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

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Query: EC:3.1.3.9 (glucose-6-phosphatase)
3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The New Zealand obese mouse, a model of NIDDM, is characterized by hyperglycemia, hyperinsulinemia, and hepatic and peripheral insulin resistance. The aim of this study was to investigate the biochemical basis of hepatic insulin resistance in NZO mice. Glycolytic and gluconeogenic enzyme activities were measured in fed and overnight fasted 19- to 20-wk-old NZO and control New Zealand chocolate mice. The NZO mice were twice as heavy as the NZC mice. The activity of the glycolytic enzymes glucokinase and pyruvate kinase was higher, whereas that of the gluconeogenic enzymes PEPCK and glucose-6-phosphatase was lower in fed and fasted NZO mice. These enzyme changes are consistent with a normal response to the hyperinsulinemia in NZO mice. In contrast, the activity of the third regulated gluconeogenic enzyme, fructose-1,6-bisphosphatase, was similar in fed and fasted NZO and NZC mice despite the higher insulin and glucose levels in the NZO mouse. This enzyme is primarily regulated by the powerful inhibitor fructose-2,6-bisphosphate. The levels of this metabolite were measured and found to be increased in both the fed and fasted states in the NZO mouse, suggesting that the activity of the bifunctional enzyme that regulates the level of inhibitor (6-phosphofructo-2-kinase/fructose-2,6- bisphosphatase) is normally regulated in the NZO mouse. We conclude that most insulin-responsive gluconeogenic and glycolytic enzymes are normally regulated in the NZO mouse, but an abnormality in the regulation of fructose-1,6-bisphosphatase may contribute to the increase hepatic glucose production in these mice.
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PMID:Impaired regulation of hepatic fructose-1,6-bisphosphatase in the New Zealand obese mouse model of NIDDM. 824 19

Expression of key regulatory enzymes involved in glucose metabolism was studied in the livers of Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of non-insulin dependent diabetes mellitus. The activity and mRNA levels of glucokinase and L-type pyruvate kinase was increased in the liver of OLETF rats compared with control rats. There was no such remarkable change in liver-type phosphofructokinase. The activities of glucose-6-phosphatase and fructose-1,6-biphosphatase also increase despite high plasma levels of glucose and insulin. The activity of phosphoenolpyruvate carboxykinase did not show any significant change. The mRNA levels for fructose-1,6-biphosphatase, and phosphoenolpyruvate carboxykinase exhibited no marked changes. These results suggest that the expression of glucose-6-phosphatase and fructose-1,6-biphosphatase is disordered in OLETF rats.
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PMID:Disordered expression of hepatic glycolytic and gluconeogenic enzymes in Otsuka Long-Evans Tokushima fatty rats with spontanteous long-term hyperglycemia. 860 25

As demonstrated previously, liver acini draining the blood from intraportally transplanted pancreatic islets in streptozotocin-diabetic rats are altered in various respects. The hepatocytes in these acini store glycogen and/or fat, and they show an increase in proliferation as well as in apoptotic activity. Thus, they are phenotypically similar to carcinogen-induced preneoplastic liver foci (glycogen-storing foci and sometimes also mixed cell foci). By means of catalytic enzyme histochemistry or immunohistochemistry, we investigated the activity of key enzymes of alternative pathways of carbohydrate metabolism and some additional marker enzymes (well known from studies on preneoplastic hepatic foci) in the altered liver acini surrounding the islet isografts. In addition, the expression of glucose transporter proteins 1 and 2 (GLUT-1 and GLUT-2) were investigated immunohistochemically. The activities of hexokinase, pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, and glucose-6-phosphate dehydrogenase were increased, whereas the activities of glycogen phosphorylase, adenylate cyclase, glucose-6-phosphatase, and membrane-bound adenosine triphosphatase were decreased in the altered liver acini. The expression of GLUT-2 was also decreased. GLUT-1 and glutathione S-transferase placental form were not expressed, and the activities of glycogen synthase and gamma-glutamyl-transferase remained unchanged. All changes of the enzyme activities were in line with the well known effects of insulin and resembled alterations characteristic of preneoplastic liver foci observed in different models of hepatocarcinogenesis. It remains to be clarified in long-term experiments whether or not these foci represent preneoplastic lesions and may proceed to neoplasia.
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PMID:Altered liver acini induced in diabetic rats by portal vein islet isografts resemble preneoplastic hepatic foci in their enzymic pattern. 864 65

