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Sample records for alters liver glycogen

  1. The early alterations in some enzymatic activity, blood glucose and liver glycogen levels induced by atropine injection and whole

    International Nuclear Information System (INIS)

    Abdel-Fattah, K.I.; El-Sayed, N.M.; Abou-Safi, H.M.; Hussain, A.H.

    1999-01-01

    Detecting the early physiological and biochemical changes in the biological material after exposure to gamma irradiation is very helpful in the techniques of protection against radiation. The present work was designed for detecting the early changes in plasma phosphatases, transaminases, glucose and liver glycogen levels after irradiation and the role of atropine injected before irradiation on these parameters. Rats were divided into four groups: control. injected (i. m.) with atropine (0.5 mg/100 g B.Wt), irradiated at 6 Gy, and injected with atropine before irradiation. Plasma was collected at 1.3 and 5 hr after radiation exposure. Results showed that atropine exerted some amelioration during the first three hours, mainly, on acid phosphatase and GPT activities and on glucose and liver glycogen one hour only post irradiation. Generally, the limited radioprotective role of atropine is related, to its physiological mechanism in the body

  2. Threonine phosphorylation of rat liver glycogen synthase

    International Nuclear Information System (INIS)

    Arino, J.; Arro, M.; Guinovart, J.J.

    1985-01-01

    32 P-labeled glycogen synthase specifically immunoprecipitated from 32 P-phosphate incubated rat hepatocytes contains, in addition to [ 32 P] phosphoserine, significant levels of [ 32 P] phosphothreonine. When the 32 P-immunoprecipitate was cleaved with CNBr, the [ 32 P] phosphothreonine was recovered in the large CNBr fragment (CB-2, Mapp 28 Kd). Homogeneous rat liver glycogen synthase was phosphorylated by all the protein kinases able to phosphorylate CB-2 in vitro. After analysis of the immunoprecipitated enzyme for phosphoaminoacids, it was observed that only casein kinase II was able to phosphorylate on threonine and 32 P-phosphate was only found in CB-2. These results demonstrate that rat liver glycogen synthase is phosphorylated at threonine site(s) contained in CB-2 and strongly indicate that casein kinase II may play a role in the ''in vivo'' phosphorylation of liver glycogen synthase. This is the first protein kinase reported to phosphorylate threonine residues in liver glycogen synthase

  3. Molecular Structure of Human-Liver Glycogen.

    Directory of Open Access Journals (Sweden)

    Bin Deng

    Full Text Available Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.

  4. Mechanism of activation of liver glycogen synthase by swelling

    NARCIS (Netherlands)

    Meijer, A. J.; Baquet, A.; Gustafson, L.; van Woerkom, G. M.; Hue, L.

    1992-01-01

    The mechanism linking the stimulation of liver glycogen synthesis to swelling induced either by amino acids or hypotonicity was studied in hepatocytes, in gel-filtered liver extracts, and in purified preparations of particulate glycogen to which glycogen-metabolizing enzymes are bound. High

  5. Effects of gamma-irradiation on the glycogen and lipid contents of the rat liver cells

    Energy Technology Data Exchange (ETDEWEB)

    Nahed, R H.A.; Al-Zahaby, Al-Ahmmady, S.; Sanad, S M.K.; Roushdy, H M

    1986-01-01

    Histochemical changes in the glycogen and lipid contents of the rat liver cells were studied at different intervals following whole body gamma-irradiation at the exposure dose level of 600 rads. The glycogen and lipid contents were significantly altered, the changes were time-dependent.

  6. Dysfunctional Muscle and Liver Glycogen Metabolism in mdx Dystrophic Mice

    Science.gov (United States)

    Stapleton, David I.; Lau, Xianzhong; Flores, Marcelo; Trieu, Jennifer; Gehrig, Stefan M.; Chee, Annabel; Naim, Timur; Lynch, Gordon S.; Koopman, René

    2014-01-01

    Background Duchenne muscular dystrophy (DMD) is a severe, genetic muscle wasting disorder characterised by progressive muscle weakness. DMD is caused by mutations in the dystrophin (dmd) gene resulting in very low levels or a complete absence of the dystrophin protein, a key structural element of muscle fibres which is responsible for the proper transmission of force. In the absence of dystrophin, muscle fibres become damaged easily during contraction resulting in their degeneration. DMD patients and mdx mice (an animal model of DMD) exhibit altered metabolic disturbances that cannot be attributed to the loss of dystrophin directly. We tested the hypothesis that glycogen metabolism is defective in mdx dystrophic mice. Results Dystrophic mdx mice had increased skeletal muscle glycogen (79%, (Pglycogen synthesis is initiated by glycogenin, the expression of which was increased by 50% in mdx mice (PGlycogen synthase activity was 12% higher (Pglycogen branching enzyme activity was 70% lower (Pglycogen breakdown, glycogen phosphorylase, had 62% lower activity (Pglycogen debranching enzyme expression was 50% higher (Pglycogen (Pglycogen metabolism in mdx mice identified reduced glycogenin protein expression (46% less; Pglycogen but reduced amounts of liver glycogen. PMID:24626262

  7. Patterns of glycogen turnover in liver characterized by computer modeling

    International Nuclear Information System (INIS)

    Youn, J.H.; Bergman, R.N.

    1987-01-01

    The authors used a computer model of liver glycogen turnover to reexamine the data of Devos and Hers, who reported the time course of accumulation in and loss from glycogen of label originating in [1- 14 C]galactose injected at different times after the start of refeeding of 40-h fasted mice or rats. In the present study computer representation of individual glycogen molecules was utilized to account for growth and degradation of glycogen according to specific hypothetical patterns. Using this model they could predict the accumulation and localization within glycogen of labeled glucose residues and compare the predictions with the previously published data. They considered three specific hypotheses of glycogen accumulation during refeeding: (1) simultaneous, (2) sequential, and (3) accelerating growth. Hypothetical patterns of glycogen degradation were (1) ordered and (2) random degradation. The pattern of glycogen synthesis consistent with experimental data was a steadily increasing number of growing glycogen molecules, whereas during degradation glycogen molecules are exposed to degrading enzymes randomly, rather than in a specific reverse order of synthesis. These patterns predict the existence of a specific mechanism for the steadily increasing seeding of new glycogen molecules during synthesis

  8. Muscle and liver glycogen, protein, and triglyceride in the rat

    DEFF Research Database (Denmark)

    Richter, Erik; Sonne, Bente; Joensen Mikines, Kari

    1984-01-01

    in skeletal muscle was accompanied by increased breakdown of triglyceride and/or protein. Thus, the effect of exhausting swimming and of running on concentrations of glycogen, protein, and triglyceride in skeletal muscle and liver were studied in rats with and without deficiencies of the sympatho......-adrenal system. In control rats, both swimming and running decreased the concentration of glycogen in fast-twitch red and slow-twitch red muscle whereas concentrations of protein and triglyceride did not decrease. In the liver, swimming depleted glycogen stores but protein and triglyceride concentrations did...... not decrease. In exercising rats, muscle glycogen breakdown was impaired by adrenodemedullation and restored by infusion of epinephrine. However, impaired glycogen breakdown during exercise was not accompanied by a significant net breakdown of protein or triglyceride. Surgical sympathectomy of the muscles did...

  9. Diurnal variation in glycogen phosphorylase activity in rat liver. A quantitative histochemical study

    NARCIS (Netherlands)

    Frederiks, W. M.; Marx, F.; Bosch, K. S.

    1987-01-01

    The diurnal variations of the glycogen content and of glycogen phosphorylase activity in periportal and pericentral areas of rat liver parenchyma have been analyzed in periodic acid Schiff (PAS)-stained cryostat sections using quantitative microdensitometry. Glycogen content and phosphorylase

  10. Serum glucose and liver glycogen in gamma irradiated rats

    International Nuclear Information System (INIS)

    Ahlersova, E.; Ahlers, I.; Molcanova, A.

    1988-01-01

    Overnight fasted male rats of Wistar strain were irradiated with single whole-body doses of 4.78-7.17-9.57 and 14.35 Gy of gamma rays. After decapitation at intervals 1-28 d (4.78 and 7.17 Gy), 1-7 d (9.57 Gy) and 1-3 d (14.35 Gy) glucose concentration in serum and glycogen concentration in liver of irradiated and non-irradiated animals were determined. The higher was radiation dose the more expressive extent and depth of changes (hyperglycemia, accumulation of glycogen) occured. Blood glucose and liver glycogen may serve as a reliable and dose-dependent biological indicators of metabolic changes in irradiated rats. (author)

  11. Examination of liver and muscle glycogen and blood glucose levels ...

    African Journals Online (AJOL)

    Administrator

    2011-09-05

    Sep 5, 2011 ... changes in fish affect the conversion of liver glycogen into blood ... province, altitude 1248 m and surface area of 86 km2, 20 km in length 4.5 km in width ... alcohol (95% pure) were added, followed by boiling for a further 15 min. ..... water temperature on the blood glucose level of chub (Leuciscus cephalus ...

  12. Starch Binding Domain-containing Protein 1 Plays a Dominant Role in Glycogen Transport to Lysosomes in Liver.

    Science.gov (United States)

    Sun, Tao; Yi, Haiqing; Yang, Chunyu; Kishnani, Priya S; Sun, Baodong

    2016-08-05

    A small portion of cellular glycogen is transported to and degraded in lysosomes by acid α-glucosidase (GAA) in mammals, but it is unclear why and how glycogen is transported to the lysosomes. Stbd1 has recently been proposed to participate in glycogen trafficking to lysosomes. However, our previous study demonstrated that knockdown of Stbd1 in GAA knock-out mice did not alter lysosomal glycogen storage in skeletal muscles. To further determine whether Stbd1 participates in glycogen transport to lysosomes, we generated GAA/Stbd1 double knock-out mice. In fasted double knock-out mice, glycogen accumulation in skeletal and cardiac muscles was not affected, but glycogen content in liver was reduced by nearly 73% at 3 months of age and by 60% at 13 months as compared with GAA knock-out mice, indicating that the transport of glycogen to lysosomes was suppressed in liver by the loss of Stbd1. Exogenous expression of human Stbd1 in double knock-out mice restored the liver lysosomal glycogen content to the level of GAA knock-out mice, as did a mutant lacking the Atg8 family interacting motif (AIM) and another mutant that contains only the N-terminal 24 hydrophobic segment and the C-terminal starch binding domain (CBM20) interlinked by an HA tag. Our results demonstrate that Stbd1 plays a dominant role in glycogen transport to lysosomes in liver and that the N-terminal transmembrane region and the C-terminal CBM20 domain are critical for this function. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Liver glycogen reduces food intake and attenuates obesity in a high-fat diet-fed mouse model.

    Science.gov (United States)

    López-Soldado, Iliana; Zafra, Delia; Duran, Jordi; Adrover, Anna; Calbó, Joaquim; Guinovart, Joan J

    2015-03-01

    We generated mice that overexpress protein targeting to glycogen (PTG) in the liver (PTG(OE)), which results in an increase in liver glycogen. When fed a high-fat diet (HFD), these animals reduced their food intake. The resulting effect was a lower body weight, decreased fat mass, and reduced leptin levels. Furthermore, PTG overexpression reversed the glucose intolerance and hyperinsulinemia caused by the HFD and protected against HFD-induced hepatic steatosis. Of note, when fed an HFD, PTG(OE) mice did not show the decrease in hepatic ATP content observed in control animals and had lower expression of neuropeptide Y and higher expression of proopiomelanocortin in the hypothalamus. Additionally, after an overnight fast, PTG(OE) animals presented high liver glycogen content, lower liver triacylglycerol content, and lower serum concentrations of fatty acids and β-hydroxybutyrate than control mice, regardless of whether they were fed an HFD or a standard diet. In conclusion, liver glycogen accumulation caused a reduced food intake, protected against the deleterious effects of an HFD, and diminished the metabolic impact of fasting. Therefore, we propose that hepatic glycogen content be considered a potential target for the pharmacological manipulation of diabetes and obesity. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  14. Salinity Effects on Strategies of Glycogen Utilization in Livers of Euryhaline Milkfish (Chanos chanos under Hypothermal Stress

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    Chia-Hao Chang

    2018-02-01

    Full Text Available The fluctuation of temperature affects many physiological responses in ectothermic organisms, including feed intake, growth, reproduction, and behavior. Changes in environmental temperatures affect the acquisition of energy, whereas hepatic glycogen plays a central role in energy supply for the homeostasis of the entire body. Glycogen phosphorylase (GP, which catalyzes the rate-limiting step in glycogenolysis, is also an indicator of environmental stress. Here, we examined the effects of salinity on glycogen metabolism in milkfish livers under cold stress. A reduction of feed intake was observed in both freshwater (FW and seawater (SW milkfish under cold adaptation. At normal temperature (28°C, compared to the FW milkfish, the SW milkfish exhibited greater mRNA abundance of the liver isoform of GP (Ccpygl, higher GP activity, and less glycogen content in the livers. Upon hypothermal (18°C stress, hepatic Ccpygl mRNA expression of FW milkfish surged at 3 h, declined at 6 and 12 h, increased again at 24 h, and increased significantly after 96 h. Increases in GP protein, GP activity, and the phosphorylation state and the breakdown of glycogen were also found in FW milkfish livers after 12 h of exposure at 18°C. Conversely, the Ccpygl transcript levels in SW milkfish were downregulated after 1 h of exposure at 18°C, whereas the protein abundance of GP, GP activity, and glycogen content were not significantly altered. Taken together, under 18°C cold stress, FW milkfish exhibited an acute response with the breakdown of hepatic glycogen for maintaining energy homeostasis of the entire body, whereas no change was observed in the hepatic glycogen content and GP activity of SW milkfish because of their greater tolerance to cold conditions.

  15. Acid hydrolysis and molecular density of phytoglycogen and liver glycogen helps understand the bonding in glycogen α (composite particles.

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    Prudence O Powell

    Full Text Available Phytoglycogen (from certain mutant plants and animal glycogen are highly branched glucose polymers with similarities in structural features and molecular size range. Both appear to form composite α particles from smaller β particles. The molecular size distribution of liver glycogen is bimodal, with distinct α and β components, while that of phytoglycogen is monomodal. This study aims to enhance our understanding of the nature of the link between liver-glycogen β particles resulting in the formation of large α particles. It examines the time evolution of the size distribution of these molecules during acid hydrolysis, and the size dependence of the molecular density of both glucans. The monomodal distribution of phytoglycogen decreases uniformly in time with hydrolysis, while with glycogen, the large particles degrade significantly more quickly. The size dependence of the molecular density shows qualitatively different shapes for these two types of molecules. The data, combined with a quantitative model for the evolution of the distribution during degradation, suggest that the bonding between β into α particles is different between phytoglycogen and liver glycogen, with the formation of a glycosidic linkage for phytoglycogen and a covalent or strong non-covalent linkage, most probably involving a protein, for glycogen as most likely. This finding is of importance for diabetes, where α-particle structure is impaired.

  16. Acid Hydrolysis and Molecular Density of Phytoglycogen and Liver Glycogen Helps Understand the Bonding in Glycogen α (Composite) Particles

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    Powell, Prudence O.; Sullivan, Mitchell A.; Sheehy, Joshua J.; Schulz, Benjamin L.; Warren, Frederick J.; Gilbert, Robert G.

    2015-01-01

    Phytoglycogen (from certain mutant plants) and animal glycogen are highly branched glucose polymers with similarities in structural features and molecular size range. Both appear to form composite α particles from smaller β particles. The molecular size distribution of liver glycogen is bimodal, with distinct α and β components, while that of phytoglycogen is monomodal. This study aims to enhance our understanding of the nature of the link between liver-glycogen β particles resulting in the formation of large α particles. It examines the time evolution of the size distribution of these molecules during acid hydrolysis, and the size dependence of the molecular density of both glucans. The monomodal distribution of phytoglycogen decreases uniformly in time with hydrolysis, while with glycogen, the large particles degrade significantly more quickly. The size dependence of the molecular density shows qualitatively different shapes for these two types of molecules. The data, combined with a quantitative model for the evolution of the distribution during degradation, suggest that the bonding between β into α particles is different between phytoglycogen and liver glycogen, with the formation of a glycosidic linkage for phytoglycogen and a covalent or strong non-covalent linkage, most probably involving a protein, for glycogen as most likely. This finding is of importance for diabetes, where α-particle structure is impaired. PMID:25799321

  17. Characterization of the growth and degradation of glycogen in the liver

    International Nuclear Information System (INIS)

    Youn, J.; Bergman, R.

    1986-01-01

    The patterns of the growth and degradation of hepatic glycogen were studied using a computer model. The database was that of Devos and Hers on the distribution of label in glycogen from [1- 14 C] galactose injected at different times after the start of refeeding 40 h fasted mice. The data was simulated to examine the following hypotheses (H): Glycogen Synthesis H.S1: all glycogen molecules grow simultaneously. H.S2: at each moment of synthesis only a fixed number of molecules grow. H.S3: the number of growing molecules increases linearly with respect to time. H.S4: increase in the number of growing molecules is accelerated as glycogen is synthesized. Glycogen Degradation H.D1: glycogen molecules to be attacked by degrading enzymes are randomly chosen. H.D2: glycogen molecules are degraded sequentially in the reverse order of synthesis. H.D3: glycogen molecules have different probabilities of degradation depending upon the time of synthesis. The growth and degradation according to hypotheses S4 and D3, respectively, could best account for the data. The modelling study predicts that, at the beginning of refeeding, only a small number of molecules grow. But, as glycogen is synthesized, the rate of seeding of new glycogen molecules increases with time, causing a nonlinear proliferation of the number of growing molecules. During degradation glycogen molecules synthesized later have a greater chance to be degraded first, a characteristic which may be explained by the rosette structure of liver glycogen

  18. Ursolic acid and luteolin-7-glucoside improve lipid profiles and increase liver glycogen content through glycogen synthase kinase-3.

    Science.gov (United States)

    Azevedo, Marisa F; Camsari, Cagri; Sá, Carla M; Lima, Cristovao F; Fernandes-Ferreira, Manuel; Pereira-Wilson, Cristina

    2010-06-01

    In the present study, two phytochemicals - ursolic acid (UA) and luteolin-7-glucoside (L7G) - were assessed in vivo in healthy rats regarding effects on plasma glucose and lipid profile (total cholesterol, HDL and LDL), as well as liver glycogen content, in view of their importance in the aetiology of diabetes and associated complications. Both UA and L7G significantly decreased plasma glucose concentration. UA also significantly increased liver glycogen levels accompanied by phosphorylation of glycogen synthase kinase-3 (GSK3). The increase in glycogen deposition induced by UA (mediated by GSK3) could have contributed to the lower plasma glucose levels observed. Both compounds significantly lowered total plasma cholesterol and low-density lipoprotein levels, and, in addition, UA increased plasma high-density lipoprotein levels. Our results show that UA particularly may be useful in preventable strategies for people at risk of developing diabetes and associated cardiovascular complications by improving plasma glucose levels and lipid profile, as well as by promoting liver glycogen deposition.

  19. Effect of D-tagatose on liver weight and glycogen content of rats.

    Science.gov (United States)

    Bär, A; Lina, B A; de Groot, D M; de Bie, B; Appel, M J

    1999-04-01

    D-tagatose is an incompletely absorbed ketohexose (stereoisomer of D-fructose) which has potential as an energy-reduced alternative sweetener. In an earlier 90-day toxicity study, rats fed diets with 10, 15 and 20% D-tagatose exhibited increased liver weights, but no histopathological alterations. To determine whether there might be any toxicological relevance to this effect, three studies were conducted in male, adult Sprague-Dawley rats. In the first study, four groups received Purina diet (group A), Purina diet with 20% D-tagatose (group B), SDS diet (group C), or SDS diet with 20% D-tagatose (group D). For groups A and B, the 28-day treatment period was followed by a 14-day recovery period (Purina diet). Food remained available to all animals until the time of sacrifice. Groups of 10 rats were killed on days 14 (groups A and B), 28 (groups A-D), and 42 (groups A and B). Body weights, as well as weights of wet and lyophilized livers, were determined. The lyophilized livers collected on day 28 from groups A and B were analyzed for protein, total lipid, glycogen, DNA, and residual moisture. By day 14, relative wet liver weights had increased by 23% in group B. On day 28, the increase was 38% in group B and 44% in group D. At the end of the recovery period, the increase had diminished to 14% in group B. On day 28, liver glycogen content (in %) was significantly increased, and liver protein, lipid, and DNA contents were significantly decreased in group B compared to group A. Total amounts per liver of protein, total lipid, glycogen, and DNA were significantly increased. In the second study, four groups of 20 rats each received SDS diet with 0, 5, 10, and 20% D-tagatose for 29-31 days. The food was available until the time of sacrifice. At termination, plasma was obtained from 10 rats/group for clinicochemical analyses. Five rats/group were subjected to whole-body perfusion, followed by processing of livers for qualitative and quantitative electron microscopic

  20. Quantification of the glycogen cascade system: the ultrasensitive responses of liver glycogen synthase and muscle phosphorylase are due to distinctive regulatory designs

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    Venkatesh KV

    2005-05-01

    Full Text Available Abstract Background Signaling pathways include intricate networks of reversible covalent modification cycles. Such multicyclic enzyme cascades amplify the input stimulus, cause integration of multiple signals and exhibit sensitive output responses. Regulation of glycogen synthase and phosphorylase by reversible covalent modification cycles exemplifies signal transduction by enzyme cascades. Although this system for regulating glycogen synthesis and breakdown appears similar in all tissues, subtle differences have been identified. For example, phosphatase-1, a dephosphorylating enzyme of the system, is regulated quite differently in muscle and liver. Do these small differences in regulatory architecture affect the overall performance of the glycogen cascade in a specific tissue? We address this question by analyzing the regulatory structure of the glycogen cascade system in liver and muscle cells at steady state. Results The glycogen cascade system in liver and muscle cells was analyzed at steady state and the results were compared with literature data. We found that the cascade system exhibits highly sensitive switch-like responses to changes in cyclic AMP concentration and the outputs are surprisingly different in the two tissues. In muscle, glycogen phosphorylase is more sensitive than glycogen synthase to cyclic AMP, while the opposite is observed in liver. Furthermore, when the liver undergoes a transition from starved to fed-state, the futile cycle of simultaneous glycogen synthesis and degradation switches to reciprocal regulation. Under such a transition, different proportions of active glycogen synthase and phosphorylase can coexist due to the varying inhibition of glycogen-synthase phosphatase by active phosphorylase. Conclusion The highly sensitive responses of glycogen synthase in liver and phosphorylase in muscle to primary stimuli can be attributed to distinctive regulatory designs in the glycogen cascade system. The different

  1. Variations in Glycogen Synthesis in Human Pluripotent Stem Cells with Altered Pluripotent States

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    Chen, Richard J.; Zhang, Guofeng; Garfield, Susan H.; Shi, Yi-Jun; Chen, Kevin G.; Robey, Pamela G.; Leapman, Richard D.

    2015-01-01

    Human pluripotent stem cells (hPSCs) represent very promising resources for cell-based regenerative medicine. It is essential to determine the biological implications of some fundamental physiological processes (such as glycogen metabolism) in these stem cells. In this report, we employ electron, immunofluorescence microscopy, and biochemical methods to study glycogen synthesis in hPSCs. Our results indicate that there is a high level of glycogen synthesis (0.28 to 0.62 μg/μg proteins) in undifferentiated human embryonic stem cells (hESCs) compared with the glycogen levels (0 to 0.25 μg/μg proteins) reported in human cancer cell lines. Moreover, we found that glycogen synthesis was regulated by bone morphogenetic protein 4 (BMP-4) and the glycogen synthase kinase 3 (GSK-3) pathway. Our observation of glycogen bodies and sustained expression of the pluripotent factor Oct-4 mediated by the potent GSK-3 inhibitor CHIR-99021 reveals an altered pluripotent state in hPSC culture. We further confirmed glycogen variations under different naïve pluripotent cell growth conditions based on the addition of the GSK-3 inhibitor BIO. Our data suggest that primed hPSCs treated with naïve growth conditions acquire altered pluripotent states, similar to those naïve-like hPSCs, with increased glycogen synthesis. Furthermore, we found that suppression of phosphorylated glycogen synthase was an underlying mechanism responsible for altered glycogen synthesis. Thus, our novel findings regarding the dynamic changes in glycogen metabolism provide new markers to assess the energetic and various pluripotent states in hPSCs. The components of glycogen metabolic pathways offer new assays to delineate previously unrecognized properties of hPSCs under different growth conditions. PMID:26565809

  2. Liver glycogen in type 2 diabetic mice is randomly branched as enlarged aggregates with blunted glucose release.

    Science.gov (United States)

    Besford, Quinn Alexander; Zeng, Xiao-Yi; Ye, Ji-Ming; Gray-Weale, Angus

    2016-02-01

    Glycogen is a vital highly branched polymer of glucose that is essential for blood glucose homeostasis. In this article, the structure of liver glycogen from mice is investigated with respect to size distributions, degradation kinetics, and branching structure, complemented by a comparison of normal and diabetic liver glycogen. This is done to screen for differences that may result from disease. Glycogen α-particle (diameter ∼ 150 nm) and β-particle (diameter ∼ 25 nm) size distributions are reported, along with in vitro γ-amylase degradation experiments, and a small angle X-ray scattering analysis of mouse β-particles. Type 2 diabetic liver glycogen upon extraction was found to be present as large loosely bound, aggregates, not present in normal livers. Liver glycogen was found to aggregate in vitro over a period of 20 h, and particle size is shown to be related to rate of glucose release, allowing a structure-function relationship to be inferred for the tissue specific distribution of particle types. Application of branching theories to small angle X-ray scattering data for mouse β-particles revealed these particles to be randomly branched polymers, not fractal polymers. Together, this article shows that type 2 diabetic liver glycogen is present as large aggregates in mice, which may contribute to the inflexibility of interconversion between glucose and glycogen in type 2 diabetes, and further that glycogen particles are randomly branched with a size that is related to the rate of glucose release.

  3. Glycogen synthesis in liver and skeletal muscle after exercise: participation of the gluconeogenic pathway

    International Nuclear Information System (INIS)

    Johnson, J.L.

    1986-01-01

    Hepatic glycogenesis occurs by both the uptake of plasma glucose (direct pathway) as well as from gluconeogenesis (indirect pathway). In vitro studies suggest that skeletal muscle can also synthesize glycogen from lactate. The purpose of the present studies was to assess the contribution of the indirect pathway to liver and muscle glycogen synthesis after exercise with various substrata infusions. The authors hypothesis was the contribution of the indirect pathway of hepatic glycogenesis would increase after exercise. To this end, fasted rats were depleted of glycogen by exhaustive exercise; a second group of fasted rats remained rested. Both groups were then infused intravenously with glucose containing tracer quantities of [6- 3 H] and [U- 14 C] glucose for 4 hrs. The ensuing hyperglycemic response was exaggerated in post-exercised rats; whereas, plasma lactate levels were lower than those of nonexercised rats. The percent of hepatic glycogen synthesized from gluconeogenic precursors did not differ between exercised (39%) and nonexercised (36%) rats

  4. Monitoring of liver glycogen synthesis in diabetic patients using carbon-13 MR spectroscopy

    International Nuclear Information System (INIS)

    Tomiyasu, Moyoko; Obata, Takayuki; Nishi, Yukio; Nakamoto, Hiromitsu; Nonaka, Hiroi; Takayama, Yukihisa; Autio, Joonas; Ikehira, Hiroo; Kanno, Iwao

    2010-01-01

    To investigate the relationship between liver glucose, glycogen, and plasma glucose in diabetic patients, in vivo liver carbon-13 magnetic resonance spectroscopy ( 13 C MRS) with a clinical 3.0 T MR system was performed. Subjects were healthy male volunteers (n = 5) and male type-2 diabetic patients (n = 5). Pre- and during oral glucose tolerance tests (OGTT), 13 C MR spectra without proton decoupling were acquired in a monitoring period of over 6 h, and in total seven spectra were obtained from each subject. For OGTT, 75 g of glucose, including 5 g of [1- 13 C]glucose, was administered. The MR signals of liver [1- 13 C]glucose and glycogen were detected and their time-course changes were assessed in comparison with the plasma data obtained at screening. The correlations between the fasting plasma glucose level and liver glycogen/glucose rate (Spearman: ρ = -0.68, p 13 C MRS can perform noninvasive measurement of glycogen storage/degradation ability in the liver individually and can assist in tailor-made therapy for diabetes. In conclusion, 13 C MRS has a potential to become a powerful tool in diagnosing diabetes multilaterally.

  5. Review: Alterations in placental glycogen deposition in complicated pregnancies: Current preclinical and clinical evidence.

    Science.gov (United States)

    Akison, Lisa K; Nitert, Marloes Dekker; Clifton, Vicki L; Moritz, Karen M; Simmons, David G

    2017-06-01

    Normal placental function is essential for optimal fetal growth. Transport of glucose from mother to fetus is critical for fetal nutrient demands and can be stored in the placenta as glycogen. However, the function of this glycogen deposition remains a matter of debate: It could be a source of fuel for the placenta itself or a storage reservoir for later use by the fetus in times of need. While the significance of placental glycogen remains elusive, mounting evidence indicates that altered glycogen metabolism and/or deposition accompanies many pregnancy complications that adversely affect fetal development. This review will summarize histological, biochemical and molecular evidence that glycogen accumulates in a) placentas from a variety of experimental rodent models of perturbed pregnancy, including maternal alcohol exposure, glucocorticoid exposure, dietary deficiencies and hypoxia and b) placentas from human pregnancies with complications including preeclampsia, gestational diabetes mellitus and intrauterine growth restriction (IUGR). These pregnancies typically result in altered fetal growth, developmental abnormalities and/or disease outcomes in offspring. Collectively, this evidence suggests that changes in placental glycogen deposition is a common feature of pregnancy complications, particularly those associated with altered fetal growth. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  6. Glycogen content in hepatocytes is related with their size in normal rat liver but not in cirrhotic one.

    Science.gov (United States)

    Bezborodkina, Natalia N; Chestnova, Anna Yu; Vorobev, Mikhail L; Kudryavtsev, Boris N

    2016-04-01

    Hepatocytes differ from one another by the degree of the ploidy, size, position in the liver lobule, and level of the DNA-synthetic processes. It is believed, that the cell size exerts substantial influence on the metabolism of the hepatocytes and the glycogen content in them. The aim of the present study was to test this hypothesis. Dry weight of hepatocytes, their ploidy and glycogen content were determined in the normal and the cirrhotic rat liver. Liver cirrhosis in rats was produced by chronic inhalation of CCl4 vapours in the course of 6 months. A combined cytophotometric method was used. Dry weight of the cell, its glycogen and DNA content were successively measured on a mapped preparation. Hepatocytes of each ploidy class in the normal and the cirrhotic rat liver accumulated glycogen at the same rate. In the normal liver, there was a distinct correlation between the size of hepatocytes and glycogen content in them. This correlation was observed in each ploidy class, and was especially pronounced in the class of mononucleate tetraploid hepatocytes. In the cirrhotic liver, there was no correlation between the size of the cells and their glycogen content. The impairment of liver lobular structure probably explains the observed lack of correlation between hepatocyte size and their glycogen content in the cirrhotic liver. © 2016 International Society for Advancement of Cytometry. © 2016 International Society for Advancement of Cytometry.

  7. Posthemorrhage glycogen and lactate metabolism in the liver: an experimental study with postprandial rats

    International Nuclear Information System (INIS)

    Boija, P.O.; Nylander, G.; Suhaili, A.; Ware, J.

    1988-01-01

    Glycogen and lactate metabolism was studied in livers from three groups of postprandial rats sustaining 70 mm Hg hemorrhagic hypotension for variable periods, 60 min (60H group), 120 min (120H group), and nonbled controls. The donor livers were investigated after completed hemorrhage using an in vitro perfusion system with L-lactate as substrate, together with U- 14 C-lactate. The residual glycogen stores were determined after perfusions. The incorporation of labelled lactate to glucose was increased in the 120H group by 66.7% and 116.8% compared to the 60H group and controls (p less than 0.01), but glycogenolysis was still the main source of glucose released in the 120H group. Glycogen formation from labelled lactate was 46.6% higher in the 120H group compared to controls (p less than 0.05) and lactate oxidation was decreased by 67.5% (p less than 0.05). The data suggest that hepatocytes are capable of rapid change from glycolysis to gluconeogenesis during hemorrhagic hypovolemia. However, energy-sparing glycogen breakdown is given priority over gluconeogenesis as long as glycogen remains available

  8. Fructose effect to enhance liver glycogen deposition is due to inhibition of glycogenolysis

    International Nuclear Information System (INIS)

    Youn, J.; Kaslow, H.; Bergman, R.

    1987-01-01

    The effect of fructose on glycogen degradation was examined by measuring flux of [ 14 C] from prelabeled glycogen in perfused rat livers. During 2 h refeeding of fasted rats hepatic glycogen was labeled by injection of [U 14 C] galactose (0.1 mg and 0.02 μCi/g of body weight). Refed livers were perfused for 30 min with glucose only (10 mM) and for 60 min with glucose (10 mM) without (n=5) or with fructose (1, 2, 10 mM; n=5 for each). With fructose, label production immediately declined and remained suppressed through the end of perfusion (P < 0.05). Suppression was dose-dependent: steady state label production was suppressed 45, 64, and 72% by 1, 2, and 10 mM fructose (P < 0.0001), without significant changes in glycogen synthase or phosphorylase. These results suggest the existence of allosteric inhibition of phosphorylase in the presence of fructose. Fructose 1-phosphate (F1P) accumulated in proportion to fructose (0.11 +/- 0.01 without fructose, 0.86 +/- 0.03, 1.81 +/- 0.18, and 8.23 +/- 0.6 μmoles/g of liver with 1, 2, and 10 mM fructose. Maximum inhibition of phosphorylase was 82%; FIP concentration for half inhibition was 0.57 μmoles/g of liver, well within the concentration of F1P attained in refeeding. Fructose enhances net glycogen synthesis in liver by suppressing glycogenolysis and the suppression is presumably caused by allosteric inhibition of phosphorylase by F1P

  9. Changes in liver glycogen reserve in Wistar rats as a result of polysaccharide treatment and single sublethal gamma-irradiation

    International Nuclear Information System (INIS)

    Metodiev, S.; Lambov, V.; Pavlova, N.

    1993-01-01

    The phase changes in the quantity of liver glycogen after single sublethal irradiation are investigated. The lowest concentration levels are registered at days 1, 3, 8 and 13 post irradiation. The effect of polysaccharide radioresistance modulation on the liver glycogen concentration is evaluated. The subcutaneous polysaccharide application of the immuno-active product PL prevents the sharp decrease of the liver glycogen concentration level, as a result of radiation provoked damages. The polysaccharide protection is most effective 5 - 21 days after irradiation. The conclusions are based on enzymic and hystomorphological studies. (author)

  10. Lack of liver glycogen causes hepatic insulin resistance and steatosis in mice.

    Science.gov (United States)

    Irimia, Jose M; Meyer, Catalina M; Segvich, Dyann M; Surendran, Sneha; DePaoli-Roach, Anna A; Morral, Nuria; Roach, Peter J

    2017-06-23

    Disruption of the Gys2 gene encoding the liver isoform of glycogen synthase generates a mouse strain (LGSKO) that almost completely lacks hepatic glycogen, has impaired glucose disposal, and is pre-disposed to entering the fasted state. This study investigated how the lack of liver glycogen increases fat accumulation and the development of liver insulin resistance. Insulin signaling in LGSKO mice was reduced in liver, but not muscle, suggesting an organ-specific defect. Phosphorylation of components of the hepatic insulin-signaling pathway, namely IRS1, Akt, and GSK3, was decreased in LGSKO mice. Moreover, insulin stimulation of their phosphorylation was significantly suppressed, both temporally and in an insulin dose response. Phosphorylation of the insulin-regulated transcription factor FoxO1 was somewhat reduced and insulin treatment did not elicit normal translocation of FoxO1 out of the nucleus. Fat overaccumulated in LGSKO livers, showing an aberrant distribution in the acinus, an increase not explained by a reduction in hepatic triglyceride export. Rather, when administered orally to fasted mice, glucose was directed toward hepatic lipogenesis as judged by the activity, protein levels, and expression of several fatty acid synthesis genes, namely, acetyl-CoA carboxylase, fatty acid synthase, SREBP1c, chREBP, glucokinase, and pyruvate kinase. Furthermore, using cultured primary hepatocytes, we found that lipogenesis was increased by 40% in LGSKO cells compared with controls. Of note, the hepatic insulin resistance was not associated with increased levels of pro-inflammatory markers. Our results suggest that loss of liver glycogen synthesis diverts glucose toward fat synthesis, correlating with impaired hepatic insulin signaling and glucose disposal. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Insights into Brain Glycogen Metabolism

    Science.gov (United States)

    Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-01-01

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

  12. Glycogen metabolism in the liver of Indian desert gerbils (Meriones hurrianae, Jerdon) exposed to internal beta irradiation

    International Nuclear Information System (INIS)

    Gupta, N.K.

    1996-01-01

    Glycogen content and the activities of phosphorylase, glycogen synthetase, phosphohexose isomerase, glucose-6-phosphatase, succinate dehydrogenase, alanine and aspartate aminotransferases have been biochemically determined in the liver of Indian desert gerbils following radiocalcium internal irradiation. Decline in glycogen, phosphohexose isomerase, with a concomitant increase in phosphorylase, succinate dehydrogenase reveals a switch over from glycolytic to oxidative metabolism in liver. Activities of aminotransferases indicate the utilization of transamination products of alanine and aspartate in oxidative pathway during early periods. Transiently increased glucose-6-phosphatase seems to restrict glycogenolytic and glycolytic metabolism and thereby pave way for the acceleration of oxidative metabolism. (author). 52 refs., 2 tabs

  13. CHEMICAL CHARACTERIZATION OF A HYPOGLYCEMIC EXTRACT FROM CUCURBITA FICIFOLIA BOUCHE THAT INDUCES LIVER GLYCOGEN ACCUMULATION IN DIABETIC MICE.

    Science.gov (United States)

    Jessica, Garcia Gonzalez; Mario, Garcia Lorenzana; Alejandro, Zamilpa; Cesar, Almanza Perez Julio; Ivan, Jasso Villagomez E; Ruben, Roman Ramos; Javier, Alarcon-Aguilar Francisco

    2017-01-01

    The aqueous extract of Cucurbita ficifolia ( C. ficifolia ) fruit has demonstrated hypoglycemic effect, which may be attributed to some components in the extract. However, the major secondary metabolites in this fruit have not yet been identified and little is known about its extra-pancreatic action, in particular, on liver carbohydrate metabolism. Therefore, in addition to the isolation and structural elucidation of the principal components in the aqueous extract of C. ficifolia , the aim of this study was to determine whether or not the hypoglycemic effect of the aqueous extract of Cucurbita ficifolia ( C. ficifolia ) fruit is due to accumulation of liver glycogen in diabetic mice. The aqueous extract from fruit of C. ficifolia was fractionated and its main secondary metabolites were purified and chemically characterized (NMR and GC-MS). Alloxan-induced diabetic mice received daily by gavage the aqueous extract (30 days). The liver glycogen content was quantified by spectroscopic method and by PAS stain; ALT and AST by spectrometric method; glycogen synthase, glycogen phosphorylase and GLUT2 by Western blot; the mRNA expression of GLUT2 and glucagon-receptor by RT-PCR; while serum insulin was quantified by ELISA method. A liver histological analysis was also performed by H&E stain. Chemical fingerprint showed five majoritarian compounds in the aqueous extract of C. ficifolia : p -coumaric acid, p-hydroxybenzoic acid, salicin, stigmast-7,2,2-dien-3-ol and stigmast-7-en-3-ol. The histological analysis showed accumulation of liver glycogen. Also, increased glycogen synthase and decreased glycogen phosphorylase were observed. Interestingly, the histological architecture evidenced a liver-protective effect due the extract. Five compounds were identified in C. ficifolia aqueous extract. The hypoglycemic effect of this extract may be partially explained by liver glycogen accumulation. The bioactive compound responsible for the hypoglycemic effect of this extract will be

  14. Histochemical Effects of “Verita WG” on Glycogen and Lipid Storage in Common Carp (Cyprinus carpio L. Liver

    Directory of Open Access Journals (Sweden)

    Elenka Georgieva

    2013-12-01

    Full Text Available We aimed in the present work is to study the effects of fosetyl-Al and fenamidone based fungicide (“Verita WG” on glycogen storage and expression of lipid droplets in common carp (Cyprinus carpio, L. liver. Concentrations of the test chemical were 30 mg/L, 38 mg/L and 50 mg/L under laboratory conditions. We used PAS-reaction for detection of glycogen storage and Sudan III staining for detection of lipid droplets in common carp hepatocytes. Hence, we found that the amount of glycogen and the fat storage in the liver increased proportionally with the increased fungicide concentrations. We also found conglomerates of accumulated glycogen in certain hepatocytes at all used concentrations. Overall, the results demonstrated enhanced glyconeogenesis and fat accumulation in the common carp liver, exposed to the test chemical.

  15. Muscle and liver glycogen utilization during prolonged lift and carry exercise: male and female responses.

    Science.gov (United States)

    Price, Thomas B; Sanders, Kimberly

    2017-02-01

    This study examined the use of carbohydrates by men and women during lift/carry exercise. Effects of menstrual cycle variation were examined in women. Twenty-five subjects (15 M, 10 F) were studied; age 25 ± 2y M, 26 ± 3y F, weight 85 ± 3 kg* M, 63 ± 3 kg F, and height 181 ± 2 cm* M, 161 ± 2 cm F (* P  Glycogen utilization was tracked with natural abundance C-13 NMR of quadriceps femoris and biceps brachialis muscles, and in the liver at rest and throughout the exercise period. Males completed more of the 180 min protocol than females [166 ± 9 min M, 112 ± 16 min* F (L), 88 ± 16 min** F (F) (* P  = 0.0036, ** P  glycogen depletion was similar between sexes and within females in L/F phases [4.7 ± 0.8 mmol/L-h M, 4.5 ± 2.4 mmol/L-h F (L), 10.3 ± 3.5 mmol/L-h F (F)]. Biceps glycogen depletion was greater in females [2.7 ± 0.9 mmol/L-h M, 10.3 ± 1.3 mmol/L-h* F (L), 16.8 ± 4.8 mmol/L-h** F (F) (* P  = 0.0004, ** P  = 0.0122)]. Resting glycogen levels were higher in females during the follicular phase ( P  = 0.0077). Liver glycogen depletion increased during exercise, but was not significant. We conclude that with non-normalized lift/carry exercise: (1) Based on their smaller size, women are less capable of completing and work their upper body harder than men. (2) Women and men work their lower body at similar levels. (3) Women store more quadriceps carbohydrate during the follicular phase. (4) The liver is not significantly challenged by this protocol. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  16. Effect of intraperitoneal selenium administration on liver glycogen levels in rats subjected to acute forced swimming.

    Science.gov (United States)

    Akil, Mustafa; Bicer, Mursel; Kilic, Mehmet; Avunduk, Mustafa Cihat; Mogulkoc, Rasim; Baltaci, Abdulkerim Kasim

    2011-03-01

    There are a few of studies examining how selenium, which is known to reduce oxidative damage in exercise, influences glucose metabolism and exhaustion in physical activity. The present study aims to examine how selenium administration affects liver glycogen levels in rats subjected to acute swimming exercise. The study included 32 Sprague-Dawley type male rats, which were equally allocated to four groups: Group 1, general control; Group 2; selenium-supplemented control (6 mg/kg/day sodium selenite); Group 3, swimming control; Group 4, selenium-supplemented swimming (6 mg/kg/day sodium selenite). Liver tissue samples collected from the animals at the end of the study were fixed in 95% ethyl alcohol. From the tissue samples buried into paraffin, 5-µm cross-sections were obtained using a microtome, put on a microscope slide, and stained with PAS. Stained preparations were assessed using a Nikon Eclipse E400 light microscope. All images obtained with the light microscope were transferred to a PC and evaluated using Clemex PE 3.5 image analysis software. The highest liver glycogen levels were found in groups 1 and 2 (p swimming exercise can be restored by selenium administration. It can be argued that physiological doses of selenium administration can contribute to performance.

  17. Role of the direct and indirect pathways for glycogen synthesis in rat liver in the postprandial state

    International Nuclear Information System (INIS)

    Huang, M.T.; Veech, R.L.

    1988-01-01

    The pathway for hepatic glycogen synthesis in the postprandial state was studied in meal-fed rats chronically cannulated in the portal vein. Plasma glucose concentration in the portal vein was found to be 4.50 +/- 1.01 mM (mean +/- SE; n = 3) before a meal and 11.54 +/- 0.70 mM (mean +/- SE; n = 4) after a meal in rats meal-fed a diet consisting of 100% commercial rat chow for 7 d. The hepatic-portal difference of plasma glucose concentration showed that liver released glucose in the fasted state and either extracted or released glucose after feeding depending on plasma glucose concentration in the portal vein. The concentration of portal vein glucose at which liver changes from glucose releasing to glucose uptake was 8 mM, the Km of glucokinase. The rate of glycogen synthesis in liver during meal-feeding was found to be approximately 1 mumol glucosyl U/g wet wt/min in rats meal-fed a 50% glucose supplemented chow diet. The relative importance of the direct vs. indirect pathway for the replenishment of hepatic glycogen was determined by the incorporation of [3- 3 H,U- 14 C]glucose into liver glycogen. Labeled glucose was injected into the portal vein at the end of meal-feeding. The ratio of 3 H/ 14 C in the glucosyl units of glycogen was found to be 83-92% of the ratio in liver free glucose six minutes after the injection, indicating that the majority of exogenous glucose incorporated into glycogen did not go through glycolysis. The percent contribution of the direct versus indirect pathway was quantitated from the difference in the relative specific activity (RSA) of [ 3 H] and [ 14 C]-glycogen in rats infused with [3- 3 H,U- 14 C]glucose. No significant difference was found between the RSA of [ 3 H]glycogen and [ 14 C]glycogen, indicating further that the pathway for glycogen synthesis in liver from exogenous glucose is from the direct pathway

  18. Glucose phosphorylation is not rate limiting for accumulation of glycogen from glucose in perfused livers from fasted rats

    International Nuclear Information System (INIS)

    Youn, J.H.; Ader, M.; Bergman, R.N.

    1989-01-01

    Incorporation of Glc and Fru into glycogen was measured in perfused livers from 24-h fasted rats using [6-3H]Glc and [U-14C]Fru. For the initial 20 min, livers were perfused with low Glc (2 mM) to deplete hepatic glycogen and were perfused for the following 30 min with various combinations of Glc and Fru. With constant Fru (2 mM), increasing perfusate Glc increased the relative contribution of Glc carbons to glycogen (7.2 +/- 0.4, 34.9 +/- 2.8, and 59.1 +/- 2.7% at 2, 10, and 20 mM Glc, respectively; n = 5 for each). During perfusion with substrate levels seen during refeeding (10 mM Glc, 1.8 mumol/g/min gluconeogenic flux from 2 mM Fru), Fru provided 54.7 +/- 2.7% of the carbons for glycogen, while Glc provided only 34.9 +/- 2.8%, consistent with in vivo estimations. However, the estimated rate of Glc phosphorylation was at least 1.10 +/- 0.11 mumol/g/min, which exceeded by at least 4-fold the glycogen accumulation rate (0.28 +/- 0.04 mumol of glucose/g/min). The total rate of glucose 6-phosphate supply via Glc phosphorylation and gluconeogenesis (2.9 mumol/g/min) exceeded reported in vivo rates of glycogen accumulation during refeeding. Thus, in perfused livers of 24-h fasted rats there is an apparent redundancy in glucose 6-phosphate supply. These results suggest that the rate-limiting step for hepatic glycogen accumulation during refeeding is located between glucose 6-phosphate and glycogen, rather than at the step of Glc phosphorylation or in the gluconeogenic pathway

  19. Effect of oral D-tagatose on liver volume and hepatic glycogen accumulation in healthy male volunteers.

    Science.gov (United States)

    Boesch, C; Ith, M; Jung, B; Bruegger, K; Erban, S; Diamantis, I; Kreis, R; Bär, A

    2001-04-01

    Standard toxicity tests with high levels of D-tagatose showed a reversible enlargement of the liver in Sprague-Dawley rats without increase of liver enzymes. The present study tests the hypotheses that partial substitution of dietary sucrose by D-tagatose for 28 days increases the volume of human liver and the concentration of liver glycogen. Twelve healthy, male volunteers were studied in a double-blind crossover study with ingestion of D-tagatose (3x15 g daily) and placebo (sucrose, 3x15 g daily) for periods of 28 days each. Liver volume and glycogen concentration have been determined by magnetic resonance (MR) imaging and spectroscopy, which were accompanied by routine medical examinations. MR examinations before and after the treatments revealed no effects (P>0.05) of treatment, period, or subject for changes in liver volume or glycogen concentration. A steady increase of liver volumes, independent of the D-tagatose or placebo intake, has been observed over the study in parallel with a slight increase in body weight. The treatment with D-tagatose was not associated with clinically relevant changes of the examined clinico-chemical and hematological parameters, including liver enzymes and uric acid. Copyright 2001 Academic Press.

  20. Effect of irradiation with fast electrons on the uridindiphosphateglucose mechanism of glycogen synthesis in NKly tumours, spleen and liver of mice having tumours

    International Nuclear Information System (INIS)

    Goryukhina, T.A.; Misheneva, V.S.; Burova, T.M.; Seits, I.F.

    1976-01-01

    A marked and stable decrease in the glycogen content of the liver has been observed within the entire 96-hour period after a single exposure to fast electrons (1000 rads) of mice having NKly tumour. Tumour cells maintain a low glycogen level that is peculiar for them. Activity of enzymes (UDPG-pyrophosphorylase, phosphoglucomutase and UDPG-glycogensynthetase) considerably changes but, in most cases, there is no parallelism between the glycogen content and glycogensynthetase activity

  1. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887

    Science.gov (United States)

    Merrill, A. H. Jr; Hoel, M.; Wang, E.; Mullins, R. E.; Hargrove, J. L.; Jones, D. P.; Popova, I. A.; Merrill AH, J. r. (Principal Investigator)

    1990-01-01

    To determine the possible biochemical effects of prolonged weightlessness on liver function, samples of liver from rats that had flown aboard Cosmos 1887 were analyzed for protein, glycogen, and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. Among the parameters measured, the major differences were elevations in the glycogen content and hydroxymethylglutaryl-CoA (HMG-CoA) reductase activities for the rats flown on Cosmos 1887 and decreases in the amount of microsomal cytochrome P-450 and the activities of aniline hydroxylase and ethylmorphine N-demethylase, cytochrome P-450-dependent enzymes. These results support the earlier finding of differences in these parameters and suggest that altered hepatic function could be important during spaceflight and/or the postflight recovery period.

  2. Glycogenic hepatopathy is an under-recognised cause of hepatomegaly and elevated liver transaminases in type 1 diabetes mellitus.

    Science.gov (United States)

    Irani, N R; Venugopal, K; Kontorinis, N; Lee, M; Sinniah, R; Bates, T R

    2015-07-01

    Glycogenic hepatopathy (GH) is an under-recognised complication of type 1 diabetes mellitus (T1DM) not controlled to target resulting in hepatomegaly and elevated liver transaminases. We report the case of a 19-year-old man with T1DM not controlled to target who presented with abdominal pain, hepatomegaly and deranged liver transaminases. He was subsequently diagnosed with GH on liver biopsy, with the mainstay of treatment being reduction in caloric intake and insulin. © 2015 Royal Australasian College of Physicians.

  3. Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists.

    Science.gov (United States)

    Gonzalez, Javier T; Fuchs, Cas J; Smith, Fiona E; Thelwall, Pete E; Taylor, Roy; Stevenson, Emma J; Trenell, Michael I; Cermak, Naomi M; van Loon, Luc J C

    2015-12-15

    The purpose of this study was to define the effect of glucose ingestion compared with sucrose ingestion on liver and muscle glycogen depletion during prolonged endurance-type exercise. Fourteen cyclists completed two 3-h bouts of cycling at 50% of peak power output while ingesting either glucose or sucrose at a rate of 1.7 g/min (102 g/h). Four cyclists performed an additional third test for reference in which only water was consumed. We employed (13)C magnetic resonance spectroscopy to determine liver and muscle glycogen concentrations before and after exercise. Expired breath was sampled during exercise to estimate whole body substrate use. After glucose and sucrose ingestion, liver glycogen levels did not show a significant decline after exercise (from 325 ± 168 to 345 ± 205 and 321 ± 177 to 348 ± 170 mmol/l, respectively; P > 0.05), with no differences between treatments. Muscle glycogen concentrations declined (from 101 ± 49 to 60 ± 34 and 114 ± 48 to 67 ± 34 mmol/l, respectively; P glycogen concentrations declined during exercise when only water was ingested. Both glucose and sucrose ingestion prevent liver glycogen depletion during prolonged endurance-type exercise. Sucrose ingestion does not preserve liver glycogen concentrations more than glucose ingestion. However, sucrose ingestion does increase whole body carbohydrate utilization compared with glucose ingestion. This trial was registered at https://www.clinicaltrials.gov as NCT02110836. Copyright © 2015 the American Physiological Society.

  4. Effect of D-tagatose on liver weight and glycogen content of rats

    NARCIS (Netherlands)

    Bär, A.; Lina, B.A.R.; Groot, D.M.G. de; Bie, B. de; Appel, M.J.

    1999-01-01

    D-Tagatose is an incompletely absorbed ketohexose (stereoisomer of D-fructose) which has potential as an energy-reduced alternative sweetener. In an earlier 90-day toxicity study, rats fed diets with 10, 15 and 20% D-tagatose exhibited increased liver weights, but no histopathological alterations.

  5. Glycogen metabolism in humans

    OpenAIRE

    Adeva-Andany, María M.; González-Lucán, Manuel; Donapetry-García, Cristóbal; Fernández-Fernández, Carlos; Ameneiros-Rodríguez, Eva

    2016-01-01

    In the human body, glycogen is a branched polymer of glucose stored mainly in the liver and the skeletal muscle that supplies glucose to the blood stream during fasting periods and to the muscle cells during muscle contraction. Glycogen has been identified in other tissues such as brain, heart, kidney, adipose tissue, and erythrocytes, but glycogen function in these tissues is mostly unknown. Glycogen synthesis requires a series of reactions that include glucose entrance into the cell through...

  6. Virtual determination of liver and muscle glycogen obtained from fed rats and from 24-hour fasted rats

    Directory of Open Access Journals (Sweden)

    V.M.T.T. Trindidade et al

    2014-08-01

    Full Text Available Introduction: Glycogen is the storage polysaccharide of animals, composed by glucoseresidues forming a branched polymer. The liver glycogen metabolism and hepaticgluconeogenesis are important buffer systems of blood glucose in different physiological orpathological situations, such as, during a fast period. Fasting muscle glycogenolysis alsooccurs, however, the release of glucose into the bloodstream is negligible because themuscle doesn’t have the enzyme glucose-6-P phosphatase, which is present in the liver.Objectives: This panel presents a learning object, mediated by computer, which simulatesthe determination of liver and muscle glycogen obtained from fed rats and from 24-hourfasted rats Materials and Methods: At first, cartoons were planned in order to show themethodology procedures and biochemical fundamentals. The most representative imageswere selected, edited, organized in a scene menu and inserted into an animationdeveloped with the aid of the Adobe ® Flash 8 software. The validation of this object wasperformed by the students of Biochemistry I (Pharmacy-UFRGS from the secondsemester of 2009 until the second semester of 2013. Results and Discussion: Theanalysis of students' answers revealed that 83% of them attributed the excellence rate tothe navigation program, to the display format and to the learning help. Conclusion:Therefore, this learning object can be considered an adequate teaching resource as wellas an innovative support in the construction of theoretical and practical knowledge ofBiochemistry. Support: SEAD-UFRGSAvailable at: http://www.ufrgs.br/gcoeb/obtencaodosagemglicogenio/

  7. Curative effect of spleen homogenate against radiation injury to serum glucose, liver glycogen and plasma protein fractions in rats

    International Nuclear Information System (INIS)

    Roushdy, H.M.; Ibrahim, H.A.; Edrees, G.M.F.

    1984-01-01

    The influence of the spleen homogenate injection as a curative substance against gamma irradiation effects has been investigated in male albino rats. The parameters tested were, life span, serum glucose level, liver glycogen content, serum protein fractions and A/G ratio. The results obtained are as follows: Irradiated group showed 100% mortality over 22 days, this percentage dropped to 60% over 30 days for irradiated group received spleen homogenate treatment. Irradiated animals, recorded initial hyperglycaemia which diminished by time, whereas the liver glycogen concentration showed first to initially increase then to decrease abruptly. Treatment with spleen homogenate after irradiation ameliorated the magnitude of radiation induced hyperglycaemia and liver glycogen depletion. The serum Albumin/Globulin ratio decreased by irradiation due to the decrease in the serum albumin accompanied by an increase in the serum globulin content. This ratio could be restored towards its normal level in irradiated animals received spleen homogenate treatment. The data obtained suggests the possibility of using spleen homogenate for the treatment of accidental radiation syndrome

  8. Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

    KAUST Repository

    Lavoie, Suzie

    2016-04-21

    Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

  9. Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

    KAUST Repository

    Lavoie, Suzie; Steullet, Pascal; Kulak, Anita; Preitner, Frederic; Do, Kim Q.; Magistretti, Pierre J.

    2016-01-01

    Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

  10. Brain glycogen

    DEFF Research Database (Denmark)

    Obel, Linea Lykke Frimodt; Müller, Margit S; Walls, Anne B

    2012-01-01

    Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia....... In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies-it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic...... activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms...

  11. Developmental changes of protein, RNA, DNA, lipid, and glycogen in the liver, skeletal muscle, and brain of the piglet

    International Nuclear Information System (INIS)

    Hakkarainen, J.

    1975-01-01

    A scheme for the sequential quantitative separation and determination of protein, RNA, DNA, lipid, and glycogen from rat-liver homogenate is modified for application to frozen tissues of the piglet. The biochemical methods, including the biuret method, used in the present investigation are described and thoroughly checked. The effects of freezing and storage on the recovery of major tissue constituents are recorded. The modified scheme is applied to the determination of protein, RNA, DNA, lipid, and glycogen in the liver, skeletal muscle, and brain of the developing piglet. Developmental changes for these major tissue constituents, including the biuret protein, are described with special reference to protein synthesis and physiology of growth at the cellular level from 45 days of foetal age to 35-42 days of postnatal age for liver and skeletal muscle, and from birth to 31-40 days of postnatal age for the cerebrum and cerebellum. The uniformly labelled amino acid, 14 C-L-leucine, is used to study protein synthesis. Developmental patterns of labelling of protein and lipid in the liver, skeletal muscle, cerebrum, and cerebellum of the piglet from birth up to the age of two weeks are described. The results of the methodological, developmental, and experimental studies are thoroughly discussed in the light of the relevant literature and compared with those obtained in developmental and experimental studies on rats and other mammal species. (author)

  12. Glycogen synthase kinase 3β promotes liver innate immune activation by restraining AMP-activated protein kinase activation.

    Science.gov (United States)

    Zhou, Haoming; Wang, Han; Ni, Ming; Yue, Shi; Xia, Yongxiang; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Lu, Ling; Wang, Xuehao; Zhai, Yuan

    2018-02-13

    Glycogen synthase kinase 3β (Gsk3β [Gsk3b]) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischaemia and reperfusion injuries (IRIs) have been well documented, the underlying mechanisms remain ambiguous, in part because of the lack of cell-specific tools in vivo. We created a myeloid-specific Gsk3b knockout (KO) strain to study the function of Gsk3β in macrophages in a murine liver partial warm ischaemia model. Compared with controls, myeloid Gsk3b KO mice were protected from IRI, with diminished proinflammatory but enhanced anti-inflammatory immune responses in livers. In bone marrow-derived macrophages, Gsk3β deficiency resulted in an early reduction of Tnf gene transcription but sustained increase of Il10 gene transcription on Toll-like receptor 4 stimulation in vitro. These effects were associated with enhanced AMP-activated protein kinase (AMPK) activation, which led to an accelerated and higher level of induction of the novel innate immune negative regulator small heterodimer partner (SHP [Nr0b2]). The regulatory function of Gsk3β on AMPK activation and SHP induction was confirmed in wild-type bone marrow-derived macrophages with a Gsk3 inhibitor. Furthermore, we found that this immune regulatory mechanism was independent of Gsk3β Ser9 phosphorylation and the phosphoinositide 3-kinase-Akt signalling pathway. In vivo, myeloid Gsk3β deficiency facilitated SHP upregulation by ischaemia-reperfusion in liver macrophages. Treatment of Gsk3b KO mice with either AMPK inhibitor or SHP small interfering RNA before the onset of liver ischaemia restored liver proinflammatory immune activation and IRI in these otherwise protected hosts. Additionally, pharmacological activation of AMPK protected wild-type mice from liver IRI, with reduced proinflammatory immune activation. Inhibition of the AMPK-SHP pathway by liver ischaemia was demonstrated in tumour resection

  13. Effect of long-term intraperitoneal zinc administration on liver glycogen levels in diabetic rats subjected to acute forced swimming.

