Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) increase the risk of type 2 diabetes in humans and rats. Unsuppressed endogenous hepatic glucose production is a common component of the insulin resistance associated with type 2 diabetes. Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) mediates hepatic glucose production by controlling mRNA levels of glucose-6-phosphatase (G-6-Pase), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1,6-bisphosphatase (FBPase). We therefore hypothesized that gene expression of PGC-1 would be increased in juvenile IUGR rat livers, and this increase would directly correlate with hepatic mRNA levels of PEPCK, G-6-Pase, and FBPase, but not glucokinase. We found that IUGR hepatic PGC-1 protein levels were increased to 230 +/- 32% and 310 +/- 47% of control values at d 0 and d 21 of life, respectively. Similarly, IUGR hepatic PGC-1 mRNA levels were significantly elevated at both ages. Concurrent with the increased PGC-1 gene expression, IUGR hepatic mRNA levels of G-6-Pase, PEPCK, and FBPase were also significantly increased, whereas glucokinase mRNA levels were significantly decreased. These data suggest that increased PGC-1 expression and subsequent hepatic glucose production contribute to the insulin resistance observed in the IUGR juvenile rat.
...
PMID:Increased hepatic peroxisome proliferator-activated receptor-gamma coactivator-1 gene expression in a rat model of intrauterine growth retardation and subsequent insulin resistance. 1207 78

It has been shown recently that glutamine is taken up by the mouse kidney in vivo. However, knowledge about the fate of this amino acid and the regulation of its metabolism in the mouse kidney remains poor. Given the physiological and pathophysiological importance of renal glutamine metabolism and the increasing use of genetically modified mice in biological research, we have conducted a study to characterize glutamine metabolism in the mouse kidney. Proximal tubules isolated from fed and 48 h-starved mice and then incubated with a physiological concentration of glutamine, removed this amino acid and produced ammonium ions at similar rates. In agreement with this observation, activities of the ammoniagenic enzymes, glutaminase and glutamate dehydrogenase, were not different in the renal cortex of fed and starved mice, but the glutamate dehydrogenase mRNA level was elevated 4.5-fold in the renal cortex from starved mice. In contrast, glucose production from glutamine was greatly stimulated whereas the glutamine carbon removed, that was presumably completely oxidized in tubules from fed mice, was virtually suppressed in tubules from starved animals. In accordance with the starvation-induced stimulation of glutamine gluconeogenesis, the activities and mRNA levels of glucose-6-phosphatase, and especially of phosphoenolpyruvate carboxykinase, but not of fructose-1,6-bisphosphatase, were increased in the renal cortex of starved mice. On the basis of our in vitro results, the elevated urinary excretion of ammonium ions observed in starved mice probably reflected an increased transport of these ions into the urine at the expense of those released into the renal veins rather than a stimulation of renal ammoniagenesis.
...
PMID:Effect of starvation on glutamine ammoniagenesis and gluconeogenesis in isolated mouse kidney tubules. 1216 89

The role of protein-tyrosine phosphatase 1B (PTP1B) in diabetes was investigated using an antisense oligonucleotide in ob/ob and db/db mice. PTP1B antisense oligonucleotide treatment normalized plasma glucose levels, postprandial glucose excursion, and HbA(1C). Hyperinsulinemia was also reduced with improved insulin sensitivity. PTP1B protein and mRNA were reduced in liver and fat with no effect in skeletal muscle. Insulin signaling proteins, insulin receptor substrate 2 and phosphatidylinositol 3 (PI3)-kinase regulatory subunit p50alpha, were increased and PI3-kinase p85alpha expression was decreased in liver and fat. These changes in protein expression correlated with increased insulin-stimulated protein kinase B phosphorylation. The expression of liver gluconeogenic enzymes, phosphoenolpyruvate carboxykinase, and fructose-1,6-bisphosphatase was also down-regulated. These findings suggest that PTP1B modulates insulin signaling in liver and fat, and that therapeutic modalities targeting PTP1B inhibition may have clinical benefit in type 2 diabetes.
...
PMID:PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. 1216 59

Our objective was to understand the influence of dietary gluconeogenic amino acids on hepatic glucose metabolism in rainbow trout (Oncorhynchus mykiss). We analyzed the effects of partial substitution of dietary protein by a single gluconeogenic dispensable amino acid (DAA: alanine, aspartic acid or glutamic acid), on the regulation of hepatic glycolytic and gluconeogenic enzymes. We fed juvenile rainbow trout with isonitrogenous and isoenergetic diets in which part of nitrogen from fishmeal was replaced by nitrogen from one of the three DAA. Fish were fed over 9 weeks and samples withdrawn 6 h after feeding or 5 days after food deprivation. Our data did not show a clear effect of an excess of DAA on activities of glycolytic enzymes (glucokinase and pyruvate kinase) compared to the control diet. In contrast, feeding caused a significant repression of gluconeogenic enzyme activities (glucose-6-phosphatase, fructose-1,6-bisphosphatase and mitochondrial phosphoenolpyruvate carboxykinase) only in fish fed the three DAA substituted diets. However, these differences were insufficient to affect postprandial glycemia significantly. In conclusion, an excess of dietary DAA tested does not seem to modify glycemia or to have a negative impact on dietary carbohydrate utilization in rainbow trout.
...
PMID:Effect of partial substitution of dietary protein by a single gluconeogenic dispensable amino acid on hepatic glucose metabolism in rainbow trout (Oncorhynchus mykiss). 1254 63

