Perturbation of fuel homeostasis caused by overexpression of the glucose-6-phosphatase catalytic subunit in liver of normal rats

The terminal step in hepatic gluconeogenesis is catalyzed by glucose-6-phosphatase, an enzyme activity residing in the endoplasmic reticulum and consisting of a catalytic subunit (glucose-6-phosphatase (G6Pase)) and putative accessory transport proteins. We show that Zucker diabetic fatty rats (fa/fa), which are known to exhibit impaired suppression of hepatic glucose output, have 2.4-fold more glucose-6-phosphatase activity in liver than lean controls. To define the potential contribution of increased hepatic G6Pase to development of diabetes, we infused recombinant adenoviruses containing the G6Pase cDNA (AdCMV-G6Pase) or the beta-galactosidase gene into normal rats. Animals were studied by one of three protocols as follows: protocol 1, fed ad libitum for 7 days; protocol 2, fed ad libitum for 5 days, fasted overnight, and subjected to an oral glucose tolerance test; protocol 3, fed ad libitum for 4 days, fasted for 48 h, subjected to oral glucose tolerance test, and then allowed to refeed overnight. Hepatic glucose-6-phosphatase enzymatic activity was increased by 1.6-3-fold in microsomes isolated from AdCMV-G6Pase-treated animals in all three protocols, and the resultant metabolic profile was similar in each case. AdCMV-G6Pase-treated animals exhibited several of the abnormalities associated with early stage non-insulin-dependent diabetes mellitus, including glucose intolerance, hyperinsulinemia, decreased hepatic glycogen content, and increased peripheral (muscle) triglyceride stores. These animals also exhibited significant decreases in circulating free fatty acids and triglycerides, changes not normally associated with the disease. Our studies show that overexpression of G6Pase in liver is sufficient to perturb whole animal glucose and lipid homeostasis, possibly contributing to the development of metabolic abnormalities associated with diabetes.     

The ontogeny of key endoplasmic reticulum proteins in human embryonic and fetal red blood cells

Recently, using immunohistochemical methods, we surprisingly found that endoplasmic reticulum glucose-6-phosphatase is present in human embryonic and fetal red blood cells (RBCs) but not in adult RBCs. The fact that an endoplasmic reticulum enzyme, whose major site of expression in adults is the liver, is present in human embryonic and fetal RBCs, particularly nucleated cells, indicated that it would be sensible to determine whether these cells also contain other endoplasmic reticulum enzyme systems normally found in adult liver. Therefore, we have studied the expression of other endoplasmic reticulum proteins and found that human embryonic and fetal RBC precursors contain other protein components of the glucose-6-phosphatase system, ie, the phosphate and glucose transport proteins as well as other enzymes (eg, uridine diphosphate-glucuronosyltransferases, cytochrome P450 isozymes, nicotinamide adenine dinucleotide phosphate cytochrome P450 oxidoreductase, and prostaglandin H synthase). In addition, we also found the predominantly cytosolic markers 15-hydroxyprostaglandin dehydrogenase, prostaglandins PGE2 and 13,14-dihydro-15-keto-PGE2. The expression of key enzymes that control glucose production, detoxification of endobiotics and xenobiotics, and the regulation of prostaglandin levels in embryonic and early fetal RBCs means that these cells may have an important role in protecting the developing conceptus before it establishes an efficient circulation and before all tissues fully express their normal complement of these enzymes.     

Detection of specific glucose-3-phosphatase activity in rat liver

Sugar-3-phosphates are related to aspects of diabetes which depend on protein glycosylation events. Sorbitol-3-phosphate and fructose-3-phosphate occur in normal and diabetic individuals, and glucose-3-phosphate is a potential intermediate in their biosynthesis. Almost nothing is known about enzyme pathways for their metabolic turnover. We have found that part of the phosphohydrolytic activity on glucose-3-phosphate in rat liver supernatants corresponds to a specific, Mg(2+)-dependent, glucose-3-phosphatase much less or not active on other phosphate esters, including glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, fructose-6-phosphate and p-nitrophenyl-phosphate. This finding opens a route to a better understanding of the metabolism and role of sugar-3-phosphates.     

A role for astrocytes in glucose delivery to neurons?