Mouse renal cell tumors (RCT) were induced in male CBA male mice by 5 subcutaneous injections of 8 mg 1,2-dimethylhydrazine (DMH) per kg body weight once a week. After a lag period of two years the kidneys were removed, and serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: Glycogen content, basophilia, and activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malic enzyme (ME), succinate dehydrogenase (SDH), alkaline phosphatase (ALPase) and glutamyl-transpeptidase (GGT). RCT displayed the same histochemical profile irrespective of their size and growth pattern. In comparison with normal kidney epithelium, the neoplastic cells exhibited elevated activities of enzymes for glycolysis (HK, PK LDH) and the pentose phosphate pathway (G6PDH) while negative G6Pase and low SDH activity were observed in these cells. The majority of RCT showed high PHO activity and weak staining for SYN. Activities of ALPase and GGT were negative in most of the RCT. Giant cells were detected in some large RCT. Higher activities of glycolytic and mitochondrial enzymes and G6PDH were found in giant cells compared with other tumor cells. Tubular preneoplastic lesions were similar to neoplastic lesions in morphological and histochemical characteristics. The present study revealed that a markedly elevated capacity for glycolysis and the pentose phosphate pathway occurred in renal cell tumors in mice. A similar histochemical pattern in the few preneoplastic tubular lesions observed suggests that these metabolic aberrations emerge early in carcinogenesis, but studies on earlier stages of renal carcinogenesis are needed to substantiate this assumption.
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PMID:[Enzymic spectrum of preneoplastic and neoplastic changes induced by 1,2-dimethylhydrazine in mouse kidneys]. 874 89

The effectiveness of gossypol as an antifertilizing agent is due to the severe injuries or death that this drug produces on spermatozoa and spermatides. Several in vitro and in vivo studies have shown that spermatozoal lactic and malic dehydrogenases are inhibited by gossypol; and that these are more susceptible than the somatic enzymes. Notwithstanding, the in vivo effects on other somatic enzymes have been poorly analyzed. The present study shows that gossypol did not produce toxic effects on eight erythrocytic enzymes of male hamsters that were fed daily with 20 mg of gossypol/kg, for 1, 3, 5 or 10 days. The enzymatic activities analyzed were: adenylate kinase, hexokinase, glucose-6-phosphatase, glucose phosphoisomerase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglyceratokinase and pyruvate kinase.
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PMID:Orally administered gossypol has no effect on eight hamster erythrocytic enzymes. 874 2

In non-nervous tissues, glucocorticoids (GCs) counteract the effects of insulin and stimulate gluconeogenesis. The present study was designed to investigate whether or not adrenalectomy (ADX) and glucocorticoid substitution influence the pathway of both glucose and glycogen metabolism in cerebral parietotemporal cortex and hippocampus, and if so how. The activities of respective key enzymes, such as hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), glucose-6-phosphatase (G6Pase) and phosphorylase a (PLa), and the concentrations of the intermediates, such as glucose (Glu), glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), fructose-1,6-bisphosphate (F16PP), pyruvate (Pyr), lactate (Lac), glycogen (Glyc) and glucose-1-phosphate (G1P), were measured in the brains of 1-year-old male Wistar rats under controlled conditions 3 days after ADX or sham operation and in a pilot study after ADX and substitution with corticosterone (CST) suspended in sesame oil or after ADX and subcutaneous administration of the vehicle only. An increase in both glycolytic flux and glycogen breakdown and a decrease in gluconeogenesis in cerebral cortex but not in hippocampus were observed after ADX. After substitution with CST in adrenalectomized rats the effect of ADX on enzyme activities was reversed: significant differences from adrenalectomized rats that received vehicle only was shown for PK and G6Pase activities in both areas of the rat brain investigated.
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PMID:Effect of adrenalectomy and corticosterone substitution on glucose and glycogen metabolism in rat brain. 902 80

