Gene/Protein
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Drug
Enzyme
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Gene/Protein
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Target Concepts:
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Query: EC:2.6.1.2 (
alanine aminotransferase
)
26,722
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Previous studies indicate that pretreatment with acetone or isopropanol, fasting, and streptozotocin-induced
diabetes
enhance hepatic microsomal nitroso-dimethylamine (NDMA) demethylase in rats. This study demonstrates that these same treatments also potentiate the hepatotoxicity of NDMA as indicated by plasma glutamic
pyruvate transaminase
(GPT) levels and histologic data. Pretreatment with acetone or isopropanol (2.5 ml/kg) and 2 days of fasting caused a 2-fold potentiation of NDMA-induced plasma GPT elevation, whereas streptozotocin-induced
diabetes
caused a 4.6-fold potentiation. The centrilobular necrosis produced by NDMA was more severe after pretreatment with the inducers. NDMA treatment also decreased hepatic microsomal demethylase activity. These results lend support to the concept that a NDMA demethylase is responsible for the activation of NDMA in vivo to a toxic intermediate, and induction of this enzyme activity potentiates NDMA hepatotoxicity.
...
PMID:Potentiation of the hepatotoxicity of N-nitrosodimethylamine by fasting, diabetes, acetone, and isopropanol. 671 61
Nine different liver function tests (LFT) were assessed in 175 unselected diabetic outpatients stabilized on diet, insulin, or oral hypoglycemic drugs. In another group of 72 diabetic inpatients having diagnostic liver biopsy, relationships between LFT and histologic changes in the liver were investigated. Abnormalities in at least one of the tests were noted in 57% of the outpatients, and two tests gave pathologic results in 27%. The non-insulin-dependent diabetic patients more often had abnormal LFT results than did the insulin-dependent diabetic patients. Serum chenodeoxycholic acid concentrations were increased in 27%, gamma-glutamyl transpeptidase (gGT) activities in 19%, and
alanine aminotransferase
(Alt) activities in 17% of the outpatients, but the increases were rarely more than twice the upper limit of normal. In multivariate analysis, outpatients who were overweight, showed poor
diabetes
control during a short duration of
diabetes
controlled by treatment with diet or oral agents, and had a mature age at onset of
diabetes
displayed the most significant clinical explanatory variables associated with abnormal Alt. In the inpatients, the percentages of abnormal Alt and gGT results were augmented, along with increasing severity of histologic changes, but the mean values of Alt and gGT did not differ significantly between the various histologic groups. In addition, the diabetic patients with nonspecific inflammatory changes or increase in liver fibrosis often showed normal or only minor elevations in these test values.
Diabetes
Care
PMID:Liver function tests in diabetic patients. 673 94
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.
...
PMID:The effects of a high fat diet on chronic streptozotocin-diabetic rats. 692 68
1. Methods are described for monitoring the metabolic flux through phenylalanine hydroxylase, the tyrosine catabolic pathway and phenylalanine:
pyruvate transaminase
in isolated liver cell incubations. 2. The relationship between hydroxylase flux and phenylalanine concentration is sigmoidal. 3. Glucagon increases hydroxylase activity at low, near-physiological, substrate concentrations only. The hormone does not affect the rate of formation of phenylpyruvate. 4. Experimental
diabetes
(for 10 days) increases phenylalanine catabolism, and this is further increased by glucagon. 5. These results are discussed in the light of the known mechanisms for control of phenylalanine hydroxylase activity in vitro.
...
PMID:Phenylalanine metabolism in isolated rat liver cells. Effects of glucagon and diabetes. 732 31
The intravenous injection of zinc chloride immediately before and 15 minutes after alloxan or dithizone prevented the usual hyperglycaemia observed 24 hours after induction of
diabetes
. The intravenous injection of manganese chloride prevented any marked rise of blood glucose, while chromium and cobalt chlorides lowered the blood glucose level to a certain extent. In alloxan diabetic rats, serum GOT and
GPT
levels were significantly higher than normal. The serum GOT levels were higher in animals injected with chromium than cobalt, zinc and manganese; while serum
GPT
levels were higher in cobalt than in chromium, zinc and manganese. In dithizone
diabetes
, serum GOT and
GPT
were increased in animals injected with cobalt than chromium, zinc and manganese. Alloxan diabetic rats showed lower serum alkaline phosphatase levels and higher in animals injected with cobalt than chromium, zinc and manganese. For dithizone, there are statistically significant differences in all cases. In alloxan
diabetes
, coeruloplasmin was higher than normal, while intravenous injection of dithizone was without effect on serum coeruloplasmin.
...