The present paper examines the possible role of astrocytes in the delivery of glycogen-derived glucose for neuronal metabolism. Such a process would require astrocytic expression of glucose-6-phosphatase. The degree and significance of brain expression of glucose-6-phosphatase (EC 3.1.3.9) has been a subject of controversy. Published immunohistochemical data are consistent with expression of glucose-6-phosphatase by astrocytes, both in vivo and in vitro. In this paper additional confirmation of the expression of glucose-6-phosphatase mRNA in rat brain is presented. Although cultured astrocytes demonstrate glucose-6-phosphatase activity in vitro under assay conditions, there is very limited in vitro evidence that this activity confers a glucose-export capacity on astrocytes. Under most conditions in vitro, lactate export predominates, however this may relate to aspects of the in vitro phenotype. Data relating to astrocytic glucose and lactate export are considered in the context of hypotheses of trafficking by astrocytes of substrates for neuronal metabolism, hypotheses that imply and require compartmentation of these substances, in contrast with current formulations of glucose transport into and within brain that imply no glucose compartmentation. Microdialysis studies of the properties of the brain extracellular fluid (ECF) glucose pool in the freely moving rat were performed seeking evidence of glucose compartmentation. Results of these studies do imply compartmentalisation of brain glucose, and are consistent with a model envisaging the majority of glucose reaching the neuron via the astrocytic intracellular space and the ECF. In addition, such studies provide evidence that rises in ECF glucose concentration are not the direct result of local recruitment of cerebral blood flow, but suggest the influence of intermediate, astrocyte-based mechanisms. Astrocytic glucose-6-phosphatase may permit astrocytes to modulate the trans-astrocytic flux of glucose to adjacent neurons in response to signals reflecting increased neuronal demand.     

The effects of duodenal glucose infusion on some hepatic enzyme activities in sheep

1. Two experiments were performed to examine the effects of duodenal glucose infusion on hepatic enzyme activities in sheep. 2. Glucose infusion significantly increased the specific activities of phosphofructokinase, pyruvate kinase and 6-phosphogluconate dehydrogenase and significantly reduced the specific activity of glucose-6-phosphatase suggesting that the pathways of glucose breakdown are increased, and gluconeogenesis decreased, in glucose-infused animals. 3. The results are discussed in relation to the effects of diet on liver metabolism in sheep.     

Phosphatidylinositol 3-kinase translocates onto liver endoplasmic reticulum and may account for the inhibition of glucose-6-phosphatase during refeeding

By using a rapid procedure of isolation of microsomes, we have shown that the liver glucose-6-phosphatase activity was lowered by about 30% (p < 0.001) after refeeding for 360 min rats previously unfed for 48 h, whereas the amount of glucose-6-phosphatase protein was not lowered during the same time. The amount of the regulatory subunit (p85) and the catalytic activity of phosphatidylinositol 3-kinase (PI3K) were higher by a factor of 2.6 and 2.4, respectively (p < 0.01), in microsomes from refed as compared with fasted rats. This resulted from a translocation process because the total amount of p85 was the same in the whole liver homogenates from fasted and refed rats. The amount of insulin receptor substrate 1 (IRS1) was also higher by a factor of 2.6 in microsomes from refed rats (p < 0. 01). Microsome-bound IRS1 was only detected in p85 immunoprecipitates. These results strongly suggest that an insulin-triggered mechanism of translocation of PI3K onto microsomes occurs in the liver of rats during refeeding. This process, via the lipid products of PI3K, which are potent inhibitors of glucose-6-phosphatase (Mithieux, G., Danièle, N., Payrastre, B., and Zitoun, C. (1998) J. Biol. Chem. 273, 17-19), may account for the inhibition of the enzyme and participate to the inhibition of hepatic glucose production occurring in this situation.     

Three thiol groups are important for the activity of the liver microsomal glucose-6-phosphatase system. Unusual behavior of one thiol located in the glucose-6-phosphate translocase

Liver microsomal glucose-6-phosphatase (Glc-6-Pase) is a multicomponent system involving both substrate and product carriers and a catalytic subunit. We have investigated the inhibitory effect of N-ethylmaleimide (NEM), a rather specific sulfhydryl reagent, on rat liver Glc-6-Pase activity. Three thiol groups are important for Glc-6-Pase system activity. Two of them are located in the glucose-6-phosphate (Glc-6-P) translocase, and one is located in the catalytic subunit. The other transporters (phosphate and glucose) are not affected by NEM treatment. The NEM alkylation of the catalytic subunit sulfhydryl residue is prevented by preincubating the disrupted microsomes with saturating concentrations of substrate or product. This suggests either that the modified cysteine is located in the protein active site or that substrate binding hides the thiol group via a conformational change in the enzyme structure. Two other thiols important for the Glc-6-Pase system activity are located in the Glc-6-P translocase and are more reactive than the one located in the catalytic subunit. The study of the NEM inhibition of the translocase has provided evidence of the existence of two distinct areas in the protein that can behave independently, with conformational changes occurring during Glc-6-P binding to the transporter. The recent cloning of a human putative Glc-6-P carrier exhibiting homologies with bacterial phosphoester transporters, such as Escherichia coli UhpT (a Glc-6-P translocase), is compatible with the fact that two cysteine residues are important for the bacterial Glc-6-P transport.     

