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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)

Pancreatic islets from healthy (control) and neonatally streptozocin-induced diabetic (STZ-D) rats, a model for non-insulin-dependent diabetes mellitus, were incubated with 3H2O and 5.5 or 16.7 mM glucose. At 5.5 mM glucose, no detectable [3H]glucose was formed. At 16.7 mM, 2.2 patom.islet-1.h-1 of 3H was incorporated into glucose by the control islets and 5.4 patom.islet-1.h-1 by STZ-D islets. About 75% of the 3H was bound to carbon-2 of the glucose. Glucose utilization was 35.3 pmol.islet-1.h-1 by the control and 19.0 pmol.islet-1.h-1 by the STZ-D islets. Therefore, 4.5% of the glucose-6-phosphate formed by the control islets and 15.7% by the STZ-D islets was dephosphorylated. This presumably occurred in the beta-cells of the islets catalyzed by glucose-6-phosphatase. An increased glucose cycling, i.e., glucose----glucose-6-phosphate----glucose, in islets of STZ-D rats may contribute to the decreased insulin secretion found in these animals.
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PMID:Glucose cycling in islets from healthy and diabetic rats. 218 Jul 57

To determine the diabetogenic effect(s) of thyroid hormones, we simultaneously measured glucose turnover in six hyperthyroid patients and six normal subjects. All had normal fasting blood glucose concentration and oral glucose tolerance test values. We determined hepatic total glucose output (HTGO) and total glucose phosphorylation with [2-3H]glucose and hepatic glucose production (HGP) and irreversible glucose uptake using [6-3H]glucose. The difference between the two turnover rates indicates the extent of hepatic glucose cycling (glucose in equilibrium glucose-6-phosphate). Measurements were made both in the postabsorptive steady state and during a 2-h glucose infusion (11.1 mumol/kg.min). The postabsorptive HTGO and total glucose phosphorylation were increased in the hyperthyroid patients [13.5 +/- 0.8 (+/- SE) vs. 11.3 +/- 0.4 mumol/kg.min; P less than 0.05]. HGP and irreversible glucose uptake also were slightly but not significantly higher. During the glucose infusion, HTGO and HGP were less suppressed in the hyperthyroid patients than in the normal subjects, while the increments in peripheral glucose uptake were normal. In hyperthyroidism, glucose cycling was increased both postabsorptively (2.35 +/- 0.27 vs. 1.17 +/- 0.25 mumol/kg.min; P less than 0.025) and during glucose infusion (2.57 +/- 0.34 vs. 1.31 +/- 0.35 mumol/kg.min; P less than 0.05). We conclude that increases in HTGO and HGP are important features of hyperthyroidism, especially during glucose infusion. The increase in GC indicates increased activities of both glucokinase and glucose-6-phosphatase. The diabetogenic effect of hyperthyroidism, as revealed most markedly by [2-3H]glucose, could be accounted for by augmented glucose production, possibly due to increased glucose-6-phosphatase activity.
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PMID:Glucose turnover in hyperthyroid patients with normal glucose tolerance. 253 42

Guinea pig liver microsomal membranes were cholesterol-enriched by feeding guinea pigs a high-cholesterol diet. Cholesterol enrichment as well as partial lipid removal of normal native microsomes by acetone-butanol extraction resulted in 40-50% loss in activity of the glucose-6-phosphate phosphohydrolase (G-6-Pase) (EC 3.1.3.9) enzyme system. The activity was restored by supplementation of microsomal total phospholipid (PL) and its phosphatidylcholine (PC) species but not with microsomal neutral lipids, cholesterol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, sphingomyelin or diphosphatidylglycerol (cardiolipin). The activity was decreased by sodium deoxycholate but enhanced by dimethylsulfoxide. Egg-yolk PC and asolectin influenced the activity of the enzyme to the same extent as microsomal PC did. Lipid depletion and cholesterol produced an increase in Km while the Vmax was lowered. The non-linearity in the Arrhenius plot of the native microsomes was lost on lipid removal and cholesterol enrichment. The energy of activation (Ea) calculated from the continuous line was found to be lowered to the level that was observed above the break points in intact microsomes. Addition of microsomal PC to the assay system decreased the Km of the enzymatic reaction in native membranes, in partially lipid-depleted and cholesterol-enriched membranes, but did not alter the Vmax values and only marginally influenced the non-linear relationship of the Arrhenius expression of temperature dependence. The ability of immature rat liver phospholipid exchange protein to introduce alien PL into microsomal membrane was used to study the lipid dependence of G-6-Pase. Protein-catalyzed and detergent (cholate)-mediated membrane PL exchange for egg-yolk PC from the PC/cholesterol unilamellar liposomes resulted in substantial loss of enzyme activity. The discrepancies in the influence of PC on G-6-Pase were interpreted by assuming that the enzyme was a two-component system, a surface-located substrate transporter unit and a membrane integral catalytic phosphohydrolase unit. The lipid microenvironment and PL requirement in particular, could be different for the two components, although they represented a single functional unit at the time of enzymatic reaction.
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PMID:Glucose-6-phosphate phosphohydrolase activity in guinea pig liver microsomes is influenced by phosphatidylcholine. Interaction with cholesterol-enriched membranes. 254 91