    Science.gov (United States)

    Bicer, Mursel; Gunay, Mehmet; Akil, Mustafa; Avunduk, Mustafa Cihat; Mogulkoc, Rasim; Baltaci, Abdulkerim Kasim

    2011-03-01

    This study aims to examine the effect of zinc administration on liver glycogen levels of rats in which diabetes was induced with streptozotocin and which were subjected to acute swimming exercise. The study was conducted on 80 adult Sprague-Dawley male rats, which were equally allocated to eight groups: group 1, general control; group 2, zinc-administrated control; group 3, zinc-administrated diabetic control; group 4, swimming control; group 5, zinc-administrated swimming; group 6, zinc-administrated diabetic swimming; group 7, diabetic swimming; group 8, diabetic control group. In order to induce diabetes, animals were injected with 40 mg/kg intraperitoneal (ip) streptozotocin. The injections were repeated in the same dose after 24 h. Animals which had blood glucose at or above 300 mg/dl 6 days after the last injections were accepted as diabetic. Zinc was administrated ip for 4 weeks as 6 mg/kg/day per rat. Hepatic tissue samples taken from the animals at the end of the study were fixed in 95% ethyl alcohol. Cross sections of 5 µm thickness, taken by the help of a microtome from the tissue samples buried in paraffin, were placed on a microscope slide and stained with periodic acid-Schiff and evaluated by light microscope. All microscopic images were transferred to a PC and assessed with the help of Clemex PE3.5 image analysis software. The lowest liver glycogen levels in the study were obtained in groups 3, 4, 6, 7, and 8. Liver glycogen levels in group 5 were higher than groups 3, 4, 6, 7, and 8, but lower than groups 1 and 2 (p swimming exercise were restored by zinc administration and that diabetes induced in rats prevented the protective effect of zinc.

  14. Abnormal metabolism of glycogen phosphate as a cause for Lafora disease.

    Science.gov (United States)

    Tagliabracci, Vincent S; Girard, Jean Marie; Segvich, Dyann; Meyer, Catalina; Turnbull, Julie; Zhao, Xiaochu; Minassian, Berge A; Depaoli-Roach, Anna A; Roach, Peter J

    2008-12-05

    Lafora disease is a progressive myoclonus epilepsy with onset in the teenage years followed by neurodegeneration and death within 10 years. A characteristic is the widespread formation of poorly branched, insoluble glycogen-like polymers (polyglucosan) known as Lafora bodies, which accumulate in neurons, muscle, liver, and other tissues. Approximately half of the cases of Lafora disease result from mutations in the EPM2A gene, which encodes laforin, a member of the dual specificity protein phosphatase family that is able to release the small amount of covalent phosphate normally present in glycogen. In studies of Epm2a(-/-) mice that lack laforin, we observed a progressive change in the properties and structure of glycogen that paralleled the formation of Lafora bodies. At three months, glycogen metabolism remained essentially normal, even though the phosphorylation of glycogen has increased 4-fold and causes altered physical properties of the polysaccharide. By 9 months, the glycogen has overaccumulated by 3-fold, has become somewhat more phosphorylated, but, more notably, is now poorly branched, is insoluble in water, and has acquired an abnormal morphology visible by electron microscopy. These glycogen molecules have a tendency to aggregate and can be recovered in the pellet after low speed centrifugation of tissue extracts. The aggregation requires the phosphorylation of glycogen. The aggregrated glycogen sequesters glycogen synthase but not other glycogen metabolizing enzymes. We propose that laforin functions to suppress excessive glycogen phosphorylation and is an essential component of the metabolism of normally structured glycogen.

  15. Insights into Brain Glycogen Metabolism: THE STRUCTURE OF HUMAN BRAIN GLYCOGEN PHOSPHORYLASE.

    Science.gov (United States)

    Mathieu, Cécile; Li de la Sierra-Gallay, Ines; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-08-26

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Radiation and Heat Stress Impact on Plasma Levels of Thyroid Hormones, Lipid Fractions, Glucose and Liver Glycogen in rats

    International Nuclear Information System (INIS)

    Abdel-Fattah, K.I.; Abou-Safi, H.M.

    2003-01-01

    Since Egypt is classified as a hot country, the present work has been directed to study the combined effect of heat stress and gamma radiation exposure on blood thyroid hormonal levels and some other parameters. Four groups of rats were served as: control, whole-body gamma irradiated (6Gy), exposed to ambient heat stress (38 C-40 C) and a group exposed to heat stress and irradiation. Four time intervals 1, 3, 5 and 7 days were determined for heat stress or exposure to heat followed by irradiation. Blood samples and liver specimens were taken at the end of each time interval in the third group and after one hour of irradiation in the second and fourth groups. To detect the radiation effects after the different periods of heat stress, plasma levels of thyroid hormones (T3 and T4), lipid fractions (triglycerides, total cholesterol, HDL- and LDL-cholesterol), glucose and liver glycogen content were determined. The results revealed that exposure to heat and ionizing radiation leads to a decrease in the levels of thyroid hormones, which was mostly pronounced in the T3 levels. Plasma glucose levels showed significant elevations in both, the heat-stressed group and the heat-treated then irradiated group. While, liver glycogen content exhibited similar elevations only during the 1st, 3 rd and 5 th days of heating followed by irradiation treatment as compared to the heat stressed group. Yet, it showed significant declines in comparison with both control and irradiated groups. Enormous increments in all determined plasma lipid fractions were induced by heat stress and / or gamma radiation

  17. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    OpenAIRE

    Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B.; Lee, Young Mok; Chou, Janice Y.; Byrne, Barry J.; Correia, Catherine E.; Mah, Cathryn S.; Weinstein, David A.; Conlon, Thomas J.

    2011-01-01

    A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size,...

  18. Glycogen storage disease type Ia in canines: a model for human metabolic and genetic liver disease.

    Science.gov (United States)

    Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B; Lee, Young Mok; Chou, Janice Y; Byrne, Barry J; Correia, Catherine E; Mah, Cathryn S; Weinstein, David A; Conlon, Thomas J

    2011-01-01

    A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including "lactic acidosis", larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  19. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    Directory of Open Access Journals (Sweden)

    Andrew Specht

    2011-01-01

    Full Text Available A canine model of Glycogen storage disease type Ia (GSDIa is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  20. Effect of heavy metals on the level of vitamin E, total lipid and glycogen reserves in the liver of common carp (Cyprinus carpio L.

    Directory of Open Access Journals (Sweden)

    Vinodhini Rajamanickam

    2008-06-01

    Full Text Available The aim of this study is to examine some changes in the biochemical profile of the liver tissue of common carp (Cyprinus carpio L. exposed to a sublethal concentration of heavy metal mixture (cadmium, chromium, nickel and lead. The biochemical profile, specifically glycogen, total lipid and vitamin E content in the liver tissue was examined and compared to that of the control group. The exposed group showed a marked decline in glycogen and vitamin E reserves. Conversely an increase in total lipid in comparison to control was observed. The result reflects the sensitivity of these biochemical parameters to the effects of sublethal levels of combined heavy metals for this the widely consumed freshwater fish.

  1. Technical and experimental features of Magnetic Resonance Spectroscopy of brain glycogen metabolism.

    Science.gov (United States)

    Soares, Ana Francisca; Gruetter, Rolf; Lei, Hongxia

    2017-07-15

    In the brain, glycogen is a source of glucose not only in emergency situations but also during normal brain activity. Altered brain glycogen metabolism is associated with energetic dysregulation in pathological conditions, such as diabetes or epilepsy. Both in humans and animals, brain glycogen levels have been assessed non-invasively by Carbon-13 Magnetic Resonance Spectroscopy ( 13 C-MRS) in vivo. With this approach, glycogen synthesis and degradation may be followed in real time, thereby providing valuable insights into brain glycogen dynamics. However, compared to the liver and muscle, where glycogen is abundant, the sensitivity for detection of brain glycogen by 13 C-MRS is inherently low. In this review we focus on strategies used to optimize the sensitivity for 13 C-MRS detection of glycogen. Namely, we explore several technical perspectives, such as magnetic field strength, field homogeneity, coil design, decoupling, and localization methods. Furthermore, we also address basic principles underlying the use of 13 C-labeled precursors to enhance the detectable glycogen signal, emphasizing specific experimental aspects relevant for obtaining kinetic information on brain glycogen. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. [13C] GC-C-IRMS analysis of methylboronic acid derivatives of glucose from liver glycogen after the ingestion of [13C] labeled tracers in rats.

    Science.gov (United States)

    Luengo, Catherine; Azzout-Marniche, Dalila; Fromentin, Claire; Piedcoq, Julien; Lemosquet, Sophie; Tomé, Daniel; Gaudichon, Claire

    2009-11-01

    We developed a complete method to measure low [(13)C] enrichments in glycogen. Fourteen rats were fed a control diet. Six of them also ingested either [U-(13)C] glucose (n=2) or a mixture of 20 [U-(13)C] amino acids (n=4). Hepatic glycogen was extracted, digested to glucose and purified on anion-cation exchange resins. After the optimization of methylboronic acid derivatization using GC-MS, [(13)C] enrichment of extracted glucose was measured by GC-C-IRMS. The accuracy was addressed by measuring the enrichment excess of a calibration curve, which observed values were in good agreement with the expected values (R=0.9979). Corrected delta values were -15.6+/-1.6 delta(13)C (per thousand) for control rats (n=8) and increased to -5 to 8 delta(13)C (per thousand) per thousand and 12-14 delta(13)C (per thousand) per thousand after the ingestion of [U-(13)C] amino acids or [U-(13)C] glucose as oral tracers, respectively. The method enabled the determination of dietary substrate transfer into glycogen. The sequestration of dietary glucose in liver glycogen 4 h after the meal was 35% of the ingested dose whereas the transfer of carbon skeletons from amino acids was only 0.25 to 1%.

  3. Sodium-Glucose Cotransporter 2 Inhibitor and a Low Carbohydrate Diet Affect Gluconeogenesis and Glycogen Content Differently in the Kidney and the Liver of Non-Diabetic Mice.

    Science.gov (United States)

    Atageldiyeva, Kuralay; Fujita, Yukihiro; Yanagimachi, Tsuyoshi; Mizumoto, Katsutoshi; Takeda, Yasutaka; Honjo, Jun; Takiyama, Yumi; Abiko, Atsuko; Makino, Yuichi; Haneda, Masakazu

    2016-01-01

    A low carbohydrate diet (LCHD) as well as sodium glucose cotransporter 2 inhibitors (SGLT2i) may reduce glucose utilization and improve metabolic disorders. However, it is not clear how different or similar the effects of LCHD and SGLT2i are on metabolic parameters such as insulin sensitivity, fat accumulation, and especially gluconeogenesis in the kidney and the liver. We conducted an 8-week study using non-diabetic mice, which were fed ad-libitum with LCHD or a normal carbohydrate diet (NCHD) and treated with/without the SGLT-2 inhibitor, ipragliflozin. We compared metabolic parameters, gene expression for transcripts related to glucose and fat metabolism, and glycogen content in the kidney and the liver among the groups. SGLT2i but not LCHD improved glucose excursion after an oral glucose load compared to NCHD, although all groups presented comparable non-fasted glycemia. Both the LCHD and SGLT2i treatments increased calorie-intake, whereas only the LCHD increased body weight compared to the NCHD, epididimal fat mass and developed insulin resistance. Gene expression of certain gluconeogenic enzymes was simultaneously upregulated in the kidney of SGLT2i treated group, as well as in the liver of the LCHD treated group. The SGLT2i treated groups showed markedly lower glycogen content in the liver, but induced glycogen accumulation in the kidney. We conclude that LCHD induces deleterious metabolic changes in the non-diabetic mice. Our results suggest that SGLT2i induced gluconeogenesis mainly in the kidney, whereas for LCHD it was predominantly in the liver.

  4. Route of administration of pentobarbital affects activity of liver glycogen phosphorylase

    DEFF Research Database (Denmark)

    Mikines, K J; Sonne, B; Richter, Erik

    1986-01-01

    pentobarbital (5 mg/100 g body wt) either intraperitoneally, as a slow intravenous infusion, or as an intravenous or intracardial bolus. Times from administration of barbiturate to sampling of the liver were 10 min, 10 min, 85 +/- 32 s (mean +/- SE), and 53 +/- 10 s, respectively. Phosphorylase a activity...... in % of total phosphorylase activity was 40 +/- 2, 56 +/- 4, 82 +/- 3, and 92 +/- 2, respectively, all significantly different. Thus the route of administration of pentobarbital affects the phosphorylase a activity and should be considered when evaluating this activity. This fact can only be partially explained...

  5. Altered morphology of liver and pancreas tissues of offsprings of ...

    African Journals Online (AJOL)

    The relationship between consumption of charred meat, which is believed to be rich in nitrosamine by pregnant mothers and the adverse effects on the growth of their offsprings, alterations in morphology of tissues like liver and pancreas were studied. Meat was subjected to charcoal fire roasting without curing and was ...

  6. [Inhibition of glycogen synthase kinase 3b activity regulates Toll-like receptor 4-mediated liver inflammation].

    Science.gov (United States)

    Ren, Feng; Zhang, Hai-yan; Piao, Zheng-fu; Zheng, Su-jun; Chen, Yu; Chen, De-xi; Duan, Zhong-ping

    2012-09-01

    To determine the mechanism underlying the therapeutic activities of glycogen synthase kinase 3b (GSK3b) against hepatic ischemia-reperfusion (H-IR) injury by investigating the inhibitive effects of GSK3b on inflammation mediated by Toll-like receptor 4 (TLR4). C57BL/6 male mice were subjected to 90 min of warm liver cephalad lobe ischemia, followed by reperfusion for various lengths of time. The mice were divided into three groups: the H-IR untreated model (control group), and the H-IR inflammation-induced models that received an intraperitoneal injection of purified lipopolysaccharide (LPS) endotoxin alone (inflammation group) or with pretreatment of the SB216763 GSK3b-specific inhibitor (intervention group). To create a parallel isolated cell system for detailed investigations of macrophages, marrow-derived stem cells were isolated from femurs of the H-IR control group of mice and used to derive primary macrophages. The cells were then divided into the same three groups as the whole mouse system: control, LPS-induced inflammation model, and inflammation model with SB216763 intervention. Differential expressions of inflammation-related proteins and genes were detected by Western blotting and real-time quantitative PCR, respectively. The phosphorylation levels of ERK, JNK and p38 MAPK were induced in liver at 1 h after reperfusion, but then steadily decreased and returned to baseline levels by 4 h after reperfusion. In addition, the phosphorylation levels of ERK and JNK were induced in macrophages at 15 min after LPS stimulation, while the phosphorylation level of p38 MAPK was induced at 1 h; SB216763 pretreatment suppressed the LPS-stimulated ERK, JNK and p38 phosphorylation in macrophages. In the mouse model, GSK3b activity was found to promote the gene expression of anti-inflammatory cytokine IL-10 (control: 0.21 ± 0.08, inflammation: 0.83 ± 0.21, intervention: 1.76 ± 0.67; F = 3.16, P = 0.027) but to significantly inhibit the gene expression of pro

  7. Structural alterations in rat liver proteins due to streptozotocin-induced diabetes and the recovery effect of selenium: Fourier transform infrared microspectroscopy and neural network study

    Science.gov (United States)

    Bozkurt, Ozlem; Haman Bayari, Sevgi; Severcan, Mete; Krafft, Christoph; Popp, Jürgen; Severcan, Feride

    2012-07-01

    The relation between protein structural alterations and tissue dysfunction is a major concern as protein fibrillation and/or aggregation due to structural alterations has been reported in many disease states. In the current study, Fourier transform infrared microspectroscopic imaging has been used to investigate diabetes-induced changes on protein secondary structure and macromolecular content in streptozotocin-induced diabetic rat liver. Protein secondary structural alterations were predicted using neural network approach utilizing the amide I region. Moreover, the role of selenium in the recovery of diabetes-induced alterations on macromolecular content and protein secondary structure was also studied. The results revealed that diabetes induced a decrease in lipid to protein and glycogen to protein ratios in diabetic livers. Significant alterations in protein secondary structure were observed with a decrease in α-helical and an increase in β-sheet content. Both doses of selenium restored diabetes-induced changes in lipid to protein and glycogen to protein ratios. However, low-dose selenium supplementation was not sufficient to recover the effects of diabetes on protein secondary structure, while a higher dose of selenium fully restored diabetes-induced alterations in protein structure.

  8. Type I Glycogen Storage Disease

    Science.gov (United States)

    ... the most common form of glycogen storage disease, accounting for 25% of all cases. It is an ... Links Videos Webinars About ALF OVERVIEW Programs About Liver Disease Ask the Experts People ALF ...

  9. Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

    Science.gov (United States)

    Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa-Wołosiuk, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

    2017-09-01

    Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Glycogen synthase activation by sugars in isolated hepatocytes.

    Science.gov (United States)

    Ciudad, C J; Carabaza, A; Bosch, F; Gòmez I Foix, A M; Guinovart, J J

    1988-07-01

    We have investigated the activation by sugars of glycogen synthase in relation to (i) phosphorylase a activity and (ii) changes in the intracellular concentration of glucose 6-phosphate and adenine nucleotides. All the sugars tested in this work present the common denominator of activating glycogen synthase. On the other hand, phosphorylase a activity is decreased by mannose and glucose, unchanged by galactose and xylitol, and increased by tagatose, glyceraldehyde, and fructose. Dihydroxyacetone exerts a biphasic effect on phosphorylase. These findings provide additional evidence proving that glycogen synthase can be activated regardless of the levels of phosphorylase a, clearly establishing that a nonsequential mechanism for the activation of glycogen synthase occurs in liver cells. The glycogen synthase activation state is related to the concentrations of glucose 6-phosphate and adenine nucleotides. In this respect, tagatose, glyceraldehyde, and fructose deplete ATP and increase AMP contents, whereas glucose, mannose, galactose, xylitol, and dihydroxyacetone do not alter the concentration of these nucleotides. In addition, all these sugars, except glyceraldehyde, increase the intracellular content of glucose 6-phosphate. The activation of glycogen synthase by sugars is reflected in decreases on both kinetic constants of the enzyme, M0.5 (for glucose 6-phosphate) and S0.5 (for UDP-glucose). We propose that hepatocyte glycogen synthase is activated by monosaccharides by a mechanism triggered by changes in glucose 6-phosphate and adenine nucleotide concentrations which have been described to modify glycogen synthase phosphatase activity. This mechanism represents a metabolite control of the sugar-induced activation of hepatocyte glycogen synthase.

  11. Obesity and type 2 diabetes in rats are associated with altered brain glycogen and amino-acid homeostasis

    DEFF Research Database (Denmark)

    Sickmann, Helle M; Waagepetersen, Helle S; Schousboe, Arne

    2010-01-01

    Obesity and type 2 diabetes have reached epidemic proportions; however, scarce information about how these metabolic syndromes influence brain energy and neurotransmitter homeostasis exist. The objective of this study was to elucidate how brain glycogen and neurotransmitter homeostasis are affected...... by these conditions. [1-(13)C]glucose was administered to Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rats. Sprague-Dawley (SprD), Zucker lean (ZL), and ZDF lean rats were used as controls. Several brain regions were analyzed for glycogen levels along with (13)C-labeling and content of glutamate, glutamine...... of glutamine and glutamate were decreased in the cerebellum of the ZO and the ZDF rats. Glycogen levels were also lower in this region. These results suggest that the obese and type 2 diabetic models were associated with lower brain glucose metabolism. Glucose metabolism through the TCA cycle was more...

  12. Glycogen synthesis in glycogenin 1-deficient patients

    DEFF Research Database (Denmark)

    Krag, Thomas O.; Ruiz-Ruiz, Cristina; Vissing, John

    2017-01-01

    Context: Glycogen storage disease (GSD) type XV is a rare disease caused by mutations in the GYG1 gene that codes for the core molecule of muscle glycogen, glycogenin 1. Nonetheless, glycogen is present in muscles of glycogenin 1-deficient patients, suggesting an alternative for glycogen buildup....... A likely candidate is glycogenin 2, an isoform expressed in the liver and heart but not in healthy skeletal muscle. Objective: We wanted to investigate the formation of glycogen and changes in glycogen metabolism in patients with GSD type XV. Design, Setting, and Patients: Two patients with mutations...... in the GYG1 gene were investigated for histopathology, ultrastructure, and expression of proteins involved in glycogen synthesis and metabolism. Results: Apart from occurrence of polyglucosan (PG) bodies in few fibers, glycogen appeared normal in most cells, and the concentration was normal in patients...

  13. Can glycogen be measured by in vivo neutron activation analysis?

    International Nuclear Information System (INIS)

    Sutcliffe, J.F.; Smith, A.H.; King, R.F.G.H.; Smith, M.A.

    1992-01-01

    The object of this note is to examine the feasibility of measuring liver glycogen using in vivo neutron activation analysis. The authors present equations which allow the mass of glycogen to be expressed in terms of the masses of oxygen, hydrogen, carbon and nitrogen. Using the most precise, published measurements of these elements, the standard deviation in the estimate of liver glycogen was 34 g. The magnitude of this error precluded observing changes in liver glycogen which are normally in the range 16 g to 72 g. However, this technique might be useful in detecting transient high concentrations of liver glycogen.(UK)

  14. Insulin induces a positive relationship between the rates of ATP and glycogen changes in isolated rat liver in presence of glucose; a 31P and 13C NMR study.

    Science.gov (United States)

    Baillet-Blanco, Laurence; Beauvieux, Marie-Christine; Gin, Henri; Rigalleau, Vincent; Gallis, Jean-Louis

    2005-11-21

    There is an emerging theory suggesting that insulin, which is known to be the predominant postprandial anabolic hormone, is also a major regulator of mitochondrial oxidative phosphorylation in human skeletal muscle. However, little is known about its effects in the liver. Since there is a theoretical relationship between glycogen metabolism and energy status, a simultaneous and continuous investigation of hepatic ATP and glycogen content was performed in intact and isolated perfused liver by 31P and 13C nuclear magnetic resonance (NMR) The hepatic rates of ATP and glycogen changes were evaluated with different concentrations of insulin and glucose during continuous and short-term supply. Liver from rats fed ad libitum were perfused with Krebs-Henseleit Buffer (KHB)(controls) or KHB containing 6 mM glucose, 30 mM glucose, insulin alone, insulin + 6 mM glucose, insulin + 30 mM glucose. In the control, glycogenolysis occurred at a rate of -0.53 +/- 0.021 % x min(-1) and ATP content decreased at a rate of -0.28 +/- 0.029 % x min(-1). In the absence of insulin, there was a close proportional relationship between the glycogen flux and the glucose concentration, whereas ATP rates never varied. With insulin + glucose, both glycogen and ATP rates were strongly related to the glucose concentration; the magnitude of net glycogen flux was linearly correlated to the magnitude of net ATP flux: flux(glycogen) = 72.543(fluxATP) + 172.08, R2 = 0.98. Only the co-infusion of 30 mM glucose and insulin led to (i) a net glycogen synthesis, (ii) the maintenance of the hepatic ATP content, and a strong positive correlation between their net fluxes. This has never previously been reported. The specific effect of insulin on ATP change is likely related to a rapid stimulation of the hepatic mitochondrial oxidative phosphorylation. We propose that variations in the correlation between rates of ATP and glycogen changes could be a probe for insulin resistance due to the action of substrates

  15. CONTENT OF GLYCOGEN IN LIVER AND KETOBODIES IN BLOOD OF JAPANESE QUAILS (COTURNIX COTURNIX JAPONICA DURING STARVATION ENVISAGED IN THE METHODS OF BALANCE EXPERIMENTS

    Directory of Open Access Journals (Sweden)

    Petar Batsalov

    2006-12-01

    Full Text Available The biochemical indexes “glycogen in liver” and “ketones in blood” of 0-72 hours feed deprived (according to methods for balanced experiments Japanese quails with and without energy additives were determined. There were 2 groups of birds- 1-st without energy supplement, 2-nd- fed with 1 g. glucose per os (as 25% solution – twice in 24 hours. The levels of liver glycogen in all the food-deprived quails were signifi cantly lower from -6910 (12-th hour of starving-to 4960mg/kg (72 hour of starving compared to the levels of the same index in fed birds (11990 mg/kg tissue. In the birds receiving energy additive they were higher compared to those deprived of the additive throughout the experimental period. The content of ketones in blood of the control birds was 0.015 mmol/l. The same index increased to 0.027 mmol/l in the feed and energy additive deprived group after the 36 hour of starving, but in the group became energy support, the contents of ketones were lower for the whole period of starving. The energy additive (1g glucose/24 hours helped the maintenance of the energy metabolism during continuous food depriving of the experimental quails.

  16. The Altered Hepatic Tubulin Code in Alcoholic Liver Disease.

    Science.gov (United States)

    Groebner, Jennifer L; Tuma, Pamela L

    2015-09-18

    The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the "tubulin code" are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease.

  17. The Altered Hepatic Tubulin Code in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Jennifer L. Groebner

    2015-09-01

    Full Text Available The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the “tubulin code” are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease.

  18. Insulin induces a positive relationship between the rates of ATP and glycogen changes in isolated rat liver in presence of glucose; a 31P and 13C NMR study

    Directory of Open Access Journals (Sweden)

    Gin Henri

    2005-11-01

    Full Text Available Abstract Background There is an emerging theory suggesting that insulin, which is known to be the predominant postprandial anabolic hormone, is also a major regulator of mitochondrial oxidative phosphorylation in human skeletal muscle. However, little is known about its effects in the liver. Since there is a theoretical relationship between glycogen metabolism and energy status, a simultaneous and continuous investigation of hepatic ATP and glycogen content was performed in intact and isolated perfused liver by 31P and 13C nuclear magnetic resonance (NMR The hepatic rates of ATP and glycogen changes were evaluated with different concentrations of insulin and glucose during continuous and short-term supply. Results Liver from rats fed ad libitum were perfused with Krebs-Henseleit Buffer (KHB(controls or KHB containing 6 mM glucose, 30 mM glucose, insulin alone, insulin + 6 mM glucose, insulin + 30 mM glucose. In the control, glycogenolysis occurred at a rate of -0.53 ± 0.021 %·min-1 and ATP content decreased at a rate of -0.28 ± 0.029 %·min-1. In the absence of insulin, there was a close proportional relationship between the glycogen flux and the glucose concentration, whereas ATP rates never varied. With insulin + glucose, both glycogen and ATP rates were strongly related to the glucose concentration; the magnitude of net glycogen flux was linearly correlated to the magnitude of net ATP flux: fluxglycogen = 72.543(fluxATP + 172.08, R2 = 0.98. Conclusion Only the co-infusion of 30 mM glucose and insulin led to (i a net glycogen synthesis, (ii the maintenance of the hepatic ATP content, and a strong positive correlation between their net fluxes. This has never previously been reported. The specific effect of insulin on ATP change is likely related to a rapid stimulation of the hepatic mitochondrial oxidative phosphorylation. We propose that variations in the correlation between rates of ATP and glycogen changes could be a probe for insulin

  19. Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs

    Science.gov (United States)

    Ramnanan, Christopher J.; Saraswathi, Viswanathan; Smith, Marta S.; Donahue, E. Patrick; Farmer, Ben; Farmer, Tiffany D.; Neal, Doss; Williams, Philip E.; Lautz, Margaret; Mari, Andrea; Cherrington, Alan D.; Edgerton, Dale S.

    2011-01-01

    In rodents, acute brain insulin action reduces blood glucose levels by suppressing the expression of enzymes in the hepatic gluconeogenic pathway, thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether a similar mechanism is functional in large animals, including humans, is unknown. Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought about by infusion of insulin into the head arteries (during a pancreatic clamp to maintain basal hepatic insulin and glucagon levels) activated hypothalamic Akt, altered STAT3 signaling in the liver, and suppressed hepatic gluconeogenic gene expression without altering EGP or gluconeogenesis. Rather, brain hyperinsulinemia slowly caused a modest reduction in net hepatic glucose output (NHGO) that was attributable to increased net hepatic glucose uptake and glycogen synthesis. This was associated with decreased levels of glycogen synthase kinase 3β (GSK3β) protein and mRNA and with decreased glycogen synthase phosphorylation, changes that were blocked by hypothalamic PI3K inhibition. Therefore, we conclude that the canine brain senses physiologic elevations in plasma insulin, and that this in turn regulates genetic events in the liver. In the context of basal insulin and glucagon levels at the liver, this input augments hepatic glucose uptake and glycogen synthesis, reducing NHGO without altering EGP. PMID:21865644

  20. Biomarker for Glycogen Storage Diseases

    Science.gov (United States)

    2017-07-03

    Fructose Metabolism, Inborn Errors; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VI; Glycogen Storage Disease Type VII; Glycogen Storage Disease Type VIII

  1. Brain glycogen in health and disease.

    Science.gov (United States)

    Duran, Jordi; Guinovart, Joan J

    2015-12-01

    Glycogen is present in the brain at much lower concentrations than in muscle or liver. However, by characterizing an animal depleted of brain glycogen, we have shown that the polysaccharide plays a key role in learning capacity and in activity-dependent changes in hippocampal synapse strength. Since glycogen is essentially found in astrocytes, the diverse roles proposed for this polysaccharide in the brain have been attributed exclusively to these cells. However, we have demonstrated that neurons have an active glycogen metabolism that contributes to tolerance to hypoxia. However, these cells can store only minute amounts of glycogen, since the progressive accumulation of this molecule leads to neuronal loss. Loss-of-function mutations in laforin and malin cause Lafora disease. This condition is characterized by the presence of high numbers of insoluble polyglucosan bodies, known as Lafora bodies, in neuronal cells. Our findings reveal that the accumulation of this aberrant glycogen accounts for the neurodegeneration and functional consequences, as well as the impaired autophagy, observed in models of this disease. Similarly glycogen synthase is responsible for the accumulation of corpora amylacea, which are polysaccharide-based aggregates present in the neurons of aged human brains. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism is important under stress conditions and that neuronal glycogen accumulation contributes to neurodegenerative diseases and to aging-related corpora amylacea formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Mitochondrial alterations in children with chronic liver disease

    African Journals Online (AJOL)

    Rabah M. Shawky

    chondrial function and structure in livers from humans with chronic liver disease ... ease, 2 with lipid storage disease, one with type I autoimmune hepatitis, one ..... a classification scheme for mitochondrial hepatopathies into primary and ...

  3. Efficacy of vitamins a and or E as antioxidants against serum glucose, liver glycogen and lipid discrepancy induced by gamma radiation during the estrus cycle of rats

    International Nuclear Information System (INIS)

    Abou-Safi, H.M.; Hussein, A.H.; El-Sayed, N.M.

    1999-01-01

    This work is directed to study the role of vitamins A and E treatment solely. or in combination against gamma-radiation effects during pro-estrus stage stage on serum glucose, liver content of glycogen, total and lipid fractions (triglycerides, total cholesterol, HDL-and LDL- cholesterol) in serum measured during the estrus stage of the rat estrus cycle. Animals were divided into six groups: untreated control, injected with sesame oil as a vehicle for vitamins injection (i.p.) whole body gamma-irradiated (6 GY), injected with vitamin A Two hours before irradiation, irradiated then injected after one hour with vitamin E, and injected with vitamins A and E pre- and post irradiation. The results demonstrated that irradiation induced significant elevations in the levels of all the measured parameters except in HDL-cholesterol. BOth vitamins ameliorated the recorded elevations during the estrus stage. The combined treatment with vitamins A and E reflected a potent harmony between protective roles of these two antioxidants pre- and post irradiation respectively, that normalized the levels of the measured parameters. The authors suggest that vitamins A and E treatment could enhance and reinforce the natural endogenous defences (steroids, particulary E 2 ) in the body against gamma irradiation and/or other environmental pollutants causing lipid peroxidation, especially during the period of ovulation. Moreover, it is worthy to consider this treatment as a hypolipidemic agent for patients with obesity, atherosclerosis and coronary artery diseases

  4. Short-term pyrrolidine dithiocarbamate administration attenuates cachexia-induced alterations to muscle and liver in ApcMin/+ mice.

    Science.gov (United States)

    Narsale, Aditi A; Puppa, Melissa J; Hardee, Justin P; VanderVeen, Brandon N; Enos, Reilly T; Murphy, E Angela; Carson, James A

    2016-09-13

    Cancer cachexia is a complex wasting condition characterized by chronic inflammation, disrupted energy metabolism, and severe muscle wasting. While evidence in pre-clinical cancer cachexia models have determined that different systemic inflammatory inhibitors can attenuate several characteristics of cachexia, there is a limited understanding of their effects after cachexia has developed, and whether short-term administration is sufficient to reverse cachexia-induced signaling in distinctive target tissues. Pyrrolidine dithiocarbamate (PDTC) is a thiol compound having anti-inflammatory and antioxidant properties which can inhibit STAT3 and nuclear factor κB (NF-κB) signaling in mice. This study examined the effect of short-term PDTC administration to ApcMin/+ mice on cachexia-induced disruption of skeletal muscle protein turnover and liver metabolic function. At 16 weeks of age ApcMin/+ mice initiating cachexia (7% BW loss) were administered PDTC (10mg/kg bw/d) for 2 weeks. Control ApcMin/+ mice continued to lose body weight during the treatment period, while mice receiving PDTC had no further body weight decrease. PDTC had no effect on either intestinal tumor burden or circulating IL-6. In muscle, PDTC rescued signaling disrupting protein turnover regulation. PDTC suppressed the cachexia induction of STAT3, increased mTORC1 signaling and protein synthesis, and suppressed the induction of Atrogin-1 protein expression. Related to cachectic liver metabolic function, PDTC treatment attenuated glycogen and lipid content depletion independent to the activation of STAT3 and mTORC1 signaling. Overall, these results demonstrate short-term PDTC treatment to cachectic mice attenuated cancer-induced disruptions to muscle and liver signaling, and these changes were independent to altered tumor burden and circulating IL-6.

  5. Short-term pyrrolidine dithiocarbamate administration attenuates cachexia-induced alterations to muscle and liver in ApcMin/+ mice

    Science.gov (United States)

    VanderVeen, Brandon N.; Enos, Reilly T.; Murphy, E. Angela; Carson, James A.

    2016-01-01

    Cancer cachexia is a complex wasting condition characterized by chronic inflammation, disrupted energy metabolism, and severe muscle wasting. While evidence in pre-clinical cancer cachexia models have determined that different systemic inflammatory inhibitors can attenuate several characteristics of cachexia, there is a limited understanding of their effects after cachexia has developed, and whether short-term administration is sufficient to reverse cachexia-induced signaling in distinctive target tissues. Pyrrolidine dithiocarbamate (PDTC) is a thiol compound having anti-inflammatory and antioxidant properties which can inhibit STAT3 and nuclear factor κB (NF-κB) signaling in mice. This study examined the effect of short-term PDTC administration to ApcMin/+ mice on cachexia-induced disruption of skeletal muscle protein turnover and liver metabolic function. At 16 weeks of age ApcMin/+ mice initiating cachexia (7% BW loss) were administered PDTC (10mg/kg bw/d) for 2 weeks. Control ApcMin/+ mice continued to lose body weight during the treatment period, while mice receiving PDTC had no further body weight decrease. PDTC had no effect on either intestinal tumor burden or circulating IL-6. In muscle, PDTC rescued signaling disrupting protein turnover regulation. PDTC suppressed the cachexia induction of STAT3, increased mTORC1 signaling and protein synthesis, and suppressed the induction of Atrogin-1 protein expression. Related to cachectic liver metabolic function, PDTC treatment attenuated glycogen and lipid content depletion independent to the activation of STAT3 and mTORC1 signaling. Overall, these results demonstrate short-term PDTC treatment to cachectic mice attenuated cancer-induced disruptions to muscle and liver signaling, and these changes were independent to altered tumor burden and circulating IL-6. PMID:27449092

  6. Investigation and management of the hepatic glycogen storage diseases.

    Science.gov (United States)

    Bhattacharya, Kaustuv

    2015-07-01

    The glycogen storage diseases (GSD) comprise a group of disorders that involve the disruption of metabolism of glycogen. Glycogen is stored in various organs including skeletal muscle, the kidneys and liver. The liver stores glycogen to supply the rest of the body with glucose when required. Therefore, disruption of this process can lead to hypoglycaemia. If glycogen is not broken down effectively, this can lead to hepatomegaly. Glycogen synthase deficiency leads to impaired glycogen synthesis and consequently the liver is small. Glycogen brancher deficiency can lead to abnormal glycogen being stored in the liver leading to a quite different disorder of progressive liver dysfunction. Understanding the physiology of GSD I, III, VI and IX guides dietary treatments and the provision of appropriate amounts and types of carbohydrates. There has been recent re-emergence in the literature of the use of ketones in therapy, either in the form of the salt D,L-3-hydroxybutyrate or medium chain triglyceride (MCT). High protein diets have also been advocated. Alternative waxy maize based starches seem to show promising early data of efficacy. There are many complications of each of these disorders and they need to be prospectively surveyed and managed. Liver and kidney transplantation is still indicated in severe refractory disease.

  7. Introduction to the Thematic Minireview Series: Brain glycogen metabolism.

    Science.gov (United States)

    Carlson, Gerald M; Dienel, Gerald A; Colbran, Roger J

    2018-05-11

    The synthesis of glycogen allows for efficient intracellular storage of glucose molecules in a soluble form that can be rapidly released to enter glycolysis in response to energy demand. Intensive studies of glucose and glycogen metabolism, predominantly in skeletal muscle and liver, have produced innumerable insights into the mechanisms of hormone action, resulting in the award of several Nobel Prizes over the last one hundred years. Glycogen is actually present in all cells and tissues, albeit at much lower levels than found in muscle or liver. However, metabolic and physiological roles of glycogen in other tissues are poorly understood. This series of Minireviews summarizes what is known about the enzymes involved in brain glycogen metabolism and studies that have linked glycogen metabolism to multiple brain functions involving metabolic communication between astrocytes and neurons. Recent studies unexpectedly linking some forms of epilepsy to mutations in two poorly understood proteins involved in glycogen metabolism are also reviewed. © 2018 Carlson et al.

  8. Effects of radiosensibilization by metronidazole on liver tissue in patients with gastric carcinomas

    International Nuclear Information System (INIS)

    D'yakova, A.M.; Stefani, N.V.; Zagrebin, V.M.; Senokosov, N.I.; Berdov, B.A.

    1985-01-01

    Metronidazole, used as radiosensitizer in preoperative radiotherapy of gastric carcinoma caused an increased glycogen accumulation in the left lobe of the liver with a radiation dose of 80-100 % of the isodose. The glycogen level was higher not only in comparison with the same liver area in patients without radiosensitizer but also with the right lobe of the own liver within in the area of stray radiation. The effect observed after radiation was considered as result of the sensitizing influence on liver tissue. The sensitizing effect of metronidazole depended on its concentration in the patient's serum. In the right lobe of the liver the glycogen level showed no alteration under metronidazole. Metronidazole reduced the activity of lactate dehydrogenase and cholinesterase in liver tissue independently of its concentration in the serum and of the radiation dose on particular parts of the liver. (author)

  9. Hepatoscintiangiography of normal liver and its alteration in hepatomas and liver abscess

    International Nuclear Information System (INIS)

    Bahk, Y.W.; Chung, S.K.

    1984-01-01

    This study was performed to establish normal hepatoscintiangiographic (HSA) pattern of hepatic blood flow and to investigate differential HSA findings of primary and metastatic carcinomas and abscess of the liver. HSA was carried out after intravenous bolus injection of l0 mCi of Tc-99m-phytate by obtaining sequential anterior images of 1-second exposure for 16 seconds. Observations included (1) baseline study of normal hepatic blood flow patterns by correlating with contrast angiogram, (2) time-sequence phasing of normal HSA, and (3) analysis of altered patterns in primary and metastatic carcinomas and abscess of the liver. Results were: (1) Normal HSA demonstrated 3 distinct phases of arterialization (AP), arterial hepatrogram (AHP), and portal venous hepatogram (PVHP). The means of each phase were 5.3, 6.3, and 8.3 seconds, respectively. Portal vein could be seen in all but one of 20 normal subjects. (2) Pattern changes in disease groups were early start of AP in carcinomas and very early start of AP in abscess. AP became prolonged in all disease groups. (3) Distinction between AHP and PVHP was sharp in metastasis and abscess but was unsharp in primary hepatoma. Cold area or areas became vascularized in primary hepatoma but not in abscess. Cold areas of metastasis were inhomogenously vascularized in late AP and throughout AHP and became relatively avascular as PVHP began. The cold area of abscess showed rim enhancement during AH and APH. These differences in HSA pattern were very useful in differential diagnosis of the diseases studied

  10. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-01-01

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  11. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  12. Glycogen dynamics of crucian carp (Carassius carassius) in prolonged anoxia.

    Science.gov (United States)

    Vornanen, Matti; Haverinen, Jaakko

    2016-12-01

    Mobilization of glycogen stores was examined in the anoxic crucian carp (Carassius carassius Linnaeus). Winter-acclimatized fish were exposed to anoxia for 1, 3, or 6 weeks at 2 °C, and changes in the size of glycogen deposits were followed. After 1 week of anoxia, a major part of the glycogen stores was mobilized in liver (79.5 %) and heart (75.6 %), and large decreases occurred in gill (46.7 %) and muscle (45.1 %). Brain was an exception in that its glycogen content remained unchanged. The amount of glycogen degraded during the first anoxic week was sufficient for the anaerobic ethanol production for more than 6 weeks of anoxia. After 3 and 6 weeks of anoxia, there was little further degradation of glycogen in other tissues except the brain where the stores were reduced by 30.1 and 49.9 % after 3 and 6 weeks of anoxia, respectively. One week of normoxic recovery following the 6-week anoxia was associated with a complete replenishment of the brain glycogen and partial recovery of liver, heart, and gill glycogen stores. Notably, the resynthesis of glycogen occurred at the expense of the existing energy reserves of the body in fasting fish. These findings indicate that in crucian carp, glycogen stores are quickly mobilized after the onset of anoxia, with the exception of the brain whose glycogen stores may be saved for putative emergency situations.

  13. Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken

    Directory of Open Access Journals (Sweden)

    Yonghong Zhang

    2018-04-01

    Full Text Available Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF diet and a methionine choline-deficient (MCD diet. The results showed that the dwarf Jingxing-Huang (JXH chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL and local Beijing-You (BJY breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism (ACACA, FASN, SCD, ACSL5, FADS2, FABP1, APOA4 and ME1. This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers.

  14. Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken

    Science.gov (United States)

    Zhang, Yonghong; Liu, Zhen; Liu, Ranran; Wang, Jie; Zheng, Maiqing; Li, Qinghe; Cui, Huanxian; Zhao, Guiping; Wen, Jie

    2018-01-01

    Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY) breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism (ACACA, FASN, SCD, ACSL5, FADS2, FABP1, APOA4 and ME1). This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers. PMID:29642504

  15. Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken.

    Science.gov (United States)

    Zhang, Yonghong; Liu, Zhen; Liu, Ranran; Wang, Jie; Zheng, Maiqing; Li, Qinghe; Cui, Huanxian; Zhao, Guiping; Wen, Jie

    2018-04-08

    Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY) breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism ( ACACA , FASN , SCD , ACSL5 , FADS2 , FABP1 , APOA4 and ME1 ). This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers.

  16. Mitochondrial alterations in children with chronic liver disease ...

    African Journals Online (AJOL)

    Background: Over recent years it has become apparent that the hepatocyte mitochondrion functions both as a cause and as a target of liver injury. Resultant dysfunction of mitochondria yields deficient oxidative phosphorylation, increased generation of reactive oxygen species, impairment of other metabolic pathways and ...

  17. Glycogen synthase kinase 3 beta alters anxiety-, depression-, and addiction-related behaviors and neuronal activity in the nucleus accumbens shell

    Science.gov (United States)

    Crofton, Elizabeth J.; Nenov, Miroslav N.; Zhang, Yafang; Scala, Federico; Page, Sean A.; McCue, David L.; Li, Dingge; Hommel, Jonathan D.; Laezza, Fernanda; Green, Thomas A.

    2017-01-01

    Psychiatric disorders such as anxiety, depression and addiction are often comorbid brain pathologies thought to share common mechanistic biology. As part of the cortico-limbic circuit, the nucleus accumbens shell (NAcSh) plays a fundamental role in integrating information in the circuit, such that modulation of NAcSh circuitry alters anxiety, depression, and addiction-related behaviors. Intracellular kinase cascades in the NAcSh have proven important mediators of behavior. To investigate glycogen-synthase kinase 3 (GSK3) beta signaling in the NAcSh in vivo we knocked down GSK3beta expression with a novel adeno-associated viral vector (AAV2) and assessed changes in anxiety- and depression-like behavior and cocaine self-administration in GSK3beta knockdown rats. GSK3beta knockdown reduced anxiety-like behavior while increasing depression-like behavior and cocaine self-administration. Correlative electrophysiological recordings in acute brain slices were used to assess the effect of AAV-shGSK3beta on spontaneous firing and intrinsic excitability of tonically active interneurons (TANs), cells required for input and output signal integration in the NAcSh and for processing reward-related behaviors. Loose-patch recordings showed that TANs transduced by AAV-shGSK3beta exhibited reduction in tonic firing and increased spike half width. When assessed by whole-cell patch clamp recordings these changes were mirrored by reduction in action potential firing and accompanied by decreased hyperpolarization-induced depolarizing sag potentials, increased action potential current threshold, and decreased maximum rise time. These results suggest that silencing of GSK3beta in the NAcSh increases depression- and addiction-related behavior, possibly by decreasing intrinsic excitability of TANs. However, this study does not rule out contributions from other neuronal sub-types. PMID:28126496

  18. Effects of hypoxia on ionic regulation, glycogen utilization and antioxidative ability in the gills and liver of the aquatic air-breathing fish Trichogaster microlepis.

    Science.gov (United States)

    Huang, Chun-Yen; Lin, Hui-Chen; Lin, Cheng-Huang

    2015-01-01

    We examined the hypothesis that Trichogaster microlepis, a fish with an accessory air-breathing organ, uses a compensatory strategy involving changes in both behavior and protein levels to enhance its gas exchange ability. This compensatory strategy enables the gill ion-regulatory metabolism to maintain homeostasis during exposure to hypoxia. The present study aimed to determine whether ionic regulation, glycogen utilization and antioxidant activity differ in terms of expression under hypoxic stresses; fish were sampled after being subjected to 3 or 12h of hypoxia and 12h of recovery under normoxia. The air-breathing behavior of the fish increased under hypoxia. No morphological modification of the gills was observed. The expression of carbonic anhydrase II did not vary among the treatments. The Na(+)/K(+)-ATPase enzyme activity did not decrease, but increases in Na(+)/K(+)-ATPase protein expression and ionocyte levels were observed. The glycogen utilization increased under hypoxia as measured by glycogen phosphorylase protein expression and blood glucose level, whereas the glycogen content decreased. The enzyme activity of several components of the antioxidant system in the gills, including catalase, glutathione peroxidase, and superoxidase dismutase, increased in enzyme activity. Based on the above data, we concluded that T. microlepis is a hypoxia-tolerant species that does not exhibit ion-regulatory suppression but uses glycogen to maintain energy utilization in the gills under hypoxic stress. Components of the antioxidant system showed increased expression under the applied experimental treatments. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice[S

    Science.gov (United States)

    Palmisano, Brian T.; Le, Thao D.; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M.

    2016-01-01

    Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. PMID:27354419

  20. Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice.

    Science.gov (United States)

    Palmisano, Brian T; Le, Thao D; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M

    2016-08-01

    Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  1. Volume I. Glycogen: A historical overview, an adjunct to thesis. Volume II. Non-glucose components of glycogen

    International Nuclear Information System (INIS)

    Kirkman, B.R.

    1988-01-01

    Investigations have been carried out on three non-glucose components of native glycogen: protein, glucosamine, and phosphate. The protein, glycogenin, appears to serve as the primer upon which new molecules of glycogen are synthesized. When cell extracts are incubated with ( 14 C)UDPG, ( 14 C)glucose becomes transferred onto pre-existing chains of alpha-1,4 linked glucose associated with free glycogenin. The transferase and glycogenin remain associated during various purification steps. Liver glycogen appears to contain less than 0.02% protein which may correspond to the presence of one molecule of glycogenin (37 kDa) per alpha particle of liver glycogen. The core beta particle within each alpha particle may be synthesized upon glycogenin, while the remaining 20-40 beta particles may arise from each other. The author has demonstrated the natural occurrence of glucosamine in liver glycogen (but not muscle glycogen) from various species in an amount of about one molecule per molecule of glycogen. The glucosamine is underivatized, appears to be randomly scattered in the glycogen, and may be derived from dietary galactosamine. Similar to Fontana (1980), the author observed that native liver glycogen could be fractionated on DEAE-cellulose apparently on the basis of phosphate content. The more strongly bound glycogen possessed a greater molecular weight and content of glucosamine and phosphate. Possible explanations for these subfractions are considered. The phosphate appears to be concentrated near the center of the glycogen molecules. About 30% appears to be associated with glucose-6P and the remainder with an unidentified phosphodiester. The phosphate may stimulate glycogen synthesis. How the phosphate becomes incorporated is unknown

  2. Extraction of glycogen on mild condition lacks AIG fraction.

    Science.gov (United States)

    Ghafouri, Z; Rasouli, M

    2016-12-01

    Extraction of animal tissues with cold water or perchloric acid yields less glycogen than is obtained with hot-alkaline. Extraction with acid and alkaline gives two fractions, acid soluble (ASG) and insoluble glycogen (AIG). The aim of this work is to examine the hypothesis that not all liver glycogen is extractable by Tris-buffer using current techniques. Rat liver was homogenized with Tris-buffer pH 8.3 and extracted for the glycogen fractions, ASG and AIG. The degree of homogenization was changed to remove all glycogen. The content of glycogen was 47.7 ± 1.2 and 11.6 ± 0.8 mg/g wet liver in the supernatant and pellet of the first extraction respectively. About 24% of total glycogen is lost through the first pellet. Increasing the extent of homogenization from 30 to 180 sec and from 15000 to 20000 rpm followed with 30 sec ultrasonication did not improve the extraction. ASG and AIG constitute about 77% and 23% of the pellet glycogen respectively. Extraction with cold Tris-buffer failed to extract glycogen completely.  Increasing the extent of homogenization followed with ultrasonication also did not improve the extraction. Thus it is necessary to re-examine the previous findings obtained by extraction with cold Tris-buffer.

  3. Astrocyte glycogen and brain energy metabolism.

    Science.gov (United States)

    Brown, Angus M; Ransom, Bruce R

    2007-09-01

    The brain contains glycogen but at low concentration compared with liver and muscle. In the adult brain, glycogen is found predominantly in astrocytes. Astrocyte glycogen content is modulated by a number of factors including some neurotransmitters and ambient glucose concentration. Compelling evidence indicates that astrocyte glycogen breaks down during hypoglycemia to lactate that is transferred to adjacent neurons or axons where it is used aerobically as fuel. In the case of CNS white matter, this source of energy can extend axon function for 20 min or longer. Likewise, during periods of intense neural activity when energy demand exceeds glucose supply, astrocyte glycogen is degraded to lactate, a portion of which is transferred to axons for fuel. Astrocyte glycogen, therefore, offers some protection against hypoglycemic neural injury and ensures that neurons and axons can maintain their function during very intense periods of activation. These emerging principles about the roles of astrocyte glycogen contradict the long held belief that this metabolic pool has little or no functional significance.

  4. Glucose 6-phosphate compartmentation and the control of glycogen synthesis

    NARCIS (Netherlands)

    Meijer, Alfred

    2002-01-01

    Using adenovirus-mediated gene transfer into FTO-2B cells, a rat hepatoma cell line, we have overexpressed hexokinase I, (HK I), glucokinase (GK), liver glycogen synthase (LGS), muscle glycogen synthase (MGS), and combinations of each of the two glucose phosphorylating enzymes with each one of the

  5. Lack of Glycogenin Causes Glycogen Accumulation and Muscle Function Impairment.

    Science.gov (United States)

    Testoni, Giorgia; Duran, Jordi; García-Rocha, Mar; Vilaplana, Francisco; Serrano, Antonio L; Sebastián, David; López-Soldado, Iliana; Sullivan, Mitchell A; Slebe, Felipe; Vilaseca, Marta; Muñoz-Cánoves, Pura; Guinovart, Joan J

    2017-07-05

    Glycogenin is considered essential for glycogen synthesis, as it acts as a primer for the initiation of the polysaccharide chain. Against expectations, glycogenin-deficient mice (Gyg KO) accumulate high amounts of glycogen in striated muscle. Furthermore, this glycogen contains no covalently bound protein, thereby demonstrating that a protein primer is not strictly necessary for the synthesis of the polysaccharide in vivo. Strikingly, in spite of the higher glycogen content, Gyg KO mice showed lower resting energy expenditure and less resistance than control animals when subjected to endurance exercise. These observations can be attributed to a switch of oxidative myofibers toward glycolytic metabolism. Mice overexpressing glycogen synthase in the muscle showed similar alterations, thus indicating that this switch is caused by the excess of glycogen. These results may explain the muscular defects of GSD XV patients, who lack glycogenin-1 and show high glycogen accumulation in muscle. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jie, E-mail: JLiu@kumc.edu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Lu, Yuan-Fu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Zhang, Youcai; Wu, Kai Connie [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Fan, Fang [Cytopathology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Klaassen, Curtis D. [University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2013-11-01

    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential. - Highlights: • Oleanolic acid at higher doses and long-term use may produce liver injury. • Oleanolic acid increased serum ALT, ALP, bilirubin and bile acid concentrations. • OA produced feathery degeneration, inflammation and cell death in the liver. • OA altered bile acid homeostasis, affecting bile acid synthesis and transport.

  7. Acetaminophen-Induced Liver Injury Alters the Acyl Ethanolamine-Based Anti-Inflammatory Signaling System in Liver

    Directory of Open Access Journals (Sweden)

    Patricia Rivera

    2017-10-01

    Full Text Available Protective mechanisms against drug-induced liver injury are actively being searched to identify new therapeutic targets. Among them, the anti-inflammatory N-acyl ethanolamide (NAE-peroxisome proliferators activated receptor alpha (PPARα system has gained much interest after the identification of its protective role in steatohepatitis and liver fibrosis. An overdose of paracetamol (APAP, a commonly used analgesic/antipyretic drug, causes hepatotoxicity, and it is being used as a liver model. In the present study, we have analyzed the impact of APAP on the liver NAE-PPARα system. A dose-response (0.5–5–10–20 mM and time-course (2–6–24 h study in human HepG2 cells showed a biphasic response, with a decreased PPARα expression after 6-h APAP incubation followed by a generalized increase of NAE-PPARα system-related components (PPARα, NAPE-PLD, and FAAH, including the NAEs oleoyl ethanolamide (OEA and docosahexaenoyl ethanolamide, after a 24-h exposure to APAP. These results were partially confirmed in a time-course study of mice exposed to an acute dose of APAP (750 mg/kg. The gene expression levels of Pparα and Faah were decreased after 6 h of treatment and, after 24 h, the gene expression levels of Nape-pld and Faah, as well as the liver levels of OEA and palmitoyl ethanolamide, were increased. Repeated APAP administration (750 mg/kg/day up to 4 days also decreased the expression levels of PPARα and FAAH, and increased the liver levels of NAEs. A resting period of 15 days completely restored these impairments. Liver immunohistochemistry in a well-characterized human case of APAP hepatotoxicity confirmed PPARα and FAAH decrements. Histopathological and hepatic damage (Cyp2e1, Caspase3, αSma, Tnfα, and Mcp1-related alterations observed after repeated APAP administration were aggravated in the liver of Pparα-deficient mice. Our results demonstrate that the anti-inflammatory NAE-PPARα signaling system is implicated in liver

  8. Glycogen metabolism in radiation induced hepatocellular carcinoma in Swiss albino mice

    International Nuclear Information System (INIS)

    Gupta, N.K.; Kumar, Ashok

    1988-01-01

    Glycogen content and the activities of phosphorylase, glycogen sythetase (GS), glucose 6-phosphatase (G6Pase), phosphohexose isomerase (PHI), glucose 6-phosphodehydrogenase were biochemically determined in the heparocellular carcinoma induced in swiss albino mice following radiocalcium internal irradiation. The content glycogen and the activities of phosphorylase, glycogen synthetase, G6Pase, PHI, GPT and GOT are considerably reduced in the hepatocellular carcinoma compared to that in control liver. However, the activity of G6PDH shows an increased activity. Results indicate that the decreas ed glycogen content in the hepatocellular carcinoma is due to the reduced glycogen synthetase activity and utilization of glucose by HMP pathway. (author). 2 tabs., 24 refs

  9. Ordered synthesis and mobilization of glycogen in the perfused heart

    International Nuclear Information System (INIS)

    Brainard, J.R.; Hutson, J.Y.; Hoekenga, D.E.; Lenhoff, R.

    1989-01-01

    The molecular order of synthesis and mobilization of glycogen in the perfused heart was studied by 13 C NMR. By varying the glucose isotopomer ([1- 13 C]glucose or [2- 13 C]glucose) supplied to the heart, glycogen synthesized at different times during the perfusion was labeled at different carbon sites. Subsequently, the in situ mobilization of glycogen during ischemia was observed by detection of labeled lactate derived from glycolysis of the glucosyl monomers. When [1- 13 C]glucose was given initially in the perfusion and [2- 13 C]glucose was given second, [2- 13 C]lactate was detected first during ischemia and [3- 13 C]lactate second. This result, and the equivalent result when the glucose labels were given in the reverse order, demonstrates that glycogen synthesis and mobilization are ordered in the heart, where glycogen is found morphologically only as β particles. Previous studies of glycogen synthesis and mobilization in liver and adipocytes have suggested that the organization of β particles into α particles was partially responsible for ordered synthesis and mobilization. The observations reported here for cardiac glycogen suggest that another mechanism is responsible. In addition to examine the ordered synthesis and mobilization of cardiac glycogen, the authors have selectively monitored the NMR properties of 13 C-labeled glycogen synthesized early in the perfusion during further glycogen synthesis from a second, differently labeled substrate. During synthesis from the second labeled glucose monomer, the glycogen resonance from the first label decreased in integrated intensity and increased in line width. These results suggest either that there is significant isotopic exchange of glucosyl monomers in glycogen during net synthesis or that glucosyl residues incorporated into glycogen undergo motional restrictions as further glycogen synthesis occurs

  10. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    Science.gov (United States)

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

  11. Glycogen and its metabolism: some new developments and old themes

    Science.gov (United States)

    Roach, Peter J.; Depaoli-Roach, Anna A.; Hurley, Thomas D.; Tagliabracci, Vincent S.

    2016-01-01

    Glycogen is a branched polymer of glucose that acts as a store of energy in times of nutritional sufficiency for utilization in times of need. Its metabolism has been the subject of extensive investigation and much is known about its regulation by hormones such as insulin, glucagon and adrenaline (epinephrine). There has been debate over the relative importance of allosteric compared with covalent control of the key biosynthetic enzyme, glycogen synthase, as well as the relative importance of glucose entry into cells compared with glycogen synthase regulation in determining glycogen accumulation. Significant new developments in eukaryotic glycogen metabolism over the last decade or so include: (i) three-dimensional structures of the biosynthetic enzymes glycogenin and glycogen synthase, with associated implications for mechanism and control; (ii) analyses of several genetically engineered mice with altered glycogen metabolism that shed light on the mechanism of control; (iii) greater appreciation of the spatial aspects of glycogen metabolism, including more focus on the lysosomal degradation of glycogen; and (iv) glycogen phosphorylation and advances in the study of Lafora disease, which is emerging as a glycogen storage disease. PMID:22248338

  12. Genetics Home Reference: glycogen storage disease type 0

    Science.gov (United States)

    ... skeletal muscle, glycogen stored in muscle cells is broken down to supply the cells with energy. The ... that is stored in the liver can be broken down rapidly when glucose is needed to maintain ...

  13. Genetics Home Reference: glycogen storage disease type VI

    Science.gov (United States)

    ... or elevated levels of ketones in the blood (ketosis). Ketones are molecules produced during the breakdown of ... and may use fats for energy, resulting in ketosis. Glycogen accumulates within liver cells, causing these cells ...

  14. 1H NMR visibility of mammalian glycogen in solution

    International Nuclear Information System (INIS)

    Zang, L.H.; Rothman, D.L.; Shulman, R.G.