Effect of 3-deoxyglucosone on the activities of enzymes responsible for glucose metabolism in mouse liver

Crude extracts containing the enzymes obtained from mouse liver were incubated with 3-deoxyglucosone (3-DG), and then subjected to assay of the activities of enzymes responsible for glucose metabolism. Hexokinase and glucose-6-phosphate dehydrogenase activities were decreased by 3-DG and hexokinase activity was strongly inhibited time and concentration dependently, while glucokinase, glucose-6-phosphatase, and phosphofructokinase activities were scarcely affected. These results suggest that 3-DG inhibits the intake of glucose in the liver and a connection with development of diabetes.     

A gene on chromosome 11q23 coding for a putative glucose- 6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic

Glycogen-storage diseases type I (GSD type I) are due to a deficiency in glucose-6-phosphatase, an enzymatic system present in the endoplasmic reticulum that plays a crucial role in blood glucose homeostasis. Unlike GSD type Ia, types Ib and Ic are not due to mutations in the phosphohydrolase gene and are clinically characterized by the presence of associated neutropenia and neutrophil dysfunction. Biochemical evidence indicates the presence of a defect in glucose-6-phosphate (GSD type Ib) or inorganic phosphate (Pi) (GSD type Ic) transport in the microsomes. We have recently cloned a cDNA encoding a putative glucose-6-phosphate translocase. We have now localized the corresponding gene on chromosome 11q23, the region where GSD types Ib and Ic have been mapped. Using SSCP analysis and sequencing, we have screened this gene, for mutations in genomic DNA, from patients from 22 different families who have GSD types Ib and Ic. Of 20 mutations found, 11 result in truncated proteins that are probably nonfunctional. Most other mutations result in substitutions of conserved or semiconserved residues. The two most common mutations (Gly339Cys and 1211-1212 delCT) together constitute approximately 40% of the disease alleles. The fact that the same mutations are found in GSD types Ib and Ic could indicate either that Pi and glucose-6-phosphate are transported in microsomes by the same transporter or that the biochemical assays used to differentiate Pi and glucose-6-phosphate transport defects are not reliable.     

Effect of vitamin D deficiency and 1,25-dihydroxyvitamin D3 on metabolism and D-glucose transport in rat cerebral cortex

We previously demonstrated that feeding rats Steenbock and Black's rickets-inducing diet produces remarkable changes in the metabolic pattern of the intestinal mucosa, kidney, and liver and in some membrane transport systems of intestinal mucosa and kidney. 1,25-Dihydroxyvitamin D3 administration to rachitic rats did not always prove to be effective in restoring normal values. We have now investigated the effect of 1,25-dihydroxyvitamin D3 on the levels of some metabolites in rat cerebral cortex, on the activity of some enzymes, and on the transport of 2-deoxy-D-glucose and D-glucose in synaptosomes. Our experiments were carried out on three rat groups: control, rachitic, and rachitic treated with 1,25-dihydroxyvitamin D3. The decrease in phosphorus content and the increase in citrate concentration observed in rachitic rat cerebral cortex were corrected by 1,25-dihydroxyvitamin D3 treatment. The activity of acetylcholinesterase, glucose-6-phosphate dehydrogenase, and acyl phosphatase significantly increased in rachitic rat synaptosomes, as well as NAD(+)-dependent isocitrate dehydrogenase in cerebral cortex mitochondria; the administration of 1,25-dihydroxyvitamin D3 to rachitic rats restored enzyme levels to normal. The transport of 2-deoxy-D-glucose and D-glucose in rachitic rat synaptosomes was lower than in the control group and returned to control values in consequence of 1,25-dihydroxyvitamin D3 treatment. The results reported here support the hypothesis of a participation of 1,25-dihydroxyvitamin D3 in some aspects of cerebral cortex metabolism.     

