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)

Mice homozygous for the targeted deletion of the c/ebp alpha gene, which expresses the CCAAT/enhancer-binding protein alpha (C/EBP alpha), did not store hepatic glycogen and died from hypoglycemia within 8 hours after birth. In these mutant mice, the amounts of glycogen synthase messenger RNA were 50 to 70 percent of normal and the transcriptional induction of the genes for two gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, was delayed. The hepatocytes and adipocytes of the mutant mice failed to accumulate lipid and the expression of the gene for uncoupling protein, the defining marker of brown adipose tissue, was reduced. This study demonstrates that C/EBP alpha is critical for the establishment and maintenance of energy homeostasis in neonates.
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PMID:Impaired energy homeostasis in C/EBP alpha knockout mice. 765 57

Glucose production and utilization and activities of key enzymes involved in liver and muscle glucose metabolism were studied in post-absorptive streptozotocin-diabetic rats after 12 h of severe hyperglycaemia (17.5 +/- 0.5 mmol/l) and insulinopenia (5 +/- 1 microU/ml). Basal glucose production was increased: 36.6 +/- 3.0 mg.kg.min-1, vs 24.4 +/- 2.5 in controls (p < 0.05); liver glycogen concentration was decreased by 40% (p < 0.05); liver phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities were increased by 375 and 156%, respectively (p < 0.001 and < 0.01). During a euglycaemic clamp at a plasma insulin level of 200 microU/ml, glucose production was totally suppressed in controls, but persisted at 20% of basal in diabetic rats. In these rats, glucose production was suppressed at a plasma insulin level of 2500 microU/ml. Basal whole body glucose utilization rate, 2-deoxy-1-[3H]-D-glucose ([3H]-2DG) uptake by muscles and muscle glycogen concentrations were similar in both groups, as well as total and active forms of pyruvate dehydrogenase and glycogen synthase activities. During the euglycaemic clamp, the total body glucose utilization rates and [3H]-2DG uptake by muscles were similar in control and diabetic rats at a plasma insulin level of 200 microU/ml, but lower in diabetic rats at a plasma insulin level of 2500 microU/ml. We conclude 1) in recent-onset severely insulinopenic rats, an excessive glucose production via gluconeogenesis prevailed, mainly accounting for the concomitant hyperglycaemia. This excess glucose output cannot be attributed to liver insulin resistance: the gluconeogenic pathway is physiologically less sensitive than glycogenolysis to the inhibition by insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Excessive glucose production, rather than insulin resistance, accounts for hyperglycaemia in recent-onset streptozotocin-diabetic rats. 775 74

3-Mercaptopicolinate (3-MP) inhibits D-glucose-6-phosphate (G6P) phosphohydrolase activity of the glucose-6-phosphatase system (Bode et al. (1993) Biochem. Cell Biol. 71, 113-121). We therefore attempted to maximize the inhibition by varying the physical state of microsomes, the concentration of 3-MP, and the time of preliminary incubation of 3-MP with the enzyme. The inhibition was irreversible and time- and inhibitor-concentration-dependent, with G6P phosphohydrolase activity of intact rat liver microsomes, but there was no inhibition with detergent-treated microsomes. The effectiveness of 3-MP as a time-dependent inhibitor of glucose 6-phosphatase was demonstrated in situ by measuring glycogenolysis in isolated, perfused livers from fed rats. We first exposed the livers to 2 mM 3-MP for 40 min, and then assessed the inhibitory effects on glycogenolysis. It was lowered by 50%. These observations establish that 3-MP at the mM level may be useful as an experimental probe in the study of the role(s) of G6P in the regulation of glycogenolysis as well as glycogenesis. Further, they validate the use of much lower (microM) concentrations of 3-MP to block gluconeogenesis (at the phosphoenolpyruvate carboxykinase step) without interfering with glucose 6-phosphatase. We also explored the mechanism of 3-MP inhibition. The time-dependent inhibition of carbamoyl-phosphate:glucose phosphotransferase activity with microsomes incubated with 1 mM 3-MP for 60 or 90 min and then assayed with 1 mM carbamoyl phosphate and 180 mM glucose was modest compared with inhibition of G6P phosphohydrolase. When G6P production by carbamoyl-phosphate:glucose phosphotransferase was reduced by decreasing glucose concentration to 60 mM, no inhibition by 3-MP was discernible. There was no inhibition of inorganic pyrophosphatase activity. These studies support the model of time-dependent, irreversible reaction of 3-MP with the G6P translocase component of the glucose-6-phosphatase system.
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PMID:Time-dependent inhibition of glucose 6-phosphatase by 3-mercaptopicolinic acid. 794 52

Chronic effects of benfluorex on some parameters of carbohydrate metabolism have been studied in 24-month-old Sprague-Dawley rats. Treatment once a day for 14 days with 25 mg benfluorex per kg body weight lowered body weight, decreased circulating insulin and resulted in an increase in hepatic glycogen. Measurement of the activities of several important regulatory enzymes of hepatic carbohydrate metabolism showed a significant decrease in the activities of phosphoenolpyruvate carboxykinase and glycogen phosphorylase. The activity of glucose-6-phosphatase, on the other hand, was slightly increased. Taken collectively, our data offer an explanation for the observed inhibition of hepatic glucose production by chronic benfluorex treatment in cases of hyperinsulinemia.
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PMID:Effects of chronic benfluorex treatment on the activities of key enzymes of hepatic carbohydrate metabolism in old Sprague-Dawley rats. 824 Apr 8