    1990-01-01

    High-resolution 1 H NMR spectra of rabbit liver glycogen in 2 H 2 O were obtained at 500 MHz, and several resonances were assigned by comparison with the chemical shifts of α-linked diglucose molecules. The NMR relaxation times T 1 and T 2 of glycogen in 2 H 2 O were determined to be 1.1 and 0.029 s, respectively. The measured natural linewidth of the carbon-1 proton is in excellent agreement with that calculated from T 2 . The visibility measurements made by digesting glycogen and comparing glucose and glycogen signal intensities demonstrate that in spite of the very high molecular weight, all of the proton nuclei in glycogen contribute to the NMR spectrum. The result is not unexpected, since 100% NMR visibility was previously observed from the carbon nuclei of glycogen, due to the rapid intramolecular motions

  15. Alteration of liver parameters in non-alcoholic fatty liver disease in patients with metabolic síndrome

    Directory of Open Access Journals (Sweden)

    Alicia Sahuquillo Martínez

    2016-06-01

    Full Text Available The interest of non-alcoholic fatty liver disease (NAFLD is growing due to several reasons: high prevalence of the disease in the Western World, its capability to progress towards more aggressive histological forms and its association with diseases that increase cardiovascular risk. Objective: To analyze the alteration of liver parameters in NAFLD in patients with metabolic syndrome. Methods: A transverse, descriptive study of 100 patients with two or more cardiovascular risk factors was conducted. All patients signed informed consent. Patients selected were among those attending our Medical Office of Primary Attention and who had very little or no alcoholic consumption. A complete battery of analysis was performed including total abdominal ultrasound. Steatosis was evaluated and, if determined positive, patients were stratified in three degrees. The following determinations were collected: sex, personal and familial history of diabetes, arterial hypertension, dyslipidemia, age, weight, BMI, present pharmacological treatment, analytical parameters, blood pressure and abdominal perimeter. Results: 100 patients were included in the study, 56 (56% women and 44 (44% men, with an average age of 61,84 + 9,5 years 23% of all patients did not have NAFLD; 29% had mild NAFLD, 29% had moderate NAFLD and 19% had severe NAFLD. 82% of men presented NAFLD. 29% of women did not nave NAFLD. 22% were overweight and 38% were obese. Blood pressure was altered in 22% of men and 18% of women. 60% had altered fasting blood glucose. 36% had hypertriglyceridemia, 41% hypercholesterolemia with 65% high LDL cholesterol and 16% of low HDL cholesterol. 83% of patients had two or more criteria of metabolic syndrome. Average transaminases were: ALT 24.98 u/i; AST 32.19 u/i; GGT 55,65 u/i; ALT/AST ratio: 0.77. Lactate dehydrogenase 255.30 u/L. Alkaline phosphatase 82.80 u/L and bilirubin 0.78 mg/dL Conclusions: We did not find correlation between liver steatosis and alteration

  16. Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict liver regeneration.

    Science.gov (United States)

    Viswanathan, Preeti; Sharma, Yogeshwar; Gupta, Priya; Gupta, Sanjeev

    2018-03-05

    Acetaminophen hepatotoxicity is a leading cause of hepatic failure with impairments in liver regeneration producing significant mortality. Multiple intracellular events, including oxidative stress, mitochondrial damage, inflammation, etc., signify acetaminophen toxicity, although how these may alter cell cycle controls has been unknown and was studied for its significance in liver regeneration. Assays were performed in HuH-7 human hepatocellular carcinoma cells, primary human hepatocytes and tissue samples from people with acetaminophen-induced acute liver failure. Cellular oxidative stress, DNA damage and cell proliferation events were investigated by mitochondrial membrane potential assays, flow cytometry, fluorescence staining, comet assays and spotted arrays for protein expression after acetaminophen exposures. In experimental groups with acetaminophen toxicity, impaired mitochondrial viability and substantial DNA damage were observed with rapid loss of cells in S and G2/M and cell cycle restrictions or even exit in the remainder. This resulted from altered expression of the DNA damage regulator, ATM and downstream transducers, which imposed G1/S checkpoint arrest, delayed entry into S and restricted G2 transit. Tissues from people with acute liver failure confirmed hepatic DNA damage and cell cycle-related lesions, including restrictions of hepatocytes in aneuploid states. Remarkably, treatment of cells with a cytoprotective cytokine reversed acetaminophen-induced restrictions to restore cycling. Cell cycle lesions following mitochondrial and DNA damage led to failure of hepatic regeneration in acetaminophen toxicity but their reversibility offers molecular targets for treating acute liver failure. © 2018 John Wiley & Sons Ltd.

  17. THE LIVER OF WOODCHUCKS CHRONICALLY INFECTED WITH THE WOODCHUCK HEPATITIS VIRUS CONTAINS FOCI OF VIRUS CORE ANTIGEN NEGATIVE HEPATOCYTES WITH BOTH ALTERED AND NORMAL MORPHOLOGY

    Science.gov (United States)

    Xu, Chunxiao; Yamamoto, Toshiki; Zhou, Tianlun; Aldrich, Carol E.; Frank, Katy; Cullen, John M.; Jilbert, Allison R.; Mason, William S.

    2007-01-01

    The livers of woodchucks chronically infected with woodchuck hepatitis virus (WHV) contain foci of morphologically altered hepatocytes (FAH) with “basophilic”, “amphophilic” and “clear cell” phenotypes, which are possibly pre-neoplastic in nature. Interestingly, most fail to express detectable levels of WHV proteins and nucleic acids. We studied sections of WHV-infected liver tissue to determine if all foci of hepatocytes that failed to express detectable levels of WHV, as assessed by immunoperoxidase staining for WHV core antigen, could be classified morphologically as FAH. We found that at least half of the foci of WHV core antigen negative hepatocytes did not show clear morphological differences in either H&E or PAS (periodic acid Schiff) stained sections from surrounding hepatocytes, and were therefore not designated as FAH. In the second approach, we assayed core antigen negative foci for the presence of fetuin B, a serum protein produced by normal hepatocytes, but not by neoplastic hepatocytes in hepatocellular carcinomas. Basophilic and amphophilic FAH had reduced levels of fetuin B compared to hepatocytes present in the surrounding liver; fetuin B staining was detected in clear cell FAH but the level could not be accurately assessed because of the displacement of fetuin B to the cell periphery by accumulated glycogen. The foci of morphologically normal WHV core antigen negative hepatocytes had similar levels of fetuin B to that of the surrounding hepatocytes. The co-existence of at least four types of WHV core antigen negative foci, including those with no obvious morphologic changes, raises the possibility that the different foci arise from distinct primary events. We hypothesize that a common event is loss of the ability to express WHV, allowing these hepatocytes to escape immune mediated cell death and to undergo clonal expansion to form distinct foci. PMID:17078989

  18. Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.

    Science.gov (United States)

    Witek, Rafal P; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S; Cheong, Yeiwon; Fearing, Caitlin M; Agboola, Kolade M; Chen, Wei; Diehl, Anna Mae

    2009-01-01

    Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes, and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). MF-HSC and cholangiocytes were exposed to platelet-derived growth factor to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy and immunoblots, and applied to Hh-reporter-containing cells. Microparticles were obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, an Hh signaling inhibitor. Effects on SEC gene expression were evaluated by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Platelet-derived growth factor-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically-active Hh ligands. BDL increased release of Hh-containing exosome-enriched microparticles into plasma and bile. Transmission electron microscopy and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy.

  19. Exercise in muscle glycogen storage diseases.

    Science.gov (United States)

    Preisler, Nicolai; Haller, Ronald G; Vissing, John

    2015-05-01

    Glycogen storage diseases (GSD) are inborn errors of glycogen or glucose metabolism. In the GSDs that affect muscle, the consequence of a block in skeletal muscle glycogen breakdown or glucose use, is an impairment of muscular performance and exercise intolerance, owing to 1) an increase in glycogen storage that disrupts contractile function and/or 2) a reduced substrate turnover below the block, which inhibits skeletal muscle ATP production. Immobility is associated with metabolic alterations in muscle leading to an increased dependence on glycogen use and a reduced capacity for fatty acid oxidation. Such changes may be detrimental for persons with GSD from a metabolic perspective. However, exercise may alter skeletal muscle substrate metabolism in ways that are beneficial for patients with GSD, such as improving exercise tolerance and increasing fatty acid oxidation. In addition, a regular exercise program has the potential to improve general health and fitness and improve quality of life, if executed properly. In this review, we describe skeletal muscle substrate use during exercise in GSDs, and how blocks in metabolic pathways affect exercise tolerance in GSDs. We review the studies that have examined the effect of regular exercise training in different types of GSD. Finally, we consider how oral substrate supplementation can improve exercise tolerance and we discuss the precautions that apply to persons with GSD that engage in exercise.

  20. Hepatic glycogen synthesis in the fetal mouse: An ultrastructural, morphometric, and autoradiographic investigation of the relationship between the smooth endoplasmic reticulum and glycogen

    International Nuclear Information System (INIS)

    Breslin, J.S.

    1989-01-01

    Fetal rodent hepatocytes undergo a rapid and significant accumulation of glycogen prior to birth. The distinct association of the smooth endoplasmic reticulum (SER) with glycogen during glycogen synthesis documented in the adult hepatocyte has not been clearly demonstrated in the fetus. The experiments described in this dissertation tested the hypothesis that SER is present and functions in the synthesis of fetal hepatic glycogen. Biochemical analysis, light microscopic (LM) histochemistry and electron microscope (EM) morphometry demonstrated that fetal hepatic glycogen synthesis began on day 15, with maximum accumulation occurring between days 17-19. Glycogen accumulation began in a small population of cells. Both the number of cells containing glycogen and the quantity of glycogen per cell increased as glycogen accumulated. Smooth endoplasmic reticulum (SER) was observed on day 14 of gestation and throughout fetal hepatic glycogen synthesis, primarily as dilated ribosome-free terminal extensions of rough endoplasmic reticulum (RER), frequently associated with glycogen. SER was in close proximity to isolated particles of glycogen and at the periphery of large compact glycogen deposits. Morphometry demonstrated that the membrane surface of SER in the average fetal hepatocyte increased as glycogen accumulated through day 18 and dropped significantly as glycogen levels peaked on day 19. Parallel alterations in RER membrane surface, indicated overall increases in ER membrane surface. Autoradiography following administration of 3 H-galactose demonstrated that newly synthesized glycogen was deposited near profiles of SER at day 16 and at day 18; however, at day 18 the majority of label was uniformly distributed over glycogen remote from profiles of SER

  1. Studies of gene expression and activity of hexokinase, phosphofructokinase and glycogen synthase in human skeletal muscle in states of altered insulin-stimulated glucose metabolism

    DEFF Research Database (Denmark)

    Vestergaard, H

    1999-01-01

    been reported to increase the basal concentration of muscle GS mRNA in NIDDM patients to a level similar to that seen in control subjects although insulin-stimulated glucose disposal rates remain reduced in NIDDM patients. In the insulin resistant states examined so far, basal and insulin-stimulated......When whole body insulin-stimulated glucose disposal rate is measured in man applying the euglycaemic, hyperinsulinaemic clamp technique it has been shown that approximately 75% of glucose is taken up by skeletal muscle. After the initial transport step, glucose is rapidly phosphorylated to glucose...... critical roles in glucose oxidation/glycolysis and glucose storage, respectively. Glucose transporters and glycogen synthase activities are directly and acutely stimulated by insulin whereas the activities of hexokinases and phosphofructokinase may primarily be allosterically regulated. The aim...

  2. Use of deuterium labelled glucose in evaluating the pathway of hepatic glycogen synthesis

    International Nuclear Information System (INIS)

    Goodman, M.N.; Masuoka, L.K.; deRopp, J.S.; Jones, A.D.

    1989-01-01

    Deuterium labelled glucose has been used to study the pathway of hepatic glycogen synthesis during the fasted-refed transition in rats. Deuterium enrichment of liver glycogen was determined using nuclear magnetic resonance as well as mass spectroscopy. Sixty minutes after oral administration of deuterated glucose to fasted rats, the portal vein blood was fully enriched with deuterated glucose. Despite this, less than half of the glucose molecules incorporated into liver glycogen contained deuterium. The loss of deuterium label from glucose is consistent with hepatic glycogen synthesis by an indirect pathway requiring prior metabolism of glucose. The use of deuterium labelled glucose may prove to be a useful probe to study hepatic glycogen metabolism. Its use may also find application in the study of liver glycogen metabolism in humans by a noninvasive means

  3. Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    Cheng, Sulin; Wiklund, Petri; Autio, Reija; Borra, Ronald; Ojanen, Xiaowei; Xu, Leiting; Törmäkangas, Timo; Alen, Markku

    2015-01-01

    BACKGROUND: Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49) and women (n = 52) with and without NAFLD. METHODS: Hepatic fat content was

  4. Carbohydrate supercompensation and muscle glycogen utilization during exhaustive running in highly trained athletes

    DEFF Research Database (Denmark)

    Madsen, K; Pedersen, P K; Rose, P

    1990-01-01

    regimen (Norm), the other after a diet and training programme intended to increase muscle glycogen levels (Carb). Muscle glycogen concentration in the gastrocnemius muscle increased by 25% (P less than 0.05) from 581 mmol.kg-1 dry weight, SEM 50 to 722 mmol.kg-1 dry weight, SEM 34 after Carb. Running time...... (0.92, SEM 0.01 vs 0.89, SEM 0.01; P less than 0.05). Since muscle glycogen utilization was identical in the two tests, the indication of higher utilization of total carbohydrate appears to be related to a higher utilization of liver glycogen. We have concluded that glycogen depletion...

  5. Effect of carbon tetrachloride on glycogen metabolism in fasted and refed mice

    International Nuclear Information System (INIS)

    Pushpendran, C.K.; Shenoy, B.V.; Eapen, J.

    1977-01-01

    Hepatic glycogen was depleted rapidly in fasted mice treated with CCl 4 . Glycogen breakdown was slow when CCl 4 was administered after 1 hr of refeeding. There was an initial increase and then a reduction in liver glycogen of mice refed for 2 hr prior to CCl 4 injection. The incorporation of glucose-U- 14 C into glycogen was higher in mice which were refed before CCl 4 administration than in fasted mice treated with the hepatotoxin. The specific activity of lactate was higher in CCl 4 treated mice. The data suggested differences in glycogen metabolism of fasted and refed mice in response to CCl 4 treatment. (author)

  6. Subtoxic Alterations in Hepatocyte-Derived Exosomes: An Early Step in Drug-Induced Liver Injury?

    Science.gov (United States)

    Holman, Natalie S; Mosedale, Merrie; Wolf, Kristina K; LeCluyse, Edward L; Watkins, Paul B

    2016-06-01

    Drug-induced liver injury (DILI) is a significant clinical and economic problem in the United States, yet the mechanisms that underlie DILI remain poorly understood. Recent evidence suggests that signaling molecules released by stressed hepatocytes can trigger immune responses that may be common across DILI mechanisms. Extracellular vesicles released by hepatocytes, principally hepatocyte-derived exosomes (HDEs), may constitute one such signal. To examine HDE alterations as a function of drug-induced stress, this work utilized prototypical hepatotoxicant acetaminophen (APAP) in male Sprague-Dawley (SD) rats, SD rat hepatocytes, and primary human hepatocytes. HDE were isolated using ExoQuick precipitation reagent and analyzed by quantification of the liver-specific RNAs albumin and microRNA-122 (miR-122). In vivo, significant elevations in circulating exosomal albumin mRNA were observed at subtoxic APAP exposures. Significant increases in exosomal albumin mRNA were also observed in primary rat hepatocytes at subtoxic APAP concentrations. In primary human hepatocytes, APAP elicited increases in both exosomal albumin mRNA and exosomal miR-122 without overt cytotoxicity. However, the number of HDE produced in vitro in response to APAP did not increase with exosomal RNA quantity. We conclude that significant drug-induced alterations in the liver-specific RNA content of HDE occur at subtoxic APAP exposures in vivo and in vitro, and that these changes appear to reflect selective packaging rather than changes in exosome number. The current findings demonstrate that translationally relevant HDE alterations occur in the absence of overt hepatocellular toxicity, and support the hypothesis that HDE released by stressed hepatocytes may mediate early immune responses in DILI. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Comparison of gene expression profiles altered by comfrey and riddelliine in rat liver.

    Science.gov (United States)

    Guo, Lei; Mei, Nan; Dial, Stacey; Fuscoe, James; Chen, Tao

    2007-11-01

    Comfrey (Symphytum officinale) is a perennial plant and has been consumed by humans as a vegetable, a tea and an herbal medicine for more than 2000 years. It, however, is hepatotoxic and carcinogenic in experimental animals and hepatotoxic in humans. Pyrrolizidine alkaloids (PAs) exist in many plants and many of them cause liver toxicity and/or cancer in humans and experimental animals. In our previous study, we found that the mutagenicity of comfrey was associated with the PAs contained in the plant. Therefore, we suggest that carcinogenicity of comfrey result from those PAs. To confirm our hypothesis, we compared the expression of genes and processes of biological functions that were altered by comfrey (mixture of the plant with PAs) and riddelliine (a prototype of carcinogenic PA) in rat liver for carcinogenesis in this study. Groups of 6 Big Blue Fisher 344 rats were treated with riddelliine at 1 mg/kg body weight by gavage five times a week for 12 weeks or fed a diet containing 8% comfrey root for 12 weeks. Animals were sacrificed one day after the last treatment and the livers were isolated for gene expression analysis. The gene expressions were investigated using Applied Biosystems Rat Whole Genome Survey Microarrays and the biological functions were analyzed with Ingenuity Analysis Pathway software. Although there were large differences between the significant genes and between the biological processes that were altered by comfrey and riddelliine, there were a number of common genes and function processes that were related to carcinogenesis. There was a strong correlation between the two treatments for fold-change alterations in expression of drug metabolizing and cancer-related genes. Our results suggest that the carcinogenesis-related gene expression patterns resulting from the treatments of comfrey and riddelliine are very similar, and PAs contained in comfrey are the main active components responsible for carcinogenicity of the plant.

  8. Glycogen synthesis from lactate in a chronically active muscle

    International Nuclear Information System (INIS)

    Talmadge, R.J.; Scheide, J.I.; Silverman, H.

    1989-01-01

    In response to neural overactivity (pseudomyotonia), gastrocnemius muscle fibers from C57Bl/6Jdy2J/dy2J mice have different metabolic profiles compared with normal mice. A population of fibers in the fast-twitch superficial region of the dy2J gastrocnemius stores unusually high amounts of glycogen, leading to an increased glycogen storage in the whole muscle. The dy2J muscle also contains twice as much lactate as normal muscle. A [ 14 C]lactate intraperitoneal injection leads to preferential 14 C incorporation into glycogen in the dy2J muscle compared with normal muscle. To determine whether skeletal muscles were incorporating lactate into glycogen without body organ (liver, kidney) input, gastrocnemius muscles were bathed in 10 mM [ 14 C]lactate with intact neural and arterial supply but with impeded venous return. The contralateral gastrocnemius serves as a control for body organ input. By using this in situ procedure, we demonstrate that under conditions of high lactate both normal and dy2J muscle can directly synthesize glycogen from lactate. In this case, normal whole muscle incorporates [14C] lactate into glycogen at a higher rate than dy2J whole muscle. Autoradiography, however, suggests that the high-glycogen-containing muscle fibers in the dy2J muscle incorporate lactate into glycogen at nearly four times the rate of normal or surrounding muscle fibers

  9. Phenobarbital Induces Alterations in the Proteome of Hepatocytes and Mesenchymal Cells of Rat Livers

    Science.gov (United States)

    Klepeisz, Philip; Sagmeister, Sandra; Haudek-Prinz, Verena; Pichlbauer, Melanie; Grasl-Kraupp, Bettina; Gerner, Christopher

    2013-01-01

    Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs) have concentrated on alterations induced in hepatocytes (HCs). A potential role of non-parenchymal liver cells (NPCs) in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB) which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme. PMID:24204595

  10. Phenobarbital induces alterations in the proteome of hepatocytes and mesenchymal cells of rat livers.

    Directory of Open Access Journals (Sweden)

    Philip Klepeisz

    Full Text Available Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs have concentrated on alterations induced in hepatocytes (HCs. A potential role of non-parenchymal liver cells (NPCs in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme.

  11. Mechanism of activation of glycogen phosphorylase by fructose in the liver. Stimulation of phosphorylase kinase related to the consumption of adenosine triphosphate.

    Science.gov (United States)

    Van de Werve, G; Hers, H G

    1979-01-15

    1. A dose-dependent activation of phosphorylase and consumption of ATP was observed in isolated hepatocytes incubated in the presence of fructose; histone kinase and phosphorylase kinase activities were unchanged at doses of this sugar that were fully effective on phosphorylase. The activation of phosphorylase by fructose was also observed in cells incubated in a Ca2+-free medium as well as in the livers of rats in vivo. 2. In a liver high-speed supernatant, fructose, tagatose and sorbose stimulated the activity of phosphorylase kinase; this effect was dependent on the presence of K+ ions, which are required for the activity of fructokinase; it was accompanied by the transformation of ATP into ADP. In the presence of hexokinase, glucose also stimulated phosphorylase kinase, both in an Na+ or a K+ medium. 3. The activities of partially purified muscle or liver phosphorylase kinase were unchanged in the presence of fructose. 4. Some properties of liver phosphorylase kinase are described, including a high molecular weight and an inhibition at ATP/Mg ratios above 0.5, as well as an effect of ATP concentration on the hysteretic behaviour of this enzyme. 5. The effect of fructose on the activation of phosphorylase is discussed in relation to the comsumption of ATP.

  12. Phosphorylation of sites 3 and 2 in rabbit skeletal muscle glycogen synthase by a multifunctional protein kinase (ATP-citrate lyase kinase)

    International Nuclear Information System (INIS)

    Sheorain, V.S.; Ramakrishna, S.; Benjamin, W.B.; Soderling, T.R.

    1985-01-01

    A multifunctional protein kinase, purified from rat liver as ATP-citrate lyase kinase, has been identified as a glycogen synthase kinase. This kinase catalyzed incorporation of up to 1.5 mol of and]2number 2 PO 4 /mol of synthase subunit associated with a decrease in the glycogen synthase activity ratio from 0.85 to a value of 0.15. Approximately 65-70% of the 34 PO 4 was incorporated into site 3 and 30-35% into site 2 as determined by reverse phase high performance liquid chromatography. This multifunctional kinase was distinguished from glycogen synthase kinase-3 on the basis of nucleotide and protein substrate specificities. Since the phosphate contents in glycogen synthase of sites 3 and 2 are altered in diabetes and by insulin administration, the possible involvement of the multifunctional kinase was explored. Glycogen synthase purified from diabetic rabbits was phosphorylated in vitro by this multifunctional kinase at only 10% of the rate compared to synthase purified from control rabbits. Treatment of the diabetics with insulin restored the synthase to a form that was readily phosphorylated in vitro

  13. Glycogen accumulation in normal and irradiated minced muscle autografts on frog gastrocnemius

    International Nuclear Information System (INIS)

    Malhotra, R.K.; Kaul, R.; Malhotra, N.

    1989-01-01

    Alterations induced in glycogen content and phosphorylase activity have been studied in normal and irradiated minced muscle autografts on frog gastrocnemius at days 1, 3, 5, 7, 10, 15 and 30 postgrafting. The changes observed in the glycogen content and phosphorylase activity conform to the degeneration and regeneration phases of muscle repair. An attempt has been made to explain the altered glycogen utilizing capacities of the frog skeletal muscle during its repair and regeneration. (author)

  14. Tissue glycogen and blood glucose in irradiated rats. I

    International Nuclear Information System (INIS)

    Ahlersova, E.; Ahlers, I.; Paulikova, E.; Praslicka, M.

    1980-01-01

    Fed and starved (overnight) male rats of the Wistar strain were exposed to whole-body irradiation with 14.35 Gy (1500 R) of X-rays. After irradiation and sham-irradiation all animals were starved until examination performed 1, 6, 24, 48 and 72 h after treatment. The concentration of glucose in the blood and the concentration of glycogen in the liver, heart, skeletal muscle, brown and white adipose tissue were determined. The concentrations of blood glucose and liver glycogen were found to increase between 1 and 6 h after irradiation of the starved animals. The most pronounced increase in glycogen concentration in the liver and heart muscle was observed 24 and 48 h after irradiation. A similar increase in the concentration of blood glucose was found between 48 and 72 h after irradiation. The fed and starved irradiated rats reacted differently, particularly between 48 and 72 h; the liver glycogen concentration decreased in the fed animals and remained elevated in the starved ones. Very high values of terminal glycemia were observed in both groups. The accumulation of glycogen in the heart muscle indicates that this organ is sensitive to ionizing radiation. (author)

  15. Regulation of glycogen synthesis in rat skeletal muscle after glycogen-depleting contractile activity: effects of adrenaline on glycogen synthesis and activation of glycogen synthase and glycogen phosphorylase.

    OpenAIRE

    Franch, J; Aslesen, R; Jensen, J

    1999-01-01

    We investigated the effects of insulin and adrenaline on the rate of glycogen synthesis in skeletal muscles after electrical stimulation in vitro. The contractile activity decreased the glycogen concentration by 62%. After contractile activity, the glycogen stores were fully replenished at a constant and high rate for 3 h when 10 m-i.u./ml insulin was present. In the absence of insulin, only 65% of the initial glycogen stores was replenished. Adrenaline decreased insulin-stimulated glycogen s...

  16. Molecular Basis of Impaired Glycogen Metabolism during Ischemic Stroke and Hypoxia

    Science.gov (United States)

    Hossain, Mohammed Iqbal; Roulston, Carli Lorraine; Stapleton, David Ian

    2014-01-01

    Background Ischemic stroke is the combinatorial effect of many pathological processes including the loss of energy supplies, excessive intracellular calcium accumulation, oxidative stress, and inflammatory responses. The brain's ability to maintain energy demand through this process involves metabolism of glycogen, which is critical for release of stored glucose. However, regulation of glycogen metabolism in ischemic stroke remains unknown. In the present study, we investigate the role and regulation of glycogen metabolizing enzymes and their effects on the fate of glycogen during ischemic stroke. Results Ischemic stroke was induced in rats by peri-vascular application of the vasoconstrictor endothelin-1 and forebrains were collected at 1, 3, 6 and 24 hours post-stroke. Glycogen levels and the expression and activity of enzymes involved in glycogen metabolism were analyzed. We found elevated glycogen levels in the ipsilateral hemispheres compared with contralateral hemispheres at 6 and 24 hours (25% and 39% increase respectively; PGlycogen synthase activity and glycogen branching enzyme expression were found to be similar between the ipsilateral, contralateral, and sham control hemispheres. In contrast, the rate-limiting enzyme for glycogen breakdown, glycogen phosphorylase, had 58% lower activity (Pglycogen debranching enzyme expression 24 hours post-stroke was 77% (Pglycogen phosphorylase activity and increased glycogen accumulation but did not alter glycogen synthase activity. Furthermore, elevated glycogen levels provided metabolic support to astrocytes during hypoxia. Conclusion Our study has identified that glycogen breakdown is impaired during ischemic stroke, the molecular basis of which includes reduced glycogen debranching enzyme expression level together with reduced glycogen phosphorylase and PKA activity. PMID:24858129

  17. Sustained high plasma mannose less sensitive to fluctuating blood glucose in glycogen storage disease type Ia children

    NARCIS (Netherlands)

    Nagasaka, Hironori; Yorifuji, Tohru; Bandsma, Robert H. J.; Takatani, Tomozumi; Asano, Hisaki; Mochizuki, Hiroshi; Takuwa, Mayuko; Tsukahara, Hirokazu; Inui, Ayano; Tsunoda, Tomoyuki; Komatsu, Haruki; Hiejima, Eitaro; Fujisawa, Tomoo; Hirano, Ken-ichi; Miida, Takashi; Ohtake, Akira; Taguchi, Tadao; Miwa, Ichitomo

    Plasma mannose is suggested to be largely generated from liver glycogen-oriented glucose-6-phosphate. This study examined plasma mannose in glycogen storage disease type Ia (GSD Ia) lacking conversion of glucose-6-phosphate to glucose in the liver. We initially examined fasting-and postprandial 2

  18. Glycogen storage disease type III. A case report.

    Science.gov (United States)

    de Waal, A; Röhm, G F; Hoek, B B; Potgieter, G M; Oosthuysen, W T

    1984-01-07

    A 5-year-old Black boy presented with massive hepatomegaly and muscle weakness. Liver biopsy revealed the presence of glycogen pools in the cytoplasm and nuclei of hepatocytes. Erythrocyte glycogen levels, identified as limit dextrin, were grossly increased. The galactose tolerance test as well as the two-stage glucagon stimulation test suggested a decrease in activity of both amylo-1,6-glucosidase and glucose-6-phosphatase enzymes. This was confirmed by direct assays performed on liver tissue and erythrocytes. The decrease in glucose-6-phosphatase activity was attributed to a secondary effect of limit dextrin.

  19. Glycogen Synthesis in Glycogenin 1-Deficient Patients: A Role for Glycogenin 2 in Muscle.

    Science.gov (United States)

    Krag, Thomas O; Ruiz-Ruiz, Cristina; Vissing, John

    2017-08-01

    Glycogen storage disease (GSD) type XV is a rare disease caused by mutations in the GYG1 gene that codes for the core molecule of muscle glycogen, glycogenin 1. Nonetheless, glycogen is present in muscles of glycogenin 1-deficient patients, suggesting an alternative for glycogen buildup. A likely candidate is glycogenin 2, an isoform expressed in the liver and heart but not in healthy skeletal muscle. We wanted to investigate the formation of glycogen and changes in glycogen metabolism in patients with GSD type XV. Two patients with mutations in the GYG1 gene were investigated for histopathology, ultrastructure, and expression of proteins involved in glycogen synthesis and metabolism. Apart from occurrence of polyglucosan (PG) bodies in few fibers, glycogen appeared normal in most cells, and the concentration was normal in patients with GSD type XV. We found that glycogenin 1 was absent, but glycogenin 2 was present in the patients, whereas the opposite was the case in healthy controls. Electron microscopy revealed that glycogen was present between and not inside myofibrils in type II fibers, compromising the ultrastructure of these fibers, and only type I fibers contained PG bodies. We also found significant changes to the expression levels of several enzymes directly involved in glycogen and glucose metabolism. To our knowledge, this is the first report demonstrating expression of glycogenin 2 in glycogenin 1-deficient patients, suggesting that glycogenin 2 rescues the formation of glycogen in patients with glycogenin 1 deficiency. Copyright © 2017 Endocrine Society

  20. Dietary supplementation with hybrid palm oil alters liver function in the common Marmoset.

    Science.gov (United States)

    Spreafico, Flavia; Sales, Rafael Carvalho; Gil-Zamorano, Judit; Medeiros, Priscylla da Costa; Latasa, Maria-Jesús; Lima, Monique Ribeiro; de Souza, Sergio Augusto Lopes; Martin-Hernández, Roberto; Gómez-Coronado, Diego; Iglesias-Gutierrez, Eduardo; Mantilla-Escalante, Diana C; das Graças Tavares do Carmo, Maria; Dávalos, Alberto

    2018-02-09

    Hybrid palm oil, which contains higher levels of oleic acid and lower saturated fatty acids in comparison with African palm oil, has been proposed to be somehow equivalent to extra virgin olive oil. However, the biological effects of its consumption are poorly described. Here we have explored the effects of its overconsumption on lipid metabolism in a non-human primate model, the common marmoset. Dietary supplementation of marmoset with hyperlipidic diet containing hybrid palm oil for 3 months did not modify plasma lipids levels, but increased glucose levels as compared to the supplementation with African palm oil. Liver volume was unexpectedly found to be more increased in marmosets consuming hybrid palm oil than in those consuming African palm oil. Hepatic total lipid content and circulating transaminases were dramatically increased in animals consuming hybrid palm oil, as well as an increased degree of fibrosis. Analysis of liver miRNAs showed a selective modulation of certain miRNAs by hybrid palm oil, some of which were predicted to target genes involved in cell adhesion molecules and peroxisomal pathways. Our data suggest that consumption of hybrid palm oil should be monitored carefully, as its overconsumption compared to that of African palm oil could involve important alterations to hepatic metabolism.

  1. 13C MRS Studies of the Control of Hepatic Glycogen Metabolism at High Magnetic Fields

    Directory of Open Access Journals (Sweden)

    Corin O. Miller

    2017-06-01

    Full Text Available Introduction: Glycogen is the primary intracellular storage form of carbohydrates. In contrast to most tissues where stored glycogen can only supply the local tissue with energy, hepatic glycogen is mobilized and released into the blood to maintain appropriate circulating glucose levels, and is delivered to other tissues as glucose in response to energetic demands. Insulin and glucagon, two current targets of high interest in the pharmaceutical industry, are well-known glucose-regulating hormones whose primary effect in liver is to modulate glycogen synthesis and breakdown. The purpose of these studies was to develop methods to measure glycogen metabolism in real time non-invasively both in isolated mouse livers, and in non-human primates (NHPs using 13C MRS.Methods: Livers were harvested from C57/Bl6 mice and perfused with [1-13C] Glucose. To demonstrate the ability to measure acute changes in glycogen metabolism ex-vivo, fructose, glucagon, and insulin were administered to the liver ex-vivo. The C1 resonance of glycogen was measured in real time with 13C MRS using an 11.7T (500 MHz NMR spectrometer. To demonstrate the translatability of this approach, NHPs (male rhesus monkeys were studied in a 7 T Philips MRI using a partial volume 1H/13C imaging coil. NPHs were subjected to a variable IV infusion of [1-13C] glucose (to maintain blood glucose at 3-4x basal, along with a constant 1 mg/kg/min infusion of fructose. The C1 resonance of glycogen was again measured in real time with 13C MRS. To demonstrate the ability to measure changes in glycogen metabolism in vivo, animals received a glucagon infusion (1 μg/kg bolus followed by 40 ng/kg/min constant infusion half way through the study on the second study session.Results: In both perfused mouse livers and in NHPs, hepatic 13C-glycogen synthesis (i.e., monotonic increases in the 13C-glycogen NMR signal was readily detected. In both paradigms, addition of glucagon resulted in cessation of glycogen

  2. Incorporation of phosphate into glycogen by glycogen synthase.

    Science.gov (United States)

    Contreras, Christopher J; Segvich, Dyann M; Mahalingan, Krishna; Chikwana, Vimbai M; Kirley, Terence L; Hurley, Thomas D; DePaoli-Roach, Anna A; Roach, Peter J

    2016-05-01

    The storage polymer glycogen normally contains small amounts of covalently attached phosphate as phosphomonoesters at C2, C3 and C6 atoms of glucose residues. In the absence of the laforin phosphatase, as in the rare childhood epilepsy Lafora disease, the phosphorylation level is elevated and is associated with abnormal glycogen structure that contributes to the pathology. Laforin therefore likely functions in vivo as a glycogen phosphatase. The mechanism of glycogen phosphorylation is less well-understood. We have reported that glycogen synthase incorporates phosphate into glycogen via a rare side reaction in which glucose-phosphate rather than glucose is transferred to a growing polyglucose chain (Tagliabracci et al. (2011) Cell Metab13, 274-282). We proposed a mechanism to account for phosphorylation at C2 and possibly at C3. Our results have since been challenged (Nitschke et al. (2013) Cell Metab17, 756-767). Here we extend the evidence supporting our conclusion, validating the assay used for the detection of glycogen phosphorylation, measurement of the transfer of (32)P from [β-(32)P]UDP-glucose to glycogen by glycogen synthase. The (32)P associated with the glycogen fraction was stable to ethanol precipitation, SDS-PAGE and gel filtration on Sephadex G50. The (32)P-signal was not affected by inclusion of excess unlabeled UDP before analysis or by treatment with a UDPase, arguing against the signal being due to contaminating [β-(32)P]UDP generated in the reaction. Furthermore, [(32)P]UDP did not bind non-covalently to glycogen. The (32)P associated with glycogen was released by laforin treatment, suggesting that it was present as a phosphomonoester. The conclusion is that glycogen synthase can mediate the introduction of phosphate into glycogen, thereby providing a possible mechanism for C2, and perhaps C3, phosphorylation. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Enzymatic regulation of seasonal glycogen cycling in the freeze-tolerant wood frog, Rana sylvatica.

    Science.gov (United States)

    do Amaral, M Clara F; Lee, Richard E; Costanzo, Jon P

    2016-12-01

    Liver glycogen is an important energy store in vertebrates, and in the freeze-tolerant wood frog, Rana sylvatica, this carbohydrate also serves as a major source of the cryoprotectant glucose. We investigated how variation in the levels of the catalytic subunit of protein kinase A (PKAc), glycogen phosphorylase (GP), and glycogen synthase (GS) relates to seasonal glycogen cycling in a temperate (Ohioan) and subarctic (Alaskan) populations of this species. In spring, Ohioan frogs had reduced potential for glycogen synthesis, as evidenced by low GS activity and high PKAc protein levels. In addition, glycogen levels in spring were the lowest of four seasonal samples, as energy input was likely directed towards metabolism and somatic growth during this period. Near-maximal glycogen levels were reached by mid-summer, and remained unchanged in fall and winter, suggesting that glycogenesis was curtailed during this period. Ohioan frogs had a high potential for glycogenolysis and glycogenesis in winter, as evidenced by large glycogen reserves, high levels of GP and GS proteins, and high GS activity, which likely allows for rapid mobilization of cryoprotectant during freezing and replenishing of glycogen reserves during thawing. Alaskan frogs also achieved a near-maximal liver glycogen concentration by summer and displayed high glycogenic and glycogenolytic potential in winter, but, unlike Ohioan frogs, started replenishing their energy reserves early in spring. We conclude that variation in levels of both glycogenolytic and glycogenic enzymes likely happens in response to seasonal changes in energetic strategies and demands, with winter survival being a key component to understanding the regulation of glycogen cycling in this species.

  4. Splenectomy Leads to Amelioration of Altered Gut Microbiota and Metabolome in Liver Cirrhosis Patients

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2018-05-01

    Full Text Available Dysbiosis of gut microbiota and metabolome is a frequently encountered condition in liver cirrhosis (LC patients. The severity of liver dysfunction was found to be correlated with the degree of microbial dysbiosis. Several clinical studies have indicated liver function improvement after therapeutic splenectomy for LC-induced hypersplenism. We sought to determine whether such post-splenectomy outcome is pertinent to modulation of the abnormal gut microenvironment in LC patients. A cross-sectional study including 12 LC patients and 16 healthy volunteers was first conducted, then a before–after study in the cohort of patients was carried out before and 6 months after splenectomy. Fecal samples were collected in hospital. Temporal bacterial (n = 40 and metabolomics (n = 30 profiling was performed using 16s rRNA gene sequencing and ultra performance liquid chromatography/mass spectrometer (UPLC/MS, respectively. Our results revealed that microbial composition in patients was clearly different from that in healthy controls (HCs, evidenced by considerable taxonomic variation. Along with improved liver function (Child–Pugh score, the patients also displayed similar gut microbiota profile and predicted metagenome function to that of HCs after splenectomy. Enterobacteriaceae and Streptococcaceae, two LC-enriched families showing positive relation with Child–Pugh score, exhibited significantly decreased abundance after splenectomy. At the genus level, 11 genera were differentially abundant between patients and HCs, but 9 genera of them restituted to normal levels by certain degree after splenectomy. PICRUSt analysis showed that the relative abundance of 17 KEGG pathways was partially restored after splenectomy. Four of them were amino acid-related pathways: lysine degradation, tryptophan degradation, amino acid metabolism, and protein digestion and absorption. These findings were supported by metabonomics results which showed that relative abundance

  5. Tissue glycogen and blood glucose in irradiated rats. II

    International Nuclear Information System (INIS)

    Ahlersova, E.; Ahlers, I.; Praslicka, M.

    1980-01-01

    Male rats of the Wistar strain were continuously irradiated with 0.57 Gy (60 R) of gamma rays from a 60 Co source. Irradiation lasted from 1 to 50 days in an experimental field where also control animals shielded from radiation were placed. After a 16 h starvation, the concentration of glucose in the blood and of glycogen in the liver and the heart was determined 1, 3, 7, 14, 21, 25, 32, 39 and 50 days after the beginning of irradiation. The concentration of blood glucose in irradiated rats did not practically differ from that of control animals during the whole period of investigation. The concentration of liver glycogen in irradiated animals was higher than that in the controls during all time intervals, except for day 1. The values of glycogen in the heart muscle were approximately identical in the irradiated and control rats, except for day 21 when they sharply increased in the irradiated animals. In addition to the investigation of blood glucose and tissue glycogen during continuous irradiation, these parameters were studied immediately, and 1, 6 and 12 months after continuous irradiation with a daily exposure of 0.57 Gy (60 R) up to a total exposure of 14.35 Gy (1500 R) of gamma rays. Considerably higher values of liver glycogen were detected in the irradiated rats immediately, and 1 and 6 months after the end of irradiation. (author)

  6. The effect of alterations in total coenzyme A on metabolic pathways in the liver and heart

    International Nuclear Information System (INIS)

    Schlosser, C.A.S.

    1989-01-01

    The first set of experiments involved in vitro experiments using primary cultures of rat hepatocytes. A range of conditions were developed which resulted in cell cultures with variations in total CoA over a range of 1.3 to 2.9 nmol/mg protein with identical hormonal activation which simulated metabolic stress. Elevations of total CoA levels above that of controls due to preincubation with cyanamide plus pantothenate were correlated with diminished rates of total ketone body production, 3-hydroxybutyrate production and ratios of 3 hydroxybutyrate/acetoactetate with palmitate as substrate. In contrast, cells with elevated total CoA levels had higher rates of [ 14 C] CO 2 production from radioactive palmitate which implied greater flux of acetyl CoA units into the TCA cycle and less to the pathway of ketogenesis. The second set of experiments were designed to alter total CoA levels in vivo by maintaining rats on a chronic ethanol diet with or without pantothenate-supplementation. The effect of alterations of CoA on mitochondrial metabolism was evaluated by measuring substrate oxidation rates in liver and heat mitochondria as well as ketone body production with palmitoyl-1-carnitine as substrate

  7. Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy

    International Nuclear Information System (INIS)

    Lockwood, A.H.; Yap, E.W.; Rhoades, H.M.; Wong, W.H.

    1991-01-01

    We measured CBF and the CMRglc in normal controls and in patients with severe liver disease and evidence for minimal hepatic encephalopathy using positron emission tomography. Regions were defined in frontal, temporal, parietal, and visual cortex; the thalamus; the caudate; the cerebellum; and the white matter along with a whole-slice value obtained at the level of the thalamus. There was no difference in whole-slice CBF and CMRglc values. Individual regional values were normalized to the whole-slice value and subjected to a two-way repeated measures analysis of variance. When normalized CBF and CMRglc values for regions were compared between groups, significant differences were demonstrated (F = 5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and caudate in patients and lower values in the cortex. Standardized coefficients extracted from a discriminant function analysis permitted correct group assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The similarity of the altered pattern of cerebral metabolism and flow in our patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow and metabolism and that this, in turn, causes the clinical expression of encephalopathy

  8. Lassa virus infection in experimentally infected marmosets: liver pathology and immunophenotypic alterations in target tissues.

    Science.gov (United States)

    Carrion, Ricardo; Brasky, Kathleen; Mansfield, Keith; Johnson, Curtis; Gonzales, Monica; Ticer, Anysha; Lukashevich, Igor; Tardif, Suzette; Patterson, Jean

    2007-06-01

    Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.

  9. Why does the brain (not) have glycogen?

    Science.gov (United States)

    DiNuzzo, Mauro; Maraviglia, Bruno; Giove, Federico

    2011-05-01

    In the present paper we formulate the hypothesis that brain glycogen is a critical determinant in the modulation of carbohydrate supply at the cellular level. Specifically, we propose that mobilization of astrocytic glycogen after an increase in AMP levels during enhanced neuronal activity controls the concentration of glucose phosphates in astrocytes. This would result in modulation of glucose phosphorylation by hexokinase and upstream cell glucose uptake. This mechanism would favor glucose channeling to activated neurons, supplementing the already rich neuron-astrocyte metabolic and functional partnership with important implications for the energy compounds used to sustain neuronal activity. The hypothesis is based on recent modeling evidence suggesting that rapid glycogen breakdown can profoundly alter the short-term kinetics of glucose delivery to neurons and astrocytes. It is also based on review of the literature relevant to glycogen metabolism during physiological brain activity, with an emphasis on the metabolic pathways identifying both the origin and the fate of this glucose reserve. Copyright © 2011 WILEY Periodicals, Inc.

  10. Clinical evaluation of computed tomography in various liver diseases with diffuse pathological alteration

    International Nuclear Information System (INIS)

    Toyoda, Eiichi

    1983-01-01

    Twenty seven cases of acute hepatitis 120 of chronic hepatitis 133 of liver cirrhosis 79 of fatty liver 28 of alcoholic liver injury 5 of intrahepatic cholestasis 22 of obstructive jaundice and 100 normal adults were studied. EMI CT 5005 whole body scanner was used to obtain scan of the liver and spleen, and CT number of them was measured in EMI units, so L/S ratio was calculated by dividing both EMI number. In the patients with obesity, the EMI number of the liver and/or spleen were higher than normal controls. In acute hepatitis, EMI number of the liver, spleen and L/S ratio were no significant differences compared with controls. In chronic hepatitis inactive and active type, EMI number of the liver and spleen were no significant differences between chronic hepatitis and controls, but L/S ratio was lower than that of controls. In cirrhosis of the liver, EMI number of the liver and L/S ratio were lower than that of controls, but EMI number of the spleen had no significant differences compared with controls. In patients with fatty liver, EMI number of the liver and L/S ratio were lower than any other diffuse liver diseases. In alcoholic liver injury had no significant differences from normal controls in liver EMI number, spleen EMI number and L/S ratio. In intrahepatic cholestsis, there was weak inverse corelation between liver EMI number and serum total bilirubin, and in obstructive jaundice strong inverse corelation was seen. In diffuse liver diseases, fatty infiltration, liver cell necrosis, fibrosis or jaundice may decrease the EMI number of the liver and/or L/S ratio, but except for fatty liver, it seems difficult to diagnose the diffuse liver diseases by CT scanner. (J.P.N.)

  11. Body mass dependence of glycogen stores in the anoxia-tolerant crucian carp ( Carassius carassius L.)

    Science.gov (United States)

    Vornanen, Matti; Asikainen, Juha; Haverinen, Jaakko

    2011-03-01

    Glycogen is a vital energy substrate for anaerobic organisms, and the size of glycogen stores can be a limiting factor for anoxia tolerance of animals. To this end, glycogen stores in 12 different tissues of the crucian carp ( Carassius carassius L.), an anoxia-tolerant fish species, were examined. Glycogen content of different tissues was 2-10 times higher in winter (0.68-18.20% of tissue wet weight) than in summer (0.12-4.23%). In scale, bone and brain glycogen stores were strongly dependent on body mass (range between 0.6 and 785 g), small fish having significantly more glycogen than large fish ( p glycogen reserves, measured as a sum of glycogen from different tissues, varied from 6.1% of the body mass in the 1-g fish to 2.0% in the 800-g fish. Since anaerobic metabolic rate scales down with body size, the whole body glycogen reserves could provide energy for approximately 79 and 88 days of anoxia in small and large fish, respectively. There was, however, a drastic difference in tissue distribution of glycogen between large and small fish: in the small fish, the liver was the major glycogen store (68% of the stores), while in the large fish, the white myotomal muscle was the principal deposit of glycogen (57%). Since muscle glycogen is considered to be unavailable for blood glucose regulation, its usefulness in anoxia tolerance of the large crucian carp might be limited, although not excluded. Therefore, mobilization of muscle glycogen under anoxia needs to be rigorously tested.

  12. Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Henriette Kirchner

    2016-03-01

    Conclusion: Severely obese non-diabetic and type 2 diabetic patients have distinct alterations in the hepatic methylome and transcriptome, with hypomethylation of several genes controlling glucose metabolism within the ATF-motif regulatory site. Obesity appears to shift the epigenetic program of the liver towards increased glycolysis and lipogenesis, which may exacerbate the development of insulin resistance.

  13. Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients

    DEFF Research Database (Denmark)

    Kirchner, Henriette; Sinha, Indranil; Gao, Hui

    2016-01-01

    OBJECTIVE: Epigenetic modifications contribute to the etiology of type 2 diabetes. METHOD: We performed genome-wide methylome and transcriptome analysis in liver from severely obese men with or without type 2 diabetes and non-obese men to discover aberrant pathways underlying the development...... in four of these genes in liver of severely obese non-diabetic and type 2 diabetic patients, suggesting epigenetic regulation of transcription by altered ATF-DNA binding. CONCLUSION: Severely obese non-diabetic and type 2 diabetic patients have distinct alterations in the hepatic methylome...... and transcriptome, with hypomethylation of several genes controlling glucose metabolism within the ATF-motif regulatory site. Obesity appears to shift the epigenetic program of the liver towards increased glycolysis and lipogenesis, which may exacerbate the development of insulin resistance....

  14. Effect of L-ascorbic acid on nickel-induced alterations in serum lipid profiles and liver histopathology in rats.

    Science.gov (United States)

    Das, Kusal K; Gupta, Amrita Das; Dhundasi, Salim A; Patil, Ashok M; Das, Swastika N; Ambekar, Jeevan G

    2006-01-01

    Nickel exposure greatly depletes intracellular ascorbate and alters ascorbate-cholesterol metabolism. We studied the effect of the simultaneous oral treatment with L-ascorbic acid (50 mg/100 g body weight (BW) and nickel sulfate (2.0 mg/100 g BW, i.p) on nickelinduced changes in serum lipid profiles and liver histopathology. Nickel-treated rats showed a significant increase in serum low-density lipoprotein-cholesterol, total cholesterol, triglycerides, and a significant decrease in serum high-density lipoprotein-cholesterol. In the liver, nickel sulfate caused a loss of normal architecture, fatty changes, extensive vacuolization in hepatocytes, eccentric nuclei, and Kupffer cell hypertrophy. Simultaneous administration of L-ascorbic acid with nickel sulfate improved both the lipid profile and liver impairments when compared with rats receiving nickel sulfate only. The results indicate that L-ascorbic acid is beneficial in preventing nickel-induced lipid alterations and hepatocellular damage.

  15. 13C Mrs Studies of the Control of Hepatic Glycogen Metabolism at High Magnetic Fields

    Science.gov (United States)

    Miller, Corin O.; Cao, Jin; Zhu, He; Chen, Li M.; Wilson, George; Kennan, Richard; Gore, John C.

    2017-06-01

    Introduction: Glycogen is the primary intracellular storage form of carbohydrates. In contrast to most tissues where stored glycogen can only supply the local tissue with energy, hepatic glycogen is mobilized and released into the blood to maintain appropriate circulating glucose levels, and is delivered to other tissues as glucose in response to energetic demands. Insulin and glucagon, two current targets of high interest in the pharmaceutical industry, are well known glucose-regulating hormones whose primary effect in liver is to modulate glycogen synthesis and breakdown. The purpose of these studies was to develop methods to measure glycogen metabolism in real time non-invasively both in isolated mouse livers, and in non-human primates (NHPs) using 13C MRS. Methods: Livers were harvested from C57/Bl6 mice and perfused with [1-13C] Glucose. To demonstrate the ability to measure acute changes in glycogen metabolism ex-vivo, fructose, glucagon, and insulin were administered to the liver ex-vivo. The C1 resonance of glycogen was measured in real time with 13C MRS using an 11.7T (500 MHz) NMR spectrometer. To demonstrate the translatability of this approach, NHPs (male rhesus monkeys) were studied in a 7 T Philips MRI using a partial volume 1H/13C imaging coil. NPHs were subjected to a variable IV infusion of [1-13C] glucose (to maintain blood glucose at 3-4x basal), along with a constant 1 mg/kg/min infusion of fructose. The C1 resonance of glycogen was again measured in real time with 13C MRS. To demonstrate the ability to measure changes in glycogen metabolism in vivo, animals received a glucagon infusion (1 μg/kg bolus followed by 40 ng/kg/min constant infusion) half way through the study on the second study session. Results: In both perfused mouse livers and in NHPs, hepatic 13C-glycogen synthesis (i.e. monotonic increases in the 13C-glycogen NMR signal) was readily detected. In both paradigms, addition of glucagon resulted in cessation of glycogen synthesis

  16. Unacylated ghrelin does not alter mitochondrial function, redox state and triglyceride content in rat liver in vivo

    Directory of Open Access Journals (Sweden)

    Gianluca Gortan Cappellari

    2015-12-01

    Full Text Available Changes in liver mitochondrial function with more oxidized redox state and enhanced inflammation may contribute to the onset of obesity- and insulin resistance-associated hepatic complications, including non-alcoholic fatty liver disease and steato-hepatitis. Unacylated ghrelin (UnAG is a gastric hormone reported to be associated with lower oxidative stress in different cell types, but its potential effects on liver mitochondrial function, redox state and inflammation in vivo remains undetermined. We investigated the impact of chronic UnAG overexpression (Tg Myh6/Ghrl leading to systemic upregulation of circulating hormone on mitochondrial ATP production, redox state (oxidized-to-total glutathione and inflammation markers in lean mice. Compared to wild-type animals (wt, Tg Myh6/Ghrl had superimposable liver weight, triglyceride content and plasma lipid profile. Liver mitochondrial enzyme activities and ATP production as well as oxidized-to-total glutathione were also similar in the two groups. In addition, no differences were observed in tissue inflammation marker TNF-alpha between wild-type and Tg Myh6/Ghrl animals. Thus, chronic systemic UnAG upregulation does not alter liver triglyceride content, mitochondrial function, redox state and inflammation markers in lean mice. These findings do not support a major role of UnAG as a physiological modulator of in vivo liver oxidative-lipid metabolism and inflammation.

  17. Glycogen phosphorylation and Lafora disease.

    Science.gov (United States)

    Roach, Peter J

    2015-12-01

    Covalent phosphorylation of glycogen, first described 35 years ago, was put on firm ground through the work of the Whelan laboratory in the 1990s. But glycogen phosphorylation lay fallow until interest was rekindled in the mid 2000s by the finding that it could be removed by a glycogen-binding phosphatase, laforin, and that mutations in laforin cause a fatal teenage-onset epilepsy, called Lafora disease. Glycogen phosphorylation is due to phosphomonoesters at C2, C3 and C6 of glucose residues. Phosphate is rare, ranging from 1:500 to 1:5000 phosphates/glucose depending on the glycogen source. The mechanisms of glycogen phosphorylation remain under investigation but one hypothesis to explain C2 and perhaps C3 phosphate is that it results from a rare side reaction of the normal synthetic enzyme glycogen synthase. Lafora disease is likely caused by over-accumulation of abnormal glycogen in insoluble deposits termed Lafora bodies in neurons. The abnormality in the glycogen correlates with elevated phosphorylation (at C2, C3 and C6), reduced branching, insolubility and an enhanced tendency to aggregate and become insoluble. Hyperphosphorylation of glycogen is emerging as an important feature of this deadly childhood disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. MRI morphologic alterations after liver SBRT. Direct dose correlation with intermodal matching

    Energy Technology Data Exchange (ETDEWEB)

    Boda-Heggemann, Judit; Jahnke, Anika; Jahnke, Lennart; Vogel, Lena; Simeonova-Chergou, Anna O.; Herskind, Carsten; Wenz, Frederik; Lohr, Frank [University of Heidelberg, Department of Radiation Oncology, University Medical Center Mannheim, Mannheim (Germany); Attenberger, Ulrike; Budjan, Johannes [University of Heidelberg, Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Mannheim (Germany)

    2016-09-15

    CT morphologic and histopathologic alterations have been reported after SBRT. We analyzed the correlation of MRI morphologic alterations with radiation doses to assess the potential for MRI-based dose-effect correlation in healthy liver tissue. MRI data of 24 patients with liver metastases 7±3 weeks after image-guided SBRT in deep-inspiration breath-hold were retrospectively analyzed. MRI images were intermodally matched to the planning CT and corresponding dose distribution. Absolute doses were converted to EQD{sub 2,α/β=x} with α/β values of 2, 3 for healthy liver tissue, 8 Gy for modelled predamaged liver tissue and 10 Gy for tumor tissue. A central nonenhancing area was observed within the isodose lines of nominally 48.2 ± 15.2 Gy, EQD{sub 2Gy/α/β=10} 92.5 ± 27.7 Gy. Contrast-enhancement around the central nonenhancing area was observed within the isodose lines of nominally 46.9 ± 15.3 Gy, EQD{sub 2Gy/α/β=10} 90.5 ± 28.3 Gy. Outside the high-dose volume, in the beam path, characteristic sharply defined, nonblurred MRI morphologic alterations were observed that corresponded with the following isodose lines: T1-intensity changes occurred at isodose lines of nominally 21.9 ± 6.7 Gy (EQD{sub 2,α/β=2} 42.5 ± 8.7 Gy, EQD{sub 2,α/β=3} 38.5 ± 7.6 Gy, EQD{sub 2,α/β=8} 30.2 ±6.3 Gy). T2-hyper/hypointensity was observed within isodose lines of nominally 22.4 ± 6.6 Gy (EQD{sub 2,α/β=2} 42.7 ± 8.1 Gy, EQD{sub 2,α/β=3} 38.7 ± 7 Gy; EQD{sub 2,α/β=8} 30.5 ± 5.9 Gy). Using deformable matching, direct spatial/dosimetric correlation of SBRT-induced changes in liver tissue was possible. In the PTV high-dose region, a central nonenhancing area and peripheral contrast medium accumulation was observed. Beam path doses of 38-42 Gy (EQD{sub 2,α/β=2-3}) induce characteristic MRI morphologic alterations. (orig.) [German] CT-morphologische Veraenderungen nach SBRT sind beschrieben und korrelieren mit histopathologischen Veraenderungen. Ziel war es, MRT

  19. Possible mechanism for changes in glycogen metabolism in unloaded soleus muscle

    Science.gov (United States)

    Henriksen, E. J.; Tischler, M. E.

    1985-01-01

    Carbohydrate metabolism has been shown to be affected in a number of ways by different models of hypokinesia. In vivo glycogen levels in the soleus muscle are known to be increased by short-term denervation and harness suspension. In addition, exposure to 7 days of hypogravity also caused a dramatic increase in glycogen concentration in this muscle. The biochemical alterations caused by unloading that may bring about these increases in glycogen storage in the soleus were sought.

  20. Increased hepatic glycogen synthetase and decreased phosphorylase in trained rats

    DEFF Research Database (Denmark)

    Galbo, H; Saugmann, P; Richter, Erik

    1979-01-01

    Rats were either physically trained by a 12 wk swimming program or were freely eating or weight matched, sedentary controls. Trained rats had a higher relative liver weight and total hepatic glycogen synthetase (EC 2.4.1.11) activity and a lower phosphorylase (EC 2.4.1.1) activity than the other...

  1. Determination of aluminium induced metabolic changes in mice liver: a Fourier transform infrared spectroscopy study.

    Science.gov (United States)

    Sivakumar, S; Sivasubramanian, J; Khatiwada, Chandra Prasad; Manivannan, J; Raja, B

    2013-06-01

    In this study, we made a new approach to evaluate aluminium induced metabolic changes in liver tissue of mice using Fourier transform infrared spectroscopy analysis taking one step further in correlation with strong biochemical evidence. This finding reveals the alterations on the major biochemical constituents, such as lipids, proteins, nucleic acids and glycogen of the liver tissues of mice. The peak area value of amide A significantly decrease from 288.278±3.121 to 189.872±2.012 between control and aluminium treated liver tissue respectively. Amide I and amide II peak area value also decrease from 40.749±2.052 to 21.170±1.311 and 13.167±1.441 to 8.953±0.548 in aluminium treated liver tissue respectively. This result suggests an alteration in the protein profile. The absence of olefinicCH stretching band and CO stretching of triglycerides in aluminium treated liver suggests an altered lipid levels due to aluminium exposure. Significant shift in the peak position of glycogen may be the interruption of aluminium in the calcium metabolism and the reduced level of calcium. The overall findings exhibit that the liver metabolic program is altered through increasing the structural modification in proteins, triglycerides and quantitative alteration in proteins, lipids, and glycogen. All the above mentioned modifications were protected in desferrioxamine treated mice. Histopathological results also revealed impairment of aluminium induced alterations in liver tissue. The results of the FTIR study were found to be in agreement with biochemical studies and which demonstrate FTIR can be used successfully to indicate the molecular level changes. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Somatomedin-C stimulates glycogen synthesis in fetal rat hepatocytes

    International Nuclear Information System (INIS)

    Freemark, M.; D'Ercole, A.J.; Handwerger, S.

