Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects have been studied of streptozotocin-induced diabetes and subsequent insulin administration or feeding of a high fructose diet on the amount of enzyme protein and mRNA activity of L-type pyruvate kinase in rat liver. Diabetes markedly decreased the L-type enzyme activity in rat liver and insulin treatment resulted in restoration of the enzyme activity to normal. A high fructose diet also increased the enzyme activity in diabetic rats but to a lesser extent. Immunochemical analysis showed that these alterations in the enzyme activity were due to changes in the amount of immunoreactive enzyme protein. The mechanism of the changes was studied further by assaying the level of functional mRNA coding for this enzyme in a nuclease-treated reticulocyte lysate system with total RNA isolated from rat liver. L-type pyruvate kinase mRNA, expressed as a percentage of the total protein synthesized, was greatly decreased in diabetic rats. Insulin administration resulted in recovery of the mRNA activity to the normal level within 24 h. The lag period before accumulation of translatable mRNA of the L-type enzyme was about 4-5 h. The mRNA activity was also increased in diabetic rats fed a high fructose diet. This fructose effect, which was much smaller than the insulin effect, was maximal after feeding fructose diet for one day. These changes were approximately comparable to the changes in enzyme activity. Thus, it is suggested that regulations of rat liver L-type pyruvate kinase by insulin and by fructose are primarily due to changes in the level of translatable mRNA of this enzyme.
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PMID:Regulation of rat liver L-type pyruvate kinase mRNA by insulin and by fructose. 675 23

A radioimmunoassay specific for liver pyruvate kinase was used to determine the mechanism(s) involved in the insulin stimulation of this enzyme activity in chronically diabetic rats. Rats, made diabetic with alloxan, were fed on a high-carbohydrate (50%-sucrose) fat-free diet and treated with insulin for 12, 36 or 60 h. Livers were removed at the various times, a piece was kept for determination of glycogen, and the remainder was homogenized. The 100000 g supernatant was prepared and used for determination of pyruvate kinase activity and quantity. Glycogen increased to a maximum of approx. 7% by 12 h after insulin treatment, and was maintained at this elevated value for 60 h. Liver pyruvate kinase activity, which is depressed in diabetes, did not respond to insulin until 36 h of treatment, with a more substantial increase occurring by 60 h. Radioimmunoassay data indicated that the increase in activity was concomitant with a substantial increase in the quantity of the enzyme and a moderate increase in its specific activity. These results demonstrate that a dual mechanism, i.e. an increase in both the quantity and specific activity of the enzyme, regulates the insulin-mediated stimulation of liver pyruvate kinase in the diabetic rat.
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PMID:Insulin mediates the stimulation of pyruvate kinase by a dual mechanism. 676 Aug 59

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

Activities of pyruvate kinase, lactate and malate dehydrogenases as well as concentration of oxaloacetate, lactic and pyruvic acids and of glycerol-I-phosphate were altered in liver tissues of rats with alloxane diabetes. Alteration in activity of LDH and MDH isoenzymes appears to be responsible for regulation of the content of pyrimidine nucleotides oxidized and reduced forms, which limit the glucose oxidation.
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PMID:[Changes in liver enzyme activity in alloxan diabetes rats]. 708 Apr 80

As part of an ongoing search for diabetes susceptibility loci, we tested linkage with non-insulin-dependent diabetes mellitus (NIDDM) for 19 candidate loci or regions chosen for their potential to affect directly or indirectly the action of insulin. Loci were associated with insulin resistance, known effects on lipid metabolism, or effects on glucose metabolism or insulin action. Loci included the insulin-responsive (GLUT4) glucose transporter, hexokinase 2, glucagon, growth hormone, insulin receptor substrate 1 (IRS1), phosphoenolpyruvate carboxykinase, hepatic and muscle forms of pyruvate kinase, hepatic phosphofructokinase, the apolipoprotein B and the apolipoprotein A2 cluster, lipoprotein lipase, hepatic triglyceride lipase, the very-low-density-lipoprotein receptor, and the Pima insulin resistance locus on chromosome 4. For several candidates, no specific informative marker was available; consequently, we tested the surrounding region with highly informative markers. These regions included the diabetes-associated ras-like gene, rad, and the cholesterol ester-transfer gene, both mapped to chromosome 16. Additionally, we tested for linkage with markers at the tumor necrosis factor-alpha gene and the Friedreich's ataxia region. All regions were tested for linkage with microsatellite polymorphisms in > 450 individuals from a minimum of 16 Caucasian families under parametric (LINKAGE 5.1) and nonparametric (affected pedigree member) models.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1995 Nov
PMID:Linkage analysis of 19 candidate regions for insulin resistance in familial NIDDM. 758 21