The present studies were designed to clarify the contribution of the liver to the development of hyperglycemia in Wistar fatty rats. The hepatic activities of insulin-inducible enzymes involved in glycolysis (glucokinase; GK and pyruvate kinase) and lipogenesis (glucose-6-phosphate dehydrogenase), were higher in fatty rats than in lean rats at 4 and 8 weeks of age because of the higher insulin levels in the former. Thereafter, the GK activities of fatty rats decreased slightly in spite of severe hyperinsulinemia, and did not differ from those of lean rats. In addition, fatty rats had higher levels of insulin-suppressible gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and fructose-1, 6-diphosphatase. These findings indicate that the hepatic enzymes of fatty rats are resistant to insulin. This postulation was supported by the fact that the hepatic enzyme activities of fatty rats showed a lower response to changes in plasma insulin levels produced by fasting and refeeding. The G6Pase/GK ratio, which indicates net glucose handling in the liver, increased in fatty rats and decreased in lean rats with advancing age, suggesting that hepatic glucose production in fatty rats becomes dominant with advancing age. The changes in hepatic glycolytic intermediates supported this suggestion; the glycolytic steps both from glucose to glucose-6-phosphate and from phospho-enolpyruvate to pyruvate in fatty rats were accelerated at 5 weeks of age, but suppressed at 12 weeks of age. These results indicate that insulin resistance in the hepatic enzyme regulation may contribute to the development of hyperglycemia in Wistar fatty rats.
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PMID:Pathogenesis of hyperglycemia in genetically obese-hyperglycemic rats, Wistar fatty: presence of hepatic insulin resistance. 254 49

Glycogen storage diseases (GSD) type 1b is the first example of a genetic disorder involving the transport system of an intracellular membrane. It was revealed that the primary defect in GSD type 1b was a deficiency in the microsomal glucose-6-phosphate (G6P) translocase, based on the findings that the glucose-6-phosphatase activity was highly latent in the fresh liver homogenates. Further evidence of this defect in GSD type 1b has been provided by a membrane filter method which measures the uptake of 14C-G6P by microsomes. The clinical symptoms and enzymatic studies in our patients suggest that there is genetic heterogeneity in GSD 1b and the clinical severity depends on the level of residual activities of G6P translocase.
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PMID:Glycogen storage disease type 1b: genetic disorder involving the transport system of intracellular membrane. 283 Oct 40

The action of thyroid hormones on hepatic glucose-6-phosphatase was studied in rats. Fed and 24-h fasted rats received T3 (10 micrograms/day) or T4 (25 micrograms/day) 1 h, 1 or 3 days before sacrificing. In addition a group of fed rats was treated with T4 for 7 and 14 days. The glucose-6-phosphatase activity was measured in the isolated microsomes prepared from the liver. The intactness of the microsomal preparation was checked using 2 mM mannose-6-phosphate as a substrate. In fed rats a single injection of T3 or T4 augmented the activities of the translocase and hydrolase components of glucose-6-phosphatase provided that the rats were killed 24 h after the administration of hormone. This effect was more pronounced in animals treated for 3-14 days. As expected, fasting per se increased the activities of both components of the enzyme. Moreover, in fasted rats treatment with T3 and T4 for 3 days further augmented the activities of the translocase and the hydrolase components of glucose-6-phosphatase. In fed animals T3 and T4 increased the latency of the enzyme whereas in fasted animals thyroid hormones increased the activities of the translocase and hydrolase components in parallel, maintaining the level of latency of the enzyme system. Administration of T3 and T4 increased blood glucose level in fasted rats after one day, while in fed rats a significant hyperglycaemia appeared after 7-14 days of treatment. In conclusion, T3 and T4 increase the activities of the translocase and hydrolase components of hepatic glucose-6-phosphatase in fed and fasted rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of thyroid hormones on the activity of hepatic glucose-6-phosphatase in fed and fasted rats. 283 Nov 25

A modified Wachstein-Meisel lead salt method using glucose-6-phosphate or 2-deoxyglucose-6-phosphate as substrates was employed at the light microscopic level to map the rat brain for glucose-6-phosphatase (G-6-Pase). As has been described, most of the activity of the enzyme resided in neuronal cell bodies and dendritic stems. No differences were found between the results obtained with the two substrates. Two categories of brain structures with heavy and with moderate staining could be distinguished while the majority of brain regions contained only barely discernible neurons. Structures displaying very high enzyme activity included nuclei of cranial nerves, nuclei of the reticular formation, Purkinje cells, and some parts of the limbic system, e.g., CA 3 and CA 4 pyramidal fields of the hippocampus. It is pointed out that accurate biochemical determinations of G-6-Pase activity will critically depend on painstaking microdissection of nuclei and cell layers. The histochemical results may be pertinent to the interpretation of the 2-deoxyglucose method for assessment of regional glucose utilization rates in brain. The present observations make it unlikely that regional variations in G-6-Pase activity account for differences in uptake and retention of radioactivity from (1-14C)glucose and (14C)2-deoxyglucose reported previously by our group.
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PMID:A histochemical study of the regional distribution in the rat brain of enzymatic activity hydrolyzing glucose- and 2-deoxyglucose-6-phosphate. 283 34