    1985-01-01

    The effects of somatomedin-C/insulin-like growth factor I (Sm-C) on glycogen metabolism in cultured hepatocytes from 20-day-old rat fetuses have been examined and compared with the effects of insulin. Sm-C (25-375 ng/ml; 3.25-50 nM) stimulated dose-dependent increases in [ 14 C]glucose incorporation into glycogen (14.4-72.9% and total cell glycogen content (10.6-34.3%. Maximal stimulation of glycogen synthesis by Sm-C occurred at 2-4 h of incubation. Insulin (10 nM to 10 microM) also stimulated [ 14 C]glucose incorporation but its potency was only 1/20th that of Sm-C. The time course of stimulation of glucose incorporation by insulin was identical to that of Sm-C, the dose-response curves of the two hormones were parallel, and the maximal effects of insulin were not enhanced by simultaneous exposure of cells to Sm-C. These findings suggest that Sm-C and insulin stimulate glycogenesis in fetal liver through similar or identical mechanisms. Since the potency of Sm-C was 20 times greater than that of insulin, the glycogenic action of insulin in fetal liver may be mediated through binding to a hepatic receptor which also binds Sm-C. In addition to having mitogenic effects on fetal tissues, Sm-C may have direct anabolic effects on fetal carbohydrate metabolism

  3. A new non-degradative method to purify glycogen.

    Science.gov (United States)

    Tan, Xinle; Sullivan, Mitchell A; Gao, Fei; Li, Shihan; Schulz, Benjamin L; Gilbert, Robert G

    2016-08-20

    Liver glycogen, a complex branched glucose polymer containing a small amount of protein, is important for maintaining glucose homeostasis (blood-sugar control) in humans. It has recently been found that glycogen molecular structure is impaired in diabetes. Isolating the carbohydrate polymer and any intrinsically-attached protein(s) is an essential prerequisite for studying this structural impairment. This requires an effective, non-degradative and efficient purification method to exclude the many other proteins present in liver. Proteins and glycogen have different ranges of molecular sizes. Despite the plethora of proteins that might still be present in significant abundance after other isolation techniques, SEC (size exclusion chromatography, also known as GPC), which separates by molecular size, should separate those extraneous to glycogen from glycogen with any intrinsically associated protein(s). A novel purification method is developed for this, based on preparative SEC following sucrose gradient centrifugation. Proteomics is used to show that the new method compares favourably with current methods in the literature. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. iTRAQ-based proteomic analysis reveals alterations in the liver induced by restricted meal frequency in a pig model.

    Science.gov (United States)

    Liu, Jingbo; Liu, Zhengqun; Chen, Liang; Zhang, Hongfu

    2016-01-01

    The present study was conducted to investigate the effects of meal frequency on metabolite levels in pig plasma and hepatic proteome by isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Twenty-four pigs (60.7 ± 1.0 kg) consumed the same amount of feed either in 2 (M2, n = 12) or 12 (M12, n = 12) meals per day. After an 8-wk feeding period, plasma concentrations of metabolites and hormones, hepatic biochemical traits, and proteome (n = 4 per group) were measured. Pigs on the M12 regimen had lower average daily gain and gain-to-feed ratio than pigs fed the M2 regimen. The M2 regimen resulted in lower total lipid, glycogen, and triacylglycerol content in the liver and circulating triacylglycerol concentration than that in the M12 pigs. The metabolic hormone concentrations were not affected by meal frequency, with the exception of elevated fibroblast growth factor 21 concentrations in the M2 regimen compared with the M12 regimen. The iTRAQ-based proteomic analysis revealed 35 differentially expressed proteins in the liver between pigs fed two and 12 meals per day, and these differentially expressed proteins were involved in the regulation of general biological process such as glucose and energy metabolism, lipid metabolism, protein and amino acid metabolism, stress response, and cell redox homeostasis. Altogether, the proteomic results provide insights into the mechanism mediating the beneficial effects of restricted meal frequency on the metabolic fitness. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Short and long-term effects of internal irradiation on the murine hepatic glycogen and its metabolizing enzymes

    International Nuclear Information System (INIS)

    Gupta, N.K.

    1990-01-01

    Glycogen content and the activities of phosphorylase, phosphorhexose isomerase, glucose 6-phosphatase, glycogen synthesis' phosphorylase and succinate dehydrogenase have been biochemically determined in the liver of Swiss albino mice after radiocalcium internal irradiation up to 225 days posttreatment. Increase in the glycogen content and glycogen synthesis phosphorylase with a concomitant decrease in the activities of phosphorylase, glucose 6-phosphatase, phosphohexose isomerase and succinate dehydrogenase reveals inhibited glycolysis in the presence of normal glyogenesis and inhibited Kreb's cycle in the liver during early intervals. Decrease in the glycogen content at later stages along with decrease in the activities of all these enzymes is probably because of an inhibited glycogen biosynthesis and its catabolism through HMP shunt. (orig.)

  6. Glycogen depletion and resynthesis during 14 days of chronic low-frequency stimulation of rabbit muscle

    DEFF Research Database (Denmark)

    Prats, C; Bernal, C; Cadefau, J A

    2002-01-01

    Electro-stimulation alters muscle metabolism and the extent of this change depends on application intensity and duration. The effect of 14 days of chronic electro-stimulation on glycogen turnover and on the regulation of glycogen synthase in fast-twitch muscle was studied. The results showed that...

  7. Erythrocytes Membrane Alterations Reflecting Liver Damage in CCl₄-Induced Cirrhotic Rats: The Ameliorative Effect of Naltrexone

    Directory of Open Access Journals (Sweden)

    Fatemeh Sarhadi Kholari

    2016-11-01

    Full Text Available Cirrhosis is the consequence of chronic liver disease. Deleterious effects of oxidative stress on hepatocytes may be reflected in the erythrocyte membrane. Naltrexone (NTX has been shown to attenuate hepatocellular injury in fibrotic animal models. The aim of this study was to investigate the progressive effect of CCl4 on the liver and whether the improvement of liver cirrhosis can be monitored through alterations in the erythrocyte membrane. In this study, 84 male Wistar rats were divided into 4 groups and received reagents (i.p. as follows: 1- CCl₄, 2- NTX + CCl₄, 3- Mineral Oil (M, and 4- NTX + M. After 2, 6 and 8 weeks, the blood and liver tissue samples were collected. Plasma enzyme activities, the content of erythrocyte GSH and some membrane compositions, including protein carbonyl, protein sulfhydryl, and malondialdehyde were assessed. After 6 and 8 weeks, plasma enzyme activities and the content of protein carbonyl were higher in CCl4 group significantly, as compared to other groups (P<0.001. NTX significantly diminished protein carbonyl and plasma enzyme activities (P<0.001. GSH did not change until the 6th week. However, CCl4+NTX increased it significantly as compared to CCl₄ group (P<0.05. Protein sulfhydryl showed changes in NTX+CCl₄ group which indicated a significant increase in protein sulfhydryl content in a 6th week compared to CCl4 group (P<0.05. MDA did not show any significant alteration. CCl₄-induced cirrhosis is accompanied by increased content of oxidative stress markers, especially protein carbonyl of RBC membrane and plasma enzyme activities. This study shows that the progression of liver cirrhosis and the ameliorative effect of NTX can be followed through alterations of these markers.

  8. Small Bowel Transit and Altered Gut Microbiota in Patients With Liver Cirrhosis.

    Science.gov (United States)

    Liu, Yang; Jin, Ye; Li, Jun; Zhao, Lei; Li, Zhengtian; Xu, Jun; Zhao, Fuya; Feng, Jing; Chen, Huinan; Fang, Chengyuan; Shilpakar, Rojina; Wei, Yunwei

    2018-01-01

    Disturbance of the gut microbiota is common in liver cirrhosis (LC) patients, the underlying mechanisms of which are yet to be unfolded. This study aims to explore the relationship between small bowel transit (SBT) and gut microbiota in LC patients. Cross-sectional design was applied with 36 LC patients and 20 healthy controls (HCs). The gut microbiota was characterized by 16S rRNA gene sequencing. The Firmicutes/Bacteroidetes (F/B) ratio and the Microbial Dysbiosis index (MDI) were used to evaluate the severity of microbiota dysbiosis. The scintigraphy method was performed in patients to describe the objective values of SBT. Patients were then subdivided according to the Child-Pugh score (threshold = 5) or SBT value (threshold = 0.6) for microbiota analysis. LC patients were characterized by an altered gut microbiota; F/B ratios and MDI were higher than HC in both Child_5 (14.00 ± 14.69 vs. 2.86 ± 0.99, p gut microbiota between Child_ 5 and Child_5+ patients was inappreciable, but the SBT was relatively slower in Child_5+ patients (43 ± 26% vs. 80 ± 15%, p gut microbiota was observed between SBT_0.6- and SBT_0.6+ patients [Pr(> F ) = 0.0068, pMANOVA], with higher F/B ratios and MDI in SBT_0.6- patients (19.71 ± 16.62 vs. 7.33 ± 6.65, p gut microbiota abnormalities observed in patients with LC.

  9. Glycogen Storage Disease Type IV

    DEFF Research Database (Denmark)

    Bendroth-Asmussen, Lisa; Aksglaede, Lise; Gernow, Anne B

    2016-01-01

    molecular genetic analyses confirmed glycogen storage disease Type IV with the finding of compound heterozygosity for 2 mutations (c.691+2T>C and c.1570C>T, p.R524X) in the GBE1 gene. We conclude that glycogen storage disease Type IV can cause early miscarriage and that diagnosis can initially be made...

  10. Glycogen Synthase Kinase-3 is involved in glycogen metabolism control and embryogenesis of Rhodnius prolixus.

    Science.gov (United States)

    Mury, Flávia B; Lugon, Magda D; DA Fonseca, Rodrigo Nunes; Silva, Jose R; Berni, Mateus; Araujo, Helena M; Fontenele, Marcio Ribeiro; Abreu, Leonardo Araujo DE; Dansa, Marílvia; Braz, Glória; Masuda, Hatisaburo; Logullo, Carlos

    2016-10-01

    Rhodnius prolixus is a blood-feeding insect that transmits Trypanosoma cruzi and Trypanosoma rangeli to vertebrate hosts. Rhodnius prolixus is also a classical model in insect physiology, and the recent availability of R. prolixus genome has opened new avenues on triatomine research. Glycogen synthase kinase 3 (GSK-3) is classically described as a key enzyme involved in glycogen metabolism, also acting as a downstream component of the Wnt pathway during embryogenesis. GSK-3 has been shown to be highly conserved among several organisms, mainly in the catalytic domain region. Meanwhile, the role of GSK-3 during R. prolixus embryogenesis or glycogen metabolism has not been investigated. Here we show that chemical inhibition of GSK-3 by alsterpaullone, an ATP-competitive inhibitor of GSK3, does not affect adult survival rate, though it alters oviposition and egg hatching. Specific GSK-3 gene silencing by dsRNA injection in adult females showed a similar phenotype. Furthermore, bright field and 4'-6-diamidino-2-phenylindole (DAPI) staining analysis revealed that ovaries and eggs from dsGSK-3 injected females exhibited specific morphological defects. We also demonstrate that glycogen content was inversely related to activity and transcription levels of GSK-3 during embryogenesis. Lastly, after GSK-3 knockdown, we observed changes in the expression of the Wingless (Wnt) downstream target β-catenin as well as in members of other pathways such as the receptor Notch. Taken together, our results show that GSK-3 regulation is essential for R. prolixus oogenesis and embryogenesis.

  11. Muscle glycogen stores and fatigue

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Westerblad, Håkan; Nielsen, Joachim

    2013-01-01

      Studies performed at the beginning of the last century revealed the importance of carbohydrate as a fuel during exercise, and the importance of muscle glycogen on performance has subsequently been confirmed in numerous studies. However, the link between glycogen depletion and impaired muscle...... function during fatigue is not well understood and a direct cause-and-effect relationship between glycogen and muscle function remains to be established. The use of electron microscopy has revealed that glycogen is not homogeneously distributed in skeletal muscle fibres, but rather localized in distinct...... pools. Furthermore, each glycogen granule has its own metabolic machinery with glycolytic enzymes and regulating proteins. One pool of such glycogenolytic complexes is localized within the myofibrils in close contact with key proteins involved in the excitation-contraction coupling and Ca2+ release from...

  12. Protein targeting to glycogen is a master regulator of glycogen synthesis in astrocytes

    OpenAIRE

    E. Ruchti; P.J. Roach; A.A. DePaoli-Roach; P.J. Magistretti; I. Allaman

    2016-01-01

    The storage and use of glycogen, the main energy reserve in the brain, is a metabolic feature of astrocytes. Glycogen synthesis is regulated by Protein Targeting to Glycogen (PTG), a member of specific glycogen-binding subunits of protein phosphatase-1 (PPP1). It positively regulates glycogen synthesis through de-phosphorylation of both glycogen synthase (activation) and glycogen phosphorylase (inactivation). In cultured astrocytes, PTG mRNA levels were previously shown to be enhanced by the ...

  13. MRI and MR spectroscopy study on basal ganglia alterations in patients with liver cirrhosis

    International Nuclear Information System (INIS)

    Wu Haibo; Ma Lin; Cai Youquan; Li Tao; Li Dejun; Liang Li

    2007-01-01

    Objective: To study the signal changes and metabolic alterations in the basal ganglia (BG) by using magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) in patients with hepatic encephalopathy with and without parkinsonism. Methods: MRI and MRS in the basal ganglia were performed in 27 patients (22 males, 5 females, age ranging from 29 to 62 years) with liver cirrhosis and hepatic encephalopathy. 14 of the 27 patients were classified as having parkinsonian signs evaluated by Unified Parkinson's Disease Rating Scale (UPDRS) test. 18 age-matched healthy volunteers (13 males, 5 females, age ranging from 24 to 51 years) underwent MRI and MRS as a control group. Results: NAA/Cr levels (average numbers are 1.40±0.03, 1.35±0.03 respectively) showed no statistical difference between cirrhotic patients with hepatic encephalopathy and the control group (t=1.16, t=0.87, P>0.05). Values of signal hyperintensities (average numbers are 1.03±0.002, 1.04± 0.003 respectively) in globus pallidus and ratios of mI/Cr(average numbers are 0.63±0.01, 0.61± 0.02 respectively) and Cho/Cr (average numbers are 0.82±0.03, 0.80±0.02 respectively) showed no statistically significant differences between the control group and the 13 patients without parkinsonism (t=0.63, t=-0.52, t=-0.54, P>0.05), whereas values of signal hyperintensities (average numbers are 1.18±0.001, 1.04±0.003 respectively) in globus pallidus and ratios of mI/Cr (average numbers are 0.39±0.02, 0.63±0.01 respectively) and Cho/Cr(average numbers are 0.68±0.01, 0.82±0.03 respectively) shows statistically significant difference in patients without and with parkinsonism (t=-5.16, t=7.61, t=4.12, P<0.05). In patients with cirrhosis, the values of signal hyperintensities in globus pallidus were inversely correlated with the ratio for mI/Cr(r=-0.764, P<0.05) and Cho/Cr (r=-0.553, P<0.05), respectively. Conclusion: MRI and MRS may be useful tools in the evaluation of extrapyramidal

  14. Effect of carbon tetrachloride on glycogen metabolism in fasted and refed mice

    Energy Technology Data Exchange (ETDEWEB)

    Pushpendran, C K; Shenoy, B V; Eapen, J [Bhabha Atomic Research Centre, Bombay (India). Biochemistry and Food Technology Div.

    1977-11-01

    Hepatic glycogen was depleted rapidly in fasted mice treated with CCl/sub 4/. Glycogen breakdown was slow when CCl/sub 4/ was administered after 1 hr of refeeding. There was an initial increase and then a reduction in liver glycogen of mice refed for 2 hr prior to CCl/sub 4/ injection. The incorporation of glucose-U-/sup 14/C into glycogen was higher in mice which were refed before CCl/sub 4/ administration than in fasted mice treated with the hepatotoxin. The specific activity of lactate was higher in CCl/sub 4/ treated mice. The data suggested differences in glycogen metabolism of fasted and refed mice in response to CCl/sub 4/ treatment.

  15. Is Glycogenin Essential for Glycogen Synthesis?

    Science.gov (United States)

    Oldfors, Anders

    2017-07-05

    Glycogen synthesis requires a priming oligosaccharide, formed by autoglucosylation of glycogenin, a core protein in glycogen particles. In this edition of Cell Metabolism, Testoni et al. (2017) challenge this generally accepted concept by demonstrating that glycogenin inactivation in mice results in an increased amount of glycogen and not glycogen depletion. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Sulin Cheng

    Full Text Available Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49 and women (n = 52 with and without NAFLD.Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS. Serum samples were analyzed using a nuclear magnetic resonance (NMR metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot.Increased branched-chain amino acid (BCAA, aromatic amino acid (AAA and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all. Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all, whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all.Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

  17. Fructose-Drinking Water Induced Nonalcoholic Fatty Liver Disease and Ultrastructural Alteration of Hepatocyte Mitochondria in Male Wistar Rat

    Directory of Open Access Journals (Sweden)

    Norshalizah Mamikutty

    2015-01-01

    Full Text Available Background. Nonalcoholic fatty liver disease (NAFLD is one of the complications of the metabolic syndrome. It encompasses a wide range of disease spectrum from simple steatosis to liver cirrhosis. Structural alteration of hepatic mitochondria might be involved in the pathogenesis of NAFLD. Aims. In the present study, we used a newly established model of fructose-induced metabolic syndrome in male Wistar rats in order to investigate the ultrastructural changes in hepatic mitochondria that occur with fructose consumption and their association with NAFLD pathogenesis. Methods. The concentration of fructose-drinking water (FDW used in this study was 20%. Six male Wistar rats were supplemented with FDW 20% for eight weeks. Body composition and metabolic parameters were measured before and after 8 weeks of FDW 20%. Histomorphology of the liver was evaluated and ultrastructural changes of mitochondria were assessed with transmission electron micrograph. Results. After 8 weeks of fructose consumption, the animals developed several features of the metabolic syndrome. Moreover, fructose consumption led to the development of macrovesicular hepatic steatosis and mitochondrial ultrastructural changes, such as increase in mitochondrial size, disruption of the cristae, and reduction of matrix density. Conclusion. We conclude that in male Wistar rat 8-week consumption of FDW 20% leads to NAFLD likely via mitochondrial structural alteration.

  18. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice12345

    Science.gov (United States)

    Christensen, Karen E; Mikael, Leonie G; Leung, Kit-Yi; Lévesque, Nancy; Deng, Liyuan; Wu, Qing; Malysheva, Olga V; Best, Ana; Caudill, Marie A; Greene, Nicholas DE

    2015-01-01

    Background: Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions. Objective: Our goal was to investigate the impact of high folic acid intake on liver disease and methyl metabolism. Design: Folic acid–supplemented diet (FASD, 10-fold higher than recommended) and control diet were fed to male Mthfr+/+ and Mthfr+/− mice for 6 mo to assess gene-nutrient interactions. Liver pathology, folate and choline metabolites, and gene expression in folate and lipid pathways were examined. Results: Liver and spleen weights were higher and hematologic profiles were altered in FASD-fed mice. Liver histology revealed unusually large, degenerating cells in FASD Mthfr+/− mice, consistent with nonalcoholic fatty liver disease. High folic acid inhibited MTHFR activity in vitro, and MTHFR protein was reduced in FASD-fed mice. 5-Methyltetrahydrofolate, SAM, and SAM/S-adenosylhomocysteine ratios were lower in FASD and Mthfr+/− livers. Choline metabolites, including phosphatidylcholine, were reduced due to genotype and/or diet in an attempt to restore methylation capacity through choline/betaine-dependent SAM synthesis. Expression changes in genes of one-carbon and lipid metabolism were particularly significant in FASD Mthfr+/− mice. The latter changes, which included higher nuclear sterol regulatory element-binding protein 1, higher Srepb2 messenger RNA (mRNA), lower farnesoid X receptor (Nr1h4) mRNA, and lower Cyp7a1 mRNA, would lead to greater lipogenesis and reduced cholesterol catabolism into bile. Conclusions: We suggest that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo-MTHFR deficiency. This deficiency results in hepatocyte degeneration, suggesting a 2

  19. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice.

    Science.gov (United States)

    Christensen, Karen E; Mikael, Leonie G; Leung, Kit-Yi; Lévesque, Nancy; Deng, Liyuan; Wu, Qing; Malysheva, Olga V; Best, Ana; Caudill, Marie A; Greene, Nicholas D E; Rozen, Rima

    2015-03-01

    Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions. Our goal was to investigate the impact of high folic acid intake on liver disease and methyl metabolism. Folic acid-supplemented diet (FASD, 10-fold higher than recommended) and control diet were fed to male Mthfr(+/+) and Mthfr(+/-) mice for 6 mo to assess gene-nutrient interactions. Liver pathology, folate and choline metabolites, and gene expression in folate and lipid pathways were examined. Liver and spleen weights were higher and hematologic profiles were altered in FASD-fed mice. Liver histology revealed unusually large, degenerating cells in FASD Mthfr(+/-) mice, consistent with nonalcoholic fatty liver disease. High folic acid inhibited MTHFR activity in vitro, and MTHFR protein was reduced in FASD-fed mice. 5-Methyltetrahydrofolate, SAM, and SAM/S-adenosylhomocysteine ratios were lower in FASD and Mthfr(+/-) livers. Choline metabolites, including phosphatidylcholine, were reduced due to genotype and/or diet in an attempt to restore methylation capacity through choline/betaine-dependent SAM synthesis. Expression changes in genes of one-carbon and lipid metabolism were particularly significant in FASD Mthfr(+/-) mice. The latter changes, which included higher nuclear sterol regulatory element-binding protein 1, higher Srepb2 messenger RNA (mRNA), lower farnesoid X receptor (Nr1h4) mRNA, and lower Cyp7a1 mRNA, would lead to greater lipogenesis and reduced cholesterol catabolism into bile. We suggest that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo-MTHFR deficiency. This deficiency results in hepatocyte degeneration, suggesting a 2-hit mechanism whereby mutant hepatocytes cannot

  20. Liver

    International Nuclear Information System (INIS)

    Bernardino, M.E.; Sones, P.J. Jr.; Barton Price, R.; Berkman, W.A.

    1984-01-01

    Evaluation of the liver for focal lesions is extremely important because the liver is one of the most common sites for metastatic disease. Most patients with metastatic deposits to the liver have a survival rate of about 6 months. Thus, metastatic disease to the liver has an extremely grave prognosis. In the past patients with hepatic lesions had no therapeutic recourse. However, with recent aggressive surgical advances (such as partial hepatectomies) and hepatic artery embolization, survival of patients with hepatic metastases has increased. Thus it is important for noninvasive imaging not only to detect lesions early in their course, but also to give their true hepatic involvement and the extent of the neoplastic process elsewhere in the body. Recent advances in imaging have been rapidly changing over the past 5 years. These changes have been more rapid in computed tomography (CT) and ultrasound than in radionuclide imaging. Thus, the question addressed in this chapter is: What is the relationship of hepatic ultrasound to the other current diagnostic modalities in detecting metastatic liver disease and other focal liver lesions? Also, what is its possible future relationship to nuclear magnetic resonance?

  1. Glycogen storage disease type Ia: linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism.

    Science.gov (United States)

    Sever, Sakine; Weinstein, David A; Wolfsdorf, Joseph I; Gedik, Reyhan; Schaefer, Ernst J

    2012-01-01

    A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides >5000 mg/dL. The diagnosis of type 1A glycogen storage disease was made via the result of a liver biopsy, which showed increased glycogen and absent glucose-6-phosphatase enzyme activity. The patient was treated with dextrose administered orally, which was replaced by frequent feedings of cornstarch, which resulted in an improvement of her metabolic parameters. At age 18 years of age, she had marked hypertriglyceridemia (3860 mg/dL) and eruptive xanthomas and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels >75 mg/dL and lactate levels triglycerides 179, high-density lipoprotein cholesterol 32, and calculated low-density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m(2). Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels >75 mg/dL is critical in the management of this disease. Copyright © 2012. Published by Elsevier Inc.

  2. Type I Glycogen Storage Disease

    Science.gov (United States)

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  3. Glycogen supercompensation in rat soleus muscle during recovery from nonweight bearing

    Science.gov (United States)

    Henriksen, Erik J.; Kirby, Christopher R.; Tischler, Marc E.

    1989-01-01

    Events leading to the normalization of the glycogen metabolism in the soleus muscle of rat, altered by 72-h three days of hind-limb suspension, were investigated during the 72-h recovery period when the animals were allowed to bear weight on all four limbs. Relative importance of the factors affecting glycogen metabolism in skeletal muscle during the recovery period was also examined. Glycogen concentration was found to decrease within 15 min and up to 2 h of recovery, while muscle glucose 6-phosphate, and the fractional activities of glycogen phosphorylase and glycogen synthase increased. From 2 to 4 h, when the glycogen synthase activity remained elevated and the phosphorylase activity declined, glycogen concentration increased, until it reached maximum values at about 24 h, after which it started to decrease, reaching control values by 72 h. At 12 and 24 h, the inverse relationship between glycogen concentration and the synthase activity ratio was lost, indicating that the reloading transiently uncoupled glycogen control of this enzyme.

  4. Global Liver Proteome Analysis Using iTRAQ Reveals AMPK-mTOR-Autophagy Signaling Is Altered by Intrauterine Growth Restriction in Newborn Piglets.

    Science.gov (United States)

    Long, Baisheng; Yin, Cong; Fan, Qiwen; Yan, Guokai; Wang, Zhichang; Li, Xiuzhi; Chen, Changqing; Yang, Xingya; Liu, Lu; Zheng, Zilong; Shi, Min; Yan, Xianghua

    2016-04-01

    Intrauterine growth restriction (IUGR) impairs fetal growth and development, perturbs nutrient metabolism, and increases the risk of developing diseases in postnatal life. However, the underlying mechanisms by which IUGR affects fetal liver development and metabolism remain incompletely understood. Here, we applied a high-throughput proteomics approach and biochemical analysis to investigate the impact of IUGR on the liver of newborn piglets. As a result, we identified 78 differentially expressed proteins in the three biological replicates, including 31 significantly up-regulated proteins and 47 significantly down-regulated proteins. Among them, a majority of differentially expressed proteins were related to nutrient metabolism and mitochondrial function. Additionally, many significantly down-regulated proteins participated in the mTOR signaling pathway and the phagosome maturation signaling pathway. Further analysis suggested that glucose concentration and hepatic glycogen storage were both reduced in IUGR newborn piglets, which may contribute to AMPK activation and mTORC1 inhibition. However, AMPK activation and mTORC1 inhibition failed to induce autophagy in the liver of IUGR neonatal pigs. A possible reason is that PP2Ac, a potential candidate in autophagy regulation, is significantly down-regulated in the liver of IUGR newborn piglets. These findings may provide implications for preventing and treating IUGR in human beings and domestic animals.

  5. Alteration of Blood Parameters and Histoarchitecture of Liver and Kidney of Silver Barb after Chronic Exposure to Quinalphos

    Directory of Open Access Journals (Sweden)

    Golam Mohammod Mostakim

    2015-01-01

    Full Text Available Quinalphos (QP is commonly used for pest control in the agricultural fields surrounding freshwater reservoirs. This study was conducted to evaluate the chronic toxicity of this pesticide on blood parameters and some organs of silver barb, Barbonymus gonionotus. Fish were exposed to two sublethal concentrations, 0.47 ppm and 0.94 ppm, of QP for a period of 28 days. All the blood parameters (red blood cell, hematocrit, and hemoglobin and blood glucose except for white blood cells decreased with increasing concentration of toxicant and become significantly lower (p<0.05 at higher concentration when compared with control. The derived hematological indices of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were equally altered compared to control. Histoarchitectural changes of liver and kidney were observed after exposure to the QP. Hypertrophy of hepatocytes, mild to severe necrosis, ruptured central vein, and vacuolation were observed in the liver of treated groups. Highly degenerated kidney tubules and hematopoietic tissue, degeneration of renal corpuscle, vacuolization, and necrosis were evident in the kidney of treated groups. In conclusion, chronic exposure to QP at sublethal concentrations induced hematological and histological alterations in silver barb and offers a simple tool to evaluate toxicity derived alterations.

  6. Type I Glycogen Storage Disease

    Science.gov (United States)

    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now Glycogen Storage Disease Type ...

  7. Protein targeting to glycogen is a master regulator of glycogen synthesis in astrocytes

    KAUST Repository

    Ruchti, E.; Roach, P.J.; DePaoli-Roach, A.A.; Magistretti, Pierre J.; Allaman, I.

    2016-01-01

    to induce glycogen synthesis and accumulation. In contrast, siRNA-mediated downregulation of PTG resulted in a 2-fold decrease in glycogen levels. Interestingly, PTG downregulation strongly impaired long-term astrocytic glycogen synthesis induced by insulin

  8. A Ketone Ester Drink Increases Postexercise Muscle Glycogen Synthesis in Humans.

    Science.gov (United States)

    Holdsworth, David A; Cox, Peter J; Kirk, Tom; Stradling, Huw; Impey, Samuel G; Clarke, Kieran

    2017-09-01

    Physical endurance can be limited by muscle glycogen stores, in that glycogen depletion markedly reduces external work. During carbohydrate restriction, the liver synthesizes the ketone bodies, D-β-hydroxybutyrate, and acetoacetate from fatty acids. In animals and in the presence of glucose, D-β-hydroxybutyrate promotes insulin secretion and increases glycogen synthesis. Here we determined whether a dietary ketone ester, combined with plentiful glucose, can increase postexercise glycogen synthesis in human skeletal muscle. After an interval-based glycogen depletion exercise protocol, 12 well-trained male athletes completed a randomized, three-arm, blinded crossover recovery study that consisted of consumption of either a taste-matched, zero-calorie control or a ketone monoester drink, followed by a 10-mM glucose clamp or saline infusion for 2 h. The three postexercise conditions were control drink then saline infusion, control drink then hyperglycemic clamp, or ketone ester drink then hyperglycemic clamp. Skeletal muscle glycogen content was determined in muscle biopsies of vastus lateralis taken before and after the 2-h clamps. The ketone ester drink increased blood D-β-hydroxybutyrate concentrations to a maximum of 5.3 versus 0.7 mM for the control drink (P glycogen was 50% higher (246 vs 164 mmol glycosyl units per kilogram dry weight, P glycogen synthesis.

  9. In Vivo Acute on Chronic Ethanol Effects in Liver: A Mouse Model Exhibiting Exacerbated Injury, Altered Metabolic and Epigenetic Responses

    Directory of Open Access Journals (Sweden)

    Shivendra D. Shukla

    2015-11-01

    Full Text Available Chronic alcoholics who also binge drink (i.e., acute on chronic are prone to an exacerbated liver injury but its mechanism is not understood. We therefore investigated the in vivo effects of chronic and binge ethanol ingestion and compared to chronic ethanol followed by three repeat binge ethanol on the liver of male C57/BL6 mice fed ethanol in liquid diet (4% for four weeks followed by binge ethanol (intragastric administration, 3.5 g/kg body weight, three doses, 12h apart. Chronic followed by binge ethanol exacerbated fat accumulation, necrosis, decrease in hepatic SAM and SAM:SAH ratio, increase in adenosine levels, and elevated CYP2E1 levels. Histone H3 lysine acetylation (H3AcK9, dually modified phosphoacetylated histone H3 (H3AcK9/PS10, and phosphorylated H2AX increased after binge whereas phosphorylation of histone H3 ser 10 (H3S10 and H3 ser 28 (H3S28 increased after chronic ethanol-binge. Histone H3 lysine 4 and 9 dimethylation increased with a marked dimethylation in H3K9 in chronic ethanol binge group. Trimethylated histone H3 levels did not change. Nuclear levels of histone acetyl transferase GCN5 and histone deacetylase HDAC3 were elevated whereas phospho-CREB decreased in a distinctive manner. Taken together, acute on chronic ethanol ingestion caused amplification of liver injury and elicited characteristic profiles of histone modifications, metabolic alterations, and changes in nuclear protein levels. These findings demonstrate that chronic ethanol exposure renders liver more susceptible to repeat acute/binge ethanol induced acceleration of alcoholic liver disease.

  10. Sarcopenia in Patients with Chronic Liver Disease: Can It Be Altered by Diet and Exercise?

    Science.gov (United States)

    Kappus, Matthew R; Mendoza, Mardeli Saire; Nguyen, Douglas; Medici, Valentina; McClave, Stephen A

    2016-08-01

    Sarcopenia, a loss of muscle mass, is being increasingly recognized to have a deleterious effect on outcomes in patients with chronic liver disease. Factors related to diet and the inflammatory nature of chronic liver disease contribute to the occurrence of sarcopenia in these patients. Sarcopenia adversely influences quality of life, performance, morbidity, success of transplantation, and even mortality. Specific deficiencies in macronutrients (protein, polyunsaturated fatty acids) and micronutrients (vitamins C, D, and E, carotenoids, and selenium) have been linked to sarcopenia. Lessons learned from nutritional therapy in geriatric patient populations may provide strategies to manage sarcopenia in patients with liver disease. Combining diet modification and nutrient supplementation with an organized program of exercise may help ameliorate or even reverse the effects of sarcopenia on an already complex disease process.

  11. The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

    Energy Technology Data Exchange (ETDEWEB)

    Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H. [West Los Angeles VA Medical Center, CA (United States). Lipid Research Lab.]|[Univ. of California, Los Angeles, CA (United States). Dept. of Medicine; Giometti, C.S.; Mishler, K. [Argonne National Lab., IL (United States); Slavin, B.G. [Univ. of Southern California, Los Angeles, CA (United States)

    1997-07-01

    Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.

  12. Local depletion of glycogen with supramaximal exercise in human skeletal muscle fibres.

    Science.gov (United States)

    Gejl, Kasper D; Ørtenblad, Niels; Andersson, Erik; Plomgaard, Peter; Holmberg, Hans-Christer; Nielsen, Joachim

    2017-05-01

    Glycogen is stored in local spatially distinct compartments within skeletal muscle fibres and is the main energy source during supramaximal exercise. Using quantitative electron microscopy, we show that supramaximal exercise induces a differential depletion of glycogen from these compartments and also demonstrate how this varies with fibre types. Repeated exercise alters this compartmentalized glycogen depletion. The results obtained in the present study help us understand the muscle metabolic dynamics of whole body repeated supramaximal exercise, and suggest that the muscle has a compartmentalized local adaptation to repeated exercise, which affects glycogen depletion. Skeletal muscle glycogen is heterogeneously distributed in three separated compartments (intramyofibrillar, intermyofibrillar and subsarcolemmal). Although only constituting 3-13% of the total glycogen volume, the availability of intramyofibrillar glycogen is of particular importance to muscle function. The present study aimed to investigate the depletion of these three subcellular glycogen compartments during repeated supramaximal exercise in elite athletes. Ten elite cross-country skiers (aged 25 ± 4 years, V̇O2 max : 65 ± 4 ml kg -1  min -1 ; mean ± SD) performed four ∼4 min supramaximal sprint time trials (STT 1-4) with 45 min of recovery. The subcellular glycogen volumes in musculus triceps brachii were quantified from electron microscopy images before and after both STT 1 and 4. During STT 1, the depletion of intramyofibrillar glycogen was higher in type 1 fibres [-52%; (-89:-15%)] than type 2 fibres [-15% (-52:22%)] (P = 0.02), whereas the depletion of intermyofibrillar glycogen [main effect: -19% (-33:0%), P = 0.006] and subsarcolemmal glycogen [main effect: -35% (-66:0%), P = 0.03] was similar between fibre types. By contrast, only intermyofibrillar glycogen volume was significantly reduced during STT 4, in both fibre types [main effect: -31% (-50:-11%), P = 0

  13. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Czech Academy of Sciences Publication Activity Database

    Lake, A.D.; Novák, Petr; Shipkova, P.; Aranibar, N.; Robertson, D.; Reily, M.D.; Lu, Z.; Lehman-McKeeman, L.D.; Cherrington, N.J.

    2013-01-01

    Roč. 268, č. 2 (2013), s. 132-140 ISSN 0041-008X Institutional research plan: CEZ:AV0Z50510513 Institutional support: RVO:60077344 Keywords : Bile Acids * Liver * Metabolomics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.630, year: 2013

  14. Untargeted Metabolomics Analysis of ABCC6-Deficient Mice Discloses an Altered Metabolic Liver Profile

    DEFF Research Database (Denmark)

    Rasmussen, Mie Rostved; Nielsen, Kirstine Lykke; Christensen, Mia Benedicte Lykke Roest

    2016-01-01

    as more features were upregulated than downregulated in ABCC6-deficient mice. However, no differences of the identified metabolites in liver could be detected in plasma, whereas urine reflected some of the changes. Of note, N-acetylated amino acids and pantothenic acid (vitamin B5), which is involved...

  15. Morphometric alterations, steatosis, fibrosis and active caspase-3 detection in carbamate bendiocarb treated rabbit liver

    Czech Academy of Sciences Publication Activity Database

    Petrovová, E.; Purzyc, H.; Mazenský, D.; Luptáková, L.; Torma, N.; Sopoliga, I.; Sedmera, David

    2015-01-01

    Roč. 30, č. 2 (2015), s. 212-222 ISSN 1520-4081 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : bendiocarb * caspase-3 activity * fibrosis * toxicity * rabbit * liver Subject RIV: EA - Cell Biology Impact factor: 2.868, year: 2015

  16. Molecular cloning and characterization of glycogen synthase in Eriocheir sinensis.

    Science.gov (United States)

    Li, Ran; Zhu, Li-Na; Ren, Li-Qi; Weng, Jie-Yang; Sun, Jin-Sheng

    2017-12-01

    Glycogen plays an important role in glucose and energy homeostasis at cellular and organismal levels. In glycogen synthesis, glycogen synthase (GS) is a rate-limiting enzyme catalysing the addition of α-1,4-linked glucose units from (UDP) 3 -glucose to a nascent glycogen chain using glycogenin (GN) as a primer. While studies on mammalian liver GS (GYS2) are numerous, enzymes from crustaceans, which also use glycogen and glucose as their main energy source, have received less attention. In the present study, we amplified full-length GS cDNA from Eriocheir sinensis. Tissue expression profiling revealed the highest expression of GS in the hepatopancreas. During moulting, GS expression and activity declined, and glycogen levels in the hepatopancreas were reduced. Recombinant GS was expressed in Escherichia coli Rosetta (DE3), and induction at 37°C or 16°C yielded EsGS in insoluble inclusion bodies (EsGS-I) or in soluble form (EsGS-S), respectively. Enzyme activity was measured in a cell-free system containing glucose-6-phosphate (G6P), and both forms possessed glycosyltransferase activity, but refolded EsGS-I was more active. Enzyme activity of both GS and EsGS-I in the hepatopancreas was optimum at 25°C, which is coincident with the optimum growth temperature of Chinese mitten crab, and higher (37°C) or lower (16°C) temperatures resulted in lower enzyme activity. Taken together, the results suggest that GS may be important for maintaining normal physiological functions such as growth and reproduction. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Nucleic acid metabolism in human chronic liver disease by in vitro autoradiography. I. Altered RNA metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, T [Okayama Univ. (Japan). School of Medicine

    1976-06-01

    Biopsy liver specimens from healthy control subjects (N=5) and patients with various liver diseases (N=43) were investigated by the vitro autoradiography. The Leevy technique of adding /sup 3/H-5-uridine (/sup 3/H-U) to the incubation medium was used. In healthy subjects labeling with /sup 3/H-U was observed mostly in hepatocytes and Kupffer cells and the frequency of /sup 3/H-U labeled cells was extremely high. Higher frequencies of labeled fibrocytes and endothelial cells of the blood vessel were found in acute hepatitis than in control subjects. In the active form of chronic hepatitis, significantly higher counts of labeled fibrocytes, ductular cells and lymphocytes were found. In patients with acute hepatitis or the inactive form of chronic hepatitis, only a few labeled lymphocytes were observed. Larger numbers of labeled fibrocytes were found in patients with chronic hepatitis with sublobular hepatic necrosis, than in patients with the active form of chronic hepatitis. In cirrhotic livers, marked increases of labeled ductular cells, fibrocytes and bile duct cells were found. No significant labeling differences were observed in the hepatocytes of various liver diseases. In chronic hepatitis with sublobular hepatic necrosis, a more significant decrease of labeled Kupffer cells was present than in the inactive form of chronic hepatitis. Labeled ductular cells and fibrocytes increased as the disease progressed from acute hepatitis to liver cirrhosis. The labeling index of rosettes cells was intermediate between the hepatocytes and ductular cells. The ratio of labeled parenchymal to non-parenchymal cells decreased proportionally from chronic hepatitis to cirrhosis.

  18. Characterization of a canine model of glycogen storage disease type IIIa

    Directory of Open Access Journals (Sweden)

    Haiqing Yi

    2012-11-01

    Glycogen storage disease type IIIa (GSD IIIa is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously, a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR. The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT, aspartate transaminase (AST and alkaline phosphatase (ALP activities; serum creatine phosphokinase (CPK activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12 and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.

  19. Comparison of gene expression profiles altered by comfrey and riddelliine in rat liver

    OpenAIRE

    Fuscoe James; Dial Stacey; Mei Nan; Guo Lei; Chen Tao

    2007-01-01

    Abstract Background Comfrey (Symphytum officinale) is a perennial plant and has been consumed by humans as a vegetable, a tea and an herbal medicine for more than 2000 years. It, however, is hepatotoxic and carcinogenic in experimental animals and hepatotoxic in humans. Pyrrolizidine alkaloids (PAs) exist in many plants and many of them cause liver toxicity and/or cancer in humans and experimental animals. In our previous study, we found that the mutagenicity of comfrey was associated with th...

  20. Induction of an altered lipid phenotype by two cancer promoting treatments in rat liver.

    Science.gov (United States)

    Riedel, S; Abel, S; Swanevelder, S; Gelderblom, W C A

    2015-04-01

    Changes in lipid metabolism have been associated with tumor promotion in rat liver. Similarities and differences of lipid parameters were investigated using the mycotoxin fumonisin B1 (FB1) and the 2-acetylaminofluorene/partial hepatectomy (AAF/PH) treatments as cancer promoters in rat liver. A typical lipid phenotype was observed, including increased membranal phosphatidylethanolamine (PE) and cholesterol content, increased levels of C16:0 and monounsaturated fatty acids in PE and phosphatidylcholine (PC), as well as a decrease in C18:0 and long-chained polyunsaturated fatty acids in the PC fraction. The observed lipid changes, which likely resulted in changes in membrane structure and fluidity, may represent a growth stimulus exerted by the cancer promoters that could provide initiated cells with a selective growth advantage. This study provided insight into complex lipid profiles induced by two different cancer promoting treatments and their potential role in the development of hepatocyte nodules, which can be used to identify targets for the development of chemopreventive strategies against cancer promotion in the liver. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Hypoinsulinemic hypoglycemia triggered by liver injury in elderly subjects with low body weight: case reports

    Directory of Open Access Journals (Sweden)

    Takatoshi Anno

    2018-03-01

    Full Text Available Hypoglycemia is induced by many causes, especially over-dose of insulin or oral hypoglycemic agents in diabetic subjects. In such a case, hyperinsulinemic hypoglycemia is usually observed. On the other hand, it is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia. Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in clinical practice. Herein, we experienced similar 2 cases of non-diabetic hypoinsulinemic hypoglycemia. Both of them were elderly subjects with low body weight. Furthermore, it is likely that hypoinsulinemic hypoglycemia in both subjects was triggered by severe liver injury, at least in part, due to possible limited liver glycogen store. In elderly subjects with low body weight and/or malnutrition, metabolism in the liver is reduced and glycogen accumulation is decreased. Such alteration brings out acute and marked liver injury, which finally leads to the onset of severe hypoglycemia. It is known that not only liver injury but also multiple organ failure could be induced due to extreme emaciation in subjects. It is likely that in elderly subjects with low body weight and/or malnutrition, multiple organ failure including liver failure could be induced due to the similar reason. Therefore, we should be very careful of such subjects in order to avoid the development of multiple organ failure which leads to life-threatening situations. In conclusion, we should keep in mind the possibility of hypoinsulinemic hypoglycemia when we examine severe liver injury, especially in elderly or starving subjects with low body weight and limited liver glycogen stores.

  2. The Effects of Space Flight on Some Liver Enzymes Concerned with Carbohydrate and Lipid Metabolism in Rats

    Science.gov (United States)

    Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.

    1978-01-01

    The activities of about 30 enzymes concerned with carbohydrate and lipid metabolism and the levels of glycogen and of individual fatty acids were measured in livers of rats ex- posed to prolonged space flight (18.5 days) aboard COSMOS 986 Biosatellite. When flight stationary, (FS) and flight centrifuged (FC) rats were compared at recovery (R(sub 0)), decrceases in the activities of glycogen phosphorylase, alpha glycerphosphate, acyl transferase, diglyceride acyl transferase, acconitase and Epsilon-phosphogluconate dehydrogenase were noted in the weightless group (FS). The significance of these findings was strengthened since all activities, showing alterations at R(sub 0), returned to normal 25 days post-flight. Differences were also seen in levels of two liver constituents. When glycogen and total fatty acids of the two groups of flight animals were determined, differences that could be attributed to reduced gravity were observed, the FS group at R(sub 0) contained, on the average, more than twice the amount of glycogen than did controls ad a remarkable shift in the ratio of palmitate to palmitoleate were noted. These metabolic alterations appear to be unique to the weightless condition. Our data justify the conclusion that centrifugation during space flight is equivalent to terrestrial gravity.

  3. Pemulihan Kadar Glikogen Serta Peningkatan Konsumsi Glukosa dan Trigliserida Saat Aktivitas Fisik Pascapemberian Ekstrak Kulit Buah Manggis (GLYCOGEN RECOVERY AND INCREASE CONSUMPTION OF GLUCOSE AND TRIGLYCERIDE DURING PHYSICAL ACTIVITIES AFTER ADMINISTRA

    OpenAIRE

    I Nyoman Arsana; Ni Ketut Ayu Juliasih

    2016-01-01

    This study was aimed to investigate the effect of mangosteen rind on the glycogen recovery of themuscle and the liver, and the glucose and the triglyceride consumption during physical activities. ARandomized Block Design was applied with four treatments: control (K), physical activity (KF), physicalactivity and extract (FE),extract (E). The extract dosage was 400 mg/kg bodyweight/day administered forfour weeks. The assessed variables were the muscle glycogen, the liver glycogen, the blood gly...

  4. The hepatotoxic potential of a Prudhoe Bay crude oil: effect on mouse liver weight and composition

    International Nuclear Information System (INIS)

    Khan, S.; Irfan, M.; Rahimtula, A.D.

    1987-01-01

    The hepatotoxic properties of a Prudhoe Bay Crude Oil (PBCO) were evaluated in mice. Administration of PBCO (5.0 m1/kg body wt, daily for 2 days) to mice resulted in an increase in (i) liver wet and dry weight, (ii) hepatic total proteins RNA, glycogen and lotal lipids, and (iii) individual lipids such as cholesterol, triglycerides and phospholipids. Hepatic protein biosynthesis, determined in vivo by administration of L-[ 14 C] Leucine was increased in PBCO exposed in mice. The rate of 3 H incorporation from 3 H 2 O was significantly enhanced in liver fatty acids, cholesterol, triglycerides and thus ultimately in total lipids. Also, an increase in 3 H incorporation was noticed in hepatic glycogen after PBCO administration. The results suggest that PBCO may induce hepatotoxicity by altering the intermediary metabolism of biochemical constituents. (author) 39 refs

  5. Hexokinase 2, glycogen synthase and phosphorylase play a key role in muscle glycogen supercompensation

    DEFF Research Database (Denmark)

    Irimia, José M; Rovira, Jordi; Nielsen, Jakob N

    2012-01-01

    Glycogen-depleting exercise can lead to supercompensation of muscle glycogen stores, but the biochemical mechanisms of this phenomenon are still not completely understood.......Glycogen-depleting exercise can lead to supercompensation of muscle glycogen stores, but the biochemical mechanisms of this phenomenon are still not completely understood....

  6. Modelo experimental para restrição do crescimento fetal em ratos: efeito sobre o glicogênio hepático e morfometria intestinal e renal Experimental rat model for fetal growth restriction: effects on liver glycogen and intestinal and renal morphometry

    Directory of Open Access Journals (Sweden)

    Márcia Pereira Bueno

    2010-04-01

    Full Text Available OBJETIVO: avaliar a eficácia do modelo de RCIU por ligadura da artéria uterina simulando insuficiência placentária em ratos. MÉTODOS: fetos de ratas prenhes Sprague-Dawley foram divididos em três grupos: RCIU (restrição de crescimento intrauterino, com fetos submetidos à ligadura da artéria uterina com 18,5 dias de gestação (termo = 22 dias, C-RCIU (controle da restrição, com fetos do corno contralateral à ligadura, CE (Controle Externo, com fetos de ratas sem manipulação. Com 21,5 dias de gestação, foi realizada cesárea, os fetos foram pesados e dissecados para análise morfométrica e histológica do fígado, intestino e rins. RESULTADOS: os dados morfométricos avaliados mostraram o peso corpóreo (PC, hepático (PH e intestinal (PI dos fetos com RCIU menor que C-RCIU e CE (pPURPOSE: to evaluate the effectiveness of the IUGR model by uterine artery ligation mimicking placental insufficiency in rats. METHODS: sprague-Dawley rat fetuses were divided into three groups: IUGR (intrauterine growth restriction, with fetuses in the right horn of pregnant rats subjected to right uterine artery ligation at 18.5 days of gestation (term = 22 days; C-IUGR (control of restriction, with control fetuses in the left horn, and EC (external control, with fetuses of intact rats. Animals were harvested by cesarean section at day 21.5 days of gestation. Fetuses were weighed and then sacrificed. The intestine, liver, kidney and placenta were weighed and dissected for morphometric and histological analysis. RESULTS: the morphometric data showed decreased body weight (BW, liver weight (LW and intestinal weight (IW of fetuses with IUGR compared to C-IUGR and EC (p<0.001. The placental weight (PW, renal weight (RW and LW/BW, IW/BW, and RW/BW ratios did not change. IUGR fetuses had decreased kidney thickness (p<0.001 and decreased thickness of the intestinal mucosa and submucosa (p<0.05. Histological evaluation showed reduction of liver glycogen

  7. Cinnamon extract improves insulin sensitivity in the brain and lowers liver fat in mouse models of obesity.

    Science.gov (United States)

    Sartorius, Tina; Peter, Andreas; Schulz, Nadja; Drescher, Andrea; Bergheim, Ina; Machann, Jürgen; Schick, Fritz; Siegel-Axel, Dorothea; Schürmann, Annette; Weigert, Cora; Häring, Hans-Ulrich; Hennige, Anita M

    2014-01-01

    Treatment of diabetic subjects with cinnamon demonstrated an improvement in blood glucose concentrations and insulin sensitivity but the underlying mechanisms remained unclear. This work intends to elucidate the impact of cinnamon effects on the brain by using isolated astrocytes, and an obese and diabetic mouse model. Cinnamon components (eugenol, cinnamaldehyde) were added to astrocytes and liver cells to measure insulin signaling and glycogen synthesis. Ob/ob mice were supplemented with extract from cinnamomum zeylanicum for 6 weeks and cortical brain activity, locomotion and energy expenditure were evaluated. Insulin action was determined in brain and liver tissues. Treatment of primary astrocytes with eugenol promoted glycogen synthesis, whereas the effect of cinnamaldehyde was attenuated. In terms of brain function in vivo, cinnamon extract improved insulin sensitivity and brain activity in ob/ob mice, and the insulin-stimulated locomotor activity was improved. In addition, fasting blood glucose levels and glucose tolerance were greatly improved in ob/ob mice due to cinnamon extracts, while insulin secretion was unaltered. This corresponded with lower triglyceride and increased liver glycogen content and improved insulin action in liver tissues. In vitro, Fao cells exposed to cinnamon exhibited no change in insulin action. Together, cinnamon extract improved insulin action in the brain as well as brain activity and locomotion. This specific effect may represent an important central feature of cinnamon in improving insulin action in the brain, and mediates metabolic alterations in the periphery to decrease liver fat and improve glucose homeostasis.

  8. In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in animals and humans

    Science.gov (United States)

    Khowaja, Ameer; Choi, In-Young; Seaquist, Elizabeth R.; Öz, Gülin

    2015-01-01

    Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of 13C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the 13C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness. PMID:24676563

  9. Supplementation of glycerol or fructose via drinking water to grazing lambs on tissue glycogen level and lipogenesis.

    Science.gov (United States)

    Volpi-Lagreca, G; Duckett, S K

    2017-06-01

    Lambs ( = 18; 40.1 ± 7.4 kg BW) were used to assess supplementation of glycerol or fructose via drinking water on growth, tissue glycogen levels, postmortem glycolysis, and lipogenesis. Lambs were blocked by BW and allocated to alfalfa paddocks (2 lambs/paddock and 3 paddocks/treatment). Each paddock within a block was assigned randomly to drinking water treatments for 30 d: 1) control (CON), 2) 120 g fructose/L of drinking water (FRU), or 3) 120 g glycerol/L of drinking water (GLY). Lambs grazed alfalfa with free access to water treatments for 28 d and then were fasted in indoor pens for a final 2 d with access to only water treatments. Data were analyzed using the MIXED procedure of SAS with water treatment and time (when appropriate) in the model. During the 28-d grazing period, ADG was greater ( glycogen content × postmortem time was significant ( = 0.003) in LM and semitendinosus (ST) muscles. Glycogen content in the LM was greater ( Glycogen content in ST did not differ between treatments ( > 0.05). Liver glycogen content was over 14-fold greater ( glycogen branching enzyme in the liver. Overall, glycerol supplementation improved growth, reduced BW shrink during fasting, increased glycogen content in muscle and the liver, and stimulated de novo lipogenesis.

  10. Swelling of rat hepatocytes stimulates glycogen synthesis

    NARCIS (Netherlands)

    Baquet, A.; Hue, L.; Meijer, A. J.; van Woerkom, G. M.; Plomp, P. J.

    1990-01-01

    In hepatocytes from fasted rats, several amino acids are known to stimulate glycogen synthesis via activation of glycogen synthase. The hypothesis that an increase in cell volume resulting from amino acid uptake may be involved in the stimulation of glycogen synthesis is supported by the following

  11. Direct vs. indirect pathway of hepatic glycogen synthesis as a function of glucose infusion rate

    International Nuclear Information System (INIS)

    Bagby, G.J.; Lang, C.H.; Johnson, J.L.; Blakesly, H.L.; Spitzer, J.J.

    1986-01-01

    This study was initiated to determine the influence of the rate of exogenous glucose administration on liver glycogen synthesis by the direct (glucose uptake and incorporation into glycogen) vs the indirect pathway (glucose degradation to 3-carbon intermediates, e.g., lactate, prior to incorporation into glycogen). Catheterized rats were fasted 2 days prior to receiving a 3 hr infusion of glucose at rates of 0 to 230 μmol/min/kg containing tracer [6- 3 H]- and [U- 14 C]-glucose. Plasma glucose (r = 0.80), insulin (r = 0.90) and lactate (r = 0.84) were correlated with glucose infusion rate. The rate of liver glycogen deposition (0.46 +/- 0.03 μmol/min/g) did not differ between a glucose infusion rate of 20 and 230 μmol/min/kg. At the lowest and highest glucose infusion rates hepatic glycogenesis accounted for 87 +/- 6 and 9 +/- 1% of the total glucose load, respectively. The percent contribution of the direct pathways to glycogen deposition ([ 3 H] specific activity in hepatic glycogen/[ 3 H] specific activity in plasma glucose) increased from 16 +/- 3 to 83 +/- 5% from lowest to highest glucose infusion rates (prevailing plasma glucose concentrations: 9 +/- 1 and 21 +/- 2 mM, respectively). The results indicate that the relative contribution of the direct and indirect pathways of glucogen synthesis are dependent upon the glucose load or plasma glucose concentration

  12. The subcellular localization of yeast glycogen synthase is dependent upon glycogen content

    OpenAIRE

    Wilson, Wayne A.; Boyer, Michael P.; Davis, Keri D.; Burke, Michael; Roach, Peter J.

    2010-01-01

    The budding yeast, Saccharomyces cerevisiae, accumulates the storage polysaccharide glycogen in response to nutrient limitation. Glycogen synthase, the major form of which is encoded by the GSY2 gene, catalyzes the key regulated step in glycogen storage. Here, we utilize Gsy2p fusions to green fluorescent protein (GFP) to determine where glycogen synthase is located within cells. We demonstrate that the localization pattern of Gsy2-GFP depends upon the glycogen content of the cell. When glyco...

  13. Adrenalectomy mediated alterations in adrenergic activation of adenylate cyclase in rat liver

    International Nuclear Information System (INIS)

    El-Refai, M.; Chan, T.

    1986-01-01

    Adrenalectomy caused a large increase in the number of β-adrenergic binding sites on liver plasma membranes as measured by 125 I-iodocyanopindolol (22 and 102 fmol/mg protein for control and adrenalectomized (ADX) rats). Concomitantly an increase in the number of binding sites for 3 H-yohimbine was also observed (104 and 175 fmol/mg protein for control and adx membranes). Epinephrine-stimulated increase in cyclic AMP accumulation in isolated hepatocytes were greater in cells from ADX rats. This increase in β-adrenergic mediated action was much less than what may be expected as a result of the increase in the β-adrenergic binding in ADX membranes. In addition phenoxybenzamine (10 μM) further augmented this action of epinephrine in both control and ADX cells. To test the hypothesis that the increase in the number of the inhibitory α 2 -adrenergic receptors in adrenalectomy is responsible for the muted β-adrenergic response, the authors injected rats with pertussis toxin (PT). This treatment may cause the in vivo ribosylation of the inhibitory binding protein (Ni). Adenylate cyclase (AC) activity in liver plasma membranes prepared from treated and untreated animals was measured. In contrast with control rats, treatment of ADX rats with PT resulted in a significant increase in the basal activity of AC (5.5 and 7.7 pmol/mg protein/min for untreated and treated rats respectively). Isoproterenol (10 μM), caused AC activity to increase to 6.5 and 8.4 pmol/mg protein/min for membranes obtained from ADX untreated and ADX treated rats respectively. The α-adrenergic antagonists had no significant effect on the β-adrenergic-mediated activation of AC in liver plasma membranes from PT treated control and ADX rats. The authors conclude that the β-adrenergic activation of AC is attenuated by Ni protein both directly and as a result of activation of α-adrenergic receptors

  14. Rib fractures in chronic alcoholic men: Relationship with feeding habits, social problems, malnutrition, bone alterations, and liver dysfunction.

    Science.gov (United States)

    González-Reimers, Emilio; García-Valdecasas-Campelo, Elena; Santolaria-Fernández, Francisco; Milena-Abril, Antonio; Rodríguez-Rodríguez, Eva; Martínez-Riera, Antonio; Pérez-Ramírez, Alina; Alemán-Valls, María Remedios

    2005-10-01

    Rib fractures are common in alcoholics. This high prevalence might be due to ethanol-associated malnutrition, bone disease, liver dysfunction, or the peculiar lifestyle of the alcoholic with frequent trauma and altercations. In this study we try to discern the role of these factors on rib fracture (assessed on a plain thoracic X-ray film) in 81 consecutive alcoholic patients, 25 of them cirrhotics. Serum albumin, prothrombin aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl transpeptidase, C-terminal cross-linking telopeptide of type 1 collagen, osteocalcin, insulin growth factor 1, 1,25-dihydroxyvitamin D, parathyroid hormone, estradiol, free testosterone, and corticosterone were measured, and the patients also underwent assessment of bone mineral density by a HOLOGIC QDR-2000 bone densitometer (Waltham, MA, USA). Body mass index, triceps skinfold, and brachial perimeter were also determined, and the patients and their families were asked about tobacco consumption, social and familial links, consumption of ethanol by other members of the family, kind of job, and feeding habits. Forty-two male nondrinker sanitary workers of similar age served as controls. Forty of the 81 patients showed rib fractures. There was a statistically significant association between rib fractures and disruption of social and familial links, irregular feeding habits (in bars or pubs, not at home), ethanol consumption by close relatives, and intensity of tobacco consumption, but not between rib fractures and liver function tests, nutritional parameters, or bone mineral density, besides a nearly significant trend (p = .053) with the presence of osteopenia at the femoral neck. Patients with major withdrawal symptoms at admission also presented more frequent rib fractures. We conclude that rib fractures in alcoholics are related to the peculiar lifestyle of these patients rather than to bone alterations, liver dysfunction, or nutritional status.

