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)

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.
Diabetes Res Clin Pract 1996 Mar
PMID:High-fat hypercaloric diet induces obesity, glucose intolerance and hyperlipidemia in normal adult male Wistar rat. 879 99

The activities of the mitochondrial FAD-linked glycerophosphate dehydrogenase (m-GDH), glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, glutamate-pyruvate transaminase (GPT) and glutamate-oxaloacetate transaminase were measured in islet and liver homogenates from fetal, neonatal, adult male, adult female, pregnant and lactating rats. Either parallel or dissociated ontogenic changes were observed in islet and liver homogenates. The activity of islet m-GDH was slightly, albeit not significantly, lower in neonates than in adult rats, comparable in male and female adult animals, unaffected by pregnancy, and increased during lactation. It was much higher in fetal or adult islets cultured for 7 days than in freshly isolated islets from adult rats. In cultured islets from adult rats, the increase in m-GDH activity coincided with a dramatic decrease of GPT activity, a situation the mirror image of that found in several animal models of non-insulin-dependent diabetes mellitus. The intrinsic properties of m-GDH, as judged by comparison of measurements made by either a radioisotopic or a colorimetric procedure, were not identical in islet and liver homogenates and differed between fetal and adult islets, suggesting the existence of distinct iso-enzymes. These findings illustrate adaptive changes of islet enzymes, with exclusive or partial mitochondrial location, in ontogenic situations characterized by a remodelling of fuel homeostasis.
 ...
PMID:Ontogeny of FAD-linked glycerophosphate dehydrogenase in rat pancreatic islets. 879 9

Solubility of tail tendon collagen from normal, streptozotocin-induced diabetic Lewis rats, and diabetic animals treated with aminoguanidine and two novel advanced glycosylation end products (AGE)-formation inhibitors was investigated by limited pepsin digestion under acidic conditions. Assays were conducted using tail tendon collagen from Lewis rats obtained from two different vendors, Harlan and Charles River Laboratories. Collagen solubility was assessed by following the kinetics of pepsin digestion. The data revealed that the rate of digestion for diabetic animals is markedly slow relative to that of normals. More strikingly, the kinetics of the diabetic animals showed the feature of a lag in digestion regardless of the animal source. Experiments designed to optimize the difference in solubility between normal and diabetic animals demonstrated that Charles River animals exhibit a greater window of solubility than the Harlan animals. More importantly, a pronounced effect of aminoguanidine, an AGE-formation inhibitor, was observed in Charles River animals, but not in the Harlan animals, presumably because of the larger window of solubility between the normal and the diabetic animals in the former. These data indicated that the Charles River Lewis rats are an animal model that demonstrates greater efficacy in this assay. Analysis of in vivo screens designed to test efficacy of aminoguanidine and two novel AGE-formation inhibitors, ALT 462 and ALT 486, demonstrated that monitoring an in vivo dose response is highly dependent on the enzyme concentration as well as the time of digestion, and that 1.5 h of digestion and 10 microg/ml pepsin (5 pg pepsin/mg collagen) appeared optimal. Under these conditions, a 29% normalization of solubility was observed with aminoguanidine at 100 mg/kg body wt, whereas a similar normalization was observed at 10 mg/kg body wt for both ALT 462 and ALT 486. Thus, on a molar basis, ALT 462 and ALT 486 are at least 20 times more potent than aminoguanidine. This is the first demonstration of dose-dependent efficacy for AGE-formation inhibitors in animal models, and as such, this assay provides a method with which to assess the in vivo efficacy of other such inhibitors.
Diabetes 1996 Dec
PMID:Chronic dosing with aminoguanidine and novel advanced glycosylation end product-formation inhibitors ameliorates cross-linking of tail tendon collagen in STZ-induced diabetic rats. 892 53

Forty-two cases of necrotizing fasciitis (NF) surgically confirmed between January 1991 and October 1995 were retrospectively reviewed. This was done in order to describe the underlying diseases, clinical presentations, etiology and outcome of NF and to assess the prognostic value of a simplified severity scoring system. The system scores changes in consciousness status, body temperature, blood pressure and ventilation to determine the likely outcome of NF. Twenty-five men and 17 women with a median age of 51 years (range, 17-87 yr) were included. Diabetes mellitus (57.1%) was the most common underlying disease. The mean duration of symptoms before admission was 8 days (median, 7 d; range, 1-30 d). The extremities (66.7%) were most commonly involved. Initial clinical presentations within 48 hours of admission included skin erythema and swelling at the affected site (97.6%), pyrexia (61.9%), hypotension (33.3%), altered consciousness (28.6%), bullous lesions (26.2%) and crepitus (9.5%). The mean number of isolated pathogens was 1.8 (range, 0-6). Eight patients had mixed aerobic and anaerobic infections. The attributable case fatality rate was 23.8%. Higher severity score (> or = 4 points), hypotension, altered consciousness, respiratory failure requiring ventilator support, elevation of alanine aminotransferase levels > twofold, serum creatinine > 177 mumol/L, thrombocytopenia (< 100 x 10(9)/L), and worsening symptoms and signs within 48 hours of admission were associated with higher fatality rates (p < 0.05).
 ...
PMID:Clinical manifestations, microbiology and prognosis of 42 patients with necrotizing fasciitis. 900 Aug 8

