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)

Some experimental and clinical studies were done from the metabolic viewpoint to elucidate the characteristics of myonephropathic-metabolic syndrome. In experimental dogs with their femoral arteries ligated and two third of femoral muscles divided, aldolase and myoglobin showed remarkable increase without significant changes in electrolytes. Slight increase of GPT and GOT was observed. Amino acids showed elevation in urea, taurin, leucin, isoleucin, valine, threonine, 3-methylhistidine, phenylalanine, histidine, lysine, methionine, tyrosine and anserin and decrease in glutamine, alanine, glycine, proline, carnosine, citrullin and arginine. In patients with acute arterial occlusion, potassium, GOT, LDH, CPK, lactate and pyruvate increased moderately and myoglobin showed remarkable increase and aldolase slight increase. Amino acids showed remarkable increase in 3-methylhistidine and beta-amino-isobutyric acid and moderate increase in phenylalanine and arginine. These results revealed that measurement of free amino acid concentration, especially that of methylhistidine as well as myoglobin, pyruvate, lactate and some other enzymes might be of great help to predict the prognosis of patients with acute arterial occlusion of the extremities.
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PMID:[Metabolic study on acute arterial occlusion of the extremities]. 667 89

Abnormal liver tests, as well as morphological changes in the liver, are frequent among obese patients. Other frequent disturbances are visceral fat accumulation, insulin resistance, non-insulin-dependent diabetes mellitus (NIDDM), hypertriglyceridemia, and hypertension; these are set of aberrations known as the metabolic syndrome. In order to investigate a possible relationship between the metabolic syndrome and impaired liver status we examined associations between liver tests, metabolic variables (insulin, glucose, and triglycerids), body composition and nutrition in 1,083 men (BMI 28.8-63.8 kg/m2) and 1,367 women (BMI 26.7-68.0 kg/m2) in the ongoing intervention study of Swedish Obese Subjects (SOS). Standard biochemical techniques were used to assess liver status and metabolic variables. Lean body mass (LBM) and masses of visceral and subcutaneous adipose tissue (AT) were estimated by means of computed tomography (CT) calibrated anthropometric equations. In both genders aspartate aminotransferase and alanine aminotransferase were, or tended to be, positively correlated to fasting serum insulin, visceral AT (women), and alcohol intake. In women, the aminotransferases were also correlated with fasting blood glucose. In both genders alkaline phosphatase was, or tended to be, positively associated with visceral AT, insulin (women), and glucose. Bilirubin was negatively correlated to insulin and visceral AT in men and women. Additional multivariate analyses indicated that alcohol had less explanatory power than serum insulin for the examined liver tests, especially among women. These results suggest that pathological liver tests in the obese may represent an expression of the metabolic syndrome.
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PMID:Are elevated aminotransferases and decreased bilirubin additional characteristics of the metabolic syndrome? 911 45