  15. Alteration in Haematological and Liver Function Indices during Human Infection with Fasciola spp. Post Treatment with Triclabendazole

    Directory of Open Access Journals (Sweden)

    M.I. Edalatzadeh

    2006-07-01

    Full Text Available Introduction & Objective: Fascioliasis is a zoonotic parasitic disease, caused by the liver fluke, Fasciola spp.. Human is occasional host when ingesting the metacercaria by eating contaminated aquatic vegetable. In the two past decades, human fasciolasis was emerging as a problem of public health in the Guilan province; in Anzali city. Triclabendazole is a novel anti-helmenthic that during recent years has been used for fascioliasis treatment in this region. The aim of the present work is to study alteration in haematological and liver function indices during human infection with Fasciola spp. pre and post treatment with triclabendazoleMaterials & Methods: The present work is a longitudinal clinical trail. In this regard, fifty confirmed fasciolasis patients, were chosen for parasitological, hematological and biochemical examinations pre-therapy as well as 1 and 6 months post-therapy. Formalin-ether and modified Telemann methods were used for stool examination. For Fasciola antibody detection ELISA technique was employed. Hematological and biochemical tests were performed by standard methods. Results: Results indicated that, triclabendazole efficacy was 74% after usage as one dose of 20mg/kg and reached to 88% after repeating in the next month. Before triclabebdazole therapy the Hb and HCT of the patients were slightly found lower than normal ranges, meanwhile the ESR and eosinophil percentages were higher. However following receiving the drug, in the cured individuals, the indices returned to the normal ranges but in the non-cured individuals were not shifted to the normal. On the other hand liver function indices of the patients mostly were at normal ranges before and following drug therapy.Conclusion: In conclusion haematological indices could be valuable indicator for successful therapy of patients treated with triclabendazole.

  16. The extracellular redox state modulates mitochondrial function, gluconeogenesis, and glycogen synthesis in murine hepatocytes.

    Science.gov (United States)

    Nocito, Laura; Kleckner, Amber S; Yoo, Elsia J; Jones Iv, Albert R; Liesa, Marc; Corkey, Barbara E

    2015-01-01

    Circulating redox state changes, determined by the ratio of reduced/oxidized pairs of different metabolites, have been associated with metabolic diseases. However, the pathogenic contribution of these changes and whether they modulate normal tissue function is unclear. As alterations in hepatic gluconeogenesis and glycogen metabolism are hallmarks that characterize insulin resistance and type 2 diabetes, we tested whether imposed changes in the extracellular redox state could modulate these processes. Thus, primary hepatocytes were treated with different ratios of the following physiological extracellular redox couples: β-hydroxybutyrate (βOHB)/acetoacetate (Acoc), reduced glutathione (GSH)/oxidized glutathione (GSSG), and cysteine/cystine. Exposure to a more oxidized ratio via extracellular βOHB/Acoc, GSH/GSSG, and cysteine/cystine in hepatocytes from fed mice increased intracellular hydrogen peroxide without causing oxidative damage. On the other hand, addition of more reduced ratios of extracellular βOHB/Acoc led to increased NAD(P)H and maximal mitochondrial respiratory capacity in hepatocytes. Greater βOHB/Acoc ratios were also associated with decreased β-oxidation, as expected with enhanced lipogenesis. In hepatocytes from fasted mice, a more extracellular reduced state of βOHB/Acoc led to increased alanine-stimulated gluconeogenesis and enhanced glycogen synthesis capacity from added glucose. Thus, we demonstrated for the first time that the extracellular redox state regulates the major metabolic functions of the liver and involves changes in intracellular NADH, hydrogen peroxide, and mitochondrial respiration. Because redox state in the blood can be communicated to all metabolically sensitive tissues, this work confirms the hypothesis that circulating redox state may be an important regulator of whole body metabolism and contribute to alterations associated with metabolic diseases.

  17. The extracellular redox state modulates mitochondrial function, gluconeogenesis, and glycogen synthesis in murine hepatocytes.

    Directory of Open Access Journals (Sweden)

    Laura Nocito

    Full Text Available Circulating redox state changes, determined by the ratio of reduced/oxidized pairs of different metabolites, have been associated with metabolic diseases. However, the pathogenic contribution of these changes and whether they modulate normal tissue function is unclear. As alterations in hepatic gluconeogenesis and glycogen metabolism are hallmarks that characterize insulin resistance and type 2 diabetes, we tested whether imposed changes in the extracellular redox state could modulate these processes. Thus, primary hepatocytes were treated with different ratios of the following physiological extracellular redox couples: β-hydroxybutyrate (βOHB/acetoacetate (Acoc, reduced glutathione (GSH/oxidized glutathione (GSSG, and cysteine/cystine. Exposure to a more oxidized ratio via extracellular βOHB/Acoc, GSH/GSSG, and cysteine/cystine in hepatocytes from fed mice increased intracellular hydrogen peroxide without causing oxidative damage. On the other hand, addition of more reduced ratios of extracellular βOHB/Acoc led to increased NAD(PH and maximal mitochondrial respiratory capacity in hepatocytes. Greater βOHB/Acoc ratios were also associated with decreased β-oxidation, as expected with enhanced lipogenesis. In hepatocytes from fasted mice, a more extracellular reduced state of βOHB/Acoc led to increased alanine-stimulated gluconeogenesis and enhanced glycogen synthesis capacity from added glucose. Thus, we demonstrated for the first time that the extracellular redox state regulates the major metabolic functions of the liver and involves changes in intracellular NADH, hydrogen peroxide, and mitochondrial respiration. Because redox state in the blood can be communicated to all metabolically sensitive tissues, this work confirms the hypothesis that circulating redox state may be an important regulator of whole body metabolism and contribute to alterations associated with metabolic diseases.

  18. GSM 900 MHz Microwave RadiationInduced Alterations of Insulin Level and Histopathological Changes of Liver and Pancreas in Rat

    Directory of Open Access Journals (Sweden)

    Mortazavi S. M. J.

    2016-12-01

    Full Text Available Background: The rapidly increasing use of mobile phones has led to public concerns about possible health effects of these popular communication devices. This study is an attempt to investigate the effects of radiofrequency (RF radiation produced by GSM mobile phones on the insulin release in rats. Methods: Forty two female adult Sprague Dawley rats were randomly divided into 4 groups. Group1 were exposed to RF radiation 6 hours per day for 7 days. Group 2 received sham exposure (6 hours per day for 7 days. Groups 3 and 4 received RF radiation 3 hours per day for 7 days and sham exposure (3 hours per day, respectively. The specific absorption rate (SAR of RF was 2.0W/kg. Results: Our results showed that RF radiations emitted from mobile phone could not alter insulin release in rats. However, mild to severe inflammatory changes in the portal spaces of the liver of rats as well as damage in the cells of islet of Langerhans were observed. These changes were linked with the duration of the exposures. Conclusion: RF exposure can induce inflammatory changes in the liver as well causing damage in the cells of islet of Langerhans.

  19. Protein targeting to glycogen is a master regulator of glycogen synthesis in astrocytes

    KAUST Repository

    Ruchti, E.

    2016-10-08

    The storage and use of glycogen, the main energy reserve in the brain, is a metabolic feature of astrocytes. Glycogen synthesis is regulated by Protein Targeting to Glycogen (PTG), a member of specific glycogen-binding subunits of protein phosphatase-1 (PPP1). It positively regulates glycogen synthesis through de-phosphorylation of both glycogen synthase (activation) and glycogen phosphorylase (inactivation). In cultured astrocytes, PTG mRNA levels were previously shown to be enhanced by the neurotransmitter noradrenaline. To achieve further insight into the role of PTG in the regulation of astrocytic glycogen, its levels of expression were manipulated in primary cultures of mouse cortical astrocytes using adenovirus-mediated overexpression of tagged-PTG or siRNA to downregulate its expression. Infection of astrocytes with adenovirus led to a strong increase in PTG expression and was associated with massive glycogen accumulation (>100 fold), demonstrating that increased PTG expression is sufficient to induce glycogen synthesis and accumulation. In contrast, siRNA-mediated downregulation of PTG resulted in a 2-fold decrease in glycogen levels. Interestingly, PTG downregulation strongly impaired long-term astrocytic glycogen synthesis induced by insulin or noradrenaline. Finally, these effects of PTG downregulation on glycogen metabolism could also be observed in cultured astrocytes isolated from PTG-KO mice. Collectively, these observations point to a major role of PTG in the regulation of glycogen synthesis in astrocytes and indicate that conditions leading to changes in PTG expression will directly impact glycogen levels in this cell type.

  20. Effect of dietary and hormonal alterations on the activity of 3-methylcrotonyl-CoA carboylase in rat liver

    International Nuclear Information System (INIS)

    Paul, H.S.; Gleditsch, C.E.; Adibi, S.A.

    1986-01-01

    Previous studies have established that activities of leucine transaminase and branched-chain keto acid dehydrogenase (BCKDH) are under metabolic control. In the present experiment, the authors have investigated whether activity of 3-methylcrotonyl-CoA carboxylase (MCase), an enzyme distal to BCKDH in pathways of leucine oxidation, is also subjected to metabolic regulation. Initially, they developed optimal conditions to assay the activity of this enzyme. The assay was based on the incorporation of 14 CO 2 into 3-methylcrotonyl-CoA (MC-CoA) by liver mitochondria and required the presence of ATP and biotin. Subsequently, the authors determined the activity (nmol 14 CO 2 incorporated/mg protein/min, mean +/- SE, 6 rats) of MCase under normal (2.80 +/- 0.09) and altered conditions. The activity of MCase was not affected either by starvation (2.88 +/- 0.13), diabetes (2.95 +/- 0.11), low-protein (2.35 +/- 0.05), or high-protein diet (3.06 +/- 0.06). To further substantiate these results, they measured accumulation of MC-CoA by incubating liver mitochondria with α-ketoisocaproate (KIC). Of the KIC fraction that underwent flux through BCKDH (2.15 +/- 0.14 nmol/mg protein/min), only 0.26% accumulated as MC-CoA. Even if diabetes, when the flux through BCKDH was significantly increased (3.62 +/- 0.36), the accumulation of MC-CoA was negligible (0.33%). The authors conclude that a) MCase activity does not change in response to dietary and hormonal alterations, and b) MCase is not a rate-limiting reaction in pathways of leucine oxidation

  1. Effect of dietary and hormonal alterations on the activity of 3-methylcrotonyl-CoA carboylase in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Paul, H.S.; Gleditsch, C.E.; Adibi, S.A.

    1986-05-01

    Previous studies have established that activities of leucine transaminase and branched-chain keto acid dehydrogenase (BCKDH) are under metabolic control. In the present experiment, the authors have investigated whether activity of 3-methylcrotonyl-CoA carboxylase (MCase), an enzyme distal to BCKDH in pathways of leucine oxidation, is also subjected to metabolic regulation. Initially, they developed optimal conditions to assay the activity of this enzyme. The assay was based on the incorporation of /sup 14/CO/sub 2/ into 3-methylcrotonyl-CoA (MC-CoA) by liver mitochondria and required the presence of ATP and biotin. Subsequently, the authors determined the activity (nmol /sup 14/CO/sub 2/ incorporated/mg protein/min, mean +/- SE, 6 rats) of MCase under normal (2.80 +/- 0.09) and altered conditions. The activity of MCase was not affected either by starvation (2.88 +/- 0.13), diabetes (2.95 +/- 0.11), low-protein (2.35 +/- 0.05), or high-protein diet (3.06 +/- 0.06). To further substantiate these results, they measured accumulation of MC-CoA by incubating liver mitochondria with ..cap alpha..-ketoisocaproate (KIC). Of the KIC fraction that underwent flux through BCKDH (2.15 +/- 0.14 nmol/mg protein/min), only 0.26% accumulated as MC-CoA. Even if diabetes, when the flux through BCKDH was significantly increased (3.62 +/- 0.36), the accumulation of MC-CoA was negligible (0.33%). The authors conclude that a) MCase activity does not change in response to dietary and hormonal alterations, and b) MCase is not a rate-limiting reaction in pathways of leucine oxidation.

  2. Sorafenib metabolism is significantly altered in the liver tumor tissue of hepatocellular carcinoma patient.

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    Ling Ye

    Full Text Available BACKGROUND: Sorafenib, the drug used as first line treatment for hepatocellular carcinoma (HCC, is metabolized by cytochrome P450 (CYP 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT 1A9-mediated glucuronidation. Liver diseases are associated with reduced CYP and UGT activities, which can considerably affect drug metabolism, leading to drug toxicity. Thus, understanding the metabolism of therapeutic compounds in patients with liver diseases is necessary. However, the metabolism characteristic of sorafenib has not been systematically determined in HCC patients. METHODS: Sorafenib metabolism was tested in the pooled and individual tumor hepatic microsomes (THLMs and adjacent normal hepatic microsomes (NHLMs of HCC patients (n = 18. Commercial hepatic microsomes (CHLMs were used as a control. In addition, CYP3A4 and UGT1A9 protein expression in different tissues were measured by Western blotting. RESULTS: The mean rates of oxidation and glucuronidation of sorafenib were significantly decreased in the pooled THLMs compared with those in NHLMs and CHLMs. The maximal velocity (Vmax of sorafenib oxidation and glucuronidation were approximately 25-fold and 2-fold decreased in the pooled THLMs, respectively, with unchanged Km values. The oxidation of sorafenib in individual THLMs sample was significantly decreased (ranging from 7 to 67-fold than that in corresponding NHLMs sample. The reduction of glucuronidation in THLMs was observed in 15 out of 18 patients' samples. Additionally, the level of CYP3A4 and UGT1A9 expression were both notably decreased in the pooled THLMs. CONCLUSIONS: Sorafenib metabolism was remarkably decreased in THLMs. This result was associated with the down regulation of the protein expression of CYP3A4 and UGT1A9.

  3. Bisphenol A Causes Liver Damage and Selectively Alters the Neurochemical Coding of Intrahepatic Parasympathetic Nerves in Juvenile Porcine Models under Physiological Conditions

    Directory of Open Access Journals (Sweden)

    Michael Thoene

    2017-12-01

    Full Text Available Bisphenol A (BPA is an extremely common polymer that is used in typical everyday products throughout the world, especially in food and beverage containers. Within the last ten years, it has been found that the BPA monomer tends to leach into foodstuffs, and nanogram concentrations of it may cause a variety of deleterious health effects. These health problems are very evident in developing children and in young adults. The aim of this study was to expose developing pigs to dietary BPA at both legally acceptable and ten-fold higher levels. Livers that had been exposed to BPA showed vacuolar degeneration, sinusoidal dilatation, vascular congestion and glycogen depletion that increased with exposure levels. Furthermore, the livers of these models were then examined for irregularities and double-labeled immunofluorescence was used to check the innervated hepatic samples for varying neuronal expression of selected neuronal markers in the parasympathetic nervous system (PSNS. It was found that both the PSNS and all of the neuronal markers showed increased expression, with some of them being significant even at recommended safe exposure levels. The implications are quite serious since these effects have been observed at recommended safe levels with expression increasing in-line with exposure levels. The increased neuronal markers studied here have been previously correlated with behavioral/psychological disorders of children and young adults, as well as with childhood obesity and diabetes. However, further research must be performed in order to develop a mechanism for the above-mentioned correlations.

  4. Putative role of glycogen as a peripheral biomarker of GSK3β activity.

    Science.gov (United States)

    Frizzo, Marcos Emilio

    2013-09-01

    Glycogen synthase kinase 3-β (GSK3β) has a pivotal role in several intracellular signaling cascades that are involved in gene transcription, cytoskeletal reorganization, energy metabolism, cell cycle regulation, and apoptosis. This kinase has pleiotropic functions, and the importance of its activity has recently been shown in neurons and platelets. In addition to its regulatory function in several physiological events, changes in GSK3β activity have been associated with many psychiatric and neurodegenerative illnesses, such as Alzheimer's disease, schizophrenia and autism-spectrum disorders. Beside the reports of its involvement in several pathologies, it has become increasingly apparent that GSK3β might be a common therapeutic target for different classes of psychiatric drugs, and also that the GSK3β ratio may be a useful parameter to determine the biochemical changes that might occur during antidepressant treatment. Although GSK3β is commonly described as a key enzyme in a plethora of signaling cascades, originally it was identified as playing an important role in the regulation of glycogen synthesis, given its ability to inactivate glycogen synthase (GS) by phosphorylation. Acting as a constitutively active kinase, GSK3β phosphorylates GS, which results in a decrease of glycogen production. GSK3β phosphorylation increases glycogen synthesis and storage, while its dephosphorylation decreases glycogen synthesis. Inactivation of GSK3β leads to dephosphorylation of GS and increase in glycogen synthesis in the adipose tissue, muscle and liver. Glycogen levels are reduced by antidepressant treatment, and this effect seems to be related to an effect of drugs on GSK3β activity. Peripherally, glycogen is also abundantly found in platelets, where it is considered a major energy source, required for a variety of its functions, including the release reaction. Recently, analysis of platelets from patients with late-life major depression showed that active forms of

  5. Pluralistic roles for glycogen in the central and peripheral nervous systems.

    Science.gov (United States)

    Fryer, Kirsty L; Brown, Angus M

    2015-02-01

    Glycogen is present in the mammalian nervous system, but at concentrations of up to one hundred times lower than those found in liver and skeletal muscle. This relatively low concentration has resulted in neglect of assigning a role(s) for brain glycogen, but in the last 15 years enormous progress has been made in revealing the multifaceted roles that glycogen plays in the mammalian nervous system. Initial studies highlighted a role for glycogen in supporting neural elements (neurons and axons) during aglycemia, where glycogen supplied supplementary energy substrate in the form of lactate to fuel neural oxidative metabolism. The appropriate enzymes and membrane bound transporters have been localized to cellular locations consistent with astrocyte to neuron energy substrate shuttling. A role for glycogen in supporting the induction of long term potential (LTP) in the hippocampus has recently been described, where glycogen is metabolized to lactate and shuttled to neurons via the extracellular space by monocarboxylate transporters, where it plays an integral role in the induction process of LTP. This is the first time that glycogen has been assigned a role in a distinct, complex physiological brain function, where the lack of glycogen, in the presence of normoglycemia, results in disturbance of the function. The signalling pathway that alerts astrocytes to increased neuronal activity has been recently described, highlighting a pivotal role for increased extracellular potassium ([K(+)]o) that routinely accompanies increased neural activity. An astrocyte membrane bound bicarbonate transporter is activated by the [K(+)]o, the resulting increase in intracellular bicarbonate alkalizing the cell's interior and activating soluble adenyl cyclase (sAC). The sAC promotes glycogenolysis via increases in cyclic AMP, ultimately producing lactate, which is shuttled out of the astrocyte and presumably taken up by neurons from the extracellular space.

  6. Quantitative alterations in the liver and adrenal gland in pregnant rats induced by Pyralene 3000

    Energy Technology Data Exchange (ETDEWEB)

    Vreci, M.; Sek, S.; Lorger, J.; Bavdek, S. [Univ. of Ljubljana, Gerbiceva (Slovenia); Pogacnik, A.

    1995-06-01

    Polychlorinated biphenyls (PCBs) are among the most widespread environmental pollutants known in the world. The half-life of PCBs is very long and, therefore, once released into the environment, they accumulate in food chains and tissues of various mammals, including man. Their presence can cause numerous toxic effects, e.g., hepatotoxicity, immunotoxicity, dermatotoxicity, neurotoxicity, and disorders of the reproductive system, among others. These effects depend on the distribution route in the organism, the rate of metabolism and excretion. Their characteristics are closely associated with the number and position of the chlorine atoms in the molecule. Previous studies of trichlorobiphenyl distributions in various tissues demonstrated that low chlorinated trichlorobiphenyls do no accumulate in endocrine organs, whereas higher chlorinated biphenyls, such as hexa- and octachlorobiphenyl, are deposited and retained in the adrenal gland. A selective distribution of radioabelled tetrachlorobiphenyl to the zona fasciculata, accompanied by morphometric evidence of the hypertrophy of the zona fasciculata, was also noted. The purpose of this study was to examine changes in the tissue structure of the pregnant rat liver and adrenal gland induced experimentally by Pyralene 3000 administration. We chose this commercial low chlorinated PCB because it was in use in Slovenia and, discharged from the electroindustrial plants, caused a serious incidence of environmental pollution in the region of Bela Krajina. Our further aim was to research the transplacental influences of Pyralene 3000 in rats. 17 refs., 1 fig., 3 tabs.

  7. Muscle glycogen synthesis before and after exercise.

    Science.gov (United States)

    Ivy, J L

    1991-01-01

    The importance of carbohydrates as a fuel source during endurance exercise has been known for 60 years. With the advent of the muscle biopsy needle in the 1960s, it was determined that the major source of carbohydrate during exercise was the muscle glycogen stores. It was demonstrated that the capacity to exercise at intensities between 65 to 75% VO2max was related to the pre-exercise level of muscle glycogen, i.e. the greater the muscle glycogen stores, the longer the exercise time to exhaustion. Because of the paramount importance of muscle glycogen during prolonged, intense exercise, a considerable amount of research has been conducted in an attempt to design the best regimen to elevate the muscle's glycogen stores prior to competition and to determine the most effective means of rapidly replenishing the muscle glycogen stores after exercise. The rate-limiting step in glycogen synthesis is the transfer of glucose from uridine diphosphate-glucose to an amylose chain. This reaction is catalysed by the enzyme glycogen synthase which can exist in a glucose-6-phosphate-dependent, inactive form (D-form) and a glucose-6-phosphate-independent, active form (I-form). The conversion of glycogen synthase from one form to the other is controlled by phosphorylation-dephosphorylation reactions. The muscle glycogen concentration can vary greatly depending on training status, exercise routines and diet. The pattern of muscle glycogen resynthesis following exercise-induced depletion is biphasic. Following the cessation of exercise and with adequate carbohydrate consumption, muscle glycogen is rapidly resynthesised to near pre-exercise levels within 24 hours. Muscle glycogen then increases very gradually to above-normal levels over the next few days. Contributing to the rapid phase of glycogen resynthesis is an increase in the percentage of glycogen synthase I, an increase in the muscle cell membrane permeability to glucose, and an increase in the muscle's sensitivity to insulin

  8. Aerobic interval exercise improves parameters of nonalcoholic fatty liver disease (NAFLD) and other alterations of metabolic syndrome in obese Zucker rats.

    Science.gov (United States)

    Kapravelou, Garyfallia; Martínez, Rosario; Andrade, Ana M; Nebot, Elena; Camiletti-Moirón, Daniel; Aparicio, Virginia A; Lopez-Jurado, Maria; Aranda, Pilar; Arrebola, Francisco; Fernandez-Segura, Eduardo; Bermano, Giovanna; Goua, Marie; Galisteo, Milagros; Porres, Jesus M

    2015-12-01

    Metabolic syndrome (MS) is a group of metabolic alterations that increase the susceptibility to cardiovascular disease and type 2 diabetes. Nonalcoholic fatty liver disease has been described as the liver manifestation of MS. We aimed to test the beneficial effects of an aerobic interval training (AIT) protocol on different biochemical, microscopic, and functional liver alterations related to the MS in the experimental model of obese Zucker rat. Two groups of lean and obese animals (6 weeks old) followed a protocol of AIT (4 min at 65%-80% of maximal oxygen uptake, followed by 3 min at 50%-65% of maximal oxygen uptake for 45-60 min, 5 days/week, 8 weeks of experimental period), whereas 2 control groups remained sedentary. Obese rats had higher food intake and body weight (P metabolism and increased the liver protein expression of PPARγ, as well as the gene expression of glutathione peroxidase 4 (P < 0.001). The training protocol also showed significant effects on the activity of hepatic antioxidant enzymes, although this action was greatly influenced by rat phenotype. The present data suggest that AIT protocol is a feasible strategy to improve some of the plasma and liver alterations featured by the MS.

  9. The glycogen metabolism via Akt signaling is important for the secretion of enamel matrix in tooth development.

    Science.gov (United States)

    Ida-Yonemochi, Hiroko; Otsu, Keishi; Ohshima, Hayato; Harada, Hidemitsu

    2016-02-01

    Cells alter their energy metabolism depending on the stage of differentiation or various environments. In the ameloblast differentiation of continuous growing mouse incisors, we found temporary glycogen storage in preameloblasts before the start of enamel matrix secretion and investigated the relationship between enamel matrix secretion and glycogen metabolism. Immunohistochemistry showed that in the transitional stage from preameloblasts to secretory ameloblasts, the glycogen synthase changed from the inactive form to the active form, the expression of glycogen phosphorylase increased, and further, the levels of IGF-1, IGF-1 receptor and activated Akt increased. These results suggested that the activation of Akt signaling via IGF is linked to the onset of both glycogen metabolism and enamel matrix deposition. In the experiments using organ culture and ameloblast cell line, the activation of Akt signaling by IGF-1 stimulated glycogen metabolism through the up-regulation of Glut-1,-4 and Gsk-3β and the dephosphorylation of glycogen synthase. Subsequently, they resulted in increased enamel matrix secretion. In contrast, some inhibitors of Akt signals and glycogen synthesis/degradation down-regulated enamel matrix secretion. Taking these findings together, glycogen metabolism via Akt signaling is an essential system for the secretion of enamel matrix in ameloblast differentiation. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Alterations in the molecular species of rat liver lecithin by corn-oil feeding to essential fatty acid-deficient rats as a function of time

    NARCIS (Netherlands)

    Golde, L.M.G. van; Pieterson, W.A.; Deenen, L.L.M. van

    1968-01-01

    The present paper describes, as a function of time, the qualitative and quantitative alterations in the molecular species pattern of rat liver lecithin which are observed when corn oil is fed to essential fatty acid-deficient rats. One of the most important changes observed was a very rapid

  11. Glycogen resynthesis rate following cross-country skiing is closely correlated to skeletal muscle glycogen content

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Nielsen, Joachim; Saltin, Bengt

    on an optimal glycogen resynthesis rate before a subsequent exercise session. The purpose of present study was to evaluate the glycogen resynthesis rate in elite cross-country (cc) skiers, following exhaustive exercise, and to examine the role of muscular glycogen content on the resynthesis rate. METHOD: Ten...... as 4h and 22h after the race and analyzed for glycogen content. Figure 1. Correlation between muscle glycogen resynthesis rate and glycogen content after and in the rocery period after exercise. Line indicate best fit of all the data points (r2 = 0.41, p

  12. Lowering Temperature is the Trigger for Glycogen Build-Up and Winter Fasting in Crucian Carp (Carassius carassius).

    Science.gov (United States)

    Varis, Joonas; Haverinen, Jaakko; Vornanen, Matti

    2016-02-01

    Seasonal changes in physiology of vertebrate animals are triggered by environmental cues including temperature, day-length and oxygen availability. Crucian carp (Carassius carassius) tolerate prolonged anoxia in winter by using several physiological adaptations that are seasonally activated. This study examines which environmental cues are required to trigger physiological adjustments for winter dormancy in crucian carp. To this end, crucian carp were exposed to changing environmental factors under laboratory conditions: effects of declining water temperature, shortening day-length and reduced oxygen availability, separately and in different combinations, were examined on glycogen content and enzyme activities involved in feeding (alkaline phosphatase, AP) and glycogen metabolism (glycogen synthase, GyS; glycogen phosphorylase, GP). Lowering temperature induced a fall in activity of AP and a rise in glycogen content and rate of glycogen synthesis. Relative mass of the liver, and glycogen concentration of liver, muscle and brain increased with lowering temperature. Similarly activity of GyS in muscle and expression of GyS transcripts in brain were up-regulated by lowering temperature. Shortened day-length and oxygen availability had practically no effects on measured variables. We conclude that lowering temperature is the main trigger in preparation for winter anoxia in crucian carp.

  13. Metabolic alterations by clofibric acid in the formation of molecular species of phosphatidylcholine in rat liver.

    Science.gov (United States)

    Mizuguchi, H; Kudo, N; Kawashima, Y

    2001-10-01

    The mechanism by which p-chlorophenoxyisobutyric acid (clofibric acid) induces striking changes in the proportion of the molecular species of phosphatidylcholine (PC) in rat liver was studied. Treatment of rats with clofibric acid strikingly increased the content of 1-palmitoyl-2-oleoyl (16:0-18:1) PC, but decreased the contents of 1-palmitoyl-2-docosahexaenoyl (16:0-22:6), 1-stearoyl-2-arachidonoyl (18:0-20:4), and 1-stearoyl-2-linoleoyl (18:0-18:2) PC; the drug did not change the content of 1-palmitoyl-2-arachidonoyl (16:0-20:4) PC. The mechanism underlying these changes has been investigated with regard to the in vivo formation of the molecular species of PC by: (i) de novo synthesis, (ii) reacylation, and (iii) methylation of phosphatidylethanolamine (PE). We found that (i) the incorporation of [3H]glycerol, which was injected intravenously, into 16:0-18:1 diacylglycerol (DG) and 16:0-18:1 PC was increased markedly by clofibric acid feeding without changing the substrate specificity of CDP-choline:DG cholinephosphotransferase, (ii) the in vivo formation of 16:0-18:1 and 16:0-20:4 PC from 1-16:0-[3H]glycerophosphocholine (GPC), which was injected intraportally, was increased markedly by clofibric acid feeding, and (iii) the incorporation of [14C]ethanolamine, which was injected intravenously into 16:0-22:6, 18:0-22:6, and 18:0-20:4 PC, was decreased by clofibric acid feeding; the extent of the decrease in 16:0-20:4 PC was less than that of 18:0-20:4 PC. It was concluded, therefore, that (i) clofibric acid selectively increased the content and proportion of 16:0-18:1 PC by enhancing both the CDP-choline pathway and the remodeling of the pre-existing PC molecule, and (ii) the drug kept the content of 16:0-20:4 PC unchanged by stimulating the remodeling of the pre-existing PC molecule, whereas the formation of other more long chain, polyunsaturated molecular species, such as 16:0-22:6, 18:0-22:6, and 18:0-20:4, was decreased owing to the suppression of PE

  14. Ablation of PPP1R3G reduces glycogen deposition and mitigates high-fat diet induced obesity.

    Science.gov (United States)

    Zhang, Yongxian; Gu, Jin; Wang, Lin; Zhao, Zilong; Pan, Yi; Chen, Yan

    2017-01-05

    Glycogen and triglyceride are two major forms of energy storage in the body and provide the fuel during different phases of food deprivation. However, how glycogen metabolism is linked to fat deposition in adipose tissue has not been clearly characterized. We generated a mouse model with whole-body deletion of PPP1R3G, a glycogen-targeting subunit of protein phosphatase-1 required for glycogen synthesis. Upon feeding with high-fat diet, the body weight and fat composition are significantly reduced in the PPP1R3G -/- mice compared to the wild type controls. The metabolic rate of the mice as measured by O 2 consumption and CO 2 production is accelerated by PPP1R3G deletion. The high-fat diet-induced liver steatosis is also slightly relieved by PPP1R3G deletion. The glycogen level in adipose tissue is reduced by PPP1R3G deletion. In 3T3L1 cells, overexpression of PPP1R3G leads to increases of both glycogen and triglyceride levels. In conclusion, our study indicates that glycogen is actively involved in fat accumulation in adipose tissue and obesity development upon high-fat diet. Our study also suggests that PPP1R3G is an important player that links glycogen metabolism to lipid metabolism in vivo. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency.

    Science.gov (United States)

    Collantes, María; Serrano-Mendioroz, Irantzu; Benito, Marina; Molinet-Dronda, Francisco; Delgado, Mercedes; Vinaixa, María; Sampedro, Ana; Enríquez de Salamanca, Rafael; Prieto, Elena; Pozo, Miguel A; Peñuelas, Iván; Corrales, Fernando J; Barajas, Miguel; Fontanellas, Antonio

    2016-04-01

    Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Revisiting Glycogen Content in the Human Brain.

    Science.gov (United States)

    Öz, Gülin; DiNuzzo, Mauro; Kumar, Anjali; Moheet, Amir; Seaquist, Elizabeth R

    2015-12-01

    Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3-4 µmol/g brain glycogen content using in vivo (13)C magnetic resonance spectroscopy (MRS) in conjunction with [1-(13)C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3-5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state (13)C labeling in glycogen, here we administered [1-(13)C]glucose to healthy volunteers for 80 h. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-(13)C]glucose administration and (13)C-glycogen levels in the occipital lobe were measured by (13)C MRS approximately every 12 h. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the (13)C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain.

  17. Homozygous and heterozygous GH transgenesis alters fatty acid composition and content in the liver of Amago salmon (Oncorhynchus masou ishikawae

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    Manabu Sugiyama

    2012-08-01

    Growth hormone (GH transgenic Amago (Oncorhynchus masou ishikawae, containing the sockeye GH1 gene fused with metallothionein-B promoter from the same species, were generated and the physiological condition through lipid metabolism compared among homozygous (Tg/Tg and heterozygous GH transgenic (Tg/+ Amago and the wild type control (+/+. Previously, we have reported that the adipose tissue was generally smaller in GH transgenic fish compared to the control, and that the Δ-6 fatty acyl desaturase gene was down-regulated in the Tg/+ fish. However, fatty acid (FA compositions have not been measured previously in these fish. In this study we compared the FAs composition and content in the liver using gas chromatography. Eleven kinds of FA were detected. The composition of saturated and monounsaturated fatty acids (SFA and MUFA such as myristic acid (14:0, palmitoleic acid (16:1n-7, and cis-vaccenic acid (cis-18:1n-7 was significantly (P<0.05 decreased in GH transgenic Amago. On the other hand, the composition of polyunsaturated fatty acids (PUFAs such as linoleic acid (18:2n-6, arachidonic acid (20:4n-6, and docosapentaenoic acid (22:5n-3 was significantly (P<0.05 increased. Levels of serum glucose and triacylglycerol were significantly (P<0.05 decreased in the GH transgenics compared with +/+ fish. Furthermore, 3′-tag digital gene expression profiling was performed using liver tissues from Tg/Tg and +/+ fish, and showed that Mid1 interacting protein 1 (Mid1ip1, which is an important factor to activate Acetyl-CoA carboxylase (ACC, was down-regulated in Tg/Tg fish, while genes involved in FA catabolism were up-regulated, including long-chain-fatty-acid–CoA ligase 1 (ACSL1 and acyl-coenzyme A oxidase 3 (ACOX3. These data suggest that liver tissue from GH transgenic Amago showed starvation by alteration in glucose and lipid metabolism due to GH overexpression. The decrease of serum glucose suppressed Mid1ip1, and caused a decrease of de novo FA synthesis, resulting

  18. The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism

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    Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.

    1981-01-01

    The effects of space flight conditions on the activities of certain enzymes regulating carbohydrate and lipid metabolism in rat liver are investigated in an attempt to account for the losses in body weight observed during space flight despite preflight caloric consumption. Liver samples were analyzed for the activities of 32 cytosolic and microsomal enzymes as well as hepatic glycogen and individual fatty acid levels for ground control rats and rats flown on board the Cosmos 936 biosatellite under normal space flight conditions and in centrifuges which were sacrificed upon recovery or 25 days after recovery. Significant decreases in the activities of glycogen phosphorylase, alpha-glycerol phosphate acyl transferase, diglyceride acyl transferase, aconitase and 6-phosphogluconate dehydrogenase and an increase in palmitoyl CoA desaturase are found in the flight stationary relative to the flight contrifuged rats upon recovery, with all enzymes showing alterations returning to normal values 25 days postflight. The flight stationary group is also observed to be characterized by more than twice the amount of liver glycogen of the flight centrifuged group as well as a significant increase in the ratio of palmitic to palmitoleic acid. Results thus indicate metabolic changes which may be involved in the mechanism of weight loss during weightlessness, and demonstrate the equivalence of centrifugation during space flight to terrestrial gravity.

  19. Lafora disease offers a unique window into neuronal glycogen metabolism.

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    Gentry, Matthew S; Guinovart, Joan J; Minassian, Berge A; Roach, Peter J; Serratosa, Jose M

    2018-05-11

    Lafora disease (LD) is a fatal, autosomal recessive, glycogen-storage disorder that manifests as severe epilepsy. LD results from mutations in the gene encoding either the glycogen phosphatase laforin or the E3 ubiquitin ligase malin. Individuals with LD develop cytoplasmic, aberrant glycogen inclusions in nearly all tissues that more closely resemble plant starch than human glycogen. This Minireview discusses the unique window into glycogen metabolism that LD research offers. It also highlights recent discoveries, including that glycogen contains covalently bound phosphate and that neurons synthesize glycogen and express both glycogen synthase and glycogen phosphorylase. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism

    Science.gov (United States)

    Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.

    We have examined, in the livers of rats carried aboard the Cosmos 936 biosatellite, the activities of about 30 enzymes concerned with carbohydrate and lipid metabolism. In addition to the enzyme studies, the levels of glycogen and of the individual fatty acids in hepatic lipids were determined. Livers from flight and ground control rats at recovery (R0) and 25 days after recovery (R25) were used for these analyses. For all parameters measured, the most meaningful comparisons are those made between flight stationary (FS) and flight centrifuged (FC) animals at R0. When these two groups of flight rats were compared at R0, statistically significant decreases in the activity levels of glycogen phosphorylase, α-glycerol phosphate acyl transferase, diglyceride acyl transferase, aconitase and 6-phosphogluconate dehydrogenase and an increase in the palmitoyl CoA desaturase were noted in the weightless group (FS). The significance of these findings was strengthened by the fact that all enzyme activities showing alterations at R0 returned to normal 25 days postflight. When liver glycogen and total fatty acids of the two sets of flight animals were determined, significant differences that could be attributed to reduced gravity were observed. The weightless group (FS) at R0 contained, on the average, more than twice the amount of glycogen than did the centrifuged controls (FC) and a remarkable shift in the ratio of palmitate to palmitoleate was noted. These metabolic alterations, both in enzyme levels and in hepatic constituents, appear to be characteristic of the weightless condition. Our data seem to justify the conclusion that centrifugation during flight is equivalent to terrestrial gravity.

  1. Effect of fasting and different diets on 14C incorporation from U-14C glucose into glycogen and carbon dioxide by cerebral cortical slices of rats

    International Nuclear Information System (INIS)

    Visweswaran, P.; Binod Kumar; Sinha, A.P.; Suraiya, A.; Brahamchari, A.K.; Singh, S.P.

    1994-01-01

    There are some reports regarding change in the glycogen level due to fasting. Here an attempt is made by keeping the albino rats under fasting or feeding different diets on the rate of 14 C incorporation into glycogen and carbon dioxide from U- 14 C glucose. Our study reveals that the above conditions do not alter any significant change in the glycogen and carbon dioxide in the cerebral cortical slices of albino rats. (author). 8 refs., 1 tab

  2. Green Tea Polyphenol Epigallocatechin-3-Gallate Enhance Glycogen Synthesis and Inhibit Lipogenesis in Hepatocytes

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    Jane J. Y. Kim

    2013-01-01

    Full Text Available The beneficial effects of green tea polyphenols (GTP against metabolic syndrome and type 2 diabetes by suppressing appetite and nutrient absorption have been well reported. However the direct effects and mechanisms of GTP on glucose and lipid metabolism remain to be elucidated. Since the liver is an important organ involved in glucose and lipid metabolism, we examined the effects and mechanisms of GTP on glycogen synthesis and lipogenesis in HepG2 cells. Concentrations of GTP containing 68% naturally occurring (−-epigallocatechin-3-gallate (EGCG were incubated in HepG2 cells with high glucose (30 mM under 100 nM of insulin stimulation for 24 h. GTP enhanced glycogen synthesis in a dose-dependent manner. 10 μM of EGCG significantly increased glycogen synthesis by 2fold (P<0.05 compared with insulin alone. Western blotting revealed that phosphorylation of Ser9 glycogen synthase kinase 3β and Ser641 glycogen synthase was significantly increased in GTP-treated HepG2 cells compared with nontreated cells. 10 μM of EGCG also significantly inhibited lipogenesis (P<0.01. We further demonstrated that this mechanism involves enhanced expression of phosphorylated AMP-activated protein kinase α and acetyl-CoA carboxylase in HepG2 cells. Our results showed that GTP is capable of enhancing insulin-mediated glucose and lipid metabolism by regulating enzymes involved in glycogen synthesis and lipogenesis.

  3. Nature of complexing of glycogen with iodine in presence of CaCl2

    International Nuclear Information System (INIS)

    Bobrova, L.N.

    1986-01-01

    The absorption and dichroic absorbance of an iodine complex of muscle glycogen were studied as a function of the CaCl 2 concentration. It was found that high CaCl 2 concentrations, at which the staining of glycogen upon interaction with iodine increases sharply, destabilize the α-glucan helix and lead to a disturbance in the formation of a specific chromophore of the iodine-glycogen complex, which is indicated by the loss of dichroism. The stained chromophore appearing upon a simultaneous decrease in the dichroism is evidently produced by a nonhelical mechanism and is therefore nonspecific. This nonspecific chromophore may be the source of errors in spectrophotometric characterization of the structure of glycogens. It was shown using rabbit skeletal muscle and liver glycogens that the Krisman method, in which concentrated solutions of CaCl 2 are used, does not reveal the differences in the structure of the glycogens that are found at low CaCl 2 concentrations. The unfavorable effect of high CaCl 2 concentrations on helix formation must be kept in mind in a determination of the stoichiometry of the interaction of iodine with α-glucan

  4. Glycogen storage disease type I: clinical and laboratory profile

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    Berenice L. Santos

    2014-12-01

    Full Text Available OBJECTIVES: To characterize the clinical, laboratory, and anthropometric profile of a sample of Brazilian patients with glycogen storage disease type I managed at an outpatient referral clinic for inborn errors of metabolism. METHODS: This was a cross-sectional outpatient study based on a convenience sampling strategy. Data on diagnosis, management, anthropometric parameters, and follow-up were assessed. RESULTS: Twenty-one patients were included (median age 10 years, range 1-25 years, all using uncooked cornstarch therapy. Median age at diagnosis was 7 months (range, 1-132 months, and 19 patients underwent liver biopsy for diagnostic confirmation. Overweight, short stature, hepatomegaly, and liver nodules were present in 16 of 21, four of 21, nine of 14, and three of 14 patients, respectively. A correlation was found between height-for-age and BMI-for-age Z-scores (r = 0.561; p = 0.008. CONCLUSIONS: Diagnosis of glycogen storage disease type I is delayed in Brazil. Most patients undergo liver biopsy for diagnostic confirmation, even though the combination of a characteristic clinical presentation and molecular methods can provide a definitive diagnosis in a less invasive manner. Obesity is a side effect of cornstarch therapy, and appears to be associated with growth in these patients.

  5. Nardostachys Jatamansi root extract protects of radiation induced glycogen depletion in Albino Wistar rats

    International Nuclear Information System (INIS)

    Damodara Gowda, K.M.; Krishna, A.P.; Shetty, Lathika; Suchetha Shetty, N.; Sanjeev, Ganesh

    2013-01-01

    Exposure to ionizing radiation cause variety of pathological processes in irradiated cells. The killing action of ionizing radiation is mainly mediated through the free radicals generated from the radiolysis of cellular water. In the present study, protective effects of Nardostachys Jatamansi root extract (NJE) on radiation induced depletion of glycogen in rats exposed to 3 Gy whole body electron beam irradiation (EBR) was investigated. EBR was performed at Microtron centre, Mangalore University. Treatment of rats with NJE at a dosage of 100, 200 and 400 mg/kg bw respectively once daily for 15 days before, after and both before and after irradiation was done. The liver, kidney and muscle was separated and used for the estimation of total glycogen content using standard procedures and also for the histochemical localization of glycogen by PAS staining method. The data was analyzed by paired t test and Kruskal Wallis test. P<0.05 was the level of significance. The irradiated rats exhibited significant decline (p=0.000) in the level of total glycogen content in the tissues of liver, kidney and muscle whereas, a nonsignificant variation was recorded in rats treated with NJE. This study indicated that treatment with NJE both before and after irradiation for 15 consecutive days provided significant protection against irradiation induced depletion of glycogen. (author)

  6. Ultrastructure and cytochemistry of cardiac intramitochondrial glycogen.

    Science.gov (United States)

    Sótonyi, P; Somogyi, E; Nemes, A; Juhász-Nagy, S

    1976-01-01

    Authors have observed abnormalities of glycogen localization in cardiac muscle, after normothermic cardiac arrest. The identification of these intramitrochondrial particles as glycogen was confirmed by selective staining with periodic acid-lead citrat, periodic acid-thiosemicarbazide protein methods and by their selective removal from tissue sections by alfa-amylase. The intramitochondrial glycogen particles were of beta-type. Some intramitochondrial particles were surrounded by paired membranes which resulted from protrusion of parts of mitochondrial membrane.

  7. Protective efficacy of Emblica officinalis Linn. against radiation and cadmium induced biochemical alterations in the liver of Swiss albino mice

    International Nuclear Information System (INIS)

    Purohit, P.K.; Chakrawarti, Aruna; Agarwal, Manisha

    2012-01-01

    All organisms living on earth are being perpetually exposed to some amount of radiation originating from a variety of sources. Radiation causes deleterious effects in all forms of life due to increasing utilization and production of modern technology, a simultaneous exposure of organisms to heavy metals is also unavoidable. These heavy metals become toxic when present in large quantities, with increasing the industrial revolution and industrial waste, the emission of cadmium has increased into the environment. Thus concomitant exposure to cadmium chloride and ionizing radiation might produce deleterious effect upon biological system. The total environmental burden of toxicants may have greater effect as against their individual impact as expected by their nature. So interaction between radiation and other toxicants represents a field of great potential importance. In the recent years, immense interest has been developed in the field of chemoprotection against radiation and heavy metals induced changes. In view of the potential for practical application, a variety of compounds are being tested for their radioprotective activities. Among these, Emblica holds a great promise. In light of the above, the present study was aimed to evaluate the protective effect of Emblica against radiation and cadmium induced biochemical alterations in the liver of Swiss albino mice. The animals were exposed to 6.0 Gy of gamma rays with or without cadmium chloride treatment. The Emblica was administered seven days prior to irradiation or cadmium chloride treatment

  8. Estimation of liver glucose metabolism after refeeding

    International Nuclear Information System (INIS)

    Rognstad, R.

    1987-01-01

    Refeeding or infusing glucose to rats fasted for 24 hr or more causes rapid liver glycogen synthesis, the carbon source now considered to be largely from gluconeogenesis. While substrate cycling between plasma glucose and liver glucose-6P is known to occur, this cycling has apparently been ignored when calculations are made of % contribution of direct and indirect pathways to liver glycogen synthesis, or when hepatic glucose output is calculated from glucose turnover minus the glucose infusion rate. They show that, isotopically, an estimate of the fluxes of liver glucokinase and glucose-6-phosphatase is required to quantitate sources of carbon for liver glycogen synthesis, and to measure hepatic glucose output (or uptake). They propose a method to estimate these fluxes, involving a short infusion of a 14 C labelled gluconeogenic precursor plus (6T)glucose, with determination of isotopic yields in liver glycogen and total glucose. Given also the rate of liver glycogen synthesis, this procedure permits the estimation of net gluconeogenesis and hepatic glucose output or uptake. Also, in vitro evidence against the notion of a drastic zonation of liver carbohydrate metabolism is presented, e.g. raising the glucose concentration from 10 to 25 mM increases the 14 C yield from H 14 CO 3 - in lactate, with the increased pyruvate kinase flux and decreased gluconeogenesis occurring in the same cell type, not opposing pathways in different hepatocyte types (as has been postulated by some to occur in vivo after refeeding

  9. Determination of the Glycogen Content in Cyanobacteria.

    Science.gov (United States)

    De Porcellinis, Alice; Frigaard, Niels-Ulrik; Sakuragi, Yumiko

    2017-07-17

    Cyanobacteria accumulate glycogen as a major intracellular carbon and energy storage during photosynthesis. Recent developments in research have highlighted complex mechanisms of glycogen metabolism, including the diel cycle of biosynthesis and catabolism, redox regulation, and the involvement of non-coding RNA. At the same time, efforts are being made to redirect carbon from glycogen to desirable products in genetically engineered cyanobacteria to enhance product yields. Several methods are used to determine the glycogen contents in cyanobacteria, with variable accuracies and technical complexities. Here, we provide a detailed protocol for the reliable determination of the glycogen content in cyanobacteria that can be performed in a standard life science laboratory. The protocol entails the selective precipitation of glycogen from the cell lysate and the enzymatic depolymerization of glycogen to generate glucose monomers, which are detected by a glucose oxidase-peroxidase (GOD-POD) enzyme coupled assay. The method has been applied to Synechocystis sp. PCC 6803 and Synechococcus sp. PCC 7002, two model cyanobacterial species that are widely used in metabolic engineering. Moreover, the method successfully showed differences in the glycogen contents between the wildtype and mutants defective in regulatory elements or glycogen biosynthetic genes.

  10. Postexercise muscle glycogen resynthesis in humans.

    Science.gov (United States)

    Burke, Louise M; van Loon, Luc J C; Hawley, John A

    2017-05-01

    Since the pioneering studies conducted in the 1960s in which glycogen status was investigated using the muscle biopsy technique, sports scientists have developed a sophisticated appreciation of the role of glycogen in cellular adaptation and exercise performance, as well as sites of storage of this important metabolic fuel. While sports nutrition guidelines have evolved during the past decade to incorporate sport-specific and periodized manipulation of carbohydrate (CHO) availability, athletes attempt to maximize muscle glycogen synthesis between important workouts or competitive events so that fuel stores closely match the demands of the prescribed exercise. Therefore, it is important to understand the factors that enhance or impair this biphasic process. In the early postexercise period (0-4 h), glycogen depletion provides a strong drive for its own resynthesis, with the provision of CHO (~1 g/kg body mass) optimizing this process. During the later phase of recovery (4-24 h), CHO intake should meet the anticipated fuel needs of the training/competition, with the type, form, and pattern of intake being less important than total intake. Dietary strategies that can enhance glycogen synthesis from suboptimal amounts of CHO or energy intake are of practical interest to many athletes; in this scenario, the coingestion of protein with CHO can assist glycogen storage. Future research should identify other factors that enhance the rate of synthesis of glycogen storage in a limited time frame, improve glycogen storage from a limited CHO intake, or increase muscle glycogen supercompensation. Copyright © 2017 the American Physiological Society.

  11. Histopathological alterations observed in the liver of Poecilia vivipara (Cyprinodontiformes: Poeciliidae as a tool for the environmental quality assessment of the Cachoeira River, BA

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    DV Paulo

    Full Text Available Histopathological alterations in liver have been widely used as a tool in studies for monitoring environmental quality. To evaluate the environmental quality in the Cachoeira river, five spots were monitored between the municipal districts of Itapé and Ilhéus, using liver histological analysis. The species chosen for analysis was Poecilia vivipara due to the fact that it is one of the most abundant in the sampling. The routine technique of inclusion and impregnation in paraffin was used, and the cuts were stained with Hematoxylin and Eosin (H & E. Histopathological alterations in the liver were evaluated semi-quantitatively and based on the severity of the lesions. The results of the histopathological alteration frequency together with the average taken from the Histopathological Alteration Index from points 1 (Vila de Itapé and 2 (Fazenda Santa Amélia showed that in this area the environment is more threatened because of some stressor agent, possibly contaminants that seem to be acting in the environment and endangering the health of fish. The statistic results demonstrated that there were no significant differences among points 1, 2 and 4, which means they are very similar to one another, and are ecologically endangered.

  12. Genetics Home Reference: glycogen storage disease type VII

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    ... Home Health Conditions Glycogen storage disease type VII Glycogen storage disease type VII Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Glycogen storage disease type VII (GSDVII) is an inherited ...

  13. Genetics Home Reference: glycogen storage disease type IV

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    ... Home Health Conditions Glycogen storage disease type IV Glycogen storage disease type IV Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Glycogen storage disease type IV (GSD IV) is an ...

  14. Modifying the Dietary Carbohydrate-to-Protein Ratio Alters the Postprandial Macronutrient Oxidation Pattern in Liver of AMPK-Deficient Mice.

    Science.gov (United States)

    Chalvon-Demersay, Tristan; Even, Patrick C; Chaumontet, Catherine; Piedcoq, Julien; Viollet, Benoit; Gaudichon, Claire; Tomé, Daniel; Foretz, Marc; Azzout-Marniche, Dalila

    2017-09-01

    Background: Hepatic AMP-activated kinase (AMPK) activity is sensitive to the dietary carbohydrate-to-protein ratio. However, the role of AMPK in metabolic adaptations to variations in dietary macronutrients remains poorly understood. Objective: The objective of this study was to determine the role of hepatic AMPK in the adaptation of energy metabolism in response to modulation of the dietary carbohydrate-to-protein ratio. Methods: Male 7-wk-old wild-type (WT) and liver AMPK-deficient (knockout) mice were fed either a normal-protein and normal-carbohydrate diet (NP-NC; 14% protein, 76% carbohydrate on an energy basis), a low-protein and high-carbohydrate diet (LP-HC; 5% protein, 85% carbohydrate), or a high-protein and low-carbohydrate diet (HP-LC; 55% protein, 35% carbohydrate) for 3 wk. During this period, after an overnight fast, metabolic parameters were measured and indirect calorimetry was performed in mice during the first hours after refeeding a 1-g calibrated meal of their own diet in order to investigate lipid and carbohydrate metabolism. Results: Knockout mice fed an LP-HC or HP-LC meal exhibited 24% and 8% lower amplitudes in meal-induced carbohydrate and lipid oxidation changes. By contrast, knockout mice fed an NP-NC meal displayed normal carbohydrate and lipid oxidation profiles. These mice exhibited a transient increase in hepatic triglycerides and a decrease in hepatic glycogen. These changes were associated with a 650% higher secretion of fibroblast growth factor 21 (FGF21) 2 h after refeeding. Conclusions: The consequences of hepatic AMPK deletion depend on the dietary carbohydrate-to-protein ratio. In mice fed the NP-NC diet, deletion of AMPK in the liver led to an adaptation of liver metabolism resulting in increased secretion of FGF21. These changes possibly compensated for the absence of hepatic AMPK, as these mice exhibited normal postprandial changes in carbohydrate and lipid oxidation. By contrast, in mice fed the LP-HC and HP-LC diets, the

  15. Hypoinsulinemic hypoglycemia triggered by liver injury in elderly subjects with low body weight: case reports.

    Science.gov (United States)

    Anno, Takatoshi; Kaneto, Hideaki; Shigemoto, Ryo; Kawasaki, Fumiko; Kawai, Yasuhiro; Urata, Noriyo; Kawamoto, Hirofumi; Kaku, Kohei; Okimoto, Niro

    2018-01-01

    Hypoglycemia is induced by many causes, especially over-dose of insulin or oral hypoglycemic agents in diabetic subjects. In such a case, hyperinsulinemic hypoglycemia is usually observed. On the other hand, it is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia. Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in clinical practice. Herein, we experienced similar 2 cases of non-diabetic hypoinsulinemic hypoglycemia. Both of them were elderly subjects with low body weight. Furthermore, it is likely that hypoinsulinemic hypoglycemia in both subjects was triggered by severe liver injury, at least in part, due to possible limited liver glycogen store. In elderly subjects with low body weight and/or malnutrition, metabolism in the liver is reduced and glycogen accumulation is decreased. Such alteration brings out acute and marked liver injury, which finally leads to the onset of severe hypoglycemia. It is known that not only liver injury but also multiple organ failure could be induced due to extreme emaciation in subjects. It is likely that in elderly subjects with low body weight and/or malnutrition, multiple organ failure including liver failure could be induced due to the similar reason. Therefore, we should be very careful of such subjects in order to avoid the development of multiple organ failure which leads to life-threatening situations. In conclusion, we should keep in mind the possibility of hypoinsulinemic hypoglycemia when we examine severe liver injury, especially in elderly or starving subjects with low body weight and limited liver glycogen stores. It is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia.Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in everyday clinical practice.Herein, we reported similar 2 cases of hypoinsulinemic hypoglycemia without diabetes presumably triggered

  16. Green tea polyphenols alter lipid metabolism in the livers of broiler chickens through increased phosphorylation of AMP-activated protein kinase.

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    Jinbao Huang

    Full Text Available Our previous results showed that green tea polyphenols (GTPs significantly altered the expression of lipid-metabolizing genes in the liver of chickens. However, the underlying mechanism was not elucidated. In this study, we further characterized how GTPs influence AMP-activated protein kinase (AMPK in the regulation of hepatic fat metabolism. Thirty-six male chickens were fed GTPs at a daily dose of 0, 80 or 160 mg/kg of body weight for 4 weeks. The results demonstrated that oral administration of GTPs significantly reduced hepatic lipid content and abdominal fat mass, enhanced the phosphorylation levels of AMPKα and ACACA, and altered the mRNA levels and enzymatic activities of lipid-metabolizing enzymes in the liver. These results suggested that the activation of AMPK is a potential mechanism by which GTPs regulate hepatic lipid metabolism in such a way that lipid synthesis is reduced and fat oxidation is stimulated.

  17. Physiological and Histological Alterations in Rats Liver Induced by Sumithion NP 25/2.5 EC, an Insecticide Used in Dengue Fever Vector Control in Jeddah, Saudi Arabia

    International Nuclear Information System (INIS)

    AlJahdali, Mohammed O.; Bisher, Ameen S. Bin; Zeid, Isam M. Abu

    2009-01-01

    The hepatotoxicity of Sumithion NP 25/2.5 EC, a new formulated organophosphorous insecticide used in dengue fever vector (Aedes aegypti) control in Jeddah (Saudi Arabia), was studied in albino rats. Both levels of GPT, GOT and ALP, and the combined histological alterations were assessed after treatment. Rats were daily injected intraperitoneally for two and four weeks with 80 and 200 mg/kg of body weight (1/10 and 1/4 of the LD50, respectively). Significant increase in GPT, GOT and ALP levels relative to the increase of treatment dose and duration time was observed. The time factor effect was remarkably noticed in ALP level fluctuation. These results indicate a remarkable defect in the liver functions induced by Sumithion NP 25/2.5 EC. Also, histological alterations in the treated animal's liver were observed including: blood congestion, fatty degeneration, hepatocytes swelling and necrosis. The liver syndrome's intensity correlated with the increase in dose and duration time. The present results could prove the hepatotoxicity of Sumithion NP 25/2.5 EC and its ability to cause severe physiological and histopathological defects in the liver. Therefore, the chemical control of Aedes aegypti must be reduced and other recommended control strategies should be promoted. (author)

  18. Systemic Correction of Murine Glycogen Storage Disease Type IV by an AAV-Mediated Gene Therapy.

    Science.gov (United States)

    Yi, Haiqing; Zhang, Quan; Brooks, Elizabeth D; Yang, Chunyu; Thurberg, Beth L; Kishnani, Priya S; Sun, Baodong

    2017-03-01

    Deficiency of glycogen branching enzyme (GBE) causes glycogen storage disease type IV (GSD IV), which is characterized by the accumulation of a less branched, poorly soluble form of glycogen called polyglucosan (PG) in multiple tissues. This study evaluates the efficacy of gene therapy with an adeno-associated viral (AAV) vector in a mouse model of adult form of GSD IV (Gbe1 ys/ys ). An AAV serotype 9 (AAV9) vector containing a human GBE expression cassette (AAV-GBE) was intravenously injected into 14-day-old Gbe1 ys/ys mice at a dose of 5 × 10 11 vector genomes per mouse. Mice were euthanized at 3 and 9 months of age. In the AAV-treated mice at 3 months of age, GBE enzyme activity was highly elevated in heart, which is consistent with the high copy number of the viral vector genome detected. GBE activity also increased significantly in skeletal muscles and the brain, but not in the liver. The glycogen content was reduced to wild-type levels in muscles and significantly reduced in the liver and brain. At 9 months of age, though GBE activity was only significantly elevated in the heart, glycogen levels were significantly reduced in the liver, brain, and skeletal muscles of the AAV-treated mice. In addition, the AAV treatment resulted in an overall decrease in plasma activities of alanine transaminase, aspartate transaminase, and creatine kinase, and a significant increase in fasting plasma glucose concentration at 9 months of age. This suggests an alleviation of damage and improvement of function in the liver and muscles by the AAV treatment. This study demonstrated a long-term benefit of a systemic injection of an AAV-GBE vector in Gbe1 ys/ys mice.

  19. Pathways of hepatic glycogen formation in humans following ingestion of a glucose load in the fed state

    International Nuclear Information System (INIS)

    Magnusson, I.; Chandramouli, V.; Schumann, W.C.; Kumaran, K.; Wahren, J.; Landau, B.R.

    1989-01-01

    The relative contributions of the direct and the indirect pathways to hepatic glycogen formation following a glucose load given to humans four hours after a substantial breakfast have been examined. Glucose loads labeled with [6-( 14 )C]glucose were given to six healthy volunteers along with diflunisal (1 g) or acetaminophen (1.5 g), drugs excreted in urine as glucuronides. Distribution of 14 C in the glucose unit of the glucuronide was taken as a measure of the extent to which glucose was deposited directly in liver glycogen (ie, glucose----glucose-6-phosphate----glycogen) rather than indirectly (ie, glucose----C3-compound----glucose-6-phosphate----glycogen). The maximum contribution to glycogen formation by the direct pathway was estimated to be 77% +/- 4%, which is somewhat higher than previous estimates in humans fasted overnight (65% +/- 1%, P less than 0.05). Thus, the indirect pathway of liver glycogen formation following a glucose load is operative in both the overnight fasted and the fed state, although its contribution may be somewhat less in the fed state

  20. The significance of alteration 2-[fluorine-18]fluoro-2-deoxy-(D)-glucose uptake in the liver and skeletal muscles of patients with hyperthyroidism.