Prevention of carbon tetrachloride-induced lipid peroxidation in liver microsomes from dehydroepiandrosterone-pretreated rats

Dehydroepiandrosterone (DHEA), a lipid soluble steroid, administered to rats (100 mg/kg b.wt) by a single intraperitoneal injection, increases to twice its normal level in the liver microsomes. Microsomes so enriched become resistant to lipid peroxidation induced by incubation with carbon tetrachloride in the presence of a NADPH-regenerating system: also the lipid peroxidation-dependent inactivation of glucose-6-phosphatase and gamma-glutamyl transpetidase due to the haloalkane are prevented. Noteworthy, the liver microsomal drug-metabolizing enzymes and in particular the catalytic activity of cytochrome P450IIE1, responsible for the CCl4-activation, are not impaired by the supplementation with the steroid. Consistently, in DHEA-pretreated microsomes the protein covalent binding of the trichloromethyl radical (CCl3 degrees), is similar to that of not supplemented microsomes treated with CCl4. It thus seems likely that DHEA protects liver microsomes from oxidative damage induced by carbon tetrachloride through its own antioxidant properties rather than inhibiting the metabolism of the toxin.     

Precocious development of glucuronidating and hydroxylating enzymes in chick embryos treated with pituitary grafts

1. Initiation of precocious development of UDP-glucuronyltransferase by an endogenous factor is reported for the first time. 2. This development occurs in chick embryo liver and kidney after grafting of the cephalic lobe of chicken pars-distalis pituitary tissue on to the chorioallantoic membrane, and in liver results in a rise in the enzyme activity from virtually zero to ;adult' values. Aniline hydroxylase also precociously develops in the liver of grafted embryos, its activity rising from one-third to the full adult value. Specific activities of glucose 6-phosphatase, cytochrome P-450 and NADPH-cytochrome c reductase did not significantly change. 3. The response of the transferase does not require the presence of host pituitary gland nor, apart from 1 day's necessary initiation, the presence of the graft itself. 4. The host becomes competent to respond on the 14th day of incubation; response continues for at least 3 days after removal of the graft, and for 2 days in the isolated liver. Grafting of embryonic pars distalis younger than 17 days does not evoke a response in the host liver. 5. Secretion of the pituitary factor increases suddenly some 24-48h before the naturally developing surge in liver UDP-glucuronyltransferase activity and may be responsible for initiating this rise in vivo. 6. The factor is probably not a growth or luteinizing hormone; its nature and the likelihood of a secondary hormone acting directly on the liver are discussed.     

Mannitol 1-phosphate mediates an inhibitory effect of mannitol on the activity and the translocation of glucokinase in isolated rat hepatocytes

When tested in the presence of an inhibitor of sorbitol dehydrogenase, both mannitol and sorbitol caused a progressive inhibition of the detritiation of [2-3H]glucose in isolated rat hepatocytes. The purpose of the present work was to investigate the possibility that this effect was mediated by the regulatory protein of glucokinase. When added to hepatocytes, mannitol decreased the apparent affinity of glucokinase for glucose and increased the concentration of fructose required to stimulate detritiation, without affecting the concentration of fructose 1-phosphate. Its effect could be attributed to the formation of mannitol 1-phosphate, a potent agonist of the regulatory protein, which, similarly to fructose 6-phosphate, reinforces its inhibitory action. Formation of mannitol 1-phosphate in hepatocytes was dependent on the presence of mannitol and was stimulated by compounds that increase the concentration of glucose 6-phosphate. Liver extracts catalysed the conversion of mannitol to mannitol 1-phosphate about 7 times more rapidly in the presence of glucose 6-phosphate than of ATP. The glucose 6-phosphate-dependent formation was entirely accounted for by a microsomal enzyme, glucose-6-phosphatase and was not due to a loss of latency of this enzyme. In hepatocytes in primary culture, mannitol decreased the detritiation rate and counteracted the effect of fructose to stimulate glucokinase translocation. Taken together, these results strongly support a central role played by the regulatory protein in the control of glucokinase activity and translocation in the liver, as well as a feedback control exerted by fructose 6-phosphate on this enzyme.     