The purpose of this study was to test the hypothesis of a causal relationship between high insulin levels and the development of benign prostatic hyperplasia (BPH) and to determine the clinical, anthropometric, metabolic and insulin profile in men with fast-growing BPH compared with men with slow-growing BPH. The present study was designed as a risk factor analysis of BPH in which the estimated annual BPH growth rate was related to components of the metabolic syndrome. Two hundred and fifty patients referred to the Urological Section, Department of Surgery, Central Hospital, Varberg, Sweden, with lower urinary tract symptoms with or without manifestations of the metabolic syndrome were consecutively included. The prevalences of atherosclerotic disease manifestations, non-insulin-dependent diabetes mellitus (NIDDM) and treated hypertension were obtained. Data on blood pressure, waist and hip measurement, body height and weight were collected and body mass index (BMI) and waist/hip ratio (WHR) were calculated. Blood samples were drawn from fasting patients to determine insulin, total cholesterol, triglycerides, HDL and LDL cholesterol, uric acid, alanine aminotransferase (ALAT) and prostate-specific antigen (PSA). The prostate gland volume was determined using ultrasound. The median annual BPH growth rate was 1.04 ml/year. Men with fast-growing BPH had a higher prevalence of NIDDM (p = 0.023) and treated hypertension (p = 0.049). These patients were also taller (p=0.004) and more obese as measured by body weight (p<0.001), BMI (p=0.026), waist measurement (p <0.001), hip measurement (p = 0.006) and WHR (p=0.029). Moreover, they had elevated fasting plasma insulin levels (p = 0.018) and lower HDL cholesterol levels (p = 0.021) than men with slow-growing BPH. The annual BPH growth rate correlated positively with diastolic blood pressure (rs = 0.14; p = 0.009), BMI (rs = 0.24; p < 0.001) and four other expressions of obesity and fasting plasma insulin level (rs = 0.18; p = 0.008), and negatively with the HDL cholesterol level (rs = -0.22; p = 0.001). In conclusion, the data suggest that NIDDM, hypertension, tallness, obesity, high insulin and low HDL cholesterol levels constitute risk factors for the development of BPH. The results also suggest that BPH is a component of the metabolic syndrome and that BPH patients may share the same metabolic abnormality of a defective insulin-mediated glucose uptake and secondary hyperinsulinaemia, as patients with the metabolic syndrome. The findings support the hypothesis of a causal relationship between high insulin levels and the development of BPH, and give rise to a hypothesis of increased sympathetic nerve activity in men with BPH.
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PMID:Clinical, anthropometric, metabolic and insulin profile of men with fast annual growth rates of benign prostatic hyperplasia. 1041 80

Insulin resistant metabolic syndrome is a major clinical disorder including hyperlipidaemia, hypertension, impaired glucose tolerance and/or type 2 diabetes and central obesity, which are well established cardiovascular risk factors. We report the case of a 61-year-old woman who developed severe hypercholesterolaemia and hypertriglyceridaemia after liver transplantation. In her forties she had hypertension, mixed hyperlipidaemia, mild hyperglycaemia and moderate abdominal obesity, suggesting the presence of the metabolic syndrome. She had liver enzyme elevation and severe steatosis and hepatomegaly at ultrasonography. At age 52, cryptogenic liver cirrhosis was diagnosed and rapidly progressing liver failure developed. In 1992 she underwent liver transplantation. Seven years after transplant the patient had abdominal obesity, high blood pressure, marked hypercholesterolaemia, hypertriglyceridaemia and moderate elevation of alanine aminotransferase. She also had impaired glucose tolerance and markedly increased basal and post-glucose load plasma insulin levels. Steatohepatitis was demonstrated by serial liver biopsies. This is the first case that reports the recurrence of the metabolic syndrome following liver transplantation. We postulate that metabolic syndrome may have promoted fatty liver and subsequent progression to end stage liver disease. We also stress the need for careful management of the metabolic syndrome in order to decrease the long-term risk for cardiovascular disease.
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PMID:Recurrence of insulin resistant metabolic syndrome following liver transplantation. 1254 3

A retrospective study was performed to (1) characterize the clinical and histologic features of those with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) values, (2) compare the spectrum of NAFLD associated with normal versus elevated ALT levels, and (3) determine whether there were differences in the clinical or histologic spectrum of NAFLD between those with a low normal versus high normal ALT value. A total of 51 subjects with NAFLD and normal ALT were identified and compared with 50 consecutive subjects with NAFLD and elevated ALT. The major indications for liver biopsy in those with normal ALT were unexplained hepatomegaly (n = 21) and evaluation as a potential donor for living donor liver transplantation (n = 16). The 2 groups were comparable with respect to age, gender distribution, and ethnicity. Approximately 80% of cases in both groups had at least 1 feature of the metabolic syndrome, the major risk factor for NAFLD. The 2 groups were also comparable with respect to the grade of the individual histologic parameters of NAFLD. A total of 12 subjects with normal ALT levels had bridging fibrosis, whereas 6 had cirrhosis. Diabetes was the only factor independently associated with an increased risk of advanced fibrosis (bridging fibrosis or cirrhosis) by multivariate analysis (relative risk: 2.3, P <.01). The mean steatosis (1.6 vs. 2.16, P <.04) and perisinusoidal fibrosis scores (0.35 vs. 0.9, P <.049) were lower in those with low normal (<30 IU/L) ALT versus high normal ALT. However, the prevalence of advanced fibrosis was similar (5 of 15 vs. 13 of 36, respectively). In conclusion, (1) the entire histologic spectrum of NAFLD can be seen in individuals with normal ALT values, (2) the histologic spectrum in these individuals is not significantly different from those with elevated ALT levels, and (3) a low normal ALT value does not guarantee freedom from underlying steatohepatitis with advanced fibrosis.
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PMID:Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. 1505 21

