conclusion 1) loss of 3H relative to 14C from position 6 in glucose occurs during lactate formation in extrahepatic tissues possibly due to the GPT reaction (alanine conversion to pyruvate), and 2) even under supraphysiologic hyperinsulinemic conditions not all of plasma lactate originates from plasma glucose.
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PMID:Measurement of lactate formation from glucose using [6-3H]- and [6-14C]glucose in humans. 220 8

The rapid weight decrease at the beginning of strict slimming regimens leads often to an inconsiderate shortening of these cures. Our long-termed experience with a slimming regimen lasting 13 days and based on diet (3.7 MJ) and 4 hours of supervised exercise of low to moderate intensity was omitted by the organizers. They shortened the cure to 8 days. We checked therefore a group of obese women on the first, eighth and twelfth day in the course of this regimen. A statistically significant decrease of serum insulin, growth hormone, triiodothyronine and cholesterol was observed on the twelfth day. These trends were not significant on the eighth day. On the other hand, the step-test has shown on the eighth day a reduction of the heart rate during recovery. Nevertheless, a higher level of significance was obtained after a cure of 12 days. No significant response to the regimen was obtained in the case of blood glucose, thyroxine, cortisol, uric acid, AST and ALT. The advantages of the 12 day regimen were discussed--especially the decrease of insulinemia, because hyperinsulinemia is responsible for several complications of obesity. The importance of the decrease of cholesterolemia and the modification of heart rate after a load was also stressed. These favourable effects should not be depreciated by a smaller weight decrease on the second week due to an enhanced synthesis of proteins, stimulated by exercise and supported by a decrease of T3 which brings a protection against energy defficiency.
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PMID:[The effect of the duration of a weight reduction regimen on the hormonal, metabolic and cardiovascular response]. 224 39

In 1214 adult persons, the relationship between alcohol consumption, the "liver enzymes" and other metabolic parameters, including the serum lipids, were investigated. In 798 of the persons, glucose tolerance tests with measurement of plasma insulin were performed (young and old male and female adults, either volunteers or patients without liver-related diseases). There was a high correlation of the three transferases GOT, GPT and GGT not only with the reported alcohol consumption but also with the plasma insulin. Most of the insulin increase, however, occurred in that range of the three transferases which, so far, has erroneously been considered to be the normal one. The C-peptide showed the same behaviour. Plasma insulin was also raised in relation to overweight, but only in persons with the sum of the three transferases over 30 U/l, not in persons who did not drink alcohol and who had really normal transferases (sum of the three transferases below 30 U/l measured at 25 degrees C). The quotient of plasma insulin divided by the relative body weight (Broca Index) was constantly low in the range of really normal transferases (up to 30 U/l), thereafter rising significantly, but only in the range of the transferases so far erroneously considered to be the normal one (GOT to 17, GPT to 22, GGT to 28 U/l, thus sum up to 67). Serum glucose in the tolerance test also rose with the transferases but much less than the plasma insulin. The correlation between both GGT and the sum of the three transferases with the plasma insulin was significantly positive and independent of the relative body weight. It is concluded that overweight (which is generally believed to be the main risk factor for non-insulin-dependent diabetes), and insulin resistance (which leads to hyperinsulinaemia), are largely caused by the toxic effects of "normal" daily alcohol, more in the human male than in the female. Hyperinsulinaemia (which blocks lipolysis) is caused by a toxic effect of ethanol and its metabolites, independent of caloric input and overweight. Hyperinsulinaemia is at least in the human male at present, probably the most important cause of obesity. In obesity, caused by "normal" alcohol consumption, a vicious circle occurs: the enhancement of the triglycerides and, consequently, the free fatty acids leads to a further decrease of glucose utilization by the muscle. A continuously high glucose level has toxic effects: eventually the beta cells of the pancreas are exhausted.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The main cause of diabetes (type II): "normal" alcohol drinking]. 227 72

The mitochondrial FAD-linked enzyme glycerophosphate dehydrogenase plays a key role in the pancreatic B-cell glucose sensing device. In the present study, the activity of this enzyme was examined in islets of fa/fa rats in which inherited diabetes mellitus is associated with obesity, hyperinsulinism and severe insulin resistance. The specific activity of both FAD-linked glycerophosphate dehydrogenase and glutamate dehydrogenase were decreased in islet and liver homogenates prepared from fa/fa, as compared to Fa/Fa, rats, this coinciding with a low ratio between glutamateoxalacetate and glutamate-pyruvate transaminase activity in both islet and liver extracts, islet hyperplasia, hyperinsulinemia and hepatic steatosis in the hyperglycemic fa/fa rats. It is speculated that a low activity of FAD-linked glycerophosphate dehydrogenase in the pancreatic B-cell may participate to the perturbation of glucose homeostasis in fa/fa rats, like in other animal models of non-insulin-dependent diabetes mellitus.
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PMID:Impaired FAD-glycerophosphate dehydrogenase activity in islet and liver homogenates of fa/fa rats. 783 41