The regulation by insulin and carbohydrates of the gene expression of three key enzymes involved in glucose metabolism was studied in the liver of the Wistar fatty rat, a model of obese non-insulin-dependent diabetes mellitus. A high glucose or fructose diet, or insulin administration caused a similar magnitude of increase in the level of L-type pyruvate kinase mRNA in the liver of Wistar fatty rats and their lean littermates. However, the induction of glucokinase mRNA and repression of phosphoenolpyruvate carboxykinase mRNA by dietary glucose or insulin were impaired in the fatty rats, whereas fructose caused a similar decrease in phosphoenolpyruvate carboxykinase mRNA in both types of rats. These results indicate that the regulation of gene expression of glucokinase and phosphoenolpyruvate carboxykinase, but not of L-type pyruvate kinase, by insulin is impaired in the liver of the Wistar fatty rat.
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PMID:The regulation of gene expression by insulin is differentially impaired in the liver of the genetically obese-hyperglycemic Wistar fatty rat. 768 20

An MMLV-based retroviral vector containing the chloramphenicol acetyl transferase reporter gene under the control of a glucose-dependent internal promoter derived from the L-type pyruvate kinase gene was constructed. After transfection into psi-CRIP packaging cells, clones producing recombinant retrovirus were selected. These retroviruses were used to infect cultured established hepatocytic cells whose endogenous L-type pyruvate kinase gene is transcriptionally regulated by glucose. In the infected cells, the reporter gene was as responsive to glucose as the endogenous L-type pyruvate kinase gene, and the glucose gene activation was time- and concentration-dependent. The possibility to confer a glucose responsiveness on a transgene carried by a retroviral vector provides a powerful tool in the prospect of gene therapy for diabetes mellitus.
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PMID:Glucose responsiveness of a reporter gene transduced into hepatocytic cells using a retroviral vector. 778 83

Oral administration of tungstate for 15 days normalized glycemia in streptozotocin-induced diabetic rats. Simultaneously, the alterations in hepatic glucose metabolism due to diabetes were almost completely counteracted by this treatment. Thus, 6-phosphofructo-2-kinase, L-pyruvate kinase, and glycogen phosphorylase alpha activities reached levels similar to those observed in healthy animals. Hepatic levels of fructose 2,6-bisphosphate and glycogen also recovered. However, the recovery of glucokinase activity and hepatic levels of glucose 6-phosphate was only partial. The total activity of glycogen synthase increased, although the activation state was not recovered. Moreover, mRNA levels of hepatic glucokinase, glycogen phosphorylase, and phosphoenolpyruvate carboxykinase were also normalized. Tungstate administration in healthy animals also affected all these parameters, although to a much lesser extent. All these effects were similar to those previously reported for vanadate, suggesting a common mechanism of action in vivo.
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PMID:Insulin-like actions of tungstate in diabetic rats. Normalization of hepatic glucose metabolism. 805 Oct 90

Oral administration of vanadate to diabetic streptozotocin-treated rats decreased the high blood glucose and D-3-hydroxybutyrate levels related to diabetes. The increase in the expression of the P-enolpyruvate carboxykinase (PEPCK) gene, the main regulatory enzyme of gluconeogenesis, was counteracted in the liver and the kidney after vanadate administration to diabetic rats. Vanadate also counteracted the induction in tyrosine aminotransferase gene expression due to diabetes and was able to increase the expression of the glucokinase gene to levels even higher than those found in healthy animals. Similarly, an induction in pyruvate kinase mRNA transcripts was observed in diabetic vanadate-treated rats. These effects were correlated with changes on glucokinase and pyruvate kinase activities. Vanadate treatment caused a decrease in the expression of the liver-specific glucose transporter, GLUT-2. Thus, vanadate was able to restore liver glucose utilization and block glucose production in diabetic rats. The increase in the expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCoAS) gene, the key regulatory enzyme in the ketone bodies production pathway, observed in diabetic rats was also blocked by vanadate. Furthermore, a similar pattern in the expression of PEPCK, GLUT-2, HMGCoAS, and the transcription factor CCAAT/enhancer-binding protein alpha genes has been observed. All of these results suggest that the regulation of the expression of genes involved in the glucose and ketone bodies metabolism could be a key step in the normalization process induced by vanadate administration to diabetic rats.
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PMID:Vanadate treatment restores the expression of genes for key enzymes in the glucose and ketone bodies metabolism in the liver of diabetic rats. 810 Aug 35

The acute effects of streptozotocin-induced diabetes on several parameters of glucose metabolism were investigated in rat peritoneal macrophages. These cells accumulated in vitro about twofold more fructose 2,6-bisphosphate in the presence of increasing glucose concentration than cells from normal rats, and an increased production of lactate was observed. Phosphofructokinase-1, phosphofructokinase-2, hexokinase, and pyruvate kinase activities were increased in cells from diabetic rats compared with those from normal rats. Transport of 2-deoxy-D-glucose was increased in cells from diabetic rats. [U-14C]Glucose incorporation into glycogen was also increased in cells from diabetics and the 14CO2 liberation was less than in cells from normal animals. Moreover, macrophages from diabetics did not possess a more active pentose phosphate pathway (measure with [1-14C]glucose oxidation) nor a greater production of superoxide anion (index of activation of macrophages) than in cells from normal animals.
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PMID:Streptozotocin-induced diabetes increases fructose 2,6-bisphosphate levels and glucose metabolism in rat macrophages. 812 90


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