Decreased cerebral glucose utilization in rats during the ebb phase of thermal injury

OBJECTIVE: Thermal injury is associated with the development of encephalopathy. The mechanism(s) for the development of this condition have not been established. In the present study, the effects of thermal injury were determined on rat brain glucose utilization (Rg), using 2-[18F]fluoro-2-deoxy-D-glucose (18FDG). DESIGN: Four types of studies were performed. In one group of rats, the effect of thermal injury on total rat brain glucose utilization (Rg) was determined at 6 hours, 24 hours, and 3 weeks after injury. The brains of thermally injured rats were also assayed for hexokinase and glucose-6-phosphatase activities, since these enzyme activities are responsible for the phosphorylation and dephosphorylation of the 18FDG. We also measured total body oxygen consumption in the thermally injured rats. We wanted to compare the changes produced by thermal injury on rat brain glucose utilization (Rg) with the effects produced by compounds known to modify energy metabolism and/or rat brain glucose utilization (Rg). For that reason, in a second group of rats, an inflammatory state was produced by lipopolysaccharide injection, and rat brain glucose utilization (Rg) was determined. In the third group of rats, overall metabolism in rats was reduced by pentobarbital injection, followed by hypothermia, and rat brain glucose utilization (Rg) was determined. In the fourth group of rats, overall metabolism in rats was stimulated by 2,4-dinitrophenol injection, and rat brain glucose utilization (Rg) was determined. MATERIALS AND METHODS: Glucose utilization (Rg) by the brains of these treated rats was determined using 18FDG. Oxygen consumption in vivo, as well as glucose-6-phosphatase and hexokinase activity in vitro, were measured by standard procedures. MEASUREMENTS AND MAIN RESULTS: Glucose utilization (Rg) by rat brain was significantly reduced (p < 0.01) at 6 and 24 hours after injury, but returned to normal values 3 weeks after injury. These reductions were associated with decreases in rat brain hexokinase activity, increases in rat brain glucose-6-phosphatase activity, and decreased oxygen consumption by rats in vivo. Pentobarbital injection followed by hypothermia reduced rat brain glucose utilization (Rg) (p < 0.01), while 2,4-dinitrophenol treatment elevated rat brain glucose utilization (Rg) (p < 0.01). In contrast, LPS treatment had no effect on rat brain glucose utilization (Rg). CONCLUSIONS: These data indicate that thermal injury decreases glucose utilization (Rg) in rat brain during the hypometabolic phase. This effect can be explained, at least in part, by alterations in hexokinase and glucose-6-phosphatase activities, as well as reductions in oxygen consumption. Thus, the changes in brain glucose utilization (Rg) appear to be associated with the ebb phase of the thermal injury. The present results observed in burned rats may provide evidence to explain the encephalopathy observed in burned patients.     

Metabolic impact of adenovirus-mediated overexpression of the glucose-6-phosphatase catalytic subunit in hepatocytes

Glucose-6-phosphatase (G6Pase) catalyzes the hydrolysis of glucose 6-phosphate (Glu-6-P) to free glucose and, as the last step in gluconeogenesis and glycogenolysis in liver, is thought to play an important role in glucose homeostasis. G6Pase activity appears to be conferred by a set of proteins localized to the endoplasmic reticulum, including a glucose-6-phosphate translocase, a G6Pase phosphohydrolase or catalytic subunit, and glucose and inorganic phosphate transporters in the endoplasmic reticulum membrane. In the current study, we used a recombinant adenovirus containing the cDNA encoding the G6Pase catalytic subunit (AdCMV-G6Pase) to evaluate the metabolic impact of overexpression of the enzyme in primary hepatocytes. We found that AdCMV-G6Pase-treated liver cells contain significantly less glycogen and Glu-6-P, but unchanged UDP-glucose levels, relative to control cells. Further, the glycogen synthase activity state was closely correlated with Glu-6-P levels over a wide range of glucose concentrations in both G6Pase-overexpressing and control cells. The reduction in glycogen synthesis in AdCMV-G6Pase-treated hepatocytes is therefore not a function of decreased substrate availability but rather occurs because of the regulatory effects of Glu-6-P on glycogen synthase activity. We also found that AdCMV-G6Pase-treated-cells had significantly lower rates of lactate production and [3-3H]glucose usage, coupled with enhanced rates of gluconeogenesis and Glu-6-P hydrolysis. We conclude that overexpression of the G6Pase catalytic subunit alone is sufficient to activate flux through the G6Pase system in liver cells. Further, hepatocytes treated with AdCMV-G6Pase exhibit a metabolic profile resembling that of liver cells from patients or animals with non-insulin-dependent diabetes mellitus, suggesting that dysregulation of the catalytic subunit of G6Pase could contribute to the etiology of the disease.     