The alteration in calcium-binding protein regucalcin in the liver and serum of rats with streptozotocin (STZ)-diabetic state or ethanol ingestion was investigated. STZ (6.0 mg/100 g body weight) was subcutaneously administered in rats, and 1 or 3 weeks later they were sacrificed by bleeding. Liver regucalcin mRNA levels were not clearly altered by the diabetic state, as evidenced by Northern blotting using regucalcin cDNA (0.9 kb of open reading frame). Based on enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG, hepatic regucalcin concentration was decreased about 50% of control levels by STZ treatment. However, serum regucalcin concentration was not significantly altered by STZ treatment. Meanwhile, when rats ingested ethanol (10 and 30%) in the drinking water for 2 weeks, liver regucalcin mRNA levels were clearly increased, although hepatic regucalcin concentration was significantly decreased. Serum regucalcin concentration was not appreciably altered. Serum transaminases (GOT and GPT) activities were significantly increased at 1 or 3 weeks after STZ administration in rats, while their activities were not altered by ethanol ingestion. The present study demonstrates that hepatic regucalcin concentration is decreased independent of mRNA expression in the STZ-diabetes and during ethanol ingestion in rats.
 ...
PMID:Hepatic calcium-binding protein regucalcin concentration is decreased by streptozotocin-diabetic state and ethanol ingestion in rats. 906 95

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.
 ...
PMID:Are elevated aminotransferases and decreased bilirubin additional characteristics of the metabolic syndrome? 911 45

A 12 yr-old child without any past medical history of diseases was admitted to hospital for sopor and polyuria. At admission he was markedly dehydrated. Blood glucose was 72 mmol/l, sodium 154 mmol/l, osmolarity 381 mOsm/Kg, urinary ketons were negative. He was rehydrated with hypotonic saline and treated with insulin. The osmolality and sodium initially increased to 176 mmol/l and 408 mOsm/Kg respectively and progressively decreased to normal levels. Serum transaminases increased to GOT 336 and GPT 209 U/l in the first days of treatment and normalized after 15 days. The anti-islet antibodies were positive. The non ketotic hyperosmolar coma and Type I diabetes is rare in children but this possibility must be kept in mind especially when some familial or psychological problems are present as in our case.
 ...
PMID:Hyperosmolar nonketotic coma at the onset of type I diabetes in a child. 921 Nov 33

Course and consequences of acute hepatitis B on the group of 40 patients with diabetes mellitus and 21 patients with cholelithiasis were estimated with respect to the group has consisted of 82 person with acute hepatitis B without coexisting disorders. Hospitalization time has been longer on the group with diabetes mellitus or cholelithiasis and activity of serum alanine aminotransferase (AlAT) has brought back to normal longer than on the control group. Maximal activity of serum AlAT has been higher on the control group and maximal bilirubin concentration in serum the patients with diabetes mellitus or cholelithiasis has not differed from the control group. Acute hepatitis B passed into chronic hepatitis or cirrhosis of the liver on the group with diabetes mellitus or cholelithiasis frequently, has been observed.
 ...
PMID:[The effect of diabetes and cholelithiasis on the course and consequences of acute viral hepatitis type B]. 931 36

Elevated activities of serum aminotransferases are a common sign of liver disease and are observed more frequently among diabetics than in the general population. Whether this association is due to confounding factors is unknown. The authors investigated whether diabetes was significantly associated with elevated serum activity of alanine aminotransferase (ALT) after adjustment for factors common to both diabetes and raised ALT. Data from 2,999 men and women aged 20-74 years representative of the Mexican American population of the southwestern United States were obtained from the Hispanic Health and Nutrition Examination Survey (1982-1984). Approximately 6% of men and 2% of women had elevated serum ALT activity (>43 IU/liter). The odds ratio for diabetes as a predictor of elevated ALT was 4.1 (95% confidence interval 2.3-7.6) adjusted for age and sex, which decreased to 3.0 (95% confidence interval 0.92-9.74) after adjustment for age, sex, body mass index, alcohol consumption, and other factors. In addition to diabetes, body mass index was also significantly (p < 0.05) associated with elevated ALT activity. Heavier alcohol consumption and male sex increased the likelihood of elevated ALT, whereas coffee consumption reduced it. Diabetes and liver injury appear to be associated, even with control for factors in common.
 ...
PMID:Association between diabetes and elevated serum alanine aminotransferase activity among Mexican Americans. 932 34

Nonalcoholic steatohepatitis (NASH) is the term used for a common form of fatty liver presenting in adults with varied clinical manifestations. The most common presentation is asymptomatic elevation of liver enzymes (AST or SGOT and ALT or SGPT), which can be discovered incidentally in the course of an annual checkup, life insurance examination, or as part of surrogate screening before blood donation. At the other end of the clinical spectrum is the patient with complications from cryptogenic cirrhosis, who also shows a lack of evidence of alcohol as an etiological factor in pathogenesis. Clinical associations of probable relevance include gender (female), obesity, diabetes, and hyperlipidemia, but many patients do not conform to any of these stereotypes (e.g., young men of normal weight with normal fasting glucose and lipid levels). Liver biopsy confirms the diagnosis of NASH, the association of steatosis with an inflammatory response being the sine qua non for the condition and "creeping fibrosis" being a variable but possibly sinister feature. Newer imaging techniques may provide convincing evidence of steatosis, but they give little insight into ongoing fibrosis, and liver biopsy therefore remains the gold standard. The mainstay of treatment remains judicious weight loss coupled with positive dietary advice, including the ingestion of adequate but not excessive vitamins. After initial encouraging data. the assessment of ursodeoxycholic acid currently being studied under randomized controlled conditions is eagerly awaited.
 ...
PMID:Nonalcoholic fatty liver (NASH syndrome). 943 7


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>