Female albino rats were exposed to methadone over a 35-day period by addition of the drug in their drinking water. The final dose of the drug was 1.8 mg/kg body weight per day. After this period, the drug was withdrawn from some animals for 30 days (postexposure). Compared to unexposed controls, serum glucose levels rose during exposure and returned to control levels postexposure. Oral glucose tolerance tests showed impairment in 35-day drug-exposed animals compared to controls and postexposure. The activities of three key enzymes of glycolysis and three key enzymes of gluconeogenesis were measured in liver during and at the end of the exposure period, as well as postexposure. Compared to unexposed controls and postexposure, specific activities of two glycolytic enzymes in livers of exposed animals-hexokinase and phosphofructokinase 1-were significantly reduced, whereas the activity of a third glycolytic enzyme-pyruvate kinase-was unchanged. The specific activities of two gluconeogenic enzymes-glucose-6-phosphatase and fructose-1,6-biphosphatase-were significantly elevated in the drug-exposed animals compared to controls, whereas the activity of a third enzyme-phosphoenolpyruvate carboxykinase-was unchanged. These data indicate that methadone addiction produces a metabolic state similar to insulin-resistant diabetes.
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PMID:Effect of methadone addiction on glucose metabolism in rats. 911 73

Glucose-6-phosphatase, a key enzyme in the homeostatic regulation of blood glucose concentration, catalyzes the terminal step in gluconeogenesis and glycogenolysis. Glucose, the product of the glucose-6-phosphatase reaction, dramatically increases the level of glucose-6-phosphatase mRNA transcripts in primary hepatocytes (20-fold), and the maximum response is obtained at a glucose concentration as low as 11 mM. Glucose specifically increases glucose-6-phosphatase mRNA and L-type pyruvate kinase mRNA. In the rat hepatoma-derived cell line, Fao, glucose increases the glucose-6-phosphatase mRNA only modestly (3-fold). In the presence of high glucose concentrations, overexpression of glucokinase in Fao cells via recombinant adenovirus vectors increases lactate production to the level found in primary hepatocytes and increases glucose-6-phosphatase gene expression by 21-fold. Similar overexpression of hexokinase I in Fao cells with high levels of glucose does not increase lactate production nor does it change the response of glucose-6-phosphatase mRNA to glucose. Glucokinase overexpression in Fao cells blunts the previously reported inhibitory effect of insulin on glucose-6-phosphatase gene expression in these cells. Raising the cellular concentration of fructose-2,6-bisphosphate, a potent effector of the direction of carbon flux through the gluconeogenic and glycolytic pathways, also stimulated glucose-6-phosphatase gene expression in Fao cells. Increasing the fructose-2,6-bisphosphate concentration over a 15-fold range (12 +/- 1 to 187 +/- 17 pmol/plate) via an adenoviral vector overexpression system, led to a 6-fold increase (0.32 +/- 0. 03 to 2.2 +/- 0.33 arbitrary units of mRNA) in glucose-6-phosphatase gene expression with a concomitant increase in glycolysis and a decrease in gluconeogenesis. Also, the effects of fructose-2, 6-bisphosphate concentrations on fructose-1,6-bisphosphatase gene expression were stimulatory, leading to a 5-6-fold increase in mRNA level over a 15-fold range in fructose-2,6-bisphosphate level. Liver pyruvate kinase and phosphoenolpyruvate carboxykinase mRNA were unchanged by the manipulation of fructose-2,6-bisphosphate level.
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PMID:Stimulation of glucose-6-phosphatase gene expression by glucose and fructose-2,6-bisphosphate. 913 47