    Science.gov (United States)

    Chen, Yen-Kung; Chen, Yen-Ling; Tsui, Chih-Cheng; Wang, Su-Chen; Cheng, Ru-Hwa

    2013-10-01

    Hyperthyroidism leads to an enhanced demand for glucose. The hypothesis of the study is that 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) can demonstrate the alteration of systemic glucose metabolism in hyperthyroidism patients by measuring the FDG standard uptake value (SUV) in liver and skeletal muscle. Forty-eight active hyperthyroidism patients and 30 control participants were recruited for the study. The intensity of FDG uptake in the liver and thigh muscles was graded subjectively, comprising three groups: group I, higher FDG uptake in the liver; group II, equal FDG uptake in the liver and muscles; and group III, higher FDG uptake in the muscles. Ten subjects with FDG PET scans at hyperthyroid and euthyroid status were analyzed. Serum levels of thyroxine (T4) and triiodothyronine (T3) correlated to the SUVs of the liver and muscles. Forty-one patients (41/48, 85.4%) showed symmetrically increased FDG uptake in the muscles (22 in group I, 9 in group II, and 17 in group III). Group I patients were significantly older than group II (P = .02) and group III (P = .001) patients. The correlation coefficient between the serum T3, T4, and SUV levels in the muscles was significant (r = 0.47-0.77, P hyperthyroid and euthyroid states. In the 30 control subjects, there was normal physiological FDG uptake in the liver and muscles. In PET scans showing a pattern of decreased liver and increased skeletal muscle FDG uptake in hyperthyroidism patients, this change of FDG distribution is correspondence to the severity of hyperthyroidism status. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  1. Inherent lipid metabolic dysfunction in glycogen storage disease IIIa.

    Science.gov (United States)

    Li, Xin-Hua; Gong, Qi-Ming; Ling, Yun; Huang, Chong; Yu, De-Min; Gu, Lei-Lei; Liao, Xiang-Wei; Zhang, Dong-Hua; Hu, Xi-Qi; Han, Yue; Kong, Xiao-Fei; Zhang, Xin-Xin

    2014-12-05

    We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C > T (p.Gln40X) and c.753_756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients’ cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa.

  2. Clinical presentation and biochemical findings children with glycogen storage disease type 1A

    International Nuclear Information System (INIS)

    Saeed, A.; Suleman, H.; Arshad, H.

    2015-01-01

    To determine the clinical pattern of presentation and biochemical characteristics of glycogen storage disease (GSD) type 1a in children at a tertiary referral centre. Study Design: Descriptive/ cross sectional study. Place and Duration of Study: Department of Pediatric, division of Gastroenterology and Hepatology of the Children's hospital, Lahore over a period of 11 years. Patients and Methods: Confirmed cases of glycogen storage disease (clinical plus biochemical findings consistent with GSD 1a and proven on liver biopsy) were enrolled in this study from neonatal age till 18 years. Data was retrieved from files and electronic record for these cases. Diagnosis was made on the basis of history, clinical findings including hepatomegaly, hypertriglyceridemia, hypercholesterolemia, hypoglycemia and hyperuricemia (if present). Diagnosis was confirmed on liver biopsy. Patients with other storage disorders and benign and malignant tumours were excluded from the study. Results: Total patients included in the study were 360 with male to female ratio of 1.25:1. Median age at the time of diagnosis was 25.6 months (age range from one month to 18 years). Most common presentation was abdominal distension (83%) followed by failure to thrive (69%) and recurrent wheezing and diarrhoea (44%) each. Seizures were present in only 1/3rd of children. Other presentations included vomiting, respiratory distress, altered sensorium, nephrocalcinosis, epistaxis and hypothyroidism. Few patients around 11% presented with acute hepatitis and later were diagnosed as GSD. Significant hepatomegaly was evident in almost all patients but nephromegaly was present in only 5.5% patients. All children had marked hypertriglyceridemia but cholesterol levels were raised in 1/3rd of children. A large majority of children had deranged ALT more than 2 times of normal and around 38% children had marked anemia. Significant hypoglycemia and metabolic acidosis was documented in around 1/3rd of children

  3. Light and ultrastructural studies on liver of Oreochromis niloticus fry grown in tritiated water during embryonic development

    Energy Technology Data Exchange (ETDEWEB)

    Carino, V S; Alvendia-Casauay, A [Institute of Biology, College of Science, University of the Philippines, Diliman, Quezon City (Philippines)

    1991-01-01

    Oreochromis niloticus embryos of different developmental stages were reared in tritiated water at 3.7, 0.37, 0.037, and 0 GBq/1 and harvested at day 21 stage. In general, gross morphology of liver was altered in fry reared in higher tritium concentrations and in fry reared in tritiated water at earlier stages of development. Under light microscopy, fatty infiltration of liver parenchyma, presence of unresorped yolk sac, occasional vacuolation in cytoplasm of hepatocytes, widening of sinusoids, and increased size of space of Disse were observed in liver of fry reared in tritiated water at higher concentrations. At the electron microscope level, swollen mitochondria, fragmented rough endoplasmic reticulum, and insconspicuous glycogen granules compared to control were noted in liver of treated fish. This study give basic information on how cells may be affected by irradiation at the histological, cellular, and subcellular level. (auth.). 8 figs.; 1 tab.

  4. Refeeding-induced brown adipose tissue glycogen hyper-accumulation in mice is mediated by insulin and catecholamines.

    Directory of Open Access Journals (Sweden)

    Christopher M Carmean

    Full Text Available Brown adipose tissue (BAT generates heat during adaptive thermogenesis through a combination of oxidative metabolism and uncoupling protein 1-mediated electron transport chain uncoupling, using both free-fatty acids and glucose as substrate. Previous rat-based work in 1942 showed that prolonged partial fasting followed by refeeding led to a dramatic, transient increase in glycogen stores in multiple fat depots. In the present study, the protocol was replicated in male CD1 mice, resulting in a 2000-fold increase in interscapular BAT (IBAT glycogen levels within 4-12 hours (hr of refeeding, with IBAT glycogen stores reaching levels comparable to fed liver glycogen. Lesser effects occurred in white adipose tissues (WAT. Over the next 36 hr, glycogen levels dissipated and histological analysis revealed an over-accumulation of lipid droplets, suggesting a potential metabolic connection between glycogenolysis and lipid synthesis. 24 hr of total starvation followed by refeeding induced a robust and consistent glycogen over-accumulation similar in magnitude and time course to the prolonged partial fast. Experimentation demonstrated that hyperglycemia was not sufficient to drive glycogen accumulation in IBAT, but that elevated circulating insulin was sufficient. Additionally, pharmacological inhibition of catecholamine production reduced refeeding-induced IBAT glycogen storage, providing evidence of a contribution from the central nervous system. These findings highlight IBAT as a tissue that integrates both canonically-anabolic and catabolic stimulation for the promotion of glycogen storage during recovery from caloric deficit. The preservation of this robust response through many generations of animals not subjected to food deprivation suggests that the over-accumulation phenomenon plays a critical role in IBAT physiology.

  5. Refeeding-Induced Brown Adipose Tissue Glycogen Hyper-Accumulation in Mice Is Mediated by Insulin and Catecholamines

    Science.gov (United States)

    Carmean, Christopher M.; Bobe, Alexandria M.; Yu, Justin C.; Volden, Paul A.; Brady, Matthew J.

    2013-01-01

    Brown adipose tissue (BAT) generates heat during adaptive thermogenesis through a combination of oxidative metabolism and uncoupling protein 1-mediated electron transport chain uncoupling, using both free-fatty acids and glucose as substrate. Previous rat-based work in 1942 showed that prolonged partial fasting followed by refeeding led to a dramatic, transient increase in glycogen stores in multiple fat depots. In the present study, the protocol was replicated in male CD1 mice, resulting in a 2000-fold increase in interscapular BAT (IBAT) glycogen levels within 4–12 hours (hr) of refeeding, with IBAT glycogen stores reaching levels comparable to fed liver glycogen. Lesser effects occurred in white adipose tissues (WAT). Over the next 36 hr, glycogen levels dissipated and histological analysis revealed an over-accumulation of lipid droplets, suggesting a potential metabolic connection between glycogenolysis and lipid synthesis. 24 hr of total starvation followed by refeeding induced a robust and consistent glycogen over-accumulation similar in magnitude and time course to the prolonged partial fast. Experimentation demonstrated that hyperglycemia was not sufficient to drive glycogen accumulation in IBAT, but that elevated circulating insulin was sufficient. Additionally, pharmacological inhibition of catecholamine production reduced refeeding-induced IBAT glycogen storage, providing evidence of a contribution from the central nervous system. These findings highlight IBAT as a tissue that integrates both canonically-anabolic and catabolic stimulation for the promotion of glycogen storage during recovery from caloric deficit. The preservation of this robust response through many generations of animals not subjected to food deprivation suggests that the over-accumulation phenomenon plays a critical role in IBAT physiology. PMID:23861810

  6. Carcass glycogen repletion on carbohydrate re-feeding after starvation.

    OpenAIRE

    Cox, D J; Palmer, T N

    1987-01-01

    In mice, the response of carcass glycogen to glucose re-feeding after starvation is biphasic. The initial repletive phase is followed by partial (greater than 50%) glycogen mobilization. This turnover of carcass glycogen in response to carbohydrate re-feeding may play an important role in the provision of C3 precursors for hepatic glycogen synthesis.

  7. Zinc and calcium alter the relationship between mitochondrial respiration, ROS and membrane potential in rainbow trout (Oncorhynchus mykiss) liver mitochondria.

    Science.gov (United States)

    Sharaf, Mahmoud S; Stevens, Don; Kamunde, Collins

    2017-08-01

    At excess levels, zinc (Zn) disrupts mitochondrial functional integrity and induces oxidative stress in aquatic organisms. Although much is known about the modulation of Zn toxicity by calcium (Ca) in fish, their interactions at the mitochondrial level have scarcely been investigated. Here we assessed the individual and combined effects of Zn and Ca on the relationship between mitochondrial respiration, ROS and membrane potential (ΔΨ mt ) in rainbow trout liver mitochondria. We tested if cation uptake through the mitochondrial calcium uniporter (MCU) is a prerequisite for Zn- and/or Ca-induced alteration of mitochondrial function. Furthermore, using our recently developed real-time multi-parametric method, we investigated the changes in respiration, ΔΨ mt , and reactive oxygen species (ROS, as hydrogen peroxide (H 2 O 2 )) release associated with Ca-induced mitochondrial depolarization imposed by transient and permanent openings of the mitochondrial permeability transition pore (mPTP). We found that independent of the MCU, Zn precipitated an immediate depolarization of the ΔΨ mt that was associated with relatively slow enhancement of H 2 O 2 release, inhibition of respiration and reversal of the positive correlation between ROS and ΔΨ mt . In contrast, an equitoxic dose of Ca caused transient depolarization, and stimulation of both respiration and H 2 O 2 release, effects that were completely abolished when the MCU was blocked. Contrary to our expectation that mitochondrial transition ROS Spike (mTRS) would be sensitive to both Zn and Ca, only Ca suppressed it. Moreover, Zn and Ca in combination immediately depolarized the ΔΨ mt , and caused transient and sustained stimulation of respiration and H 2 O 2 release, respectively. Lastly, we uncovered and characterized an mPTP-independent Ca-induced depolarization spike that was associated with exposure to moderately elevated levels of Ca. Importantly, we showed the stimulation of ROS release associated with

  8. Patterns of dioxin-altered mRNA expression in livers of dioxin-sensitive versus dioxin-resistant rats

    Energy Technology Data Exchange (ETDEWEB)

    Franc, Monique A. [University of Toronto, Department of Pharmacology and Toxicology, Medical Sciences Building, Toronto, ON (Canada); Johnson and Johnson Pharmaceutical Research and Development, Department of Pharmacogenomics, 1000 Route 202 South, P.O. Box 300, Raritan, NJ (United States); Moffat, Ivy D.; Boutros, Paul C.; Okey, Allan B. [University of Toronto, Department of Pharmacology and Toxicology, Medical Sciences Building, Toronto, ON (Canada); Tuomisto, Jouni T.; Tuomisto, Jouko [National Public Health Institute, Department of Environmental Health, Centre for Environmental Health Risk Analysis, Kuopio (Finland); Pohjanvirta, Raimo [University of Helsinki, Department of Food and Environmental Hygiene, Faculty of Veterinary Medicine, Helsinki (Finland)

    2008-11-15

    Dioxins exert their major toxicologic effects by binding to the aryl hydrocarbon receptor (AHR) and altering gene transcription. Numerous dioxin-responsive genes previously were identified both by conventional biochemical and molecular techniques and by recent mRNA expression microarray studies. However, of the large set of dioxin-responsive genes the specific genes whose dysregulation leads to death remain unknown. To identify specific genes that may be involved in dioxin lethality we compared changes in liver mRNA levels following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in three strains/lines of dioxin-sensitive rats with changes in three dioxin-resistant rat strains/lines. The three dioxin-resistant strains/lines all harbor a large deletion in the transactivation domain of the aryl hydrocarbon receptor (AHR). Despite this deletion, many genes exhibited a ''Type-I'' response - that is, their responses were similar in dioxin-sensitive and dioxin-resistant rats. Several genes that previously were well established as being dioxin-responsive or under AHR regulation emerged as Type-I responses (e.g. CYP1A1, CYP1A2, CYP1B1 and Gsta3). In contrast, a relatively small number of genes exhibited a Type-II response - defined as a difference in responsiveness between dioxin-sensitive and dioxin-resistant rat strains. Type-II genes include: malic enzyme 1, ubiquitin C, cathepsin L, S-adenosylhomocysteine hydrolase and ferritin light chain 1. In silico searches revealed that AH response elements are conserved in the 5'-flanking regions of several genes that respond to TCDD in both the Type-I and Type-II categories. The vast majority of changes in mRNA levels in response to 100 {mu}g/kg TCDD were strain-specific; over 75% of the dioxin-responsive clones were affected in only one of the six strains/lines. Selected genes were assessed by quantitative RT-PCR in dose-response and time-course experiments and responses of some genes were

  9. Nuclear Glycogen Inclusions in Canine Parietal Cells.

    Science.gov (United States)

    Silvestri, S; Lepri, E; Dall'Aglio, C; Marchesi, M C; Vitellozzi, G

    2017-05-01

    Nuclear glycogen inclusions occur infrequently in pathologic conditions but also in normal human and animal tissues. Their function or significance is unclear. To the best of the authors' knowledge, no reports of nuclear glycogen inclusions in canine parietal cells exist. After initial observations of nuclear inclusions/pseudoinclusions during routine histopathology, the authors retrospectively examined samples of gastric mucosa from dogs presenting with gastrointestinal signs for the presence of intranuclear inclusions/pseudoinclusions and determined their composition using histologic and electron-microscopic methods. In 24 of 108 cases (22%), the authors observed various numbers of intranuclear inclusions/pseudoinclusions within scattered parietal cells. Nuclei were characterized by marked karyomegaly and chromatin margination around a central optically empty or slightly eosinophilic area. The intranuclear inclusions/pseudoinclusions stained positive with periodic acid-Schiff (PAS) and were diastase sensitive, consistent with glycogen. Several PAS-positive/diastase-sensitive sections were further examined by transmission electron microscopy, also using periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining to identify polysaccharides. Ultrastructurally, the nuclear inclusions were composed of electron-dense particles that were not membrane bound, without evidence of nuclear membrane invaginations or cytoplasmic organelles in the nuclei, and positive staining with PA-TCH-SP, confirming a glycogen composition. No cytoplasmic glycogen deposits were observed, suggesting that the intranuclear glycogen inclusions were probably synthesized in loco. Nuclear glycogen inclusions were not associated with gastritis or colonization by Helicobacter-like organisms ( P > .05). Our findings suggest that nuclear glycogen inclusions in canine parietal cells could be an incidental finding. Nevertheless, since nuclear glycogen is present in several pathologic

  10. Glycogen Synthase Kinase-3β

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Lenskjold, Toke; Jacoby, Anne Sophie

    2016-01-01

    cells were quantitated using enzyme immunometric assays. The activity of GSK-3β (serine-9-phosphorylated GSK-3β/total GSK-3β) was lower at baseline compared with follow-up. No significant mean change over time was observed in levels of total GSK-3β and serine-9-phosphorylated GSK-3β. Exploratory......Evidence indicates a role for glycogen synthase kinase-3β (GSK-3β) in the pathophysiology of mood disorders and in cognitive disturbances; however, the natural variation in GSK-3β activity over time is unknown. We aimed to investigate GSK-3β activity over time and its possible correlation...... with emotional lability, subjective mood fluctuations and cognitive function in healthy individuals. Thirty-seven healthy subjects were evaluated with neuropsychological tests and blood samples at baseline and 12-week follow-up. Total GSK-3β and serine-9-phosphorylated GSK-3β in peripheral blood mononuclear...

  11. Morphological alterations and acetylcholinesterase and monoamine oxidase inhibition in liver of zebrafish exposed to Aphanizomenon flos-aquae DC-1 aphantoxins

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, De Lu, E-mail: deluzh@163.com [Department of Lifescience and Biotechnology, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070 (China); Zhang, Jing [College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); Hu, Chun Xiang, E-mail: cxhu@ihb.ac.cn [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China); Wang, Gao Hong; Li, Dun Hai; Liu, Yong Ding [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China)

    2014-12-15

    Highlights: • Aphantoxins induced zebrafish hepatic physiological and morphological changes. • AChE and MAO inhibition reflected abnormality of neurotransmitter inactivation. • ROS advance and T-AOC reduction suggested oxidative stress. • ALT, AST, histological and ultrastructural alterations indicated hepatic damage. - Abstract: Aphanizomenon flos-aquae is a cyanobacterium that produces neurotoxins or paralytic shellfish poisons (PSPs) called aphantoxins, which present threats to environmental safety and human health via eutrophication of water bodies worldwide. Although the molecular mechanisms of this neurotoxin have been studied, many questions remain unsolved, including those relating to in vivo hepatic neurotransmitter inactivation, physiological detoxification and histological and ultrastructural alterations. Aphantoxins extracted from the natural strain of A. flos-aquae DC-1 were analyzed by high-performance liquid chromatography. The main components were gonyautoxins 1 and 5 (GTX1, GTX5) and neosaxitoxin (neoSTX), which comprised 34.04%, 21.28%, and 12.77% respectively. Zebrafish (Danio rerio) were exposed intraperitoneally to 5.3 or 7.61 μg STX equivalents (eq)/kg (low and high doses, respectively) of A. flos-aquae DC-1 aphantoxins. Morphological alterations and changes in neurotransmitter conduction functions of acetylcholinesterase (AChE) and monoamine oxidase (MAO) in zebrafish liver were detected at different time points 1–24 h post-exposure. Aphantoxin significantly enhanced hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histological and ultrastructural damage in zebrafish liver at 3–12 h post-exposure. Toxin exposure increased the reactive oxygen species content and reduced total antioxidative capacity in zebrafish liver, suggesting oxidative stress. AChE and MAO activities were significantly inhibited, suggesting neurotransmitter inactivation/conduction function abnormalities in zebrafish

  12. Distribution of intrahepatic T, NK and CD3(+)CD56(+)NKT cells alters after liver transplantation: Shift from innate to adaptive immunity?

    Science.gov (United States)

    Werner, Jens M; Lang, Corinna; Scherer, Marcus N; Farkas, Stefan A; Geissler, Edward K; Schlitt, Hans J; Hornung, Matthias

    2011-07-01

    The liver is an immunological organ containing a large number of T, NK and NKT cells, but little is known about intrahepatic immunity after LTx. Here, we investigated whether the distribution of T, NK and CD3(+)CD56(+)NKT cells is altered in transplanted livers under different circumstances. Core biopsies of transplanted livers were stained with antibodies against CD3 and CD56. Several cell populations including T (CD3(+)CD56(-)), NK (CD3(-)CD56(+)) and NKT cells (CD3(+)CD56(+)) were studied by fluorescence microscopy. Cell numbers were analyzed in relation to the time interval after LTx, immunosuppressive therapy and stage of acute graft rejection (measured with the rejection activity index: RAI) compared to tumor free liver tissue from patients after liver resection due to metastatic disease as control. Recruitment of CD3(+)CD56(+)NKT cells revealed a significant decrease during high RAI scores in comparison to low and middle RAI scores (RAI 7-9: 0.03±0.01/HPF vs. RAI 4-6: 0.1±0.005/HPF). CD3(+)CD56(+)NKT cells were also lower during immunosuppressive therapy with tacrolimus (0.03±0.01/HPF) than with cyclosporine (0.1±0.003/HPF), cyclosporine/MMF (0.1±0.003/HPF) or sirolimus (0.1±0.01/HPF) treatment. Intrahepatic T cell numbers increased significantly 50days after LTx compared to control liver tissue (4.5±0.2/HPF vs. 1.9±0.1/HPF). In contrast, NK cells (0.3±0.004/HPF) were significantly fewer in all biopsies after LTx compared to the control (0.7±0.04/HPF). These data indicate significant alterations in the hepatic recruitment of T, NK and CD3(+)CD56(+)NKT cells after LTx. The increase in T cells and the decrease in NK and CD3(+)CD56(+)NKT cells suggest a shift from innate to adaptive hepatic immunity in the liver graft. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Hepatic glycogen levels in female rats submitted to aquatic therapy after muscle disuse

    Directory of Open Access Journals (Sweden)

    Jefferson Pacheco Amaral Fortes

    2017-12-01

    Full Text Available The aim of the present study was to analyse the changes in liver glycogen content in rats subjected to aquatic therapy post-disuse of the paw. 32 wistar adult female rats were equally divided: Control (C, kept in the cage for two weeks without interventions; Disuse (D had the right paw immobilized with hip extension, knee and plantar flexion for two weeks; Aquatic Therapy (AT underwent aquatic therapy with increments of 3 minutes daily for two weeks, totalizing 36 minutes of training; Disused Aquatic Therapy (DTA was first subjected to immobilization for two weeks and 24 hours after withdrawal of immobilization aquatic therapy was started for two more weeks, in same protocols of D and AT groups. At the end of the experiment, the animals were sacrificed, and tissues were dissected, weighed and stored. The liver tissues were referred analysis of glycogen content. It was observed that the blood glucose levels of the AT group (104 mg/dL were different from the C group (86 mg/dL; p = 0.0213. Regarding hepatic glycogen, the D (2.35mg±0.07 and AT (2.73mg±0.07 groups had hepatic glycogen reduction by 22% and 15%, relative to C (2.51mg±0.03; p <0.0001. The DTA group presented no differences when compared to the control, suggesting the normalization of the finding. Muscle disuse by two weeks promoted changes in glycogen levels, however, two weeks after disuse condition, the aquatic therapy were able to correct the energetic reserve in liver.

  14. The protective role of nigella sativa oil against toxicity of organophosphorous pesticide tamaron on Some biochemical and histological alterations in liver and kidneys of male rats

    International Nuclear Information System (INIS)

    Afifi, E.A.; Aly, S.E.; Hafez, S.E.

    2006-01-01

    The objective of this study was to determine the potential benefits of Nigella sativa oil against the toxicity of the organophosphorous pesticide tamaron. It was carried out by evaluating the effect of the repeated daily oral doses of Nigella sativa oil (1 ml/kg) and/or tamaron (1.8 mg/kg) for five weeks on some biochemical and histological changes in liver and kidneys of male rats. The data showed that the pesticide caused disturbance in liver function revealed as a significant increase in serum transaminases (SGOT and SGPT), alkaline phosphatase (SALP), serum total cholesterol, triglycerides and albumin. Also, the alteration in the kidney function was noticed through a significant increase in creatinine level, urea and uric acid. Moreover, a significant decrease in serum testosterone level was also observed. The results also showed that extended administration of Nigella sativa oil during tamaron treatment minimized the disturbance of the liver and kidneys functions and testis injury. The histological examination revealed that, tamaron treatment showed marked degenerative changes in liver hepatocytes and vacuolar epithelial lining the renal tubules (tubular necrosis), hyalinized glomerular tuft and interstitial hemorrhage with fibrosis in kidneys. These changes were mild to moderate in the other groups. The least histological changes were noticed with Nigella sativa oil treatment

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

    International Nuclear Information System (INIS)

    Ida, Katsuya; Nakamura, Satoshi; Muro, Hiroyuki; Takai, Michikatsu; Kaneko, Masao

    1995-01-01

    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. γ-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 γ-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 PB 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. (author)

  16. Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG)

    OpenAIRE

    Worby, Carolyn A.; Gentry, Matthew S.; Dixon, Jack E.

    2007-01-01

    Lafora disease (LD) is an autosomal recessive neurodegenerative disease that results in progressive myoclonus epilepsy and death. LD is caused by mutations in either the E3 ubiquitin ligase malin or the dual-specificity phosphatase laforin. A hallmark of LD is the accumulation of insoluble glycogen in the cytoplasm of cells from most tissues. Glycogen metabolism is regulated by phosphorylation of key metabolic enzymes. One regulator of this phosphorylation is protein targeting to glycogen (PT...

  17. Effects of in ovo injection of carbohydrates on somatic characteristics and liver nutrient profiles of broiler embryos and hatchlings.

    Science.gov (United States)

    Zhai, W; Bennett, L W; Gerard, P D; Pulikanti, R; Peebles, E D

    2011-12-01

    Effects of the in ovo injection of commercial diluent supplemented with dextrin or with dextrin in combination with various other carbohydrates on the somatic characteristics and liver nutrient profiles of Ross × Ross 708 broiler embryos and chicks were investigated. Results include information concerning the gluconeogenic energy status of the liver before and after hatch. Eggs containing live embryos were injected in the amnion on d 18 of incubation using an automated multiple-egg injector for the delivery of the following carbohydrates dissolved in 0.4 mL of commercial diluent: 1) 6.25% glucose and 18.75% dextrin; 2) 6.25% sucrose and 18.75% dextrin; 3) 6.25% maltose and 18.75% dextrin; and 4) 25% dextrin. Also, a noninjected control and a 0.4-mL diluent-injected control were included. Body weight relative to set egg weight on d 19 of incubation (E19) was increased by the injection of all carbohydrate solutions, and on the day of hatch was increased by the injection of diluent, sucrose and dextrin, and maltose and dextrin solutions. Hatchability of the fertilized eggs, residual yolk sac weight, and liver weight were not affected by any injection treatment; however, as compared with the 0.4 mL diluent-injected group, all of the supplementary carbohydrates, except for the glucose and dextrin combination group, increased liver glycogen and glucose concentrations on E19. Furthermore, all carbohydrates, except for the 25% dextrin treatment, decreased liver fat concentration on E19. From E19 to the day of hatch, liver glycogen concentrations dropped dramatically from an average of 3.2 to 0.6%. Despite treatment differences observed on E19 for liver glycogen, glucose, and fat concentrations, these differences were lost by the day of hatch. Nevertheless, liver glycogen and glucose concentrations were positively correlated on the day of hatch. In conclusion, the in ovo injection of various supplemental carbohydrates dissolved in 0.4 mL of commercial diluent altered the

  18. Histopathological alterations of the gills, liver and kidneys in Anabas Testudineus (Bloch) fish living in an unused lignite mine, Li District, Lamphun Povince, Thailand

    Energy Technology Data Exchange (ETDEWEB)

    Saenphet, S.; Thaworn, W.; Saenphet, K. [Chiang Mai University, Chiang Mai (Thailand). Faculty of Science

    2009-09-15

    The acidity of mine water generally makes it toxic to most organisms. The gills, kidneys and livers of Anabas testudineus Bloch fish inhabiting the acidic water (pH 2-4) of an unused lignite mine in Li District, Lamphun Province, Thailand were examined and compared to those of farmed fish. Tissue abnormalities were found in all investigated organs. Deterioration and telangiectasia of gill filaments were found. Liver tissue revealed hemorrhages, blood congestion and necrotic cells with mononuclear cell infiltration. In addition, hypertrophy of the epithelial cells of the renal tubules with reduced lumens, aneurisms of the renal tubules, and contractions of the glomeruli in the Bowman's capsule were observed. These histopathological findings suggest the acidic water in this habitat causes severe damage to the internal organs of fish and consequently alter their physiological status. Since the water in this pond is utilized by local people, these findings highlight the need for adequate water treatment.

  19. Transcriptomic responses of the liver and adipose tissues to altered carbohydrate-fat ratio in diet: an isoenergetic study in young rats.

    Science.gov (United States)

    Tanaka, Mitsuru; Yasuoka, Akihito; Shimizu, Manae; Saito, Yoshikazu; Kumakura, Kei; Asakura, Tomiko; Nagai, Toshitada

    2017-01-01

    To elucidate the effects of altered dietary carbohydrate and fat balance on liver and adipose tissue transcriptomes, 3-week-old rats were fed three kinds of diets: low-, moderate-, and high-fat diets (L, M, and H) containing a different ratio of carbohydrate-fat (C-F) (65:15, 60:20, and 35:45 in energy percent, respectively). The rats consumed the diets for 9 weeks and were subjected to biochemical and DNA microarray analyses. The rats in the H-group exhibited lower serum triacylglycerol (TG) levels but higher liver TG and cholesterol content than rats in the L-group. The analysis of differentially expressed genes (DEGs) between each group (L vs M, M vs H, and L vs H) in the liver revealed about 35% of L vs H DEGs that were regulated in the same way as M vs H DEGs, and most of the others were L- vs H-specific. Gene ontology analysis of these L vs H DEGs indicated that those related to fatty acid synthesis and circadian rhythm were enriched. Interestingly, about 30% of L vs M DEGs were regulated in a reverse way compared with L vs H and M vs H DEGs. These reversed liver DEGs included M-up/H-down genes ( Sds for gluconeogenesis from amino acids) and M-down/H-up genes ( Gpd2 for gluconeogenesis from glycerol, Agpat9 for TG synthesis, and Acot1 for beta-oxidation). We also analyzed L vs H DEGs in white (WAT) and brown (BAT) adipose tissues and found that both oxidation and synthesis of fatty acids were inhibited in these tissues. These results indicate that the alteration of dietary C-F balance differentially affects the transcriptomes of metabolizing and energy-storing tissues.

  20. Quantitative estimation of the pathways followed in the conversion to glycogen of glucose administered to the fasted rat

    International Nuclear Information System (INIS)

    Scofield, R.F.; Kosugi, K.; Schumann, W.C.; Kumaran, K.; Landau, B.R.

    1985-01-01

    When [6- 3 H,6- 14 C]glucose was given in glucose loads to fasted rats, the average 3 H/ 14 C ratios in the glycogens deposited in their livers, relative to that in the glucoses administered, were 0.85 and 0.88. When [3- 3 H,3- 14 C]lactate was given in trace quantity along with unlabeled glucose loads, the average 3 H/ 14 C ratio in the glycogens deposited was 0.08. This indicates that a major fraction of the carbons of the glucose loads was converted to liver glycogen without first being converted to lactate. When [3- 3 H,6- 14 C]glucose was given in glucose loads, the 3 H/ 14 C ratios in the glycogens deposited averaged 0.44. This indicates that a significant amount of H bound to C-3, but not C-6, of glucose is removed within liver in the conversion of the carbons of the glucose to glycogen. This can occur in the pentose cycle and by cycling of glucose-6-P via triose phosphates. The contributions of these pathways were estimated by giving glucose loads labeled with [1- 14 C]glucose, [2- 14 C]glucose, [5- 14 C]glucose, and [6- 14 C]glucose and degrading the glucoses obtained by hydrolyzing the glycogens that deposited. Between 4 and 9% of the glucose utilized by the liver was utilized in the pentose cycle. While these are relatively small percentages a major portion of the difference between the ratios obtained with [3- 3 H]glucose and with [6- 3 H]glucose is attributable to metabolism in the pentose cycle

  1. Manipulation of Muscle Creatine and Glycogen Changes Dual X-ray Absorptiometry Estimates of Body Composition.

    Science.gov (United States)

    Bone, Julia L; Ross, Megan L; Tomcik, Kristyen A; Jeacocke, Nikki A; Hopkins, Will G; Burke, Louise M

    2017-05-01

    Standardizing a dual x-ray absorptiometry (DXA) protocol is thought to provide a reliable measurement of body composition. We investigated the effects of manipulating muscle glycogen and creatine content independently and additively on DXA estimates of lean mass. Eighteen well-trained male cyclists undertook a parallel group application of creatine loading (n = 9) (20 g·d for 5 d loading; 3 g·d maintenance) or placebo (n = 9) with crossover application of glycogen loading (12 v 6 g·kg BM per day for 48 h) as part of a larger study involving a glycogen-depleting exercise protocol. Body composition, total body water, muscle glycogen and creatine content were assessed via DXA, bioelectrical impedance spectroscopy and standard biopsy techniques. Changes in the mean were assessed using the following effect-size scale: >0.2 small, >0.6, moderate, >1.2 large and compared with the threshold for the smallest worthwhile effect of the treatment. Glycogen loading, both with and without creatine loading, resulted in substantial increases in estimates of lean body mass (mean ± SD; 3.0% ± 0.7% and 2.0% ± 0.9%) and leg lean mass (3.1% ± 1.8% and 2.6% ± 1.0%) respectively. A substantial decrease in leg lean mass was observed after the glycogen depleting condition (-1.4% ± 1.6%). Total body water showed substantial increases after glycogen loading (2.3% ± 2.3%), creatine loading (1.4% ± 1.9%) and the combined treatment (2.3% ± 1.1%). Changes in muscle metabolites and water content alter DXA estimates of lean mass during periods in which minimal change in muscle protein mass is likely. This information needs to be considered in interpreting the results of DXA-derived estimates of body composition in athletes.

  2. A study on the altered glycemic and lipid parameters and prevalence of insulin resistance in nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Sangeetha Suresh

    2018-01-01

    Full Text Available Introduction: Nonalcoholic fatty liver disease (NAFLD is a hepatic disorder that develops in the absence of alcohol intake. Obesity and diabetes are considered risk factors for the development of fatty liver; however, whether fatty liver is the cause or consequence of these conditions is not yet clear. Insulin resistance (IR is found to be a common risk factor for the development of diabetes, obesity and fatty liver. Aims and Objectives: The aim and objective of this study is to determine the prevalence of undetected diabetes, dyslipidemia, and IR in subjects with NAFLD. Materials and Methods: In apparently healthy 100 subjects, with ultrasound diagnosis of fatty liver, fasting and postprandial blood sugar levels, fasting insulin levels, and fasting lipid profile were checked. IR value was estimated using homeostatic model assessment-IR formula. Appropriate statistical methods were adopted to analyze the data. Results: A total of 66 subjects out of the 100 had IR. It was noted that IR significantly correlated with raised fasting blood sugar and fasting plasma insulin values. There was no significant correlation between IR and lipid profile values. Conclusion: The chance of developing NAFLD was high if the subjects are having IR, or vice versa. There was an increased prevalence of prediabetes and diabetes in the subjects with NAFLD. Waist circumference, rather than body mass index, was found to be a strong predictor of central adiposity and IR.

  3. Compartmentation of glycogen metabolism revealed from 13C isotopologue distributions

    Directory of Open Access Journals (Sweden)

    Marin de Mas Igor

    2011-10-01

    Full Text Available Abstract Background Stable isotope tracers are used to assess metabolic flux profiles in living cells. The existing methods of measurement average out the isotopic isomer distribution in metabolites throughout the cell, whereas the knowledge of compartmental organization of analyzed pathways is crucial for the evaluation of true fluxes. That is why we accepted a challenge to create a software tool that allows deciphering the compartmentation of metabolites based on the analysis of average isotopic isomer distribution. Results The software Isodyn, which simulates the dynamics of isotopic isomer distribution in central metabolic pathways, was supplemented by algorithms facilitating the transition between various analyzed metabolic schemes, and by the tools for model discrimination. It simulated 13C isotope distributions in glucose, lactate, glutamate and glycogen, measured by mass spectrometry after incubation of hepatocytes in the presence of only labeled glucose or glucose and lactate together (with label either in glucose or lactate. The simulations assumed either a single intracellular hexose phosphate pool, or also channeling of hexose phosphates resulting in a different isotopic composition of glycogen. Model discrimination test was applied to check the consistency of both models with experimental data. Metabolic flux profiles, evaluated with the accepted model that assumes channeling, revealed the range of changes in metabolic fluxes in liver cells. Conclusions The analysis of compartmentation of metabolic networks based on the measured 13C distribution was included in Isodyn as a routine procedure. The advantage of this implementation is that, being a part of evaluation of metabolic fluxes, it does not require additional experiments to study metabolic compartmentation. The analysis of experimental data revealed that the distribution of measured 13C-labeled glucose metabolites is inconsistent with the idea of perfect mixing of hexose

  4. Farnesoid X Receptor Agonist Treatment Alters Bile Acid Metabolism but Exacerbates Liver Damage in a Piglet Model of Short-Bowel Syndrome.

    Science.gov (United States)

    Pereira-Fantini, Prue M; Lapthorne, Susan; Gahan, Cormac G M; Joyce, Susan A; Charles, Jenny; Fuller, Peter J; Bines, Julie E

    2017-07-01

    Options for the prevention of short-bowel syndrome-associated liver disease (SBS-ALDs) are limited and often ineffective. The farnesoid X receptor (FXR) is a newly emerging pharmaceutical target and FXR agonists have been shown to ameliorate cholestasis and metabolic disorders. The aim of this study was to assess the efficacy of obeticholic acid (OCA) treatment in preventing SBS-ALDs. Piglets underwent 75% small-bowel resection (SBS) or sham surgery (sham) and were assigned to either a daily dose of OCA (2.4 mg/kg/day) or were untreated. Clinical measures included weight gain and stool studies. Histologic features were assessed. Ultraperformance liquid chromatography tandem mass spectrometry was used to determine bile acid composition in end point bile and portal serum samples. Gene expression of key FXR targets was assessed in intestinal and hepatic tissues via quantitative polymerase chain reaction. OCA-treated SBS piglets showed decreased stool fat and altered liver histology when compared with nontreated SBS piglets. OCA prevented SBS-associated taurine depletion, however, further analysis of bile and portal serum samples indicated that OCA did not prevent SBS-associated alterations in bile acid composition. The expression of FXR target genes involved in bile acid transport and synthesis increased within the liver of SBS piglets after OCA administration whereas, paradoxically, intestinal expression of FXR target genes were decreased by OCA administration. Administration of OCA in SBS reduced fat malabsorption and altered bile acid composition, but did not prevent the development of SBS-ALDs. We postulate that extensive small resection impacts the ability of the remnant intestine to respond to FXR activation.

  5. Stiffness of hyaluronic acid gels containing liver extracellular matrix supports human hepatocyte function and alters cell morphology.

    Science.gov (United States)

    Deegan, Daniel B; Zimmerman, Cynthia; Skardal, Aleksander; Atala, Anthony; Shupe, Thomas D

    2015-03-01

    Tissue engineering and cell based liver therapies have utilized primary hepatocytes with limited success due to the failure of hepatocytes to maintain their phenotype in vitro. In order to overcome this challenge, hyaluronic acid (HA) cell culture substrates were formulated to closely mimic the composition and stiffness of the normal liver cellular microenvironment. The stiffness of the substrate was modulated by adjusting HA hydrogel crosslinking. Additionally, the repertoire of bioactive molecules within the HA substrate was bolstered by supplementation with normal liver extracellular matrix (ECM). Primary human hepatocyte viability and phenotype were determined over a narrow physiologically relevant range of substrate stiffnesses from 600 to 4600Pa in both the presence and absence of liver ECM. Cell attachment, viability, and organization of the actin cytoskeleton improved with increased stiffness up to 4600Pa. These differences were not evident in earlier time points or substrates containing only HA. However, gene expression for the hepatocyte markers hepatocyte nuclear factor 4 alpha (HNF4α) and albumin significantly decreased on the 4600Pa stiffness at day 7 indicating that cells may not have maintained their phenotype long-term at this stiffness. Function, as measured by albumin secretion, varied with both stiffness and time in culture and peaked at day 7 at the 1200Pa stiffness, slightly below the stiffness of normal liver ECM at 3000Pa. Overall, gel stiffness affected primary human hepatocyte cell adhesion, functional marker expression, and morphological characteristics dependent on both the presence of liver ECM in gel substrates and time in culture. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Alterations of Liver Histomorphology in Relation to Copper Supplementation in Inorganic and Organic Form in Growing Rats

    Directory of Open Access Journals (Sweden)

    Tomaszewska Ewa

    2014-10-01

    Full Text Available The aim of this study was to define the effects of diet containing the same mineral content of mineral salt or amino acid chelate, and diet containing various levels of Cu amino acid chelate on liver histomorphometry in growing rats. Male Wistar rats were used in the 12th week experiment. The control group (n = 12 was fed standard diet, which provided Cu in an inorganic form at the level required for rats. The experimental animals were divided into four groups (each n = 12 depending on different levels (100%, 75%, 50%, 25% covered daily demand of Cu supplementation in chelated form. Cu content was determined in the liver tissue and blood plasma. Immunohistochemical staining with caspase-3 antibody was performed. Microscopic assessment of the liver structure indicated that Cu supplementation did not change the liver architecture. However, histomorphometric analysis revealed a significant increase in the number of nuclei, total cell number, and multinucleated hepatocytes in rats supplemented with the organic form of Cu at the level of 25% compared with the control group. There was a considerable increase in the number of apoptotic cells and ballooning degeneration of hepatocytes, especially in groups supplemented with organic form of Cu covering the daily demand in 100% and 75%, in comparison to control group. Moreover, there was no Cu deposition in the liver and changes in Cu content in blood. Cu provided in the diet in organic form covering an amount of its minimum daily demand in 25% appears to be the least harmful with regard to the liver. It indicates that there is a need to establish the level of diet supplementation with Cu amino acid chelates.

  7. Electron autoradiographic study of intracellular conversion of fatty acids into glycogen in rats with alloxan diabetes

    International Nuclear Information System (INIS)

    Lebkova, N.P.; Bobkov, Y.I.; Gorbonova, V.D.; Kolesova, O.E.

    1985-01-01

    An electron-autoradiographic study was undertaken of the intracellular distribution of hydrogen of fatty acids in alloxan diabetes. Alloxan diabetes was induced in rats; between 2 weeks and 2 months after development of the disease 0.1 ml of tritium-oleic or tritium-arachidonic acid was injected into the caudel vein of the rats. After decapitation, myocardial tissue from the subendocardial zone of the left ventricle, liver tissue, and glycogen isolated from the liver by a biochemical method, were taken for electron-autoradiographic investigation. Analysis of the data showed that a radioactive isotope, injected into the blood stream of the animals in the form of oleic or arachidonic acids, is incorporated into various structures of hepatocytes and cardiomyocytes. Direct proof is obtained to show that glycogen in hepatocytes and cardiomyoctyes of diabetic rats may be formed from fatty acids

  8. Does abnormal glycogen structure contribute to increased susceptibility to seizures in epilepsy?

    Science.gov (United States)

    DiNuzzo, Mauro; Mangia, Silvia; Maraviglia, Bruno; Giove, Federico

    2015-02-01

    Epilepsy is a family of brain disorders with a largely unknown etiology and high percentage of pharmacoresistance. The clinical manifestations of epilepsy are seizures, which originate from aberrant neuronal synchronization and hyperexcitability. Reactive astrocytosis, a hallmark of the epileptic tissue, develops into loss-of-function of glutamine synthetase, impairment of glutamate-glutamine cycle and increase in extracellular and astrocytic glutamate concentration. Here, we argue that chronically elevated intracellular glutamate level in astrocytes is instrumental to alterations in the metabolism of glycogen and leads to the synthesis of polyglucosans. Unaccessibility of glycogen-degrading enzymes to these insoluble molecules compromises the glycogenolysis-dependent reuptake of extracellular K(+) by astrocytes, thereby leading to increased extracellular K(+) and associated membrane depolarization. Based on current knowledge, we propose that the deterioration in structural homogeneity of glycogen particles is relevant to disruption of brain K(+) homeostasis and increased susceptibility to seizures in epilepsy.

  9. Brain glycogen and its role in supporting glutamate and GABA homeostasis in a type 2 diabetes rat model

    DEFF Research Database (Denmark)

    Sickmann, Helle Mark; Waagepetersen, Helle S.; Schousboe, Arne

    2012-01-01

    -(13)C]glucose was used to monitor metabolism. Brain levels of (13)C labeling in glucose, lactate, alanine, glutamate, GABA, glutamine and aspartate were determined. Our results show that inhibition of brain glycogen metabolism reduced the amounts of glutamate in both the control and type 2 diabetes......The number of people suffering from diabetes is hastily increasing and the condition is associated with altered brain glucose homeostasis. Brain glycogen is located in astrocytes and being a carbohydrate reservoir it contributes to glucose homeostasis. Furthermore, glycogen has been indicated...... to be important for proper neurotransmission under normal conditions. Previous findings from our laboratory suggested that glucose metabolism was reduced in type 2 diabetes, and thus we wanted to investigate more specifically how brain glycogen metabolism contributes to maintain energy status in the type 2...

  10. Astrocyte glycogen as an emergency fuel under conditions of glucose deprivation or intense neural activity.

    Science.gov (United States)

    Brown, Angus M; Ransom, Bruce R

    2015-02-01

    Energy metabolism in the brain is a complex process that is incompletely understood. Although glucose is agreed as the main energy support of the brain, the role of glucose is not clear, which has led to controversies that can be summarized as follows: the fate of glucose, once it enters the brain is unclear. It is not known the form in which glucose enters the cells (neurons and glia) within the brain, nor the degree of metabolic shuttling of glucose derived metabolites between cells, with a key limitation in our knowledge being the extent of oxidative metabolism, and how increased tissue activity alters this. Glycogen is present within the brain and is derived from glucose. Glycogen is stored in astrocytes and acts to provide short-term delivery of substrates to neural elements, although it may also contribute an important component to astrocyte metabolism. The roles played by glycogen awaits further study, but to date its most important role is in supporting neural elements during increased firing activity, where signaling molecules, proposed to be elevated interstitial K(+), indicative of elevated neural firing rates, activate glycogen phosphorylase leading to increased production of glycogen derived substrate.

  11. A Study of the Modulating Action of Quercetin on Biochemical and Histological Alterations Induced by Lead Exposure in the Liver and Kidney of Rats.

    Science.gov (United States)

    Mohammed, Ghena M.; Sedky, Azza; Elsawy, Hany

    2017-06-30

    Lead is a highly toxic metal and a very potent poison. Lead poisoning is a serious condition but can be treated. Quercetin is a flavonoid with many beneficial uses. The aim of the present study was to investigate the possible modulating action of quercetin as a model of an antioxidant against the toxic effects of lead acetate on liver and kidneys of rats. Rats were randomly divided into four groups: (i) saline group (control); (ii) lead group received i.p. lead acetate (20 mg/kg b.w.); (iii) quercetin group received i.p. quercetin (50 mg/kg b.w.); (iv) lead and quercetin group received i.p. lead acetate (20 mg/kg b.w.) followed by i.p. quercetin (50 mg/kg b.w.) for 4 weeks. The lead concentrations were determined in the liver and kidney tissues. Liver marker enzymes, bilirubin, albumin, total protein, creatinine, uric acid and urea, were assessed in the serum and light microscopic studies were performed. The results showed that lead acetate administration was associated with an increase in serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, total bilirubin, creatinine, uric acid, urea levels. Lead accumulation in kidneys and liver tissues was also found, but were associated with decrease in albumin and total protein in comparison with the respective mean values of the control. Lead acetate caused numerous histological alterations in the liver, including chronic inflammation, bilary hyperplasia, edema, congestion, Kupffer cells hyperplasia and hemosiderosis, and in the kidney, including tubular dilation, atrophy of glomerular tuft, widening of urinary space and mild fibroblast. In contrary, administration of lead acetate along with quercetin partially restored the studied parameters to normal values and improved structure of liver and kidney with significant decreases in the severity of histopathological changes when compared with the lead acetate group. In conclusion, treatment with quercetin may provide a

  12. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice.

    OpenAIRE

    Christensen, K. E.; Mikael, L. G.; Leung, K. Y.; Lévesque, N.; Deng, L.; Wu, Q.; Malysheva, O. V.; Best, A.; Caudill, M. A.; Greene, N. D.; Rozen, R.

    2015-01-01

    Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions.

  13. Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: rethinking the brain?liver axis

    OpenAIRE

    Yang, B; Ren, Q; Zhang, J-c; Chen, Q-X; Hashimoto, K

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) has a role in the pathophysiology of psychiatric disorders. The precursor proBDNF is converted to mature BDNF and BDNF pro-peptide, the N-terminal fragment of proBDNF; however, the precise function of these proteins in psychiatric disorders is unknown. We sought to determine whether expression of these proteins is altered in the brain and peripheral tissues from patients with psychiatric disorders. We measured protein expression of proBDNF, mature BDNF...

  14. Hyper-hippocampal glycogen induced by glycogen loading with exhaustive exercise.

    Science.gov (United States)

    Soya, Mariko; Matsui, Takashi; Shima, Takeru; Jesmin, Subrina; Omi, Naomi; Soya, Hideaki

    2018-01-19

    Glycogen loading (GL), a well-known type of sports conditioning, in combination with exercise and a high carbohydrate diet (HCD) for 1 week enhances individual endurance capacity through muscle glycogen supercompensation. This exercise-diet combination is necessary for successful GL. Glycogen in the brain contributes to hippocampus-related memory functions and endurance capacity. Although the effect of HCD on the brain remains unknown, brain supercompensation occurs following exhaustive exercise (EE), a component of GL. We thus employed a rat model of GL and examined whether GL increases glycogen levels in the brain as well as in muscle, and found that GL increased glycogen levels in the hippocampus and hypothalamus, as well as in muscle. We further explored the essential components of GL (exercise and/or diet conditions) to establish a minimal model of GL focusing on the brain. Exercise, rather than a HCD, was found to be crucial for GL-induced hyper-glycogen in muscle, the hippocampus and the hypothalamus. Moreover, EE was essential for hyper-glycogen only in the hippocampus even without HCD. Here we propose the EE component of GL without HCD as a condition that enhances brain glycogen stores especially in the hippocampus, implicating a physiological strategy to enhance hippocampal functions.

  15. High glycogen levels enhance glycogen breakdown in isolated contracting skeletal muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    and after 15 min of intermittent electrical muscle stimulation. Before stimulation, glycogen was higher in rats that swam on the preceding day (supercompensated rats) compared with controls. During muscle contractions, glycogen breakdown in fast-twitch red and white fibers was larger in supercompensated...

  16. Acoustically accessible window determination for ultrasound mediated treatment of glycogen storage disease type Ia patients

    Science.gov (United States)

    Wang, Shutao; Raju, Balasundar I.; Leyvi, Evgeniy; Weinstein, David A.; Seip, Ralf

    2012-10-01

    Glycogen storage disease type Ia (GSDIa) is caused by an inherited single-gene defect resulting in an impaired glycogen to glucose conversion pathway. Targeted ultrasound mediated delivery (USMD) of plasmid DNA (pDNA) to liver in conjunction with microbubbles may provide a potential treatment for GSDIa patients. As the success of USMD treatments is largely dependent on the accessibility of the targeted tissue by the focused ultrasound beam, this study presents a quantitative approach to determine the acoustically accessible liver volume in GSDIa patients. Models of focused ultrasound beam profiles for transducers of varying aperture and focal lengths were applied to abdomen models reconstructed from suitable CT and MRI images. Transducer manipulations (simulating USMD treatment procedures) were implemented via transducer translations and rotations with the intent of targeting and exposing the entire liver to ultrasound. Results indicate that acoustically accessible liver volumes can be as large as 50% of the entire liver volume for GSDIa patients and on average 3 times larger compared to a healthy adult group due to GSDIa patients' increased liver size. Detailed descriptions of the evaluation algorithm, transducer-and abdomen models are presented, together with implications for USMD treatments of GSDIa patients and transducer designs for USMD applications.

  17. Exposures to arsenite and methylarsonite produce insulin resistance and impair insulin-dependent glycogen metabolism in hepatocytes.

    Science.gov (United States)

    Zhang, Chongben; Fennel, Emily M J; Douillet, Christelle; Stýblo, Miroslav

    2017-12-01

    Environmental exposure to inorganic arsenic (iAs) has been shown to disturb glucose homeostasis, leading to diabetes. Previous laboratory studies have suggested several mechanisms that may underlie the diabetogenic effects of iAs exposure, including (i) inhibition of insulin signaling (leading to insulin resistance) in glucose metabolizing peripheral tissues, (ii) inhibition of insulin secretion by pancreatic β cells, and (iii) dysregulation of the methylation or expression of genes involved in maintenance of glucose or insulin metabolism and function. Published studies have also shown that acute or chronic iAs exposures may result in depletion of hepatic glycogen stores. However, effects of iAs on pathways and mechanisms that regulate glycogen metabolism in the liver have never been studied. The present study examined glycogen metabolism in primary murine hepatocytes exposed in vitro to arsenite (iAs 3+ ) or its methylated metabolite, methylarsonite (MAs 3+ ). The results show that 4-h exposures to iAs 3+ and MAs 3+ at concentrations as low as 0.5 and 0.2 µM, respectively, decreased glycogen content in insulin-stimulated hepatocytes by inhibiting insulin-dependent activation of glycogen synthase (GS) and by inducing activity of glycogen phosphorylase (GP). Further investigation revealed that both iAs 3+ and MAs 3+ inhibit insulin-dependent phosphorylation of protein kinase B/Akt, one of the mechanisms involved in the regulation of GS and GP by insulin. Thus, inhibition of insulin signaling (i.e., insulin resistance) is likely responsible for the dysregulation of glycogen metabolism in hepatocytes exposed to iAs 3+ and MAs 3+ . This study provides novel information about the mechanisms by which iAs exposure impairs glucose homeostasis, pointing to hepatic metabolism of glycogen as one of the targets.

  18. Phosphorylation-dependent translocation of glycogen synthase to a novel structure during glycogen resynthesis

    DEFF Research Database (Denmark)

    Prats, Clara; Cadefau, Joan A; Cussó, Roser

    2005-01-01

    Glycogen metabolism has been the subject of extensive research, but the mechanisms by which it is regulated are still not fully understood. It is well accepted that the rate-limiting enzymes in glycogenesis and glycogenolysis are glycogen synthase (GS) and glycogen phosphorylase (GPh), respectively....... Both enzymes are regulated by reversible phosphorylation and by allosteric effectors. However, evidence in the literature indicates that changes in muscle GS and GPh intracellular distribution may constitute a new regulatory mechanism of glycogen metabolism. Already in the 1960s, it was proposed...... that glycogen was present in dynamic cellular organelles that were termed glycosomas but no such cellular entities have ever been demonstrated. The aim of this study was to characterize muscle GS and GPh intracellular distribution and to identify possible translocation processes of both enzymes. Using in situ...

  19. Neuronal glycogen synthesis contributes to physiological aging.

    Science.gov (United States)

    Sinadinos, Christopher; Valles-Ortega, Jordi; Boulan, Laura; Solsona, Estel; Tevy, Maria F; Marquez, Mercedes; Duran, Jordi; Lopez-Iglesias, Carmen; Calbó, Joaquim; Blasco, Ester; Pumarola, Marti; Milán, Marco; Guinovart, Joan J

    2014-10-01

    Glycogen is a branched polymer of glucose and the carbohydrate energy store for animal cells. In the brain, it is essentially found in glial cells, although it is also present in minute amounts in neurons. In humans, loss-of-function mutations in laforin and malin, proteins involved in suppressing glycogen synthesis, induce the presence of high numbers of insoluble polyglucosan bodies in neuronal cells. Known as Lafora bodies (LBs), these deposits result in the aggressive neurodegeneration seen in Lafora's disease. Polysaccharide-based aggregates, called corpora amylacea (CA), are also present in the neurons of aged human brains. Despite the similarity of CA to LBs, the mechanisms and functional consequences of CA formation are yet unknown. Here, we show that wild-type laboratory mice also accumulate glycogen-based aggregates in the brain as they age. These structures are immunopositive for an array of metabolic and stress-response proteins, some of which were previously shown to aggregate in correlation with age in the human brain and are also present in LBs. Remarkably, these structures and their associated protein aggregates are not present in the aged mouse brain upon genetic ablation of glycogen synthase. Similar genetic intervention in Drosophila prevents the accumulation of glycogen clusters in the neuronal processes of aged flies. Most interestingly, targeted reduction of Drosophila glycogen synthase in neurons improves neurological function with age and extends lifespan. These results demonstrate that neuronal glycogen accumulation contributes to physiological aging and may therefore constitute a key factor regulating age-related neurological decline in humans. © 2014 The Authors. Aging cell published by the Anatomical Society and John Wiley & Sons Ltd.

  20. Relationship between single nucleotide polymorphism of glycogen synthase gene of Pacific oyster Crassostrea gigas and its glycogen content

    Science.gov (United States)

    Liu, Siwei; Li, Qi; Yu, Hong; Kong, Lingfeng

    2017-02-01

    Glycogen is important not only for the energy supplementary of oysters, but also for human consumption. High glycogen content can improve the stress survival of oyster. A key enzyme in glycogenesis is glycogen synthase that is encoded by glycogen synthase gene GYS. In this study, the relationship between single nucleotide polymorphisms (SNPs) in coding regions of Crassostrea gigas GYS (Cg-GYS) and individual glycogen content was investigated with 321 individuals from five full-sib families. Single-strand conformation polymorphism (SSCP) procedure was combined with sequencing to confirm individual SNP genotypes of Cg-GYS. Least-square analysis of variance was performed to assess the relationship of variation in glycogen content of C. gigas with single SNP genotype and SNP haplotype. As a consequence, six SNPs were found in coding regions to be significantly associated with glycogen content ( P glycogen content ( P glycogen content and provided molecular biological information for the selective breeding of good quality traits of C. gigas.

  1. Gas Chromatography/Mass Spectrometry-Based Metabolomic Profiling Reveals Alterations in Mouse Plasma and Liver in Response to Fava Beans.

    Science.gov (United States)

    Xiao, Man; Du, Guankui; Zhong, Guobing; Yan, Dongjing; Zeng, Huazong; Cai, Wangwei

    2016-01-01

    Favism is a life-threatening hemolytic anemia resulting from the intake of fava beans by susceptible individuals with low erythrocytic glucose 6-phosphate dehydrogenase (G6PD) activity. However, little is known about the metabolomic changes in plasma and liver after the intake of fava beans in G6PD normal and deficient states. In this study, gas chromatography/mass spectrometry was used to analyze the plasma and liver metabolic alterations underlying the effects of fava beans in C3H- and G6PD-deficient (G6PDx) mice, and to find potential biomarkers and metabolic changes associated with favism. Our results showed that fava beans induced oxidative stress in both C3H and G6PDx mice. Significantly, metabolomic differences were observed in plasma and liver between the control and fava bean treated groups of both C3H and G6PDx mice. The levels of 7 and 21 metabolites in plasma showed significant differences between C3H-control (C3H-C)- and C3H fava beans-treated (C3H-FB) mice, and G6PDx-control (G6PDx-C)- and G6PDx fava beans-treated (G6PDx-FB) mice, respectively. Similarly, the levels of 7 and 25 metabolites in the liver showed significant differences between C3H and C3H-FB, and G6PDx and G6PDx-FB, respectively. The levels of oleic acid, linoleic acid, and creatinine were significantly increased in the plasma of both C3H-FB and G6PDx-FB mice. In the liver, more metabolic alterations were observed in G6PDx-FB mice than in C3H-FB mice, and were involved in a sugar, fatty acids, amino acids, cholesterol biosynthesis, the urea cycle, and the nucleotide metabolic pathway. These findings suggest that oleic acid, linoleic acid, and creatinine may be potential biomarkers of the response to fava beans in C3H and G6PDx mice and therefore that oleic acid and linoleic acid may be involved in oxidative stress induced by fava beans. This study demonstrates that G6PD activity in mice can affect their metabolic pathways in response to fava beans.

  2. Gas Chromatography/Mass Spectrometry-Based Metabolomic Profiling Reveals Alterations in Mouse Plasma and Liver in Response to Fava Beans.