Promoting effects of phenobarbital on the enzyme-altered foci induced by intrahepatic gamma-ray-irradiation in the rat liver

Radiation-induced carcinogenesis of the rat liver using iridium-192 seeds as an intrahepatic radioactive source was studied by enzyme histochemical means. Rats were divided into six groups according to various combinations of one or two iridium-192 or stainless steel seeds and whether they were given a diet containing 0.05% phenobarbital (PB) or a basal diet (BD). Each group were sacrificed at 20, 40, and 60 weeks after intrahepatic insertion of the iridium-192 or stainless steel seeds. gamma-Glutamyl transpeptidase (GGT), glucose-6-phosphatase (G6Pase), and adenosine triphosphatase (ATPase) were stained in the liver tissues, and GGT-positive foci were quantified. Liver neoplasm was not evident, but enzyme-altered foci (EAF) were induced by gamma-ray irradiation. At every point (20, 40, and 60 weeks) after the insertion of the seeds, the GGT-positive area was larger in the rats given than those given BD. Moreover, despite the iridium-192 radioactivity decay, EAF developed continuously in the rats given PB, and persisted in those given BD from 40 to 60 weeks after insertion. These results indicated that phenobarbital promotes the development of EAF initiated by irradiation, as it promotes the process of chemical carcinogenesis in the rat liver.     

The condensing effects of egg lecithin and cholesterol on triolein monolayers are inhibited by substitution of one saturated acyl chain in the triacylglycerol

1. u.v. radiations and copper acetate, as free radical generating systems, determine a significant diminishing of glucose-6-phosphate dehydrogenase activity in the homogenates of Saccharomyces cerevisiae. 2. The inactivation is proportional to the concentration of the formed free radicals, existing a direct dependence on the action time of the free radicals generating systems and on the irradiation dose. The decrease of the enzyme catalytic activity is correlated with the increase of the malondialdehyde concentration. 3. The affinity for the substrate of the enzyme under the action of free radicals does not change significantly compared to the native enzyme: the Km value for NADP is halved, whilst that for glucose-6-phosphate remains unchanged. 4. The electrophoretic study shows evidence of five electrophoretic bands with enzymatic activity in the native extract and the disappearance of one molecular form under the free radical action.     

Liver glucose-6 phosphatase activity is inhibited by refeeding in rats

This study was conducted to determine whether inhibition of hepatic glucose-6 phosphatase is involved in the mechanism of suppression of hepatic glucose production during the postprandial period. We studied the time course of changes in the enzyme activity by refeeding food-deprived rats with nonpurified diet. The Vmax of the enzyme, assayed in homogenates from livers freeze-clamped in situ in anesthetized 48-h unfed rats (12.3 +/- 0.15 U/g wet liver, mean +/- SEM, n = 6) was progressively decreased upon refeeding: 11.1 +/- 0.5, 8.5 +/- 0.4 and 7.9 +/- 0.5 U/g, in rats refed for 90, 180 (P < 0.01) and 360 min (P < 0.01), respectively. The Km of the enzyme was not affected by refeeding. No inhibition of the enzyme was observed in microsomes purified from these homogenates, suggesting a metabolite-induced inhibition mechanism. To assess the role of insulin in the inhibition, we assayed the glucose-6 phosphatase activity in similarly processed liver homogenates from food-deprived rats perfused with insulin at physiological and supraphysiological concentrations, whereas plasma glucose was maintained at the basal level by adapted glucose perfusion (euglycemic clamps). No inhibition of glucose-6 phosphatase was found under these conditions, suggesting that insulin cannot by itself account for the inhibition observed in the refeeding experiments. These data constitute the first demonstration of the inhibition of glucose-6 phosphatase activity during the postprandial period.     

Enzymatic activity in the liver and lipogenesis processes in the fatty tissue of rats after a space flight

The rats flown aboard Cosmos-782 showed a significant increase in the activity of tyrosine aminotransferase and tryptophan pyrolase, i. e. the enzymes whose activity depends on the corticosterone level. The synchronous rats displayed a small increase in the enzyme activity. The flight and synchronous animals exhibited a slight increase in the activity of gluconeogenetic enzymes and a decrease in the activity of glucose-6-phosphatase. Immediately after flight and, to a lesser extent, after the synchronous experiment the activity of lipogenetic enzymes decreased. On the R+25 day the enzyme activity remained unchanged. The study of lipogenesis in the epididymal fat, using C14-glucose incorporation into lipids, did not reveal any differences in the flight and synchronous rats. The findings demonstrated that changes in the enzyme activity induced by the flight and synchronous experiments returned to the normal during readaptation.