There is strong evidence that genetic factors contribute to the development of obesity in humans as well as laboratory animals. Another important factor leading to obesity is an increase in energy intake. However, it is difficult to make normal rats obese by controlling daily food intake. There is no report of normal adult male Wistar rats becoming obese and diabetic on a high-fat diet. The aim of the present study was, therefore, to make normal adult Wistar rats obese by infusing high fat and hypercaloric diet through the cannula without disturbing the free movement and to investigate the influence of an increase in the caloric intake on body weight and glucose metabolism. High-fat hypercaloric diet (360 kcal/kg body wt./day; H group) or control diet (180 kcal/kg body wt./day; C group) was continuously infused into the stomach of normal adult male Wistar rats weighing approximately 300 g through gastric cannulas for 27 days. On day 28 after a 24-h fasting, serum concentrations of aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglyceride, phospholipid, and free fatty acids (FFA) were determined, and intragastric glucose loading test (2 g/kg body wt.) was performed. The average weekly body weight gain in the H group was twice as much as that of the C group (40.0 +/- 2.4 vs. 19.4 +/- 1.9 g/week, P < 0.001). Serum levels of triglyceride, phospholipid, total cholesterol, and FFA were significantly elevated in the H group compared to those in the C group. Liver weight in the H group was significantly higher than that in the C group and showed steatosis. Pancreas weight (-13%) as well as protein (-12%), amylase (-53%) and trypsin content (-26%) were all reduced, whereas pancreatic DNA content was significantly increased in the H group compared to those in the C group. Serum glucose and insulin concentrations before and after glucose loading in the H group were significantly higher than those in the C group. Moreover, the insulin response relative to glucose response in the H group was significantly high compared to that in the C group, indicating the presence of insulin resistance. These results indicate that feeding of high-fat hypercaloric diet makes normal Wistar male adult rat obese associated with hyperlipidemia, hyperinsulinemia, and glucose intolerance.
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PMID:High-fat hypercaloric diet induces obesity, glucose intolerance and hyperlipidemia in normal adult male Wistar rat. 879 99

Troglitazone is a new oral insulin-sensitizing agent from the thiazolidinedione group of compounds that has been developed in Japan Thiazolidinediones improve the insulin sensitivity at muscle, adipose tissue and liver. The overall effectiveness of troglitazone seems to be less potent than is usually seen with sulfonylureas, however, there are good responders to troglitazone, in which sulfonylurea had failed to improve glycemia. It is frequently very effective for those who are very obese and show hyperinsulinemia. Recent reports demonstrate the good therapeutic power of troglitazone in combination with a sulfonylurea or metformin, or insulin. In future, a possibility that reduction of insulin resistance by troglitazone reduce cardiovascular risk will be discussed. Unfortunately, wider use has led to recognition of potential for serious liver damage. Until now, the mechanisms of the liver toxicity has not been known. We have to monitor GOT, GPT and LDH levels as recommended.
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PMID:[Insulin-sensitizing agent]. 1019 53

Nonalcoholic steatohepatitis (NASH) is a histological diagnosis applied to a constellation of liver biopsy findings that develop in the absence of alcohol abuse. Steatosis, a mixed cellular inflammatory infiltrate across the lobule, evidence of hepatocyte injury and fibrosis are the findings that can be seen. This entity is often identified during evaluation of elevated aminotransferases after exclusion of viral, metabolic and other causes of liver disease. Obesity is a major risk factor for NASH. The role of diabetes is less certain, although evidence is accumulating that hyperinsulinism may play an important pathophysiological role. Patients sometimes suffer from right upper quadrant abdominal pain and fatigue; examination may reveal centripetal obesity and hepatomegaly. Although patients are often discovered because of persistent aminotransferase elevations, these enzymes can be normal in NASH. When they are elevated, the alanine aminotransferase level is typically significantly greater than the aspartate aminotransferase level. This can be particularly helpful for excluding occult alcohol abuse. Imaging studies identify hepatic steatosis when the amount of fat in the liver is significant; however, imaging does not distinguish benign steatosis from NASH. Ultimately a liver biopsy is needed to diagnose NASH. The biopsy may be useful for establishing prognosis based on the presence or absence of fibrosis and for excluding other unexpected causes of liver enzyme elevations. Weight loss is the mainstay of treatment for obese patients. About 15% to 40% of NASH patients develop fibrosis; how many of these cases progress to cirrhosis is unknown, but about 1% of liver transplants are performed with a pretransplant diagnosis of NASH.
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PMID:Nonalcoholic steatohepatitis: an evolving diagnosis. 1079 85


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