    Directory of Open Access Journals (Sweden)

    Man Xiao

    Full Text Available Favism is a life-threatening hemolytic anemia resulting from the intake of fava beans by susceptible individuals with low erythrocytic glucose 6-phosphate dehydrogenase (G6PD activity. However, little is known about the metabolomic changes in plasma and liver after the intake of fava beans in G6PD normal and deficient states. In this study, gas chromatography/mass spectrometry was used to analyze the plasma and liver metabolic alterations underlying the effects of fava beans in C3H- and G6PD-deficient (G6PDx mice, and to find potential biomarkers and metabolic changes associated with favism. Our results showed that fava beans induced oxidative stress in both C3H and G6PDx mice. Significantly, metabolomic differences were observed in plasma and liver between the control and fava bean treated groups of both C3H and G6PDx mice. The levels of 7 and 21 metabolites in plasma showed significant differences between C3H-control (C3H-C- and C3H fava beans-treated (C3H-FB mice, and G6PDx-control (G6PDx-C- and G6PDx fava beans-treated (G6PDx-FB mice, respectively. Similarly, the levels of 7 and 25 metabolites in the liver showed significant differences between C3H and C3H-FB, and G6PDx and G6PDx-FB, respectively. The levels of oleic acid, linoleic acid, and creatinine were significantly increased in the plasma of both C3H-FB and G6PDx-FB mice. In the liver, more metabolic alterations were observed in G6PDx-FB mice than in C3H-FB mice, and were involved in a sugar, fatty acids, amino acids, cholesterol biosynthesis, the urea cycle, and the nucleotide metabolic pathway. These findings suggest that oleic acid, linoleic acid, and creatinine may be potential biomarkers of the response to fava beans in C3H and G6PDx mice and therefore that oleic acid and linoleic acid may be involved in oxidative stress induced by fava beans. This study demonstrates that G6PD activity in mice can affect their metabolic pathways in response to fava beans.

  3. Effects of cerium dioxide nanoparticles in Oncorhynchus mykiss liver after an acute exposure: assessment of oxidative stress, genotoxicity and histological alterations

    Directory of Open Access Journals (Sweden)

    Ana Cristina Nunes

    2015-12-01

    Full Text Available At present cerium oxide nanoparticles (CeO2 NP have numerous applications ranging from industry to the household, leading to its wide distribution namely in the aquatic environment. The hereby study aimed to assess the toxic effects of CeO2 NPs in Oncorhynchus mykiss liver following an acute exposure (96h to three different concentrations (0.25, 2.5 and 25 mg/L in terms of the genotoxicity (comet assay, oxidative stress response (Catalase CAT; Glutathione S-Transferases GSTs; Thiobarbituric Acid Reactive Substances TBARS and histopathology. CeO2 NP exposure resulted in genotoxic damage in all exposure treatments, inhibition of CAT in the highest concentration and histopathological changes in all exposure concentrations with predominance of progressive and circulatory alterations. However TBARS and GSTs showed no significant differences comparatively to the control (unexposed group. The results suggest that CeO2 NP are able to cause genotoxicity, biochemical impairment and histological alterations in the liver of rainbow trout.

  4. In vivo hepatic lipid quantification using MRS at 7 Tesla in a mouse model of glycogen storage disease type 1a.

    Science.gov (United States)

    Ramamonjisoa, Nirilanto; Ratiney, Helene; Mutel, Elodie; Guillou, Herve; Mithieux, Gilles; Pilleul, Frank; Rajas, Fabienne; Beuf, Olivier; Cavassila, Sophie

    2013-07-01

    The assessment of liver lipid content and composition is needed in preclinical research to investigate steatosis and steatosis-related disorders. The purpose of this study was to quantify in vivo hepatic fatty acid content and composition using a method based on short echo time proton magnetic resonance spectroscopy (MRS) at 7 Tesla. A mouse model of glycogen storage disease type 1a with inducible liver-specific deletion of the glucose-6-phosphatase gene (L-G6pc(-/-)) mice and control mice were fed a standard diet or a high-fat/high-sucrose (HF/HS) diet for 9 months. In control mice, hepatic lipid content was found significantly higher with the HF/HS diet than with the standard diet. As expected, hepatic lipid content was already elevated in L-G6pc(-/-) mice fed a standard diet compared with control mice. L-G6pc(-/-) mice rapidly developed steatosis which was not modified by the HF/HS diet. On the standard diet, estimated amplitudes from olefinic protons were found significantly higher in L-G6pc(-/-) mice compared with that in control mice. L-G6pc(-/-) mice showed no noticeable polyunsaturation from diallylic protons. Total unsaturated fatty acid indexes measured by gas chromatography were in agreement with MRS measurements. These results showed the great potential of high magnetic field MRS to follow the diet impact and lipid alterations in mouse liver.

  5. Low-dose dioxins alter gene expression related to cholesterol biosynthesis, lipogenesis, and glucose metabolism through the aryl hydrocarbon receptor-mediated pathway in mouse liver

    International Nuclear Information System (INIS)

    Sato, Shoko; Shirakawa, Hitoshi; Tomita, Shuhei; Ohsaki, Yusuke; Haketa, Keiichi; Tooi, Osamu; Santo, Noriaki; Tohkin, Masahiro; Furukawa, Yuji; Gonzalez, Frank J.; Komai, Michio

    2008-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental contaminant. TCDD binds and activates the transcription factor aryl hydrocarbon receptor (AHR), leading to adverse biological responses via the alteration of the expression of various AHR target genes. Although small amounts of TCDD are consumed via contaminated daily foodstuffs and environmental exposures, the effects of low-dose TCDD on gene expression in animal tissues have not been clarified, while a number of genes affected by high-dose TCDD were reported. In this study, we comprehensively analyzed gene expression profiles in livers of C57BL/6N mice that were orally administered relatively low doses of TCDD (5, 50, or 500 ng/kg body weight (bw) day -1 ) for 18 days. The hepatic TCDD concentrations, measured by gas chromatography-mass spectrometry, were 1.2, 17, and 1063 pg toxicity equivalent quantity (TEQ)/g, respectively. The mRNA level of the cytochrome P450 CYP1A1 was significantly increased by treatment with only TCDD 500 ng/kg bw day -1 . DNA microarray and quantitative RT-PCR analyses revealed changes in the expression of genes involved in the circadian rhythm, cholesterol biosynthesis, fatty acid synthesis, and glucose metabolism in the liver with at all doses of TCDD employed. However, repression of expression of genes involved in energy metabolism was not observed in the livers of Ahr-null mice that were administered the same dose of TCDD. These results indicate that changes in gene expression by TCDD are mediated by AHR and that exposure to low-dose TCDD could affect energy metabolism via alterations of gene expression

  6. Influence of minerals on lead-induced alterations in liver function in rats exposed to long-term lead exposure

    International Nuclear Information System (INIS)

    Herman, D'souza Sunil; Geraldine, Menezes; T, Venkatesh

    2009-01-01

    The objective of this study was to evaluate the role of minerals on lead-induced effect on the liver. Differentiation of minerals and heavy metals pose an inherent problem due to certain common properties shared by them. With this approach to the problem of heavy metal toxicity, in the present study two groups of male Wistar albino rats, one group (well-nourished) fed on mineral rich diet and other group (undernourished) fed on diet without mineral supplements were used. Both the groups of rats were subjected to long-term lead exposure. The diet of well-nourished group was supplemented with calcium (Ca); 1.2%, phosphorous (P); 0.6%, iron (Fe); 90 mg/kg, zinc (Zn); 50 mg/kg, magnesium (Mg); 0.08%, manganese (Mn); 70 mg/kg, selenium (Se); 0.2 mg/kg, copper (Cu); 5 mg/kg, molybdenum (Mo); 0.8 mg/kg, iodine (I); 0.6 mg/kg, cobalt (Co); 3.0 mg/kg. Their blood lead and parameters of liver function were monitored periodically. Results of the study showed a very high statistically significant increase (p < 0.001) in the blood lead (PbB) levels and liver function test parameters in the undernourished subjects compared to the well-nourished subjects. Nutritional management of lead poisoning is of importance since essential elements and toxic heavy metals may interact to minimize the absorption of lead.

  7. Dietary intake of ain-93 standard diet induces Fatty liver with altered hepatic fatty acid profile in Wistar rats.

    Science.gov (United States)

    Farias Santos, Juliana; Suruagy Amaral, Monique; Lima Oliveira, Suzana; Porto Barbosa, Júnia; Rego Cabral, Cyro; Sofia Melo, Ingrid; Bezerra Bueno, Nassib; Duarte Freitas, Johnatan; Goulart Sant'ana, Antônio; Rocha Ataíde, Terezinha

    2015-05-01

    There are several standard diets for animals used in scientific research, usually conceived by scientific institutions. The AIN-93 diet is widely used, but there are some reports of fatty liver in Wistar rats fed this diet. We aimed to evaluate the hepatic repercussions of the AIN-93 diet intake in Wistar rats. Forty newly-weaned 21-day-old male Wistar rats were fed either the AIN-93 diet or a commercial diet for either 1 month or 4 months. Weight gain, serum biochemistry, hepatic histology, and hepatic fatty acid profile were analyzed. Hepatic steatosis was observed, especially in the group fed the AIN-93 diet. Serum blood glucose, absolute and relative liver weight and hepatic levels of oleic, palmitoleic, stearic, and palmitic fatty acids were related to the observed steatosis, while lipidogram and serum markers of liver function and injury were not. AIN-93 diet induced acute hepatic steatosis in Wistar rats, which may compromise its use as a standard diet for experimental studies with rodents. The hepatic fatty acid profile was associated with steatosis, with possible implications for disease prognosis. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  8. Influence of minerals on lead-induced alterations in liver function in rats exposed to long-term lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Herman, D' souza Sunil, E-mail: hermansdsouza@rediffmail.com [Department of Biotechnology, Manipal Life Sciences Centre, KMC, Manipal University, Manipal (India); Geraldine, Menezes, E-mail: gere1@rediffmail.com [Department of Biochemistry and Biophysics, St. John' s Medical College, Koramangala, Bangalore 560034, Karnataka (India); T, Venkatesh, E-mail: venky_tv@hotmail.com [Department of Biochemistry and Biophysics, St. John' s Medical College, Koramangala, Bangalore 560034, Karnataka (India)

    2009-07-30

    The objective of this study was to evaluate the role of minerals on lead-induced effect on the liver. Differentiation of minerals and heavy metals pose an inherent problem due to certain common properties shared by them. With this approach to the problem of heavy metal toxicity, in the present study two groups of male Wistar albino rats, one group (well-nourished) fed on mineral rich diet and other group (undernourished) fed on diet without mineral supplements were used. Both the groups of rats were subjected to long-term lead exposure. The diet of well-nourished group was supplemented with calcium (Ca); 1.2%, phosphorous (P); 0.6%, iron (Fe); 90 mg/kg, zinc (Zn); 50 mg/kg, magnesium (Mg); 0.08%, manganese (Mn); 70 mg/kg, selenium (Se); 0.2 mg/kg, copper (Cu); 5 mg/kg, molybdenum (Mo); 0.8 mg/kg, iodine (I); 0.6 mg/kg, cobalt (Co); 3.0 mg/kg. Their blood lead and parameters of liver function were monitored periodically. Results of the study showed a very high statistically significant increase (p < 0.001) in the blood lead (PbB) levels and liver function test parameters in the undernourished subjects compared to the well-nourished subjects. Nutritional management of lead poisoning is of importance since essential elements and toxic heavy metals may interact to minimize the absorption of lead.

  9. Intersex and liver alterations induced by long-term sublethal exposure to 17α-ethinylestradiol in adult male Cnesterodon decemmaculatus (Pisces: Poeciliidae).

    Science.gov (United States)

    Young, Brian Jonathan; López, Gabriela Carina; Cristos, Diego Sebastián; Crespo, Diana Cristina; Somoza, Gustavo Manuel; Carriquiriborde, Pedro

    2017-07-01

    The aim of the present study was to assess the responses of the gonopodium morphology and the gonadal and liver histology of adult male Cnesterodon decemmaculatus to sublethal long-term exposure concentrations of 17α-ethinylestradiol (EE2). Two experiments were conducted exposing the fish to waterborne concentrations of EE2 ranging from 20 ng/L to 200 ng/L for 8 wk, 12 wk, and 16 wk. Intersex gonads were observed after 8 wk and 16 wk in fish exposed to 200 ng EE2/L and 100 ng EE2/L, respectively. Oocytes' development from testis germ cells and replacement of the efferent duct periodic acid-Schiff-positive secretion surrounding spermatozeugmata by parenchymal tissue and duct structure alterations were the major observed changes in the gonads. In contrast, no response was observed in the gonopodium morphology. Liver histology was also altered, showing increasing steatosis, single-cell necrosis to generalized necrosis, and disruption of acinar organization from 100 ng EE2/L to 200 ng EE2/L. In summary, the present results showed that although EE2 was not able to alter the morphology of a developed gonopodium, it was capable of inducing development of testicular oocytes in adult male C. decemmaculatus at environmentally relevant concentrations. Thus, externally normal but intersex C. decemmaculatus males would be expected in the wastewater-receiving streams that the species inhabits. According to the literature, the present study would be the first indicating estrogen-induced intersex in adult male poeciliid. Environ Toxicol Chem 2017;36:1738-1745. © 2016 SETAC. © 2016 SETAC.

  10. The structure of brain glycogen phosphorylase-from allosteric regulation mechanisms to clinical perspectives.

    Science.gov (United States)

    Mathieu, Cécile; Dupret, Jean-Marie; Rodrigues Lima, Fernando

    2017-02-01

    Glycogen phosphorylase (GP) is the key enzyme that regulates glycogen mobilization in cells. GP is a complex allosteric enzyme that comprises a family of three isozymes: muscle GP (mGP), liver GP (lGP), and brain GP (bGP). Although the three isozymes display high similarity and catalyze the same reaction, they differ in their sensitivity to the allosteric activator adenosine monophosphate (AMP). Moreover, inactivating mutations in mGP and lGP have been known to be associated with glycogen storage diseases (McArdle and Hers disease, respectively). The determination, decades ago, of the structure of mGP and lGP have allowed to better understand the allosteric regulation of these two isoforms and the development of specific inhibitors. Despite its important role in brain glycogen metabolism, the structure of the brain GP had remained elusive. Here, we provide an overview of the human brain GP structure and its relationship with the two other members of this key family of the metabolic enzymes. We also summarize how this structure provides valuable information to understand the regulation of bGP and to design specific ligands of potential pharmacological interest. © 2016 Federation of European Biochemical Societies.

  11. Muscle Glycogen Remodeling and Glycogen Phosphate Metabolism following Exhaustive Exercise of Wild Type and Laforin Knockout Mice*

    Science.gov (United States)

    Irimia, Jose M.; Tagliabracci, Vincent S.; Meyer, Catalina M.; Segvich, Dyann M.; DePaoli-Roach, Anna A.; Roach, Peter J.

    2015-01-01

    Glycogen, the repository of glucose in many cell types, contains small amounts of covalent phosphate, of uncertain function and poorly understood metabolism. Loss-of-function mutations in the laforin gene cause the fatal neurodegenerative disorder, Lafora disease, characterized by increased glycogen phosphorylation and the formation of abnormal deposits of glycogen-like material called Lafora bodies. It is generally accepted that the phosphate is removed by the laforin phosphatase. To study the dynamics of skeletal muscle glycogen phosphorylation in vivo under physiological conditions, mice were subjected to glycogen-depleting exercise and then monitored while they resynthesized glycogen. Depletion of glycogen by exercise was associated with a substantial reduction in total glycogen phosphate and the newly resynthesized glycogen was less branched and less phosphorylated. Branching returned to normal on a time frame of days, whereas phosphorylation remained suppressed over a longer period of time. We observed no change in markers of autophagy. Exercise of 3-month-old laforin knock-out mice caused a similar depletion of glycogen but no loss of glycogen phosphate. Furthermore, remodeling of glycogen to restore the basal branching pattern was delayed in the knock-out animals. From these results, we infer that 1) laforin is responsible for glycogen dephosphorylation during exercise and acts during the cytosolic degradation of glycogen, 2) excess glycogen phosphorylation in the absence of laforin delays the normal remodeling of the branching structure, and 3) the accumulation of glycogen phosphate is a relatively slow process involving multiple cycles of glycogen synthesis-degradation, consistent with the slow onset of the symptoms of Lafora disease. PMID:26216881

  12. Exercise in muscle glycogen storage diseases

    DEFF Research Database (Denmark)

    Preisler, Nicolai Rasmus; Haller, Ronald G; Vissing, John

    2015-01-01

    exercise program has the potential to improve general health and fitness and improve quality of life, if executed properly. In this review, we describe skeletal muscle substrate use during exercise in GSDs, and how blocks in metabolic pathways affect exercise tolerance in GSDs. We review the studies...... that have examined the effect of regular exercise training in different types of GSD. Finally, we consider how oral substrate supplementation can improve exercise tolerance and we discuss the precautions that apply to persons with GSD that engage in exercise.......Glycogen storage diseases (GSD) are inborn errors of glycogen or glucose metabolism. In the GSDs that affect muscle, the consequence of a block in skeletal muscle glycogen breakdown or glucose use, is an impairment of muscular performance and exercise intolerance, owing to 1) an increase...

  13. No effect of glycogen level on glycogen metabolism during high intensity exercise

    DEFF Research Database (Denmark)

    Vandenberghe, Katleen; Hespel, P.; Eynde, Bart Vanden

    1995-01-01

    , either for 1 min 45 s (protocol 1; N = 18) or to exhaustion (protocol 2; N = 14). The exercise tests were preceded by either 5 d on a controlled normal (N) diet, or by 2 d of glycogen-depleting exercise accompanied by the normal diet followed by 3 d on a carbohydrate-rich (CHR) diet. In protocol 1......This study examined the effect of glycogen supercompensation on glycogen breakdown, muscle and blood lactate accumulation, blood-pH, and performance during short-term high-intensity exercise. Young healthy volunteers performed two supramaximal (125% of VO2max) exercise tests on a bicycle ergometer...

  14. Interleukin 6 stimulates hepatic glucose release from prelabeled glycogen pools

    International Nuclear Information System (INIS)

    Ritchie, D.G.

    1990-01-01

    Cytokines, derived from a wide variety of cell types, are now believed to initiate many of the physiological responses accompanying the inflammatory phase that follows either Gram-negative septicemia or thermal injury. Because hypoglycemia (after endotoxic challenge) and hyperglycemia (after thermal injury) represent well-characterized responses to these injuries, we sought to determine whether hepatic glycogen metabolism could be altered by specific cytokines. Cultured adult rat hepatocytes were prelabeled with [ 14 C]glucose for 24 h, a procedure that resulted in the labeling of hepatic glycogen pools that subsequently could be depleted (with concomitant [ 14 C]glucose release) by either glucagon or norepinephrine. After the addition of a highly concentrated human monocyte-conditioned medium (MCM) or various cytokines to these prelabeled cells, [ 14 C]glucose release was stimulated by MCM and recombinant human interleukin 6 (IL-6) but was not stimulated by other cytokines tested. Furthermore, only antisera to IL-6 were capable of reducing the glucose-releasing factor activity found in MCM. These data therefore suggest a novel glucoregulatory role for IL-6

  15. Glycogen metabolism in aerobic mixed cultures

    DEFF Research Database (Denmark)

    Dircks, Klaus; Beun, J.J.; van Loosdrecht, M.C.M.

    2001-01-01

    In this study, the metabolism of glycogen storage and consumption in mixed cultures under aerobic conditions is described. The experimental results are used to calibrate a metabolic model, which as sole stoichiometric variables has the efficiency of oxidative phosphorylation (delta) and maintenance...... of glycogen and subsequent growth occur without significant loss of energy, as compared with direct growth on glucose. For kinetic modeling, Monod kinetics is used most commonly in activated sludge models to describe the rate of microbial transformation. Monod kinetics, however, does not provide a good...

  16. The involvement of altered vesicle transport in redistribution of Ca2+, Mg2+-ATPase in cholestatic rat liver

    NARCIS (Netherlands)

    Song, J. Y.; van Noorden, C. J.; Frederiks, W. M.

    1998-01-01

    Vectorial sorting of plasma membrane protein-containing vesicles is essential for the establishment and maintenance of cell polarity. In the present study, the involvement of altered vesicle transport in the redistribution of membrane-bound Ca2+, Mg2+-ATPase resulting from cholestasis was

  17. Cell swelling and glycogen metabolism in hepatocytes from fasted rats

    NARCIS (Netherlands)

    Gustafson, L. A.; Jumelle-Laclau, M. N.; van Woerkom, G. M.; van Kuilenburg, A. B.; Meijer, A. J.

    1997-01-01

    Cell swelling is known to increase net glycogen production from glucose in hepatocytes from fasted rats by activating glycogen synthase. Since both active glycogen synthase and phosphorylase are present in hepatocytes, suppression of flux through phosphorylase may also contribute to the net increase

  18. Low folate and selenium in the mouse maternal diet alters liver gene expression patterns in the offspring after weaning.

    Science.gov (United States)

    Barnett, Matthew P G; Bermingham, Emma N; Young, Wayne; Bassett, Shalome A; Hesketh, John E; Maciel-Dominguez, Anabel; McNabb, Warren C; Roy, Nicole C

    2015-05-08

    During pregnancy, selenium (Se) and folate requirements increase, with deficiencies linked to neural tube defects (folate) and DNA oxidation (Se). This study investigated the effect of a high-fat diet either supplemented with (diet H), or marginally deficient in (diet L), Se and folate. Pregnant female mice and their male offspring were assigned to one of four treatments: diet H during gestation, lactation and post-weaning; diet L during gestation, lactation and post-weaning; diet H during gestation and lactation but diet L fed to offspring post-weaning; or diet L during gestation and lactation followed by diet H fed to offspring post-weaning. Microarray and pathway analyses were performed using RNA from colon and liver of 12-week-old male offspring. Gene set enrichment analysis of liver gene expression showed that diet L affected several pathways including regulation of translation (protein biosynthesis), methyl group metabolism, and fatty acid metabolism; this effect was stronger when the diet was fed to mothers, rather than to offspring. No significant differences in individual gene expression were observed in colon but there were significant differences in cell cycle control pathways. In conclusion, a maternal low Se/folate diet during gestation and lactation has more effects on gene expression in offspring than the same diet fed to offspring post-weaning; low Se and folate in utero and during lactation thus has persistent metabolic effects in the offspring.

  19. Low Folate and Selenium in the Mouse Maternal Diet Alters Liver Gene Expression Patterns in the Offspring after Weaning

    Directory of Open Access Journals (Sweden)

    Matthew P.G. Barnett

    2015-05-01

    Full Text Available During pregnancy, selenium (Se and folate requirements increase, with deficiencies linked to neural tube defects (folate and DNA oxidation (Se. This study investigated the effect of a high-fat diet either supplemented with (diet H, or marginally deficient in (diet L, Se and folate. Pregnant female mice and their male offspring were assigned to one of four treatments: diet H during gestation, lactation and post-weaning; diet L during gestation, lactation and post-weaning; diet H during gestation and lactation but diet L fed to offspring post-weaning; or diet L during gestation and lactation followed by diet H fed to offspring post-weaning. Microarray and pathway analyses were performed using RNA from colon and liver of 12-week-old male offspring. Gene set enrichment analysis of liver gene expression showed that diet L affected several pathways including regulation of translation (protein biosynthesis, methyl group metabolism, and fatty acid metabolism; this effect was stronger when the diet was fed to mothers, rather than to offspring. No significant differences in individual gene expression were observed in colon but there were significant differences in cell cycle control pathways. In conclusion, a maternal low Se/folate diet during gestation and lactation has more effects on gene expression in offspring than the same diet fed to offspring post-weaning; low Se and folate in utero and during lactation thus has persistent metabolic effects in the offspring.

  20. Protective effect of ginger and zinc chloride mixture on the liver and kidney alterations induced by malathion toxicity.

    Science.gov (United States)

    Baiomy, Ahmed A; Attia, Hossam F; Soliman, Mohamed M; Makrum, Omar

    2015-03-01

    This study was carried out on four groups of male Wistar rats, 10 rats per group. Group I got open access to food intake and water with normal balanced diet. Group II was administered 400 mg ginger per kg body weight (BW) and zinc chloride (ZnCl2) (300 mg/L) diluted in tap water for 4 months. Group III was administered malathion at a dose of 50 mg/kg BW/day in 0.2 mL corn oil via gavages for 4 months. This dose equal to 1/50 of the LD50. Group IV was given a mixture of 400 mg ginger per kg BW and ZnCl2 (300 mg/L) diluted in tap water in addition to 100 mg malathion/kg BW for 4 months. The liver showed histopathological changes include congestion, edema, and leucocytic infiltrations which were ameliorated by the addition of ginger and ZnCl2 mixture. The kidney showed cloudy swelling and hydropic degeneration of the renal tubules. These changes were ameliorated by the addition of ginger and ZnCl2 mixture. Ki67 immunoreactivity was localized in the cytoplasm and nuclear membrane. Its expression was estimated as the percentage of cells positively stained by the antibody in the different groups. In conclusion, malathion was toxic to the liver and kidney and must be avoided and protected by the addition of ginger and zinc mixture. © The Author(s) 2015.

  1. Effects of Petrol Exposure on Glucose, Liver and Muscle glycogen ...

    African Journals Online (AJOL)

    olayemitoyin

    Alford, R.A. and Richards, S. J. (1999). Global amphibian declines: a problem in applied ecology. Annual. Rev.Ecol. Systematics 30 (1): 133-165. Almeida, J. A., Novelli, E. L. B., Dal-Pai Silva, M.,. Alves- Junior, R. (2001). Environmental cadmium exposure and metabolic responses of the Nile tilapia Oreochromis niloticus.

  2. Genome-Wide Screening of Genes Showing Altered Expression in Liver Metastases of Human Colorectal Cancers by cDNA Microarray

    Directory of Open Access Journals (Sweden)

    Rempei Yanagawa

    2001-01-01

    Full Text Available In spite of intensive and increasingly successful attempts to determine the multiple steps involved in colorectal carcinogenesis, the mechanisms responsible for metastasis of colorectal tumors to the liver remain to be clarified. To identify genes that are candidates for involvement in the metastatic process, we analyzed genome-wide expression profiles of 10 primary colorectal cancers and their corresponding metastatic lesions by means of a cDNA microarray consisting of 9121 human genes. This analysis identified 40 genes whose expression was commonly upregulated in metastatic lesions, and 7 that were commonly downregulated. The upregulated genes encoded proteins involved in cell adhesion, or remodeling of the actin cytoskeleton. Investigation of the functions of more of the altered genes should improve our understanding of metastasis and may identify diagnostic markers and/or novel molecular targets for prevention or therapy of metastatic lesions.

  3. Insulin alters the target size of the peripheral cyclic AMP phosphodiesterase but not the integral cyclic GMP-stimulated cyclic AMP phosphodiesterase in liver plasma membranes

    International Nuclear Information System (INIS)

    Wallace, A.V.; Martin, B.R.; Houslay, M.D.

    1990-01-01

    Radiation inactivation of the two high affinity cyclic AMP phosphodiesterases (PDE) found in liver plasma membranes afforded an estimation of their molecular target sizes in situ. The activity of the peripheral plasma membrane PDE decayed as a single exponential with a target size corresponding to a monomer of circa 54 kDa. The integral, cyclic GMP-stimulated PDE decayed as a dimer of circa 125 kDa. Preincubation of plasma membranes with insulin (10nM), prior to irradiation, caused the target size of only the peripheral plasma membrane PDE to increase. We suggest that insulin addition causes the peripheral plasma membrane PDE to alter its coupling to an integral plasma membrane protein with a target size of circa 90 kDa

  4. Expression of genes for microRNA-processing enzymes is altered in advanced non-alcoholic fatty liver disease.

    Science.gov (United States)

    Sharma, Haveesh; Estep, Michael; Birerdinc, Aybike; Afendy, Arian; Moazzez, Amir; Elariny, Hazem; Goodman, Zachary; Chandhoke, Vikas; Baranova, Ancha; Younossi, Zobair M

    2013-08-01

    Recently, microRNAs (miRNA) have been linked to the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH). First transcribed as pri-miRNA, these molecules are further processed by a complex of endonuclear and cytosolic RNA binding molecules to form mature miRNAs. The aim of this study is to investigate mechanisms of miRNA regulation in the visceral adipose of obese NAFLD patients via measuring expression of miRNA processing enzymes and pri-miRNA. Total RNAs were extracted from visceral adipose tissue (VAT) samples collected from patients undergoing bariatric surgery. All patients had biopsy-proven NAFLD (NASH patients [n = 12] and non-NASH NAFLD [n = 12]). For each patient, we profiled mRNA levels for three miRNA processing elements (Drosha, DGCR8, and Dicer1) and seven pri-miRNAs (pri-miR-125b-2, pri-miR-16-2, pri-miR-26a-1, pri-miR-26a-2, pri-miR-7-1, pri-miR-7-2, and pri-miR-7-3). Expression of Dicer1, Drosha and DGCR8 was significantly increased within the NASH cohort along with expression of pri-miR-7-1. The presence of focal necrosis on the liver biopsy correlated significantly with levels of Dicer1 and DGRC8. Both NASH and ballooning degeneration of hepatocytes correlated negatively with the expression levels of hsa-miR-125b. Histologic NASH correlated positively with the expression levels of pri-miR-16-2 and pri-miR-7-1. The presence of the hepatocyte's ballooning degeneration in the liver biopsy correlated positively with pri-miR-26a-1 and pri-miR-7-1. The expression profile of pri-miR-125b-2 also correlated positively with body mass index. Our findings support the hypothesis that VAT-derived miRNA may contribute to the pathogenesis of NASH in obese patients. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  5. Altered cytochrome P450 activities and expression levels in the liver and intestines of the monosodium glutamate-induced mouse model of human obesity.

    Science.gov (United States)

    Tomankova, Veronika; Liskova, Barbora; Skalova, Lenka; Bartikova, Hana; Bousova, Iva; Jourova, Lenka; Anzenbacher, Pavel; Ulrichova, Jitka; Anzenbacherova, Eva

    2015-07-15

    Cytochromes P450 (CYPs) are enzymes present from bacteria to man involved in metabolism of endogenous and exogenous compounds incl. drugs. Our objective was to assess whether obesity leads to changes in activities and expression of CYPs in the mouse liver, small intestine and colon. An obese mouse model with repeated injection of monosodium glutamate (MSG) to newborns was used. Controls were treated with saline. All mice were sacrificed at 8 months. In the liver and intestines, levels of CYP mRNA and proteins were analyzed using RT-PCR and Western blotting. Activities of CYP enzymes were measured with specific substrates of human orthologous forms. At the end of the experiment, body weight, plasma insulin and leptin levels as well as the specific content of hepatic CYP enzymes were increased in obese mice. Among CYP enzymes, hepatic CYP2A5 activity, protein and mRNA expression increased most significantly in obese animals. Higher activities and protein levels of hepatic CYP2E1 and 3A in the obese mice were also found. No or a weak effect on CYPs 2C and 2D was observed. In the small intestine and colon, no changes of CYP enzymes were detected except for increased expression of CYP2E1 and decreased expression of CYP3A mRNAs in the colon of the obese mice. Results of our study suggest that the specific content and activities of some liver CYP enzymes (especially CYP2A5) can be increased in obese mice. Higher activity of CYP2A5 (CYP2A6 human ortholog) could lead to altered metabolism of drug substrates of this enzyme (valproic acid, nicotine, methoxyflurane). Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Glycogen Shunt Activity and Glycolytic Supercompensation in Astrocytes May Be Distinctly Mediated via the Muscle Form of Glycogen Phosphorylase

    DEFF Research Database (Denmark)

    Jakobsen, Emil; Bak, Lasse K; Walls, Anne B

    2017-01-01

    Glycogen is the main storage form of glucose in the brain. In contrast with previous beliefs, brain glycogen has recently been shown to play important roles in several brain functions. A fraction of metabolized glucose molecules are being shunted through glycogen before reentering the glycolytic ...

  7. Altered hepatic mRNA expression of immune response-associated DNA damage in mice liver induced by potassium bromate: Protective role of vanillin.

    Science.gov (United States)

    Ben Saad, Hajer; Driss, Dorra; Ben Amara, Ibtissem; Boudawara, Ons; Boudawara, Tahia; Ellouz Chaabouni, Samia; Mounir Zeghal, Khaled; Hakim, Ahmed

    2016-12-01

    Chronic exposure to potassium bromate (KBrO 3 ), a toxic halogen existing widely in the environment, environment through contaminated drinking water, has become a global problem of public health. The present study investigates the protective role of vanillin against KBrO 3 induced oxidative stress, distruption in inflammatory cytokines expression, DNA damage, and histopathological changes. Adult mice were exposed orally to KBrO 3 (2g/L of drinking water) for 2 weeks The co-administration of vanillin to the KBrO 3 -treated mice significantly prevented the plasma transaminases increase in. Furthermore, it inhibited hepatic lipid peroxidation (malondialdehyde), advanced oxidation protein product (AOPP) and protein carbonyl (PCO) formation and attenuated the KBrO 3 -mediated depletion of enzymatic and non enzymatic antioxidants catalase, superoxide dismutase, and glutathione peroxidase activities and glutathione level in the liver. In addition, vanillin markedly attenuated the expression levels of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and COX2 and prevented KBrO 3 -induced hepatic cell alteration and necrosis, as indicated by histopathological data. DNA damage, as assessed by the alkaline comet assay, was also found to be low in the co-treated group. Thus, these findings show that vanillin acts as potent chemopreventive agent against KBrO 3 -mediated liver oxidative stress and genotoxicity through its antioxidant properties. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1796-1807, 2016. © 2015 Wiley Periodicals, Inc.

  8. Histological alterations in the liver of rats induced by different gold nanoparticle sizes, doses and exposure duration

    Directory of Open Access Journals (Sweden)

    Abdelhalim Mohamed

    2012-01-01

    Full Text Available Abstract Background Nanoparticles (NPs can potentially cause adverse effects on organ, tissue, cellular, subcellular and protein levels due to their unusual physicochemical properties. Advances in nanotechnology have identified promising candidates for many biological and biomedical applications. Since the properties of NPs differ from that of their bulk materials, they are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to investigate the particle-size effect of gold nanoparticles (GNPs on the hepatic tissue in an attempt to cover and understand the toxicity and the potential threat of their therapeutic and diagnostic use. Methods To investigate particle-size effect of GNPs on the hepatic tissue, a total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 ul of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days. Results In comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and the sinusoids. The alterations in the hepatocytes were mainly summarized as hydropic degeneration, cloudy swelling, fatty degeneration, portal and lobular infiltrate by chronic inflammatory cells and congestive dilated central veins. Conclusions The induced histological alterations might be an indication of injured hepatocytes due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. These alterations were size-dependent with smaller ones induced the most effects and related with time exposure of GNPs. The appearance of hepatocytes cytoplasmic degeneration and nuclear destruction may suggest that GNPs interact with proteins and enzymes of the hepatic tissue interfering with the antioxidant defense mechanism and leading to reactive oxygen species (ROS generation which in turn may induce stress in the hepatocytes to

  9. Altered Liver Proteoglycan/Glycosaminoglycan Structure as a Manifestation of Extracellular Matrix Remodeling upon BCG-induced Granulomatosis in Mice.

    Science.gov (United States)

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2017-01-01

    Experimental BCG-induced granulomatosis in mice was used to study changes in the dynamics of individual liver proteoglycan components reflecting phasic extracellular matrix remodeling, determined by the host-parasite interaction and associated with granuloma development. In the early BCG-granulomatosis period, the increase in individual proteoglycan components promotes granuloma formation, providing conditions for mycobacteria adhesion to host cells, migration of phagocytic cells from circulation, and cell-cell interaction leading to granuloma development and fibrosis. Later, reduced reserve capacity of the extracellular matrix, development of interstitial fibrosis and granuloma fibrosis can lead to trophic shortage for cells within the granulomas, migration of macrophages out of them, and development of spontaneous necrosis and apoptosis typical of tuberculosis.

  10. Determination of the glycogen content in cyanobacteria

    DEFF Research Database (Denmark)

    Porcellinis, Alice De; Frigaard, Niels-Ulrik; Sakuragi, Yumiko

    2017-01-01

    of glycogen to generate glucose monomers, which are detected by a glucose oxidase-peroxidase (GOD-POD) enzyme coupled assay. The method has been applied to Synechocystis sp. PCC 6803 and Synechococcus sp. PCC 7002, two model cyanobacterial species that are widely used in metabolic engineering. Moreover...

  11. Pregnancies in glycogen storage disease type Ia

    NARCIS (Netherlands)

    Martens, Danielle H. J.; Rake, Jan Peter; Schwarz, Martin; Ullrich, Kurt; Weinstein, David A.; Merkel, Martin; Sauer, Pieter J. J.; Smit, G. Peter A.

    OBJECTIVE: Reports on pregnancies in women with glycogen storage disease type Ia (GSD-Ia) are scarce. Because of improved life expectancy, pregnancy is becoming an important issue. We describe 15 pregnancies by focusing on dietary treatment, biochemical parameters, and GSD-Ia complications. STUDY

  12. Glycogen with short average chain length enhances bacterial durability

    Science.gov (United States)

    Wang, Liang; Wise, Michael J.

    2011-09-01

    Glycogen is conventionally viewed as an energy reserve that can be rapidly mobilized for ATP production in higher organisms. However, several studies have noted that glycogen with short average chain length in some bacteria is degraded very slowly. In addition, slow utilization of glycogen is correlated with bacterial viability, that is, the slower the glycogen breakdown rate, the longer the bacterial survival time in the external environment under starvation conditions. We call that a durable energy storage mechanism (DESM). In this review, evidence from microbiology, biochemistry, and molecular biology will be assembled to support the hypothesis of glycogen as a durable energy storage compound. One method for testing the DESM hypothesis is proposed.

  13. Comparison of methods for glycogen analysis of in vitro fermentation pellets produced with strained ruminal inoculum.

    Science.gov (United States)

    Hall, Mary Beth; Hatfield, Ronald D

    2015-11-01

    Microbial glycogen measurement is used to account for fates of carbohydrate substrates. It is commonly applied to washed cells or pure cultures which can be accurately subsampled, allowing the use of smaller sample sizes. However, the nonhomogeneous fermentation pellets produced with strained rumen inoculum cannot be accurately subsampled, requiring analysis of the entire pellet. In this study, two microbial glycogen methods were compared for analysis of such fermentation pellets: boiling samples for 3h in 30% KOH (KOH) or for 15min in 0.2M NaOH (NaOH), followed by enzymatic hydrolysis with α-amylase and amyloglucosidase, and detection of released glucose. Total α-glucan was calculated as glucose×0.9. KOH and NaOH did not differ in the α-glucan detected in fermentation pellets (29.9 and 29.6mg, respectively; P=0.61). Recovery of different control α-glucans was also tested using KOH, NaOH, and a method employing 45min of bead beating (BB). For purified beef liver glycogen (water-soluble) recovery, BB (95.0%)>KOH (91.4%)>NaOH (87.4%; PBB (93.8%)>KOH (91.0%; Pglycogen (water-insoluble granules) did not differ among KOH (87.0%), NaOH (87.6%), and BB (86.0%; P=0.81), but recoveries for all were below 90%. Differences among substrates in the need for gelatinization and susceptibility to destruction by alkali likely affected the results. In conclusion, KOH and NaOH glycogen methods provided comparable determinations of fermentation pellet α-glucan. The tests on purified α-glucans indicated that assessment of recovery in glycogen methods can differ by the control α-glucan selected. Published by Elsevier B.V.

  14. Radiometric assays for glycerol, glucose, and glycogen

    International Nuclear Information System (INIS)

    Bradley, D.C.; Kaslow, H.R.

    1989-01-01

    We have developed radiometric assays for small quantities of glycerol, glucose and glycogen, based on a technique described by Thorner and Paulus for the measurement of glycerokinase activity. In the glycerol assay, glycerol is phosphorylated with [32P]ATP and glycerokinase, residual [32P]ATP is hydrolyzed by heating in acid, and free [32P]phosphate is removed by precipitation with ammonium molybdate and triethylamine. Standard dose-response curves were linear from 50 to 3000 pmol glycerol with less than 3% SD in triplicate measurements. Of the substances tested for interference, only dihydroxyacetone gave a slight false positive signal at high concentration. When used to measure glycerol concentrations in serum and in media from incubated adipose tissue, the radiometric glycerol assay correlated well with a commonly used spectrophotometric assay. The radiometric glucose assay is similar to the glycerol assay, except that glucokinase is used instead of glycerokinase. Dose response was linear from 5 to 3000 pmol glucose with less than 3% SD in triplicate measurements. Glucosamine and N-acetylglucosamine gave false positive signals when equimolar to glucose. When glucose concentrations in serum were measured, the radiometric glucose assay agreed well with hexokinase/glucose-6-phosphate dehydrogenase (H/GDH)-based and glucose oxidase/H2O2-based glucose assays. The radiometric method for glycogen measurement incorporates previously described isolation and digestion techniques, followed by the radiometric assay of free glucose. When used to measure glycogen in mouse epididymal fat pads, the radiometric glycogen assay correlated well with the H/GDH-based glycogen assay. All three radiometric assays offer several practical advantages over spectral assays

  15. Comparison of 3H-galactose and 3H-glucose as precursors of hepatic glycogen in control-fed rats

    International Nuclear Information System (INIS)

    Michaels, J.E.; Garfield, S.A.; Hung, J.T.; Cardell, R.R. Jr.

    1989-01-01

    Labeling of hepatic glycogen derived from 3H-galactose and 3H-glucose was compared shortly after intravenous injection in control-fed rats. The rats were allowed to accumulate 5-8% glycogen prior to receiving label. Fifteen minutes to 2 hours after labeling, liver was excised and processed for routine light (LM) and electron microscopic (EM) radioautography (RAG) or biochemical analysis. After injection of 3H-galactose, LM-RAGs revealed that the percentage of heavily labeled hepatocytes increased from 37% after 15 minutes to 68% after 1 hour but showed no further increase after 2 hours. alpha-Amylase treatment removed most glycogen and incorporated label; thus few silver grains were observed, indicating little incorporation of label except into glycogen. EM-RAGs demonstrated that most label occurred where glycogen was located. Biochemical analysis showed initially a high blood level of label that rapidly plateaued at a reduced level by 5 minutes. Concomitantly, glycogen labeling determined by liquid scintillation counting reflected the increases observed in the RAGs. After injection of 3H-glucose, LM-RAGs revealed that only 12% of the hepatocytes were heavily labeled at 1 hour and 20% at 2 hours. In tissue treated with alpha-amylase, glycogen was depleted and label was close to background level at each interval observed. EM-RAGs showed most grains associated with glycogen deposits. Biochemically, blood levels of label persisted at a high level for 30 minutes and tissue levels increased slowly over the 2-hour period. This study shows that incorporation from 3H-galactose was more rapid than incorporation of 3H-glucose; however, label derived from both carbohydrates appeared to be incorporated mainly into glycogen

  16. Schwann Cell Glycogen Selectively Supports Myelinated Axon Function

    Science.gov (United States)

    Brown, Angus M; Evans, Richard D; Black, Joel; Ransom, Bruce R

    2012-01-01

    Objectives Interruption of energy supply to peripheral axons is a cause of axon loss. We determined if glycogen was present in mammalian peripheral nerve, and if it supported axon conduction during aglycemia. Methods We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. Results Glycogen was present in sciatic nerve, its concentration varying directly with ambient [glucose]. Electron microscopy detected glycogen granules primarily in myelinating Schwann cell cytoplasm and these diminished after exposure to aglycemia. During aglycemia, conduction failure in large myelinated axons (A fibers) mirrored the time-course of glycogen loss. Latency to CAP failure was directly related to nerve glycogen content at aglycemia onset. Glycogen did not benefit the function of slow-conducting, small diameter unmyelinated axons (C fibers) during aglycemia. Blocking glycogen breakdown pharmacologically accelerated CAP failure during aglycemia in A fibers, but not in C fibers. Lactate was as effective as glucose in supporting sciatic nerve function, and was continuously released into the extracellular space in the presence of glucose and fell rapidly during aglycemia. Interpretation Our findings indicated that glycogen is present in peripheral nerve, primarily in myelinating Schwann cells, and exclusively supports large diameter, myelinated axon conduction during aglycemia. Available evidence suggests that peripheral nerve glycogen breaks down during aglycemia and is passed, probably as lactate, to myelinated axons to support function. Unmyelinated axons are not protected by glycogen and are more vulnerable to dysfunction during periods of hypoglycemia. PMID:23034913

  17. Systemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo

    Directory of Open Access Journals (Sweden)

    Principi E

    2016-09-01

    Full Text Available Elisa Principi,1,* Rossana Girardello,2,* Antonino Bruno,1,* Isabella Manni,3 Elisabetta Gini,2 Arianna Pagani,1 Annalisa Grimaldi,2 Federico Ivaldi,4 Terenzio Congiu,5 Daniela De Stefano,1 Giulia Piaggio,3 Magda de Eguileor,2 Douglas M Noonan,1,2 Adriana Albini1 1Vascular Biology and Angiogenesis, Scientific and Technology Pole, IRCCS MultiMedica, Milano, 2Department of Biotechnology and Life Sciences, University of Insubria, Varese, 3Department of Research, Advanced Diagnosis and Innovation, Regina Elena National Cancer Institute, Rome, 4Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, 5Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy *These authors contributed equally to this work Abstract: The increasing use of carbon nanotubes (CNTs in several industrial applications raises concerns on their potential toxicity due to factors such as tissue penetrance, small dimensions, and biopersistence. Using an in vivo model for CNT environmental exposure, mimicking CNT exposition at the workplace, we previously found that CNTs rapidly enter and disseminate in the organism, initially accumulating in the lungs and brain and later reaching the liver and kidneys via the bloodstream in CD1 mice. Here, we monitored and traced the accumulation of single-walled CNTs (SWCNTs, administered systemically in mice, in different organs and the subsequent biological responses. Using the novel in vivo model, MITO-Luc bioluminescence reporter mice, we found that SWCNTs induce systemic cell proliferation, indicating a dynamic response of cells of both bone marrow and the immune system. We then examined metabolic (water/food consumption and dejections, functional (serum enzymes, and morphological (organs and tissues alterations in CD1 mice treated with SWCNTs, using metabolic cages, performing serum analyses, and applying histological, immunohistochemical, and ultrastructural (transmission electron

  18. Grape Seed Procyanidins and Cholestyramine Differentially Alter Bile Acid and Cholesterol Homeostatic Gene Expression in Mouse Intestine and Liver.

    Directory of Open Access Journals (Sweden)

    Rebecca M Heidker

    Full Text Available Bile acid (BA sequestrants, lipid-lowering agents, may be prescribed as a monotherapy or combination therapy to reduce the risk of coronary artery disease. Over 33% of adults in the United States use complementary and alternative medicine strategies, and we recently reported that grape seed procyanidin extract (GSPE reduces enterohepatic BA recirculation as a means to reduce serum triglyceride (TG levels. The current study was therefore designed to assess the effects on BA, cholesterol and TG homeostatic gene expression following co-administration with GSPE and the BA sequestrant, cholestyramine (CHY. Eight-week old male C57BL/6 mice were treated for 4 weeks with either a control or 2% CHY-supplemented diet, after which, they were administered vehicle or GSPE for 14 hours. Liver and intestines were harvested and gene expression was analyzed. BA, cholesterol, non-esterified fatty acid and TG levels were also analyzed in serum and feces. Results reveal that GSPE treatment alone, and co-administration with CHY, regulates BA, cholesterol and TG metabolism differently than CHY administration alone. Notably, GSPE decreased intestinal apical sodium-dependent bile acid transporter (Asbt gene expression, while CHY significantly induced expression. Administration with GSPE or CHY robustly induced hepatic BA biosynthetic gene expression, especially cholesterol 7α-hydroxylase (Cyp7a1, compared to control, while co-administration further enhanced expression. Treatment with CHY induced both intestinal and hepatic cholesterologenic gene expression, while co-administration with GSPE attenuated the CHY-induced increase in the liver but not intestine. CHY also induced hepatic lipogenic gene expression, which was attenuated by co-administration with GSPE. Consequently, a 25% decrease in serum TG levels was observed in the CHY+GSPE group, compared to the CHY group. Collectively, this study presents novel evidence demonstrating that GSPE provides additive and

  19. Short and Long Term Effects of High-Intensity Interval Training on Hormones, Metabolites, Antioxidant System, Glycogen Concentration, and Aerobic Performance Adaptations in Rats.

    Science.gov (United States)

    de Araujo, Gustavo G; Papoti, Marcelo; Dos Reis, Ivan Gustavo Masselli; de Mello, Maria A R; Gobatto, Claudio A

    2016-01-01

    The purpose of the study was to investigate the effects of short and long term High-Intensity Interval Training (HIIT) on anaerobic and aerobic performance, creatinine, uric acid, urea, creatine kinase, lactate dehydrogenase, catalase, superoxide dismutase, testosterone, corticosterone, and glycogen concentration (liver, soleus, and gastrocnemius). The Wistar rats were separated in two groups: HIIT and sedentary/control (CT). The lactate minimum (LM) was used to evaluate the aerobic and anaerobic performance (AP) (baseline, 6, and 12 weeks). The lactate peak determination consisted of two swim bouts at 13% of body weight (bw): (1) 30 s of effort; (2) 30 s of passive recovery; (3) exercise until exhaustion (AP). Tethered loads equivalent to 3.5, 4.0, 4.5, 5.0, 5.5, and 6.5% bw were performed in incremental phase. The aerobic capacity in HIIT group increased after 12 weeks (5.2 ± 0.2% bw) in relation to baseline (4.4 ± 0.2% bw), but not after 6 weeks (4.5 ± 0.3% bw). The exhaustion time in HIIT group showed higher values than CT after 6 (HIIT = 58 ± 5 s; CT = 40 ± 7 s) and 12 weeks (HIIT = 62 ± 7 s; CT = 49 ± 3 s). Glycogen (mg/100 mg) increased in gastrocnemius for HIIT group after 6 weeks (0.757 ± 0.076) and 12 weeks (1.014 ± 0.157) in comparison to baseline (0.358 ± 0.024). In soleus, the HIIT increased glycogen after 6 weeks (0.738 ± 0.057) and 12 weeks (0.709 ± 0.085) in comparison to baseline (0.417 ± 0.035). The glycogen in liver increased after HIIT 12 weeks (4.079 ± 0.319) in relation to baseline (2.400 ± 0.416). The corticosterone (ng/mL) in HIIT increased after 6 weeks (529.0 ± 30.5) and reduced after 12 weeks (153.6 ± 14.5) in comparison to baseline (370.0 ± 18.3). In conclusion, long term HIIT enhanced the aerobic capacity, but short term was not enough to cause aerobic adaptations. The anaerobic performance increased in HIIT short and long term compared with CT, without differences between HIIT short and long term. Furthermore, the

  20. SHORT AND LONG TERM EFFECTS OF HIGH-INTENSITY INTERVAL TRAINING ON HORMONES, METABOLITES, ANTIOXIDANT SYSTEM, GLYCOGEN CONCENTRATION AND AEROBIC PERFORMANCE ADAPTATIONS IN RATS

    Directory of Open Access Journals (Sweden)

    Gustavo Gomes De Araujo

    2016-10-01

    Full Text Available The purpose of the study was to investigate the effects of short and long term High-Intensity Interval Training (HIIT on anaerobic and aerobic performance, creatinine, uric acid, urea, creatine kinase, lactate dehydrogenase, catalase, superoxide dismutase, testosterone, corticosterone and glycogen concentration (liver, soleus and gastrocnemius. The Wistar were separated in two groups: HIIT and sedentary/control (CT. The lactate minimum (LM was used to evaluate the aerobic and anaerobic performance (AP (baseline, 6 and 12 wk. The lactate peak determination consisted of two swim bouts at 13% of body weight (bw: 1 30 s of effort; 2 30 s of passive recovery; 3 exercise until exhaustion (AP. Tethered loads equivalent to 3.5, 4.0, 4.5, 5.0, 5.5 and 6.5% bw were performed in incremental phase. The aerobic capacity in HIIT group increased after 12 wk (5.2±0.2 % bw in relation to baseline (4.4±0.2 % bw, but not after 6 wk (4.5±0.3 % bw. The exhaustion time in HIIT group showed higher values than CT after 6 (HIIT= 58±5 s; CT=40±7 s and 12 wk (HIIT=62±7 s; CT=49±3 s. Glycogen (mg/100mg increased in gastrocnemius for HIIT group after 6 wk (0.757±0.076 and 12 wk (1.014±0.157 in comparison to baseline (0.358±0.024. In soleus, the HIIT increased glycogen after 6 wk (0.738±0.057 and 12 wk (0.709±0.085 in comparison to baseline (0.417±0.035. The glycogen in liver increased after HIIT 12 wk (4.079±0.319 in relation to baseline (2.400±0.416. The corticosterone (ng/mL in HIIT increased after 6 wk (529.0±30.5 and reduced after 12 wk (153.6±14.5 in comparison to baseline (370.0±18.3. In conclusion, long term HIIT enhanced the aerobic capacity, but short term (6wk was not enough to cause aerobic adaptations. The anaerobic performance increased in HIIT short and long term compared with CT, without differences between HIIT short and long term. Furthermore, the glycogen super-compensantion increased after short and long term HIIT in comparison to

  1. A Moderate Zinc Deficiency Does Not Alter Lipid and Fatty Acid Composition in the Liver of Weanling Rats Fed Diets Rich in Cocoa Butter or Safflower Oil.

    Science.gov (United States)

    Weigand, Edgar; Egenolf, Jennifer

    2017-01-01

    The aim of the study was to examine whether a moderate zinc deficiency alters hepatic lipid composition. Male weanling rats, assigned to five groups (8 animals each), were fed low-carbohydrate high-fat diets supplemented with 7 or 50 mg Zn/kg (LZ or HZ) and 22% cocoa butter (CB) or 22% safflower oil (SF) for four weeks. One group each had free access to the LZ-CB and LZ-SF diets, one group each was restrictedly fed the HZ-CB and HZ-SF diets in matching amounts, and one group had free access to the HZ-SF diet (ad libitum control). The rats fed the LZ diets had significantly lower energy intakes and final body weights than the ad libitum control group, and lower plasma and femur Zn concentrations than the animals consuming the HZ diets. Hepatic cholesterol, triacylglycerol and phospholipid concentrations, and fatty acid composition of hepatic triacylglycerols and phospholipids did not significantly differ between the LZ and their respective HZ groups, but were greatly affected by dietary fat source. In conclusion, the moderate Zn deficiency did not significantly alter liver lipid concentrations and fatty acid composition.

  2. A Moderate Zinc Deficiency Does Not Alter Lipid and Fatty Acid Composition in the Liver of Weanling Rats Fed Diets Rich in Cocoa Butter or Safflower Oil

    Directory of Open Access Journals (Sweden)

    Edgar Weigand

    2017-01-01

    Full Text Available The aim of the study was to examine whether a moderate zinc deficiency alters hepatic lipid composition. Male weanling rats, assigned to five groups (8 animals each, were fed low-carbohydrate high-fat diets supplemented with 7 or 50 mg Zn/kg (LZ or HZ and 22% cocoa butter (CB or 22% safflower oil (SF for four weeks. One group each had free access to the LZ-CB and LZ-SF diets, one group each was restrictedly fed the HZ-CB and HZ-SF diets in matching amounts, and one group had free access to the HZ-SF diet (ad libitum control. The rats fed the LZ diets had significantly lower energy intakes and final body weights than the ad libitum control group, and lower plasma and femur Zn concentrations than the animals consuming the HZ diets. Hepatic cholesterol, triacylglycerol and phospholipid concentrations, and fatty acid composition of hepatic triacylglycerols and phospholipids did not significantly differ between the LZ and their respective HZ groups, but were greatly affected by dietary fat source. In conclusion, the moderate Zn deficiency did not significantly alter liver lipid concentrations and fatty acid composition.

  3. Characterization of the highly branched glycogen from the thermoacidophilic red microalga Galdieria sulphuraria and comparison with other glycogens.

    Science.gov (United States)

    Martinez-Garcia, Marta; Stuart, Marc C A; van der Maarel, Marc J E C

    2016-08-01

    The thermoacidophilic red microalga Galdieria sulphuraria synthesizes glycogen when growing under heterotrophic conditions. Structural characterization revealed that G. sulphuraria glycogen is the most highly branched glycogen described to date, with 18% of α-(1→6) linkages. Moreover, it differs from other glycogens because it is composed of short chains only and has a substantially smaller molecular weight and particle size. The physiological role of this highly branched glycogen in G. sulphuraria is discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Processivity and Subcellular Localization of Glycogen Synthase Depend on a Non-catalytic High Affinity Glycogen-binding Site*

    OpenAIRE

    Díaz, Adelaida; Martínez-Pons, Carlos; Fita, Ignacio; Ferrer, Juan C.; Guinovart, Joan J.

    2011-01-01

    Glycogen synthase, a central enzyme in glucose metabolism, catalyzes the successive addition of α-1,4-linked glucose residues to the non-reducing end of a growing glycogen molecule. A non-catalytic glycogen-binding site, identified by x-ray crystallography on the surface of the glycogen synthase from the archaeon Pyrococcus abyssi, has been found to be functionally conserved in the eukaryotic enzymes. The disruption of this binding site in both the archaeal and the human muscle glycogen synth...

  5. Increased lipogenesis and resistance of lipoproteins to oxidative modification in two patients with glycogen storage disease type 1a

    NARCIS (Netherlands)

    Bandsma, RHJ; Rake, JP; Visser, G; Neese, RA; Hellerstein, MK; van Duyvenvoorde, W; Princen, HMG; Stellaard, F; Smit, GPA; Kuipers, F

    We describe 2 patients with glycogen storage disease type la and severe hyperlipidemia without premature atherosclerosis. Susceptibility of low-density lipoproteins to oxidation was decreased, possibly related to the similar to40-fold increase in palmitate synthesis altering lipoprotein saturated

  6. Cadmium sulfate and CdTe-quantum dots alter DNA repair in zebrafish (Danio rerio) liver cells

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Song; Cai, Qingsong [The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX 79416 (United States); Chibli, Hicham [Department of Biomedical Engineering, McGill University, Montréal, QC H3A 2B4 (Canada); Allagadda, Vinay [The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX 79416 (United States); Nadeau, Jay L. [Department of Biomedical Engineering, McGill University, Montréal, QC H3A 2B4 (Canada); Mayer, Gregory D., E-mail: greg.mayer@ttu.edu [The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX 79416 (United States)

    2013-10-15

    Increasing use of quantum dots (QDs) makes it necessary to evaluate their toxicological impacts on aquatic organisms, since their contamination of surface water is inevitable. This study compares the genotoxic effects of ionic Cd versus CdTe nanocrystals in zebrafish hepatocytes. After 24 h of CdSO{sub 4} or CdTe QD exposure, zebrafish liver (ZFL) cells showed a decreased number of viable cells, an accumulation of Cd, an increased formation of reactive oxygen species (ROS), and an induction of DNA strand breaks. Measured levels of stress defense and DNA repair genes were elevated in both cases. However, removal of bulky DNA adducts by nucleotide excision repair (NER) was inhibited with CdSO{sub 4} but not with CdTe QDs. The adverse effects caused by acute exposure of CdTe QDs might be mediated through differing mechanisms than those resulting from ionic cadmium toxicity, and studying the effects of metallic components may be not enough to explain QD toxicities in aquatic organisms. - Highlights: • Both CdSO{sub 4} and CdTe QDs lead to cell death and Cd accumulation. • Both CdSO{sub 4} and CdTe QDs induce cellular ROS generation and DNA strand breaks. • Both CdSO{sub 4} and CdTe QDs induce the expressions of stress defense and DNA repair genes. • NER repair capacity was inhibited with CdSO{sub 4} but not with CdTe QDs.

  7. Apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ.

    Directory of Open Access Journals (Sweden)

    Jiaojiao Chu

    Full Text Available Apelin, a novel adipokine, is the specific endogenous ligand of G protein-coupled receptor APJ. Consistent with its putative role as an adipokine, apelin has been linked to states of insulin resistance. However, the function of apelin in hepatic insulin resistance, a vital part of insulin resistance, and its underlying mechanisms still remains unclear. Here we define the impacts of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes. Our studies indicate that apelin reversed TNF-α-induced reduction of glycogen synthesis in HepG2 cells, mouse primary hepatocytes and liver tissues of C57BL/6J mice by improving JNK-IRS1-AKT-GSK pathway. Moreover, Western blot revealed that APJ, but not apelin, expressed in the hepatocytes and liver tissues of mice. We found that F13A, a competitive antagonist for G protein-coupled receptor APJ, suppressed the effects of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes, suggesting APJ is involved in the function of apelin. In conclusion, we show novel evidence suggesting that apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ. Apelin appears as a beneficial adipokine with anti-insulin resistance properties, and thus as a promising therapeutic target in metabolic disorders.