Chronic liver disease is a major cause of morbidity and mortality in the United States. Although often used to detect liver disease, the prevalence and etiology of elevated aminotransferases are unknown. We analyzed data on adults ages 17 yr and older (N = 15,676) from the Third National Health and Nutrition Examination Survey (1988-1994). Participants were classified as having elevated aminotransferase levels if either aspartate aminotransferase or alanine aminotransferase was elevated above normal. Aminotransferase elevation was classified as "explained" if there was laboratory evidence of hepatitis B or C infection, iron overload, or if there was a history of alcohol consumption. Analyses were weighted to provide national estimates. The prevalence of aminotransferase elevation in the United States was 7.9%. Aminotransferase elevation was more common in men compared to women (9.3% vs 6.6%, p = 0.002), in Mexican Americans (14.9%) and non-Hispanic blacks (8.1%) compared to non-Hispanic whites (7.1%, p < 0.001). High alcohol consumption, hepatitis B or C infection and high transferrin saturation were found in only 31.0% of cases. Aminotransferase elevation was unexplained in the majority (69.0%). In both men and women, unexplained aminotransferase elevation was significantly associated with higher body mass index, waist circumference, triglycerides, fasting insulin, and lower HDL; and with type 2 diabetes and hypertension in women (all p < 0.05). Aminotransferase elevation was common in the United States, and the majority could not be unexplained by alcohol consumption, viral hepatitis or hemochromatosis. Unexplained aminotransferase elevation was strongly associated with adiposity and other features of the metabolic syndrome, and thus may represent nonalcoholic fatty liver disease.
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PMID:The prevalence and etiology of elevated aminotransferase levels in the United States. 1280 14

Recent studies indicate that some patients with nonalcoholic fatty liver have ongoing liver injury that may progress from steatosis to steatohepatitis or fibrosis. The present study was designed to clarify the clinical features of liver dysfunction observed in the course of workplace physical check-ups in relation to multiple risk factor syndrome including obesity, hyperlipidemia, hypertension, and impaired glucose tolerance, and to clarify the involvement of aldehyde dehydrogenase 2 (ALDH2) and beta(3)-adrenergic receptor (beta3-AR) gene polymorphisms in elevation of liver enzymes. One hundred forty-eight male workers 35 years of age were enrolled. They were requested to answer questionnaires about drinking and smoking habits, and underwent urinalysis, physical and peripheral blood examinations, blood chemistry, electrocardiogram and chest x-rays. The genotypes of ALDH2 and beta3-AR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subjects were divided into active ALDH2 or inactive ALDH2 groups. They were also divided into 2 groups according to the beta3-AR genotype. The relationships between ALDH2 and beta3-AR gene polymorphism and the results of the physical examination including liver function tests were analyzed. The subjects were also divided according to the number of components of metabolic syndrome. The prevalence of elevated alanine aminotransferase (ALT) level increased with the accumulation of components of metabolic syndrome. Active ALDH2 was associated with elevated ALT level to a greater degree than beta3-AR polymorphism. Among those with normal body mass index (BMI), the genotypes of ALDH2 and beta3-AR were strongly associated with elevated ALT level. Logistic regression analysis revealed that BMI, triglyceride level, and ALDH2 genotype were associated with ALT elevation. In conclusion, evaluating the genotype of ALDH2 and beta3-AR may assist in predicting and preventing the development of fatty liver which may be related to multiple risk factor syndrome.
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PMID:Aldehyde dehydrogenase 2 and beta3-adrenergic receptor gene polymorphisms: their association with elevated liver enzymes and metabolic syndrome. 1450 13