The effect of 4,4'-diisothiocyanostilbene 2,2'-disulfonic acid (DIDS) on microsomal glucose 6-phosphate hydrolysis has been reinvestigated and characterized in order to elucidate the topological and functional properties of the interacting sites of the glucose-6-phosphatase. The studies were performed on microsomal membranes, partially purified and reconstituted glucose-6-phosphatase preparations and show the following. (a) DIDS inhibits activity of the glucose-6-phosphatase of native microsomes as well as the partially purified glucose-6-phosphatase. (b) Inhibition is reversed when the microsomes and the partially purified phosphohydrolase, incorporated into asolectin liposomes, are modified with Triton X-114. (c) Treatment of native microsomes with DIDS and the following purification of glucose-6-phosphatase from these labeled membranes leads to an enzyme preparation which is labeled and inhibited by DIDS. (d) Preincubation of native microsomes or partially purified glucose-6-phosphatase with a 3000-fold excess of glucose 6-phosphate cannot prevent the DIDS-induced inhibition. (e) Inhibition of glucose-6-phosphatase by DIDS is completely prevented when reactive sulfhydryl groups of the phosphohydrolase are blocked by p-mecuribenzoate. (f) Reactivation of enzyme activity is obtained when DIDS-labeled microsomes are incubated with 2-mercaptoethanol or dithiothreitol. Therefore, we conclude that inhibition of microsomal glucose 6-phosphate hydrolysis by DIDS cannot result from binding of this agent to a putative glucose-6-phosphate-carrier protein. Our results rather suggest that inhibition is caused by chemical modification of sulfhydryl groups of the integral phosphohydrolase accessible to DIDS attack itself. An easy interpretation of these results can be obtained on the basis of a modified conformational model representing the glucose-6-phosphatase as an integral channel-protein located within the hydrophobic interior of the microsomal membrane [Schulze et al. (1986) J. Biol. Chem. 261, 16,571-16,578].
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PMID:On the nature of the interaction between 4,4'-diisothiocyanostilbene 2,2'-disulfonic acid and microsomal glucose-6-phosphatase. Evidence for the involvement of sulfhydryl groups of the phosphohydrolase. 283 98

The effect of oral administration of vanadate on the transport and hydrolytic components of the glucose-6-phosphatase system in liver homogenates from streptozotocin-induced diabetic rats was examined. Blood glucose was normalized in diabetic rats receiving 0.8 mg/ml vanadate but a catabolic effect was observed on body and liver weight. Significant changes in the coupled reactions for glucose-6-phosphate transport by T1 and hydrolysis by the enzyme were noted. The dramatic elevation in the maximal velocity of glucose-6-phosphatase brought about by diabetes was suppressed by vanadate administration. As a result, the relationship between T1 and the enzyme returned to the normal range. It is concluded that the suppression of glucose-6-phosphate hydrolysis in diabetes may contribute to the normalizing effect of vanadate on blood glucose.
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PMID:Suppression of the hepatic glucose-6-phosphatase system in diabetic rats by vanadate. 285 61

Interrelationships between the catalytic properties of glucose-6-phosphatase and the membrane structure of rat liver microsomes were investigated. Membrane modification and solubilization employing the nonionic surfactant Triton X-114 were standardized and analysed by ultracentrifugation, surface tension- and turbidity measurements. The effect of Triton X-114 on the glucose-6-phosphatase activity was studied systematically and the whole magnitude of time- and temperature-dependent inactivation of this enzyme has been demonstrated. The results show that the activity measured is always a resultant of two processes, the beginning of inactivation and the release of latency. Maximal activation of about 600% (83% of apparent latency) was obtained at 0 degree C. A correlation between membrane modification and solubilization and the conditions under preincubation and test incubation reveals that studies on detergent-disrupted microsomes are performed on structures reassembled from solubilizates and this implies a modified microenvironment in the reconstitutes. Kinetic analyses suggest interrelationships between Triton X-114 and the permeability barrier of the glucose-6-phosphatase system. At 0 degree C 2-propanol and ethanol are more potent tools for membrane modification than Triton X-114 and release 88% and 86% latent activity corresponding to an activation of the glucose-6-phosphatase of about 850% and 700%, respectively. These observations suggest that detergent treatment of microsomes could not preserve the functional integrity of the glucose-6-phosphate phosphohydrolase, which is one dogma of the substrate-transport hypothesis developed by Arion and his co-workers (Arion, W.J., et al. (1975) Mol. Cell. Biochem. 6, 75-83).
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PMID:Latency studies on rat liver microsomal glucose-6-phosphatase. Correlation of membrane modification and solubilization by Triton X-114 with the enzymatic activity. 298 63


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