Long-term caloric restriction (CR) has been shown to extend maximum life span in laboratory rodents. We investigated the activities of gluconeogenic and transaminase enzymes in the livers of old and young mice fed either control or calorie-restricted diets. Livers were sampled 48 h after the last scheduled feeding time. Old mice on CR showed significant increases in the activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase when compared with controls, indicating increased gluconeogenesis. Increased activities of tyrosine, tryptophan, histidine, phenylalanine, alanine and aspartate transaminases, as well as of malate and glutamate dehydrogenases were also observed, while branched-chain amino acid transaminase was unchanged. Young mice on CR showed a significant increase only in the phosphoenolpyruvate carboxykinase activity in the gluconeogenic pathway, while transaminases were increased significantly, except for tryptophan and branched-chain amino acid transaminases. Glutamate dehydrogenase also showed increased activity but malate dehydrogenase was unchanged. Increases in the level of acetyl-CoA and [Acetyl-CoA]/[CoA] ratio were observed only in the old CR mice. Our results demonstrate increased gluconeogenic activity in CR mice and are consistent with a state of increased hepatic gluconeogenesis and protein turnover during CR.
...
PMID:Caloric restriction increases gluconeogenic and transaminase enzyme activities in mouse liver. 1258 90

A truncated form (deltanMDH2) of yeast cytosolic malate dehydrogenase (MDH2) lacking 12 residues on the amino terminus was found to be inadequate for gluconeogenic function in vivo because the mutant enzyme fails to restore growth of a Deltamdh2 strain on minimal medium with ethanol or acetate as the carbon source. The DeltanMDH2 enzyme was also previously found to be refractory to the rapid glucose-induced inactivation and degradation observed for authentic MDH2. In contrast, kinetic properties measured for purified forms of MDH2 and deltanMDH2 enzymes are very similar. Yeast two-hybrid assays indicate weak interactions between MDH2 and yeast phosphoenolpyruvate carboxykinase (PCK1) and between MDH2 and fructose-1,6-bisphosphatase (FBP1). These interactions are not observed for deltanMDH2, suggesting that differences in cellular function between authentic and truncated forms of MDH2 may be related to their ability to interact with other gluconeogenic enzymes. Additional evidence was obtained for interaction of MDH2 with PCK1 using Hummel-Dreyer gel filtration chromatography, and for interactions of MDH2 with PCK1 and with FBP1 using surface plasmon resonance. Experiments with the latter technique demonstrated a much lower affinity for interaction of deltanMDH2 with PCK1 and no interaction between deltanMDH2 and FBP1. These results suggest that the interactions of MDH2 with other gluconeogenic enzymes are dependent on the amino terminus of the enzyme, and that these interactions are important for gluconeogenic function in vivo.
...
PMID:Physical and genetic interactions of cytosolic malate dehydrogenase with other gluconeogenic enzymes. 1273 Feb 40

The importance of renal and hepatic gluconeogenesis in glucose homeostasis is well established, but the cellular localization of the key gluconeogenic enzymes liver fructose-1,6-bisphosphatase (FBPase) and cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in these organs and the potential contribution of other tissues in this process has not been investigated in detail. Therefore, we analyzed the human tissue localization and cellular distribution of FBPase and PEPCK immunohistochemically. The localization analysis demonstrated that FBPase was expressed in many tissues that had not been previously reported to contain FBPase activity (e.g., prostate, ovary, suprarenal cortex, stomach, and heart). In some multicellular tissues, this enzyme was detected in specialized areas such as epithelial cells of the small intestine and prostate or lung pneumocytes II. Interestingly, FBPase was also present in pancreas and cortex cells of the adrenal gland, organs that are involved in the control of carbohydrate and lipid metabolism. Although similar results were obtained for PEPCK localization, different expression of this enzyme was observed in pancreas, adrenal gland, and pneumocytes type I. These results show that co-expression of FBPase and PEPCK occurs not only in kidney and liver, but also in a variety of organs such as the small intestine, stomach, adrenal gland, testis, and prostate which might also contribute to gluconeogenesis. Our results are consistent with published data on the expression of glucose-6-phosphatase in the human small intestine, providing evidence that this organ may play an important role in the human glucose homeostasis.
...
PMID:Broad expression of fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase provide evidence for gluconeogenesis in human tissues other than liver and kidney. 1450 58