PMID:Serum enzyme changes due to trace amounts of some transition metal ions on the induction of experimental diabetes. 742 63
Moderate elevations of serum transaminases are frequently found in patients with
diabetes mellitus
and are often attributed to fatty infiltration of the liver without further investigation. Recent studies of patients with end-stage liver disease have suggested a possible association between Hepatitis C virus (HCV) antibody positivity and the development of
diabetes
(mostly Type 2). As a first step in the examination of any potential association between HCV and Type 2
diabetes
in subjects without overt liver disease, we examined 200 British patients with Type 2
diabetes
(100 White Caucasians, 50 Asians, and 50 Afro-Caribbeans), recruited from the United Kingdom Prospective Study of
Diabetes
, half of whom had a significant elevation of
alanine aminotransferase
(
ALT
) on at least two occasions and half of whom had consistently normal
ALT
levels. In Afro-Caribbean Type 2 diabetic subjects 7/25 (28%) patients with abnormal
ALT
and 1/25 (4%) with normal
ALT
were HCV antibody positive. Among White Caucasian subjects 6/50 (12%) patients with abnormal LFTs and 0/50 with normal LFTs were HCV antibody positive and in Asians the prevalence was 2/25 (8%) and 0/25, respectively. This study suggests that persistent mild to moderate elevation of serum transaminases in a patient with Type 2
diabetes
should not automatically be attributed to the metabolic disturbances of
diabetes
. Particularly in Afro-Caribbean subjects, HCV infection is a major diagnostic consideration. The question of whether HCV infection itself may have a diabetogenic action is worthy of further investigation.
...
PMID:High prevalence of hepatitis C infection in Afro-Caribbean patients with type 2 diabetes and abnormal liver function tests. 753 25
We investigated the effect of Probucol in preventing fatty liver in monosodium-L-glutamate (MSG) treated obese mice and control mice fed a high fat diet. MSG mice became significantly obese 9 weeks after birth with higher levels of serum blood glucose, total cholesterol, HDL-cholesterol,
GPT
, and cholinesterase, and had greater triglyceride contents in their livers relative to control mice. Morphologically, MSG obese mice also had a marked fatty liver. Administration of Probucol mixed with the high fat diet for 2 weeks significantly decreased the serum levels of total cholesterol and HDL-cholesterol, and liver triglyceride contents in both MSG and control mice. Morphologically, the livers were less fatty after Probucol treatment. These results suggest that Probucol prevents the development of fatty liver, and in addition reduces hypercholesterolemia.
Exp Clin Endocrinol
Diabetes
1995
PMID:Probucol prevents the progression of fatty liver in MSG obese mice. 755 75
Overproportional GLDH-increase was found to be the most frequently appearing pathological enzyme pattern in canine practice. Thus it could be shown that GLDH deviates, in spite of its mitochondrial localization and greater molecular weight, more frequently and to a higher degree from its reference value than the parameters
ALT
, AST, AP, GGT and Bilirubin. The results of the study suggest that the liberation of the enzyme is less determined by the intensity than by the intralobular target of the liver insult. Therefore an increase in GLDH-activity should no longer be interpreted as the result of severe liver damage. On the contrary, the enzyme appeared to be the most sensitive indicator for the diagnosis of primary and secondary hepatopathies. The phenomenon of isolated GLDH-increase could be interpreted in almost every disease group as an appearance of the over-proportional increase and can therefore be understood as a serological expression of a slight, perivenous liver affection. Only with effusion patients the enzyme pattern should be regarded as an independent finding, because it has extrahepatic reasons. The induction of the enzyme in cases of
diabetes mellitus
is discussed.
...
PMID:[Diagnostic value of glutamate dehydrogenase determination in the dog]. 771 55
The aim of the present study is to compare normal and tumoral pancreatic islet cells in terms of both the activity of selected cytosolic and mitochondrial enzymes participating to nutrient catabolism and the intrinsic properties of FAD-glycerophosphate dehydrogenase. The activity of the glycolytic enzymes hexokinase and lactate dehydrogenase was higher in tumoral (RINm5F) than normal islet cells. The opposite was seen for glutamate decarboxylase, glutamate-oxaloacetate transaminase, glutamate-
pyruvate transaminase
, glutamate dehydrogenase, 2-ketoglutarate dehydrogenase and FAD-glycerophosphate dehydrogenase (m-GDH). These findings are consistent with the high rates of glycolysis and protein synthesis seen in tumoral islet cells compared with normal islet cells, which favour mitochondrial oxidative events associated with the catabolism of D-glucose and amino acids. The intrinsic catalytic properties of m-GDH were comparable, albeit not identical, in normal and tumoral islet cells. Since a deficiency of m-GDH in pancreatic islets may represent a contributing factor in the pathogenesis of non-insulin-dependent
diabetes
, it is proposed that RINm5F cells may readily yield sufficient islet m-GDH for purification and further gene cloning.
...
PMID:Activity of cytosolic and mitochondrial enzymes participating in nutrient catabolism of normal and tumoral islet cells. 776 86
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
.
...
PMID:Impaired FAD-glycerophosphate dehydrogenase activity in islet and liver homogenates of fa/fa rats. 783 41
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