The effects of cortisol on hepatic and renal gluconeogenic enzyme activities were investigated in sheep fetuses during late gestation and after experimental manipulation of plasma cortisol levels by fetal adrenalectomy and exogenous infusion of cortisol. Hepatic and renal gluconeogenic enzyme activities increased with increasing gestational age in parallel with the normal rise in fetal cortisol levels towards term (146 +/- 2 days). For the majority of enzymes this increase in activity towards term was prevented when the prepartum cortisol surge was abolished by fetal adrenalectomy and stimulated prematurely in fetuses younger than 130 days by exogenous infusion of cortisol. When the data from all the fetuses were combined irrespective of treatment or gestational age, there were significant positive correlations between the log plasma cortisol concentration in utero and the activities of glucose-6-phosphatase, fructose diphosphatase, phosphoenolpyruvate carboxykinase and aspartate transaminase in the fetal liver and kidney, and pyruvate carboxylase in the fetal liver but not in the kidney. No correlation was observed between log plasma cortisol and alanine aminotransferase activity in either fetal liver or kidney. These findings show that cortisol is a physiological regulator of most of the fetal gluconeogenic enzymes and enhances the glucogenic capacity of the sheep fetus during late gestation.
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PMID:The effects of cortisol on hepatic and renal gluconeogenic enzyme activities in the sheep fetus during late gestation. 832 49

Fetal glucose production has been observed in the chronically hypoglycemic, hypoinsulinemic (HH) fetal lamb. The purpose of this study was to test the hypothesis that induction of hepatic gluconeogenic enzymes occurs in this condition. The activities of both mitochondrial and cytosolic phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase, and glucose-6-phosphatase, three key enzymes of gluconeogenesis, were determined in fetal sheep liver from HH lambs and controls (CONT). Pregnant ewes were maintained chronically hypoglycemic by continuous hyperinsulinemic clamps from approximately 80 d of gestational age (53% of gestation) for 6 wk. Fetuses (gestational age: HH = 136 +/- 2.6, CONT = 133 +/- 3.7 d) were maintained chronically hypoglycemic [HH = 0.51 +/- 0.05 versus CONT = 1.22 +/- 0.11 mmol/L (9.2 +/- 1.0 versus 21.9 +/- 11.9 mg/dL)] and hypoinsulinemic (HH = 3.3 +/- 0.6 versus CONT = 12.0 +/- 2.2 microU/mL) and delivered by cesarean section after measurement of fetal glucose production rate. Hepatic cytosolic PEPCK was 6.0 +/- 1.4 nmol/min/mg protein in CONT and 19.7 +/- 2.5 in HH lamb (p < 0.05), whereas mitochondrial PEPCK was not different between the two groups. Neither fructose-1,6-diphosphatase or glucose-6-phosphatase activities nor plasma glucagon levels were different between groups. These results suggest that chronic fetal hypoglycemia and hypoinsulinemia prematurely induce hepatic cytosolic PEPCK in the fetal lamb. The observed fetal glucose production in the HH fetal lamb may be due to gluconeogenesis.
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PMID:Induction of cytosolic phosphoenolpyruvate carboxykinase in the ovine fetal liver by chronic fetal hypoglycemia and hypoinsulinemia. 851 Oct 22

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

Gluconeogenesis, or the formation of glucose from mainly lactate/ pyruvate, glycerol and alanine, plays an essential role in the maintenance of normoglycaemia during fasting. Inborn deficiencies are known of each of the four enzymes of the glycolytic-gluconeogenic pathway that ensure a unidirectional flux from pyruvate to glucose: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase. In this paper, the clinical picture, pathophysiology, diagnostic tests, genetics, treatment and prognosis of the deficiencies of fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase are reviewed.
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PMID:Disorders of gluconeogenesis. 888 71

Sepsis alters energy production and utilization by the liver. Changes in both metabolic pathways that produce substrate (gluconeogenesis or ketogenesis) for organism-wide consumption or provide an alternative source of fuel for the liver (beta-oxidation and amino acid metabolism) have been identified. In this study, we test the hypothesis that these changes occur via an alteration in the transcription of key enzymes within each pathway. Male Sprague-Dawley rats were made septic using cecal ligation and single puncture with sham operated animals serving as controls. Hepatic tissue was harvested at 0, 3, 6, 16, 24, 48, and 72 h had either total RNA or hepatic nuclei were isolated. Using Northern blot hybridization analysis, the steady-state levels of phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, carnitine palmitoyl transferase II, acetyl coenzyme A-acyltransferase, and ornithine transcarbamylase mRNAs were determined. Using transcript elongation analysis, the rate of transcription of each gene was investigated. Relative to control, steady-state mRNA levels and rates of transcription for all five genes were decreased by ligation and single puncture. These decreases were persistent, with only partial recovery of either mRNA levels or transcription rates at 72 h. These findings could explain in part the long-term alterations in gluconeogenesis, beta-oxidation, and ureagenesis observed in sepsis. More importantly, decreased transcription of certain genes seems to be a characteristic of sepsis-induced changes in hepatic function. Understanding the mechanisms that decrease transcription also may explain other aspects of sepsis in the liver and other organ systems.
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PMID:Altered hepatic gene expression in fecal peritonitis: changes in transcription of gluconeogenic, beta-oxidative, and ureagenic genes. 906 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


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