Callus cultures of Arabidopsis thaliana (cv. Columbia) in Petri dishes were exposed to altered g-forces by centrifugation (1-10 g). Using semi-quantitative RT-PCR transcripts of genes coding for metabolic key enzymes (ADP-glucose pyrophosphorylase, ADPG-PP; beta-amylase, fructose-1,6-bisphosphatase, FBPase; glyceraldehyde-P dehydrogenase, GAPDH; hydroxymethylglutaryl-CoA reductase, HMG; phenylalanine-ammonium-lyase, PAL; PEP carboxylase, PEPC) were used to monitor threshold conditions for g-number (all) and time of exposure (beta-amylase) which led to altered amounts of the gene product. Exposure to approximately 5 g and higher for 1 h resulted in altered transcript levels: transcripts of beta-amylase, PAL, and PEPC were increased, those of ADPG-PP decreased, while those of FBPase, GAPDH, and HMG were not affected. This probably indicates a shift from starch synthesis to starch degradation and increased rates of anaplerosis (PEPC: supply of ketoacids for amino acid synthesis). In order to get more information about g-related effects on gene expression, we used a 1-h exposure to 7 g for a microarray analysis, using a commercial A. thaliana chip with 4105 unique annotated clusters/genes (IncyteGenomics). Transcripts of more than 200 genes were significantly increased in amount (ratio 7 g/1 g control; 2(1.6) and larger). They fall into several categories. Transcripts coding for enzymes of major pathways form the largest group (25%), followed by gene products involved in cellular organization and cell wall formation/rearrangement (17%), signalling, phosphorylation/dephosphorylation (12%), proteolysis and transport (10% each), hormone synthesis plus related events (8%), defense (4%), stress-response (2%), and gravi-sensing (2%). Many of the alterations are part of a general stress response, but some changes related to the synthesis/rearrangement of cell wall components could be more hyper-g-specific. We only found few gene products, which were decreased in relation to 1 g controls, and these were less significant (ratio < 2(1.6)). We thus assume that g-forces above a threshold of about 5 g for 1 h are sensed by plant cells in general, causing distinct metabolic responses, which obviously in part, are regulated by gene expression.
...
PMID:Hyper-gravity effects on the Arabidopsis transcriptome. 1455 51

Primary aldosteronism is associated with glucose intolerance and diabetes, which is due in part to impaired insulin release caused by reduction of potassium, although other possibilities remain to be elucidated. To evaluate the in vivo effects of aldosterone on glucose metabolism, a single dose of aldosterone was administered to mice, which resulted in elevation of the blood glucose level. In primary cultured mouse hepatocytes, the gene expression of gluconeogenic enzymes such as glucose-6-phosphatase (G6Pase), fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase increased in response to aldosterone in a dose-dependent manner even at a concentration similar to a physiological condition (10(-9) M). The inhibitory effect of insulin on G6Pase gene expression was partially suppressed by aldosterone. Furthermore, aldosterone enhanced G6Pase promoter activity in human hepatoma cell line HepG2, which was prevented by co-treatment with a glucocorticoid antagonist RU-486, but not a mineralocorticoid antagonist spironolactone. In contrast, aldosterone had no effects on major insulin signaling pathways including insulin receptor substrate-1, protein kinase B, and forkhead transcription factor. These results suggest that aldosterone may affect the inhibitory effect of insulin on hepatic gluconeogenesis through the glucocorticoid receptor, which may be one of the causes of impaired glucose metabolism in primary aldosteronism.
...
PMID:Aldosterone stimulates gene expression of hepatic gluconeogenic enzymes through the glucocorticoid receptor in a manner independent of the protein kinase B cascade. 1511 77

We have previously reported that infection with Plasmodium yoelii, Plasmodium chabaudi, or injection of extracts from malaria-parasitized red blood cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in streptozotocin (STZ)-diabetic mice. P yoelii glycosylphosphatidylinositols (GPIs) were extracted in chloroform:methanol:water (CMW) (10:10:3), purified by high-performance thin layer chromatography (HPTLC) and tested for their insulin-mimetic activities. The effects of P yoelii GPIs on blood glucose were investigated in insulin-resistant C57BL/ks-db/db diabetic mice. A single intravenous injection of GPIs (9 and 30 nmol/mouse) induced a significant dose-related decrease in blood glucose (P < .001), but insignificantly increased plasma insulin concentrations. A single oral dose of 2.7 micromol GPIs per db/db mouse significantly lowered blood glucose (P < .01). P yoelii GPIs in vitro (0.062 to 1 micromol/L) significantly stimulated lipogenesis in rat adipocytes in a dose-dependent manner both in the presence and absence of 10(-8) mol/L insulin (P < .01). P yoelii GPIs stimulated pyruvate dehydrogenase phosphatase (PDH-Pase) and inhibited both cyclic adenosine monophosphate (cAMP)-dependent protein kinase A and glucose-6-phosphatase (G6Pase). P yoelii GPIs had no effect on the activity of the gluconeogenic enzymes fructose-1,6-bisphosphatase (FBPase) and phosphoenolpyruvate carboxykinase (PEPCK). This is the first report of the hypoglycemic effect of P yoelii GPIs in murine models of type 2 diabetes. In conclusion, P yoelii GPIs demonstrated acute antidiabetic effects in db/db mice and in vitro. We suggest that P yoelii GPIs, when fully characterized, may provide structural information for the synthesis of new drugs for the management of diabetes.
...
PMID:Improvement of glucose homeostasis in obese diabetic db/db mice given Plasmodium yoelii glycosylphosphatidylinositols. 1528 Oct 17


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

---