Hepatic gene expression of P-enolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (Glc-6-Pase) is regulated in response to changes in the availability of substrates, in particular glucose (Glc; Massillon, D., Barzilai, N., Chen, W., Hu, M., and Rossetti, L. (1996) J. Biol. Chem. 271, 9871-9874). We investigated the mechanism(s) in conscious rats. Hyperglycemia per se caused a rapid and marked increase in Glc-6-Pase mRNA abundance and protein levels. By contrast, hyperglycemia decreased the abundance of PEPCK mRNA. Importantly, inhibition of glucokinase activity by glucosamine infusion blunted both the stimulation of Glc-6-Pase and the inhibition of PEPCK gene expression by Glc, suggesting that an intrahepatic signal (metabolite) generated by the metabolism of glucose at or beyond Glc-6-P was responsible for the regulatory effect of Glc. The effect of Glc on the L-type pyruvate kinase gene is mediated by xylulose-5-P (Doiron, B., Cuif, M., Chen, R., and Kahn, A. (1996) J. Biol. Chem. 271, 5321-5324). Thus, we next investigated whether an isolated increase in the hepatic concentration of this metabolite can also reproduce the effects of Glc on Glc-6-Pase and PEPCK gene expression in vivo. Xylitol, which is directly converted to xylulose-5-P in the liver, was infused to raise the hepatic concentration of xylulose-5-P by approximately 3-fold. Xylitol infusion did not alter the levels of Glc-6-P and of fructose-2,6-biphosphate. However, it replicated the effects of hyperglycemia on Glc-6-Pase and PEPCK gene expression and resulted in a 75% increase in the in vivo flux through Glc-6-Pase (total glucose output).
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PMID:Carbon flux via the pentose phosphate pathway regulates the hepatic expression of the glucose-6-phosphatase and phosphoenolpyruvate carboxykinase genes in conscious rats. 941 69

Preneoplastic liver foci and neoplasms of different morphological phenotypes were induced in rats with N-nitrosomorpholine (NNM; 120 mg/l in drinking water for 7 weeks) and the peroxisome proliferator dehydroepiandrosterone (DHEA; 0.6% in the diet for up to 84 weeks). Preneoplastic glycogen storage foci (GSF) occurred mainly upon treatment with NNM, and amphophilic cell foci (APF) were mainly observed in rats treated with DHEA alone or in combination with NNM. The 2 types of lesions belong to 2 different cellular lineages, the glycogenotic/basophilic lineage and the amphophilic lineage, which are characterized by distinct patterns of alterations in key enzymes of energy metabolism. Whereas in GSF enzymes of glucose metabolizing pathways were modified (increase in glucose-6-phosphate dehydrogenase and pyruvate kinase, decrease in glucose-6-phosphatase), APF mainly demonstrated alterations in mitochondrial enzymes (increase in cytochrome c oxidase, succinate dehydrogenase and glycerol-3-phosphate dehydrogenase) and, to a lower extent, in peroxisomal enzymes (increase in peroxisomal hydratase and acyl-CoA oxidase). The alterations in enzyme expression reflect an insulinomimetic effect in GSF and a thyromimetic effect in APF. Neoplasms resulting from APF show a more differentiated phenotype than those arising from GSF. We suggest that the different and in many aspects opposite effects of the 2 carcinogens on key enzymes of distinct pathways of energy metabolism modulate the process of neoplastic liver cell transformation and result in phenotypically different preneoplasias and neoplasias reflecting different cellular lineages.
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PMID:Differential expression of key enzymes of energy metabolism in preneoplastic and neoplastic rat liver lesions induced by N-nitrosomorpholine and dehydroepiandrosterone. 964 43


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