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease for which there is no known effective therapy. A proportion of patients with NASH progress to advanced fibrosis and cirrhosis. NASH is considered one of the clinical features of the metabolic syndrome in which insulin resistance plays a central role. This prospective study evaluates the role of insulin-sensitizing agent in treatment of NASH. Eighteen nondiabetic patients with biopsy-proven NASH were treated with pioglitazone (30 mg daily) for 48 weeks. Tests of insulin sensitivity and body composition as well as liver biopsies were performed before and at the end of treatment. By 48 weeks, serum alanine aminotransferase values fell to normal in 72% of patients. Hepatic fat content and size as determined by magnetic resonance imaging decreased, and glucose and free fatty acid sensitivity to insulin were uniformly improved. Histological features of steatosis, cellular injury, parenchymal inflammation, Mallory bodies, and fibrosis were significantly improved from baseline (all P < 0.05). Using strict criteria, histological improvement occurred in two-thirds of patients. Pioglitazone was well tolerated; the main side effects were weight gain (averaging 4%) and an increase in total body adiposity. In conclusion, these results indicate that treatment with an insulin-sensitizing agent can lead to improvement in biochemical and histological features of NASH and support the role of insulin resistance in the pathogenesis of this disease. The long-term safety and benefits of pioglitazone require further study.
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PMID:A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. 1475 37

We examined the association of serum alanine aminotransferase (ALT) with features of the metabolic syndrome and whether it predicted incident diabetes independently of routinely measured factors in 5,974 men in the West of Scotland Coronary Prevention Study. A total of 139 men developed new diabetes over 4.9 years of follow-up. ALT, but not aspartate aminotransferase, levels increased progressively with the increasing number of metabolic syndrome abnormalities from (means +/- SD) 20.9 +/- 7.6 units/l in those with none to 28.1 +/- 10.1 units/l in those with four or more (P < 0.001). In a univariate analysis, men with ALT in the top quartile (ALT >/=29 units/l) had an elevated risk for diabetes (hazard ratio 3.38 [95% CI 1.99-5.73]) versus those in the bottom quartile (<17 units/l). ALT remained a predictor with adjustment for age, BMI, triglycerides, HDL cholesterol, systolic blood pressure, glucose, and alcohol intake (2.04 [1.16-3.58] for the fourth versus first quartile). In stepwise regression, incorporating ALT and C-reactive protein (CRP) together with metabolic syndrome criteria, elevated ALT (>/=29 units/l), and CRP (>/=3 mg/l) predicted incident diabetes, but low HDL cholesterol and hypertension did not. Thus, elevated ALT levels within the "normal" range predict incident diabetes. The simplicity of ALT measurement and its availability in routine clinical practice suggest that this enzyme activity could be included in future diabetes prediction algorithms.
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PMID:Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the west of Scotland coronary prevention study. 1550 65

Insulin is involved in coronary heart disease through diabetes and metabolic syndrome. A great deal is known about insulin and its correlates, as well as factors related to changes in insulin. However, few studies consider the broad variety of correlates simultaneously. Therefore, the aims of the present study were to characterize the main factors of biological variation affecting serum insulin concentration and to establish reference limits of insulinemia in a presumably healthy French population. Insulin was measured using a microparticular enzymatic immunoassay. A total of 646 subjects aged 11-58 years from the STANISLAS cohort and divided into four groups of 162 males, 157 females, 163 boys and 164 girls, were included in the statistical analyses. In the whole population, serum insulin concentration varied from 0.80 to 54.60 microU/ml. Significant factors affecting insulin were age, gender, body mass index and glucose, in addition to alanine aminotransferase and high-density lipoprotein cholesterol in men, triglycerides and oral contraceptive use in women, and alkaline phosphatase in girls. In summary, we presented biological correlates of insulin in both healthy French male and female adults and children/adolescents and determined reference limits for insulin for each group. These results will contribute to a better interpretation of insulin data in further studies and laboratory investigations.
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PMID:Age- and sex-related reference values for serum insulin concentration and its biological determinants in a French healthy population. The STANISLAS cohort. 1555 73


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