  8. Epinephrine-stimulated glycogen breakdown activates glycogen synthase and increases insulin-stimulated glucose uptake in epitrochlearis muscles

    DEFF Research Database (Denmark)

    Kolnes, Anders J; Birk, Jesper Bratz; Eilertsen, Einar

    2015-01-01

    Adrenaline increases glycogen synthase (GS) phosphorylation and decreases GS activity but also stimulates glycogen breakdown and low glycogen content normally activates GS. To test the hypothesis that glycogen content directly regulates GS phosphorylation, glycogen breakdown was stimulated...... in condition with decreased GS activation. Saline or adrenaline (0.02mg/100g rat) was injected subcutaneously in Wistar rats (~130 g) with low (24 h fasted), normal (normal diet) and high glycogen content (fasted-refed) and epitrochlearis muscles were removed after 3 h and incubated ex vivo eliminating...... adrenaline action. Adrenaline injection reduced glycogen content in epitrochlearis muscles with high (120.7±17.8 vs 204.6±14.5 mmol•kg(-1); pglycogen (89.5±7.6 vs 152.6±8.1 mmol•kg(-1); pglycogen (90.0±5.0 vs 102.8±7.8 mmol•kg(-1); p=0...

  9. Functional significance of brain glycogen in sustaining glutamatergic neurotransmission.

    Science.gov (United States)

    Sickmann, Helle M; Walls, Anne B; Schousboe, Arne; Bouman, Stephan D; Waagepetersen, Helle S

    2009-05-01

    The involvement of brain glycogen in sustaining neuronal activity has previously been demonstrated. However, to what extent energy derived from glycogen is consumed by astrocytes themselves or is transferred to the neurons in the form of lactate for oxidative metabolism to proceed is at present unclear. The significance of glycogen in fueling glutamate uptake into astrocytes was specifically addressed in cultured astrocytes. Moreover, the objective was to elucidate whether glycogen derived energy is important for maintaining glutamatergic neurotransmission, induced by repetitive exposure to NMDA in co-cultures of cerebellar neurons and astrocytes. In the astrocytes it was shown that uptake of the glutamate analogue D-[3H]aspartate was impaired when glycogen degradation was inhibited irrespective of the presence of glucose, signifying that energy derived from glycogen degradation is important for the astrocytic compartment. By inhibiting glycogen degradation in co-cultures it was evident that glycogen provides energy to sustain glutamatergic neurotransmission, i.e. release and uptake of glutamate. The relocation of glycogen derived lactate to the neuronal compartment was investigated by employing d-lactate, a competitive substrate for the monocarboxylate transporters. Neurotransmitter release was affected by the presence of d-lactate indicating that glycogen derived energy is important not only in the astrocytic but also in the neuronal compartment.

  10. Glycogen storage disease type I: clinical and laboratory profile

    Directory of Open Access Journals (Sweden)

    Berenice L. Santos

    2014-11-01

    Full Text Available Objectives: To characterize the clinical, laboratory, and anthropometric profile of a sample of Brazilian patients with glycogen storage disease type I managed at an outpatient referral clinic for inborn errors of metabolism. Methods: This was a cross-sectional outpatient study based on a convenience sampling strategy. Data on diagnosis, management, anthropometric parameters, and follow-up were assessed. Results: Twenty-one patients were included (median age 10 years, range 1–25 years, all using uncooked cornstarch therapy. Median age at diagnosis was 7 months (range, 1–132 months, and 19 patients underwent liver biopsy for diagnostic confirmation. Overweight, short stature, hepatomegaly, and liver nodules were present in 16 of 21, four of 21, nine of 14, and three of 14 patients, respectively. A correlation was found between height-for-age and BMI-for-age Z-scores (r = 0.561; p = 0.008. Conclusions: Diagnosis of glycogen storage disease type I is delayed in Brazil. Most patients undergo liver biopsy for diagnostic confirmation, even though the combination of a characteristic clinical presentation and molecular methods can provide a definitive diagnosis in a less invasive manner. Obesity is a side effect of cornstarch therapy, and appears to be associated with growth in these patients. Resumo: Objetivos: Caracterizar o perfil clínico, laboratorial e antropométrico de uma amostra de pacientes brasileiros com doença de depósito de glicogênio tipo I tratados em um ambulatório de referência para erros inatos do metabolismo. Métodos: Este foi um estudo ambulatorial transversal com base em uma estratégia de amostragem de conveniência. Foram avaliados os dados com relação ao diagnóstico, tratamento, parâmetros antropométricos e acompanhamento. Resultados: Foram incluídos 21 pacientes (idade média de 10 anos, faixa 1-25 anos de idade, e todos se encontravam em terapia de amido de milho cru. A idade média na época do diagn

  11. Role of Maltose Enzymes in Glycogen Synthesis by Escherichia coli▿

    Science.gov (United States)

    Park, Jong-Tae; Shim, Jae-Hoon; Tran, Phuong Lan; Hong, In-Hee; Yong, Hwan-Ung; Oktavina, Ershita Fitria; Nguyen, Hai Dang; Kim, Jung-Wan; Lee, Tae Soo; Park, Sung-Hoon; Boos, Winfried; Park, Kwan-Hwa

    2011-01-01

    Mutants with deletion mutations in the glg and mal gene clusters of Escherichia coli MC4100 were used to gain insight into glycogen and maltodextrin metabolism. Glycogen content, molecular mass, and branch chain distribution were analyzed in the wild type and in ΔmalP (encoding maltodextrin phosphorylase), ΔmalQ (encoding amylomaltase), ΔglgA (encoding glycogen synthase), and ΔglgA ΔmalP derivatives. The wild type showed increasing amounts of glycogen when grown on glucose, maltose, or maltodextrin. When strains were grown on maltose, the glycogen content was 20 times higher in the ΔmalP strain (0.97 mg/mg protein) than in the wild type (0.05 mg/mg protein). When strains were grown on glucose, the ΔmalP strain and the wild type had similar glycogen contents (0.04 mg/mg and 0.03 mg/mg protein, respectively). The ΔmalQ mutant did not grow on maltose but showed wild-type amounts of glycogen when grown on glucose, demonstrating the exclusive function of GlgA for glycogen synthesis in the absence of maltose metabolism. No glycogen was found in the ΔglgA and ΔglgA ΔmalP strains grown on glucose, but substantial amounts (0.18 and 1.0 mg/mg protein, respectively) were found when they were grown on maltodextrin. This demonstrates that the action of MalQ on maltose or maltodextrin can lead to the formation of glycogen and that MalP controls (inhibits) this pathway. In vitro, MalQ in the presence of GlgB (a branching enzyme) was able to form glycogen from maltose or linear maltodextrins. We propose a model of maltodextrin utilization for the formation of glycogen in the absence of glycogen synthase. PMID:21421758

  12. Effects of commercially available pneumatic compression on muscle glycogen recovery after exercise.

    Science.gov (United States)

    Keck, Nathan A; Cuddy, John S; Hailes, Walter S; Dumke, Charles L; Ruby, Brent C

    2015-02-01

    The purpose of this study was to investigate the effects of pneumatic compression pants on postexercise glycogen resynthesis. Active male subjects (n = 10) completed 2 trials consisting of a 90-minute glycogen depleting ride, followed by 4 hours of recovery with either a pneumatic compression device (PCD) or passive recovery (PR) in a random counterbalanced order. A carbohydrate beverage (1.8 g·kg bodyweight) was provided at 0 and 2 hours after exercise. Muscle biopsies (vastus lateralis) were obtained immediately and 4 hours after exercise for glycogen analyses. Blood samples were collected throughout recovery to measure glucose and insulin. Eight fingerstick blood samples for lactate were collected in the last 20 minutes of the exercise period and during the initial portion of the recovery period. Heart rate was monitored throughout the trial. During the PCD trial, subjects recovered using a commercially available recovery device (NormaTec PCD) operational at 0-60 and 120-180 minutes into recovery period. The same PCD was worn during the PR trial but was not turned on to create pulsatile pressures. There was no difference in muscle glycogen resynthesis during the recovery period (6.9 ± 0.8 and 6.9 ± 0.5 mmol·kg wet wt·h for the PR and PCD trials, respectively). Blood glucose, insulin, and lactate concentrations changed with respect to time but were not different between trials (p > 0.05). The use of PCD did not alter the rate of muscle glycogen resynthesis, blood lactate, or blood glucose and insulin concentrations associated with a postexercise oral glucose load.

  13. Liver transplant

    Science.gov (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  14. The modulation of the symbiont/host interaction between Wolbachia pipientis and Aedes fluviatilis embryos by glycogen metabolism.

    Directory of Open Access Journals (Sweden)

    Mariana da Rocha Fernandes

    Full Text Available Wolbachia pipientis, a maternally transmitted bacterium that colonizes arthropods, may affect the general aspects of insect physiology, particularly reproduction. Wolbachia is a natural endosymbiont of Aedes fluviatilis, whose effects in embryogenesis and reproduction have not been addressed so far. In this context, we investigated the correlation between glucose metabolism and morphological alterations during A. fluviatilis embryo development in Wolbachia-positive (W+ and Wolbachia-negative (W- mosquito strains. While both strains do not display significant morphological and larval hatching differences, larger differences were observed in hexokinase activity and glycogen contents during early and mid-stages of embryogenesis, respectively. To investigate if glycogen would be required for parasite-host interaction, we reduced Glycogen Synthase Kinase-3 (GSK-3 levels in adult females and their eggs by RNAi. GSK-3 knock-down leads to embryonic lethality, lower levels of glycogen and total protein and Wolbachia reduction. Therefore, our results suggest that the relationship between A. fluviatilis and Wolbachia may be modulated by glycogen metabolism.

  15. In vivo hepatic glycogen metabolism in the baboon

    International Nuclear Information System (INIS)

    Jehenson, P.; Canioni, P.; Hantraye, P.; Gueron, M.; Syrota, A.

    1988-01-01

    This paper describes hepatic glycogen synthesis from glucose studied in the baboon by C-13 MR spectroscopy at 2 T. Glycogen synthesis was followed for 3 hours on natural abundance spectra during glucose infusion. (1-C-13)-glucose (3g) was then injected. It produced a ten times larger rate of increase of glycogen-C 1 , which is much lower than expected, suggesting that glycogen synthesis mainly occurred from unlabeled gluconeogenic substrates. Signal-to-noise ratio was 50 for glycogen-C 1 on 2-minute H-1 decoupled spectra. Labeling of C 1 but also C 2 , C 5 and C 6 of glycogen indicated a 15% contribution of indirect pathways to its synthesis from glucose

  16. Analysis of genes involved in glycogen degradation in Escherichia coli.

    Science.gov (United States)

    Strydom, Lindi; Jewell, Jonathan; Meier, Michael A; George, Gavin M; Pfister, Barbara; Zeeman, Samuel; Kossmann, Jens; Lloyd, James R

    2017-02-01

    Escherichia coli accumulate or degrade glycogen depending on environmental carbon supply. Glycogen phosphorylase (GlgP) and glycogen debranching enzyme (GlgX) are known to act on the glycogen polymer, while maltodextrin phosphorylase (MalP) is thought to remove maltodextrins released by GlgX. To examine the roles of these enzymes in more detail, single, double and triple mutants lacking all their activities were produced. GlgX and GlgP were shown to act directly on the glycogen polymer, while MalP most likely catabolised soluble malto-oligosaccharides. Interestingly, analysis of a triple mutant lacking all three enzymes indicates the presence of another enzyme that can release maltodextrins from glycogen. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Qualitative and Quantitative Analyses of Glycogen in Human Milk.

    Science.gov (United States)

    Matsui-Yatsuhashi, Hiroko; Furuyashiki, Takashi; Takata, Hiroki; Ishida, Miyuki; Takumi, Hiroko; Kakutani, Ryo; Kamasaka, Hiroshi; Nagao, Saeko; Hirose, Junko; Kuriki, Takashi

    2017-02-22

    Identification as well as a detailed analysis of glycogen in human milk has not been shown yet. The present study confirmed that glycogen is contained in human milk by qualitative and quantitative analyses. High-performance anion exchange chromatography (HPAEC) and high-performance size exclusion chromatography with a multiangle laser light scattering detector (HPSEC-MALLS) were used for qualitative analysis of glycogen in human milk. Quantitative analysis was carried out by using samples obtained from the individual milks. The result revealed that the concentration of human milk glycogen varied depending on the mother's condition-such as the period postpartum and inflammation. The amounts of glycogen in human milk collected at 0 and 1-2 months postpartum were higher than in milk collected at 3-14 months postpartum. In the milk from mothers with severe mastitis, the concentration of glycogen was about 40 times higher than that in normal milk.

  18. Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease.

    Science.gov (United States)

    Valles-Ortega, Jordi; Duran, Jordi; Garcia-Rocha, Mar; Bosch, Carles; Saez, Isabel; Pujadas, Lluís; Serafin, Anna; Cañas, Xavier; Soriano, Eduardo; Delgado-García, José M; Gruart, Agnès; Guinovart, Joan J

    2011-11-01

    Lafora disease (LD) is caused by mutations in either the laforin or malin gene. The hallmark of the disease is the accumulation of polyglucosan inclusions called Lafora Bodies (LBs). Malin knockout (KO) mice present polyglucosan accumulations in several brain areas, as do patients of LD. These structures are abundant in the cerebellum and hippocampus. Here, we report a large increase in glycogen synthase (GS) in these mice, in which the enzyme accumulates in LBs. Our study focused on the hippocampus where, under physiological conditions, astrocytes and parvalbumin-positive (PV(+)) interneurons expressed GS and malin. Although LBs have been described only in neurons, we found this polyglucosan accumulation in the astrocytes of the KO mice. They also had LBs in the soma and some processes of PV(+) interneurons. This phenomenon was accompanied by the progressive loss of these neuronal cells and, importantly, neurophysiological alterations potentially related to impairment of hippocampal function. Our results emphasize the relevance of the laforin-malin complex in the control of glycogen metabolism and highlight altered glycogen accumulation as a key contributor to neurodegeneration in LD. Copyright © 2011 EMBO Molecular Medicine.

  19. Glycogen distribution in adult and geriatric mice brains

    KAUST Repository

    Alrabeh, Rana

    2017-05-01

    Astrocytes, the most abundant glial cell type in the brain, undergo a number of roles in brain physiology; among them, the energetic support of neurons is the best characterized. Contained within astrocytes is the brain’s obligate energy store, glycogen. Through glycogenolysis, glycogen, a storage form of glucose, is converted to pyruvate that is further reduced to lactate and transferred to neurons as an energy source via MCTs. Glycogen is a multi-branched polysaccharide synthesized from the glucose uptaken in astrocytes. It has been shown that glycogen accumulates with age and contributes to the physiological ageing process in the brain. In this study, we compared glycogen distribution between young adults and geriatric mice to understand the energy consumption of synaptic terminals during ageing using computational tools. We segmented and densely reconstructed neuropil and glycogen granules within six (three 4 month old old and three 24 month old) volumes of Layer 1 somatosensory cortex mice brains from FIB-SEM stacks, using a combination of semi-automated and manual tools, ilastik and TrakEM2. Finally, the 3D visualization software, Blender, was used to analyze the dataset using the DBSCAN and KDTree Nearest neighbor algorithms to study the distribution of glycogen granules compared to synapses, using a plugin that was developed for this purpose. The Nearest Neighbors and clustering results of 6 datasets show that glycogen clusters around excitatory synapses more than inhibitory synapses and that, in general, glycogen is found around axonal boutons more than dendritic spines. There was no significant accumulation of glycogen with ageing within our admittedly small dataset. However, there was a homogenization of glycogen distribution with age and that is consistent with published literature. We conclude that glycogen distribution in the brain is not a random process but follows a function distribution.

  20. Novel method for detection of glycogen in cells.

    Science.gov (United States)

    Skurat, Alexander V; Segvich, Dyann M; DePaoli-Roach, Anna A; Roach, Peter J

    2017-05-01

    Glycogen, a branched polymer of glucose, functions as an energy reserve in many living organisms. Abnormalities in glycogen metabolism, usually excessive accumulation, can be caused genetically, most often through mutation of the enzymes directly involved in synthesis and degradation of the polymer leading to a variety of glycogen storage diseases (GSDs). Microscopic visualization of glycogen deposits in cells and tissues is important for the study of normal glycogen metabolism as well as diagnosis of GSDs. Here, we describe a method for the detection of glycogen using a renewable, recombinant protein which contains the carbohydrate-binding module (CBM) from starch-binding domain containing protein 1 (Stbd1). We generated a fusion protein containing g lutathione S-transferase, a cM c eptitope and the tbd1 BM (GYSC) for use as a glycogen-binding probe, which can be detected with secondary antibodies against glutathione S-transferase or cMyc. By enzyme-linked immunosorbent assay, we demonstrate that GYSC binds glycogen and two other polymers of glucose, amylopectin and amylose. Immunofluorescence staining of cultured cells indicate a GYSC-specific signal that is co-localized with signals obtained with anti-glycogen or anti-glycogen synthase antibodies. GYSC-positive staining inside of lysosomes is observed in individual muscle fibers isolated from mice deficient in lysosomal enzyme acid alpha-glucosidase, a well-characterized model of GSD II (Pompe disease). Co-localized GYSC and glycogen signals are also found in muscle fibers isolated from mice deficient in malin, a model for Lafora disease. These data indicate that GYSC is a novel probe that can be used to study glycogen metabolism under normal and pathological conditions. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  1. A Different Perspective for Management of Diabetes Mellitus: Controlling Viral Liver Diseases.

    Science.gov (United States)

    Zhao, Yingying; Xing, Huichun

    2017-01-01

    Knowing how to prevent and treat diabetes mellitus (DM) earlier is essential to improving outcomes. Through participating in synthesis and catabolism of glycogen, the liver helps to regulate glucose homeostasis. Viral related liver diseases are associated with glycometabolism disorders, which means effective management of viral liver diseases may be a therapeutic strategy for DM. The present article reviews the correlation between DM and liver diseases to give an update of the management of DM rooted by viral liver diseases.

  2. Alterations to proteome and tissue recovery responses in fish liver caused by a short-term combination treatment with cadmium and benzo[a]pyrene

    International Nuclear Information System (INIS)

    Costa, P.M.; Chicano-Galvez, E.; Lopez Barea, J.; DelValls, T.A.; Costa, M.H.

    2010-01-01

    The livers of soles (Solea senegalensis) injected with subacute doses of cadmium (Cd), benzo[a]pyrene (B[a]P), or their combination, were screened for alterations to cytosolic protein expression patterns, complemented by cytological and histological analyses. Cadmium and B[a]P, but not combined, induced hepatocyte apoptosis and Kupfer cell hyperplasia. Proteomics, however, suggested that apoptosis was triggered through distinct pathways. Cadmium and B[a]P caused upregulation of different anti-oxidative enzymes (peroxiredoxin and glutathione peroxidase, respectively) although co-exposure impaired induction. Similarly, apoptosis was inhibited by co-exposure, to which may have contributed a synergistic upregulation of tissue metalloproteinase inhibitor, β-actin and a lipid transport protein. The regulation factors of nine out of eleven identified proteins of different types revealed antagonistic or synergistic effects between Cd and B[a]P at the prospected doses after 24 h of exposure. The results indicate that co-exposure to Cd and B[a]P may enhance toxicity by impairing specific responses and not through cumulative damage. - The interaction between cadmium and benzo[a]pyrene impairs specific responses to toxicity and tissue repair mechanisms.

  3. High glycogen levels in the hippocampus of patients with epilepsy

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Madsen, Flemming F; Secher, Niels H

    2006-01-01

    During intense cerebral activation approximately half of the glucose plus lactate taken up by the human brain is not oxidized and could replenish glycogen deposits, but the human brain glycogen concentration is unknown. In patients with temporal lobe epilepsy, undergoing curative surgery, brain......, glycogen was similarly higher than in grey and white matter. Consequently, in human grey and white matter and, particularly, in the hippocampus of patients with temporal lope epilepsy, glycogen constitutes a large, active energy reserve, which may be of importance for energy provision during sustained...

  4. Tyrosine glycosylation is involved in muscle-glycogen synthesis

    International Nuclear Information System (INIS)

    Rodriguez, I.R.; Tandecarz, J.S.; Kirkman, B.R.; Whelan, W.J.

    1986-01-01

    Rabbit-muscle glycogen contains a covalently bound protein having Mr 37,000 that the authors will henceforth refer to as glycogenin. It is completely insoluble in water at pH 5, and may be generated as a precipitate as a result of the combined action on glycogen of α-amylase and glucoamylase, or by treatment with anhydrous hydrogen fluoride. In the former case the protein still carries some of the glucose residues of glycogen (10-30 per mole of glycogenin). The linkage between glycogen and glycogenin has been identified as a novel glycosidic-amino acid bond. The authors demonstrated glucosylation with UDP[/sup 14/C]glucose by a muscle extract of two rabbit-muscle proteins contained in the same extract. The relation of these proteins to glycogenin, and whether the amino acid undergoing glucosylation is tyrosine, remains to be explored. The discovery of glycogenin is, the authors believe, an important clue to the mechanism of biogenesis of glycogen and may represent a previously unsuspected means of metabolic control of the glycogen content of the cell and the location of glycogen within the cell. The facts that the linkage between glycogen and glycogenin is via tyrosine, that insulin stimulates glycogen synthesis, and acts on its receptor by causing it to become an active tyrosine kinase, may be linked by a common thread

  5. Drug induced exocytosis of glycogen in Pompe disease.

    Science.gov (United States)

    Turner, Christopher T; Fuller, Maria; Hopwood, John J; Meikle, Peter J; Brooks, Doug A

    2016-10-28

    Pompe disease is caused by a deficiency in the lysosomal enzyme α-glucosidase, and this leads to glycogen accumulation in the autolysosomes of patient cells. Glycogen storage material is exocytosed at a basal rate in cultured Pompe cells, with one study showing up to 80% is released under specific culture conditions. Critically, exocytosis induction may reduce glycogen storage in Pompe patients, providing the basis for a therapeutic strategy whereby stored glycogen is redirected to an extracellular location and subsequently degraded by circulating amylases. The focus of the current study was to identify compounds capable of inducing rapid glycogen exocytosis in cultured Pompe cells. Here, calcimycin, lysophosphatidylcholine and α-l-iduronidase each significantly increased glycogen exocytosis compared to vehicle-treated controls. The most effective compound, calcimycin, induced exocytosis through a Ca 2+ -dependent mechanism, although was unable to release a pool of vesicular glycogen larger than the calcimycin-induced exocytic pore. There was reduced glycogen release from Pompe compared to unaffected cells, primarily due to increased granule size in Pompe cells. Drug induced exocytosis therefore shows promise as a therapeutic approach for Pompe patients but strategies are required to enhance the release of large molecular weight glycogen granules. Copyright © 2016. Published by Elsevier Inc.

  6. Abnormal Glycogen Storage by Retinal Neurons in Diabetes.

    Science.gov (United States)

    Gardiner, Tom A; Canning, Paul; Tipping, Nuala; Archer, Desmond B; Stitt, Alan W

    2015-12-01

    It is widely held that neurons of the central nervous system do not store glycogen and that accumulation of the polysaccharide may cause neurodegeneration. Since primary neural injury occurs in diabetic retinopathy, we examined neuronal glycogen status in the retina of streptozotocin-induced diabetic and control rats. Glycogen was localized in eyes of streptozotocin-induced diabetic and control rats using light microscopic histochemistry and electron microscopy, and correlated with immunohistochemical staining for glycogen phosphorylase and phosphorylated glycogen synthase (pGS). Electron microscopy of 2-month-old diabetic rats (n = 6) showed massive accumulations of glycogen in the perinuclear cytoplasm of many amacrine neurons. In 4-month-old diabetic rats (n = 11), quantification of glycogen-engorged amacrine cells showed a mean of 26 cells/mm of central retina (SD ± 5), compared to 0.5 (SD ± 0.2) in controls (n = 8). Immunohistochemical staining for glycogen phosphorylase revealed strong expression in amacrine and ganglion cells of control retina, and increased staining in cell processes of the inner plexiform layer in diabetic retina. In control retina, the inactive pGS was consistently sequestered within the cell nuclei of all retinal neurons and the retinal pigment epithelium (RPE), but in diabetics nuclear pGS was reduced or lost in all classes of retinal cell except the ganglion cells and cone photoreceptors. The present study identifies a large population of retinal neurons that normally utilize glycogen metabolism but show pathologic storage of the polysaccharide during uncontrolled diabetes.

  7. Altered Function and Expression of ABC Transporters at the Blood–Brain Barrier and Increased Brain Distribution of Phenobarbital in Acute Liver Failure Mice

    Directory of Open Access Journals (Sweden)

    Li Liu

    2018-03-01

    Full Text Available This study investigated alterations in the function and expression of P-glycoprotein (P-GP, breast cancer resistance protein (BCRP, and multidrug resistance-associated protein 2 (MRP2 at the blood–brain barrier (BBB of acute liver failure (ALF mice and its clinical significance. ALF mice were developed using intraperitoneal injection of thioacetamide. P-GP, BCRP, and MRP2 functions were determined by measuring the ratios of brain-to-plasma concentration of rhodamine 123, prazosin, and dinitrophenyl-S-glutathione, respectively. The mRNA and proteins expression levels of P-GP, BCRP, and MRP2 were evaluated with quantitative real-time PCR and western blot, respectively. MDCK-MDR1 and HCMEC/D3 cells were used to document the effects of the abnormally altered components in serum of ALF mice on the function and expression of P-GP. The clinical significance of alteration in P-GP function and expression was investigated by determining the distribution of the P-GP substrate phenobarbital (60 mg/kg, intravenous administration in the brain and loss of righting reflex (LORR induced by the drug (100 mg/kg. The results showed that ALF significantly downregulated the function and expression of both P-GP and BCRP, but increased the function and expression of MRP2 in the brain of mice. Cell study showed that increased chenodeoxycholic acid may be a reason behind the downregulated P-GP function and expression. Compared with control mice, ALF mice showed a significantly higher brain concentration of phenobarbital and higher brain-to-plasma concentration ratios. In accordance, ALF mice showed a significantly larger duration of LORR and shorter latency time of LORR by phenobarbital, inferring the enhanced pharmacological effect of phenobarbital on the central nervous system (CNS. In conclusion, the function and expression of P-GP and BCRP decreased, while the function and expression of MRP2 increased in the brain of ALF mice. The attenuated function and expression

  8. Polyamine and amino acid content, and activity of polyamine-synthesizing decarboxylases, in liver of streptozotocin-induced diabetic and insulin-treated diabetic rats

    OpenAIRE

    Brosnan, Margaret E.; Roebothan, Barbara V.; Hall, Douglas E.

    1980-01-01

    1. Concentrations of polyamines, amino acids, glycogen, nucleic acids and protein, and activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, were measured in livers from control, streptozotocin-diabetic and insulin-treated diabetic rats. 2. Total DNA per liver and protein per mg of DNA were unaffected by diabetes, whereas RNA per mg of DNA and glycogen per g of liver were decreased. Insulin treatment of diabetic rats induced both hypertrophy and hyperplasia, as indicat...

  9. A highly prevalent equine glycogen storage disease is explained by constitutive activation of a mutant glycogen synthase

    DEFF Research Database (Denmark)

    Maile, C A; Hingst, Janne Rasmuss; Mahalingan, K K

    2017-01-01

    BACKGROUND: Equine type 1 polysaccharide storage myopathy (PSSM1) is associated with a missense mutation (R309H) in the glycogen synthase (GYS1) gene, enhanced glycogen synthase (GS) activity and excessive glycogen and amylopectate inclusions in muscle. METHODS: Equine muscle biochemical...... had significantly higher glycogen content than control horse muscle despite no difference in GS expression. GS activity was significantly higher in muscle from homozygous mutants than from heterozygote and control horses, in the absence and presence of the allosteric regulator, glucose 6 phosphate (G6...

  10. Hepatic protein phosphatase 1 regulatory subunit 3B (Ppp1r3b) promotes hepatic glycogen synthesis and thereby regulates fasting energy homeostasis.

    Science.gov (United States)

    Mehta, Minal B; Shewale, Swapnil V; Sequeira, Raymond N; Millar, John S; Hand, Nicholas J; Rader, Daniel J

    2017-06-23

    Maintenance of whole-body glucose homeostasis is critical to glycemic function. Genetic variants mapping to chromosome 8p23.1 in genome-wide association studies have been linked to glycemic traits in humans. The gene of known function closest to the mapped region, PPP1R3B (protein phosphatase 1 regulatory subunit 3B), encodes a protein (G L ) that regulates glycogen metabolism in the liver. We therefore sought to test the hypothesis that hepatic PPP1R3B is associated with glycemic traits. We generated mice with either liver-specific deletion ( Ppp1r3b Δ hep ) or liver-specific overexpression of Ppp1r3b The Ppp1r3b deletion significantly reduced glycogen synthase protein abundance, and the remaining protein was predominantly phosphorylated and inactive. As a consequence, glucose incorporation into hepatic glycogen was significantly impaired, total hepatic glycogen content was substantially decreased, and mice lacking hepatic Ppp1r3b had lower fasting plasma glucose than controls. The concomitant loss of liver glycogen impaired whole-body glucose homeostasis and increased hepatic expression of glycolytic enzymes in Ppp1r3b Δ hep mice relative to controls in the postprandial state. Eight hours of fasting significantly increased the expression of two critical gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, above the levels in control livers. Conversely, the liver-specific overexpression of Ppp1r3b enhanced hepatic glycogen storage above that of controls and, as a result, delayed the onset of fasting-induced hypoglycemia. Moreover, mice overexpressing hepatic Ppp1r3b upon long-term fasting (12-36 h) were protected from blood ketone-body accumulation, unlike control and Ppp1r3b Δ hep mice. These findings indicate a major role for Ppp1r3b in regulating hepatic glycogen stores and whole-body glucose/energy homeostasis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Contributions of Glycogen to Astrocytic Energetics during Brain Activation

    Science.gov (United States)

    Dienel, Gerald A.; Cruz, Nancy F.

    2014-01-01

    Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 mol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K+ level, oxidative stress management, and memory consolidation; it is a multi-functional compound. PMID:24515302

  12. Contributions of glycogen to astrocytic energetics during brain activation.

    Science.gov (United States)

    Dienel, Gerald A; Cruz, Nancy F

    2015-02-01

    Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 μmol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K(+) level, oxidative stress management, and memory consolidation; it is a multi-functional compound.

  13. Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis.

    NARCIS (Netherlands)

    Serlie, M.J.; Haan, J.H.A. de; Tack, C.J.J.; Verberne, H.J.; Ackermans, M.T.; Heerschap, A.; Sauerwein, H.P.

    2005-01-01

    The introduction of 13C magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus

  14. Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis

    NARCIS (Netherlands)

    Serlie, Mireille J. M.; de Haan, Jacco H.; Tack, Cees J.; Verberne, Hein J.; Ackermans, Mariette T.; Heerschap, Arend; Sauerwein, Hans P.

    2005-01-01

    The introduction of C-13 magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus

  15. Muscular glycogen storage diseases without increased glycogen content on histoplathological examination

    NARCIS (Netherlands)

    Hoeksma, M.; den Dunnen, W. F. A.; Niezen-Koning, K. E.; van Diggelen, O. P.; van Spronsen, F. J.

    Histopathological findings of muscle biopsies from five patients with two different muscular glycogen storage diseases (mGSD) were presented. From these investigations it emerged that the yield of histopathology in mGSD is low. In only one of five patients histopathological findings gave a clue

  16. Long-term obestatin treatment of mice type 2 diabetes increases insulin sensitivity and improves liver function.

    Science.gov (United States)

    Kołodziejski, Paweł A; Pruszyńska-Oszmałek, Ewa; Strowski, Mathias Z; Nowak, Krzysztof W

    2017-06-01

    Obestatin and ghrelin are peptides encoded by the preproghrelin gene. Obestatin inhibits food intake, in addition to regulation of glucose and lipid metabolism. Here, we test the ability of obestatin at improving metabolic control and liver function in type 2 diabetic animals (type 2 diabetes mellitus). The effects of chronic obestatin treatment of mice with experimentally induced type 2 diabetes mellitus on serum levels of glucose and lipids, and insulin sensitivity are characterized. In addition, alterations of hepatic lipid and glycogen contents are evaluated. Obestatin reduced body weight and decreased serum glucose, fructosamine, and β-hydroxybutyrate levels, as well as total and low-density lipoprotein fractions of cholesterol. In addition, obestatin increased high-density lipoproteins cholesterol levels and enhanced insulin sensitivity in mice with type 2 diabetes mellitus. Moreover, obestatin diminished liver mass, hepatic triglycerides and cholesterol contents, while glycogen content was higher in livers of healthy and mice with type 2 diabetes mellitus treated with obestatin. These changes were accompanied by reduction of increased alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transpeptidase in T2DM mice with type 2 diabetes mellitus. Obestatin increased adiponectin levels and reduced leptin concentration. Obestatin influenced the expression of genes involved in lipid and carbohydrate metabolism by increasing Fabp5 and decreasing G6pc, Pepck, Fgf21 mRNA in the liver. Obestatin increased both, AKT and AMPK phosphorylation, and sirtuin 1 (SIRT1) protein levels as well as mRNA expression in the liver. Obestatin improves metabolic abnormalities in type 2 diabetes mellitus, restores hepatic lipid contents and decreases hepatic enzymes. Therefore, obestatin could potentially have a therapeutic relevance in treating of insulin resistance and metabolic dysfunctions in type 2 diabetes mellitus.

  17. Functional significance of brain glycogen in sustaining glutamatergic neurotransmission

    DEFF Research Database (Denmark)

    Sickmann, Helle M; Walls, Anne B; Schousboe, Arne

    2009-01-01

    The involvement of brain glycogen in sustaining neuronal activity has previously been demonstrated. However, to what extent energy derived from glycogen is consumed by astrocytes themselves or is transferred to the neurons in the form of lactate for oxidative metabolism to proceed is at present u...

  18. Glycogen metabolism and the homeostatic regulation of sleep

    KAUST Repository

    Petit, Jean-Marie; Burlet-Godinot, Sophie; Magistretti, Pierre J.; Allaman, Igor

    2014-01-01

    In 1995 Benington and Heller formulated an energy hypothesis of sleep centered on a key role of glycogen. It was postulated that a major function of sleep is to replenish glycogen stores in the brain that have been depleted during wakefulness which

  19. Free fatty acids increase hepatic glycogen content in obese males

    NARCIS (Netherlands)

    Allick, G.; Sprangers, F.; Weverling, G. J.; Ackermans, M. T.; Meijer, A. J.; Romijn, J. A.; Endert, E.; Bisschop, P. H.; Sauerwein, H. P.

    2004-01-01

    Obesity is associated with increased hepatic glycogen content. In vivo and in vitro data suggest that plasma free fatty acids (FFA) may cause this increase. In this study we investigated the effect of physiological plasma FFA levels on hepatic glycogen metabolism by studying intrahepatic glucose

  20. Muscle glycogen and cell function--Location, location, location.

    Science.gov (United States)

    Ørtenblad, N; Nielsen, J

    2015-12-01

    The importance of glycogen, as a fuel during exercise, is a fundamental concept in exercise physiology. The use of electron microscopy has revealed that glycogen is not evenly distributed in skeletal muscle fibers, but rather localized in distinct pools. In this review, we present the available evidence regarding the subcellular localization of glycogen in skeletal muscle and discuss this from the perspective of skeletal muscle fiber function. The distribution of glycogen in the defined pools within the skeletal muscle varies depending on exercise intensity, fiber phenotype, training status, and immobilization. Furthermore, these defined pools may serve specific functions in the cell. Specifically, reduced levels of these pools of glycogen are associated with reduced SR Ca(2+) release, muscle relaxation rate, and membrane excitability. Collectively, the available literature strongly demonstrates that the subcellular localization of glycogen has to be considered to fully understand the role of glycogen metabolism and signaling in skeletal muscle function. Here, we propose that the effect of low muscle glycogen on excitation-contraction coupling may serve as a built-in mechanism, which links the energetic state of the muscle fiber to energy utilization. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Exercise intolerance in Glycogen Storage Disease Type III

    DEFF Research Database (Denmark)

    Preisler, Nicolai; Pradel, Agnès; Husu, Edith

    2013-01-01

    Myopathic symptoms in Glycogen Storage Disease Type IIIa (GSD IIIa) are generally ascribed to the muscle wasting that these patients suffer in adult life, but an inability to debranch glycogen likely also has an impact on muscle energy metabolism. We hypothesized that patients with GSD IIIa can...

  2. Systematic review with meta-analysis: risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients.

    Science.gov (United States)

    Sookoian, S; Pirola, C J

    2017-07-01

    The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is closely associated with the co-occurrence of multiple pathological conditions characterising the metabolic syndrome (MetS), obesity in particular. However, NAFLD also develops in lean subjects, whose risk factors remain poorly defined. We performed a meta-analysis of 15 studies, along with the data pertaining to our own population (n=336 patients). Data from lean (n=1966) and obese (n=5938) patients with NAFLD were analysed; lean (n=9946) and obese (n=6027) subjects without NAFLD served as controls. Relative to the lean non-NAFLD controls, lean patients with NAFLD were older (3.79±0.72 years, P=1.36×10 -6 ) and exhibited the entire spectrum of the MetS risk factors. Specifically, they had a significant (P=10 -10 ) increase in plasma glucose levels (6.44±1.12 mg/dL) and HOMA-IR (0.52±0.094-unit increment), blood lipids (triglycerides: 48.37±3.6, P=10 -10 and total cholesterol: 7.04±3.8, mg/dL, P=4.2×10 -7 ), systolic (5.64±0.7) and diastolic (3.37±0.9) blood pressure (mm Hg), P=10 -10 , and waist circumference (5.88±0.4 cm, P=10 -10 ); values denote difference in means±SE. Nevertheless, the overall alterations in the obese group were much more severe when compared to lean subjects, regardless of the presence of NAFLD. Meta-regression suggested that NAFLD is a modifier of the level of blood lipids. Lean and obese patients with NAFLD share a common altered metabolic and cardiovascular profile. The former, while having normal body weight, showed excess of abdominal adipose tissue as well as other MetS features. © 2017 John Wiley & Sons Ltd.

  3. Hepatic glycogen in humans. I. Direct formation after oral and intravenous glucose or after a 24-h fast

    International Nuclear Information System (INIS)

    Radziuk, J.

    1989-01-01

    The formation of hepatic glycogen by the direct pathway is assessed in humans after a 12-h fast and oral loading (100 g) or intravenous infusion (90 g) and after a 24-h fast and the same oral glucose load. The methodology used is based on the double tracer method. [3- 3 H]glucose is infused at a constant rate for the determination of the metabolic clearance of glucose. [1- 14 C]glucose is administered with the glucose load. One hour after absorption or the intravenous glucose infusion is terminated, a glucagon infusion is initiated to mobilize the glycogen labeled with [1- 14 C]glucose and formed during the absorptive period. At this time a third tracer, [6- 3 H]glucose, is administered to measure glucose clearance. It was found that after the 12-h fast and oral glucose loading 7.2 +/- 1.1 g of hepatic glycogen appears to be formed directly from glucose compared with 8.4 +/- 1.0 g after the same load and a 24-h fast and 8.5 +/- 0.4 g after a 12-h fast and an equivalent intravenous glucose infusion. When the amount of label ([ 14 C]glucose) mobilized that was not corrected for metabolic recycling was calculated, the data suggested that the amount of glycogen formed by gluconeogenic pathways was probably at least equal to that formed by direct uptake. It was also approximately 60% greater after a 24-h fast. It can be concluded that the amount of hepatic glycogen formed directly from glucose during glucose loading is not significantly altered by the route of entry or the extension of the fasting period to 24 h. The data suggest, however, that gluconeogenetic formation of glycogen increases with fasting

  4. Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review.

    Science.gov (United States)

    Magoulas, Pilar L; El-Hattab, Ayman W; Roy, Angshumoy; Bali, Deeksha S; Finegold, Milton J; Craigen, William J

    2012-06-01

    Glycogen storage disease type IV is a rare autosomal recessive disorder of glycogen metabolism caused by mutations in the GBE1 gene that encodes the 1,4-alpha-glucan-branching enzyme 1. Its clinical presentation is variable, with the most common form presenting in early childhood with primary hepatic involvement. Histologic manifestations in glycogen storage disease type IV typically consist of intracytoplasmic non-membrane-bound inclusions containing abnormally branched glycogen (polyglucosan bodies) within hepatocytes and myocytes. We report a female infant with classic hepatic form of glycogen storage disease type IV who demonstrated diffuse reticuloendothelial system involvement with the spleen, bone marrow, and lymph nodes infiltrated by foamy histiocytes with intracytoplasmic polyglucosan deposits. Sequence analysis of the GBE1 gene revealed compound heterozygosity for a previously described frameshift mutation (c.1239delT) and a novel missense mutation (c.1279G>A) that is predicted to alter a conserved glycine residue. GBE enzyme analysis revealed no detectable activity. A review of the literature for glycogen storage disease type IV patients with characterized molecular defects and deficient enzyme activity reveals most GBE1 mutations to be missense mutations clustering in the catalytic enzyme domain. Individuals with the classic hepatic form of glycogen storage disease type IV tend to be compound heterozygotes for null and missense mutations. Although the extensive reticuloendothelial system involvement that was observed in our patient is not typical of glycogen storage disease type IV, it may be associated with severe enzymatic deficiency and a poor outcome. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Muscle glycogen and cell function - Location, location, location

    DEFF Research Database (Denmark)

    Ørtenblad, N; Nielsen, Joachim

    2015-01-01

    The importance of glycogen, as a fuel during exercise, is a fundamental concept in exercise physiology. The use of electron microscopy has revealed that glycogen is not evenly distributed in skeletal muscle fibers, but rather localized in distinct pools. In this review, we present the available...... evidence regarding the subcellular localization of glycogen in skeletal muscle and discuss this from the perspective of skeletal muscle fiber function. The distribution of glycogen in the defined pools within the skeletal muscle varies depending on exercise intensity, fiber phenotype, training status......, and immobilization. Furthermore, these defined pools may serve specific functions in the cell. Specifically, reduced levels of these pools of glycogen are associated with reduced SR Ca(2+) release, muscle relaxation rate, and membrane excitability. Collectively, the available literature strongly demonstrates...

  6. Synthesis of glycogen from fructose in the presence of elevated levels of glycogen phosphorylase a in rat hepatocytes.

    Science.gov (United States)

    Ciudad, C J; Massagué, J; Salavert, A; Guinovart, J J

    1980-03-20

    Incubation of hepatocytes with glucose promoted the increase in the glycogen synthase (-glucose 6-phosphate/+glucose 6-phosphate) activity ratio, the decrease in the levels of phosphorylase a and a marked increase in the intracellular glycogen level. Incubation with fructose alone promoted the simultaneous activation of glycogen synthase and increase in the levels of phosphorylase a. Strikingly, glycogen deposition occurred in spite of the elevated levels of phosphorylase a. When glucose and fructose were added to the media the activation of glycogen synthase was always higher than when the hexoses were added separately. On the other hand the effects on glycogen phosphorylase were a function of the relative concentrations of both sugars. Inactivation of glycogen phosphorylase occurred when the fructose to glucose ratio was low while activation took place when the ratio was high. The simultaneous presence of glucose and fructose resulted, in all cases, in an enhancement in the deposition of glycogen. The effects described were not limited to fructose as D-glyceraldehyde, dihydroxyacetone, L-sorbose, D-tagatose and sorbitol, compounds metabolically related to fructose, provoked the same behaviour.

  7. GLYCOGEN IN BACILLUS-SUBTILIS - MOLECULAR CHARACTERIZATION OF AN OPERON ENCODING ENZYMES INVOLVED IN GLYCOGEN BIOSYNTHESIS AND DEGRADATION

    NARCIS (Netherlands)

    KIEL, JAKW; BOELS, JM; BELDMAN, G; VENEMA, G

    Although it has never been reported that Bacillus subtilis is capable of accumulating glycogen, we have isolated a region from the chromosome of B. subtilis containing a glycogen operon. The operon is located directly downstream from trnB, which maps at 275 degrees on the B. subtilis chromosome. It

  8. Glycogen synthase from the parabasalian parasite Trichomonas vaginalis: An unusual member of the starch/glycogen synthase family.

    Science.gov (United States)

    Wilson, Wayne A; Pradhan, Prajakta; Madhan, Nayasha; Gist, Galen C; Brittingham, Andrew

    2017-07-01

    Trichomonas vaginalis, a parasitic protist, is the causative agent of the common sexually-transmitted infection trichomoniasis. The organism has long been known to synthesize substantial glycogen as a storage polysaccharide, presumably mobilizing this compound during periods of carbohydrate limitation, such as might be encountered during transmission between hosts. However, little is known regarding the enzymes of glycogen metabolism in T. vaginalis. We had previously described the identification and characterization of two forms of glycogen phosphorylase in the organism. Here, we measure UDP-glucose-dependent glycogen synthase activity in cell-free extracts of T. vaginalis. We then demonstrate that the TVAG_258220 open reading frame encodes a glycosyltransferase that is presumably responsible for this synthetic activity. We show that expression of TVAG_258220 in a yeast strain lacking endogenous glycogen synthase activity is sufficient to restore glycogen accumulation. Furthermore, when TVAG_258220 is expressed in bacteria, the resulting recombinant protein has glycogen synthase activity in vitro, transferring glucose from either UDP-glucose or ADP-glucose to glycogen and using both substrates with similar affinity. This protein is also able to transfer glucose from UDP-glucose or ADP-glucose to maltose and longer oligomers of glucose but not to glucose itself. However, with these substrates, there is no evidence of processivity and sugar transfer is limited to between one and three glucose residues. Taken together with our earlier work on glycogen phosphorylase, we are now well positioned to define both how T. vaginalis synthesizes and utilizes glycogen, and how these processes are regulated. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  9. Glycogen synthase kinase-3 regulation of urinary concentrating ability.

    Science.gov (United States)

    Rao, Reena

    2012-09-01

    Glycogen synthase kinase-3 (GSK3) is an enzyme that is gaining prominence as a critical signaling molecule in the epithelial cells of renal tubules. This review will focus on recent findings exploring the role of GSK3 in renal collecting ducts, especially its role in urine concentration involving vasopressin signaling. Recent studies using inhibition or tissue-specific gene deletion of GSK3 revealed the mechanism by which GSK3 regulates aquaporin 2 water channels via adenylate cyclase or the prostaglandin-E2 pathway. In other studies, postnatal treatment with lithium, an inhibitor of GSK3, increased cell proliferation and led to microcyst formation in rat kidneys. These studies suggest that loss of GSK3 activity could interfere with renal water transport at two levels. In the short term, it could disrupt vasopressin signaling in collecting duct cells and in the long term it could alter the structure of the collecting ducts, making them less responsive to the hydro-osmotic effects of vasopressin. Ongoing studies reveal the crucial role played by GSK3 in the regulation of vasopressin action in the renal collecting ducts and suggest a possible use of GSK3 inhibitors in disease conditions associated with disrupted vasopressin signaling.

  10. Glycogen metabolism and the homeostatic regulation of sleep

    KAUST Repository

    Petit, Jean-Marie

    2014-11-16

    In 1995 Benington and Heller formulated an energy hypothesis of sleep centered on a key role of glycogen. It was postulated that a major function of sleep is to replenish glycogen stores in the brain that have been depleted during wakefulness which is associated to an increased energy demand. Astrocytic glycogen depletion participates to an increase of extracellular adenosine release which influences sleep homeostasis. Here, we will review some evidence obtained by studies addressing the question of a key role played by glycogen metabolism in sleep regulation as proposed by this hypothesis or by an alternative hypothesis named “glycogenetic” hypothesis as well as the importance of the confounding effect of glucocorticoïds. Even though actual collected data argue in favor of a role of sleep in brain energy balance-homeostasis, they do not support a critical and direct involvement of glycogen metabolism on sleep regulation. For instance, glycogen levels during the sleep-wake cycle are driven by different physiological signals and therefore appear more as a marker-integrator of brain energy status than a direct regulator of sleep homeostasis. In support of this we provide evidence that blockade of glycogen mobilization does not induce more sleep episodes during the active period while locomotor activity is reduced. These observations do not invalidate the energy hypothesis of sleep but indicate that underlying cellular mechanisms are more complex than postulated by Benington and Heller.

  11. Heteropoly acid catalyzed hydrolysis of glycogen to glucose

    International Nuclear Information System (INIS)

    Klein, Miri; Pulidindi, Indra Neel; Perkas, Nina; Gedanken, Aharon

    2015-01-01

    Complete conversion of glycogen to glucose is achieved by using H 3 PW 12 O 40 ·nH 2 O (HPW) and H 4 SiW 12 O 40 ·nH 2 O (HSiW) as catalysts for the hydrolysis under optimized hydrothermal conditions (mass fraction of catalyst 2.4%, 373 K and 2 h reaction time). The reusability of the catalyst (HPW) was demonstrated. In addition to carrying out the glycogen hydrolysis in an autoclave, other novel methods such as microwave irradiation and sonication have also been investigated. At higher mass fraction of the heteropoly acids (10.5%), glycogen could be completely converted to glucose under microwave irradiation. Sonication of an aqueous solution of glycogen in the presence of HPW and HSiW also yielded glucose. Thus, heteropoly acids are efficient, environmentally friendly and reusable catalysts for the conversion of glycogen to glucose. - Highlights: • Hydrothermal, microwave and sonication based methods of hydrolysis. • Heteropoly acids are green catalysts for glycogen hydrolysis. • Glycogen from cyanobacteria is demonstrated as a potential feedstock for glucose

  12. Liver Transplant

    Science.gov (United States)

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  13. Glycogen branching enzyme (GBE1) mutation causing equine glycogen storage disease IV.

    Science.gov (United States)

    Ward, Tara L; Valberg, Stephanie J; Adelson, David L; Abbey, Colette A; Binns, Matthew M; Mickelson, James R

    2004-07-01

    Comparative biochemical and histopathological evidence suggests that a deficiency in the glycogen branching enzyme, encoded by the GBE1 gene, is responsible for a recently identified recessive fatal fetal and neonatal glycogen storage disease (GSD) in American Quarter Horses termed GSD IV. We have now derived the complete GBE1 cDNA sequences for control horses and affected foals, and identified a C to A substitution at base 102 that results in a tyrosine (Y) to stop (X) mutation in codon 34 of exon 1. All 11 affected foals were homozygous for the X34 allele, their 11 available dams and sires were heterozygous, and all 16 control horses were homozygous for the Y34 allele. The previous findings of poorly branched glycogen, abnormal polysaccharide accumulation, lack of measurable GBE1 enzyme activity and immunodetectable GBE1 protein, coupled with the present observation of abundant GBE1 mRNA in affected foals, are all consistent with the nonsense mutation in the 699 amino acid GBE1 protein. The affected foal pedigrees have a common ancestor and contain prolific stallions that are likely carriers of the recessive X34 allele. Defining the molecular basis of equine GSD IV will allow for accurate DNA testing and the ability to prevent occurrence of this devastating disease affecting American Quarter Horses and related breeds.

  14. Impact of carbohydrate supplementation during endurance training on glycogen storage and performance

    DEFF Research Database (Denmark)

    Nybo, Lars; Pedersen, K.; Christensen, B.

    2009-01-01

    Abstract Aim: Glucose ingestion may improve exercise endurance, but it apparently also influences the transcription rate of several metabolic genes and it alters muscle metabolism during an acute exercise bout. Therefore, we investigated how chronic training responses are affected by glucose...... improvements in maximal oxygen uptake and peak power output during incremental cycling (both parameters elevated by 17% on average) and both groups lost approximately 3 kg of fat mass during the 8 weeks of training. An equal reduction in respiratory exchange ratio (0.02 units) during submaximal exercise.......05), while resting muscle glycogen increased (P influences various muscular training adaptations, but improvements...

  15. Preactivated thiolated glycogen as mucoadhesive polymer for drug delivery.

    Science.gov (United States)

    Perrone, Mara; Lopalco, Antonio; Lopedota, Angela; Cutrignelli, Annalisa; Laquintana, Valentino; Douglas, Justin; Franco, Massimo; Liberati, Elisa; Russo, Vincenzo; Tongiani, Serena; Denora, Nunzio; Bernkop-Schnürch, Andreas

    2017-10-01

    The purpose of this study was to synthesize and characterize a novel thiolated glycogen, so-named S-preactivated thiolated glycogen, as a mucosal drug delivery systems and the assessment of its mucoadhesive properties. In this regard, glycogen-cysteine and glycogen-cysteine-2-mercaptonicotinic acid conjugates were synthesized. Glycogen was activated by an oxidative ring opening with sodium periodate resulting in reactive aldehyde groups to which cysteine was bound via reductive amination. The obtained thiolated polymer displayed 2203.09±200μmol thiol groups per gram polymer. In a second step, the thiol moieties of thiolated glycogen were protected by disulfide bond formation with the thiolated aromatic residue 2-mercaptonicotinic acid (2MNA). In vitro screening of mucoadhesive properties was performed on porcine intestinal mucosa using different methods. In particular, in terms of rheology investigations of mucus/polymer mixtures, the S-preactivated thiolated glycogen showed a 4.7-fold increase in dynamic viscosity over a time period of 5h, in comparison to mucus/Simulated Intestinal Fluid control. The S-preactivated polymer remained attached on freshly excised porcine mucosa for 45h. Analogous results were obtained with tensile studies demonstrating a 2.7-fold increase in maximum detachment force and 3.1- fold increase in total work of adhesion for the S-preactivated polymer compared to unmodified glycogen. Moreover, water-uptake studies showed an over 4h continuing weight gain for the S-preactivated polymer, whereas disintegration took place for the unmodified polymer within the first hour. Furthermore, even in the highest tested concentration of 2mg/ml the new conjugates did not show any cytotoxicity on Caco-2 cell monolayer using an MTT assay. According to these results, S-preactivated glycogen represents a promising type of mucoadhesive polymers useful for the development of various mucosal drug delivery systems. Copyright © 2017 Elsevier B.V. All rights

  16. Glycogen synthesis is induced in hypoxia by the hypoxia-inducible factor and promotes cancer cell survival

    Directory of Open Access Journals (Sweden)

    Joffrey ePelletier

    2012-02-01

    Full Text Available The hypoxia-inducible factor 1 (HIF-1, in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1, were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these hypoxia-preconditioned cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO2 acts as an alarm that prepares the cells to face subsequent nutrient depletion and to survive.

  17. Glycogen Synthesis is Induced in Hypoxia by the Hypoxia-Inducible Factor and Promotes Cancer Cell Survival

    Energy Technology Data Exchange (ETDEWEB)

    Pelletier, Joffrey; Bellot, Grégory [Institute of Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, University of Nice-Sophia Antipolis, Nice (France); Gounon, Pierre; Lacas-Gervais, Sandra [Centre Commun de Microscopie Appliquée, University of Nice-Sophia Antipolis, Nice (France); Pouysségur, Jacques; Mazure, Nathalie M., E-mail: mazure@unice.fr [Institute of Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, University of Nice-Sophia Antipolis, Nice (France)

    2012-02-28

    The hypoxia-inducible factor 1 (HIF-1), in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1), were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these “hypoxia-preconditioned” cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO{sub 2} acts as an “alarm” that prepares the cells to face subsequent nutrient depletion and to survive.

  18. Glycogen Synthesis is Induced in Hypoxia by the Hypoxia-Inducible Factor and Promotes Cancer Cell Survival

    International Nuclear Information System (INIS)

    Pelletier, Joffrey; Bellot, Grégory; Gounon, Pierre; Lacas-Gervais, Sandra; Pouysségur, Jacques; Mazure, Nathalie M.

    2012-01-01

    The hypoxia-inducible factor 1 (HIF-1), in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1), were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these “hypoxia-preconditioned” cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO 2 acts as an “alarm” that prepares the cells to face subsequent nutrient depletion and to survive.

  19. Mechanisms limiting glycogen storage in muscle during prolonged insulin stimulation

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, S A; Hansen, B F

    1988-01-01

    increased muscle glycogen concentrations to maximal values 2, 3, and 3.5 times above normal fed levels in fast-twitch white, slow-twitch red, and fast-twitch red fibers, respectively. Glucose uptake decreased (mean +/- SE) from 34.9 +/- 1.2 mumol.g-1.h-1 at 0 h to 7.5 +/- 0.7 after 7 h of perfusion. During...... compared with initial values. Total muscle water concentration decreased during glycogen loading of the muscles. Mechanisms limiting glycogen storage under maximal insulin stimulation include impaired insulin-stimulated membrane transport of glucose as well as impaired intracellular glucose disposal....

  20. Rumen papillae keratinization, cell glycogen and chemical composition of the meat from young bulls fed different levels of concentrate and babassu mesocarp bran

    Directory of Open Access Journals (Sweden)

    Simone Santos Barros

    2015-06-01

    Full Text Available This study aimed to assess the rumen papillae keratinization, cellular levels of liver and muscle glycogen, and the chemical composition of meat from feedlot-finished Nellore young bulls fed with levels of concentrate and babassu mesocarp bran. Twenty-eight animals with initial age of 21 months and initial body weight of 356.7 ± 19 kg were randomized to the following treatments: two levels of concentrate in the diet (65% and 71%, with or without inclusion of 35% of babassu mesocarp bran. Fragments of liver, muscle and rumen were obtained after slaughter of the animals. Levels of concentrate and babassu mesocarp bran in the diet did not affect the quantities of liver and muscle glycogen, and did not induce hyperkeratinization of rumen papillae. The chemical composition of the meat was not affected by the studied factors. The inclusion of 35% babassu mesocarp bran in high concentrate diets does not induce hyperkeratinization of rumen papillae, and does not change the amount of muscle and liver glycogen or the chemical characteristics of meat of Nellore young bulls.

  1. Deleterious effects of neuronal accumulation of glycogen in flies and mice

    OpenAIRE

    Duran, Jordi; Tevy, María Florencia; Garcia-Rocha, Mar; Calbó, Joaquim; Milán, Marco; Guinovart, Joan J

    2012-01-01

    Under physiological conditions, most neurons keep glycogen synthase (GS) in an inactive form and do not show detectable levels of glycogen. Nevertheless, aberrant glycogen accumulation in neurons is a hallmark of patients suffering from Lafora disease or other polyglucosan disorders. Although these diseases are associated with mutations in genes involved in glycogen metabolism, the role of glycogen accumulation remains elusive. Here, we generated mouse and fly models expressing an active form...

  2. In vivo effects of diabetes, insulin and oleanolic acid on enzymes of glycogen metabolism in the skin of streptozotocin-induced diabetic male Sprague-Dawley rats.

    Science.gov (United States)

    Mukundwa, Andrew; Langa, Silvana O; Mukaratirwa, Samson; Masola, Bubuya

    2016-03-04

    The skin is the largest organ in the body and diabetes induces pathologic changes on the skin that affect glucose homeostasis. Changes in skin glycogen and glucose levels can mirror serum glucose levels and thus the skin might contribute to whole body glucose metabolism. This study investigated the in vivo effects of diabetes, insulin and oleanolic acid (OA) on enzymes of glycogen metabolism in skin of type 1 diabetic rats. Diabetic and non-diabetic adult male Sprague-Dawley rats were treated with a single daily dose of insulin (4 IU/kg body weight), OA (80 mg/kg body weight) and a combination of OA + insulin for 14 days. Glycogen phosphorylase (GP) expression; and GP, glycogen synthase (GS) and hexokinase activities as well glycogen levels were evaluated. The results suggest that diabetes lowers hexokinase activity, GP activity and GP expression with no change in GS activity whilst the treatments increased GP expression and the activities of hexokinase, GP and GS except for the GS activity in OA treated rats. Glycogen levels were increased slightly by diabetes as well as OA treatment. In conclusion diabetes, OA and insulin can lead to changes in GS and GP activities in skin without significantly altering the glycogen content. We suggest that the skin may contribute to whole body glucose homeostasis particularly in disease states. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Effects of phthalic acid esters on the liver and thyroid

    International Nuclear Information System (INIS)

    Hinton, R.H.; Mitchell, F.E.; Mann, A.; Chescoe, D.; Price, S.C.; Nunn, A.; Grasso, P.; Bridges, J.W.

    1986-01-01

    The effects, over periods from 3 days to 9 months of administration, of diets containing di-2-ethylhexyl phthalate are very similar to those observed in rats administered diets containing hypolipidemic drugs such as clofibrate. Changes occur in a characteristic order commencing with alterations in the distribution of lipid within the liver, quickly followed by proliferation of hepatic peroxisomes and induction of the specialized P-450 isoenzyme(s) catalyzing omega oxidation of fatty acids. There follows a phase of mild liver damage indicated by changes in incorporation of 3 H-thymidine into DNA, by induction of glucose-6-phosphatase activity and a loss of glycogen, eventually leading to the formation of enlarged lysosomes through autophagy and the accumulation of lipofuscin. Associated changes are found in the kidney and thyroid. The renal changes are limited to the proximal convoluted tubules and are generally similar to changes found in the liver. The effects on the thyroid are more marked. Although the levels of thyroxine in plasma fall to about half normal values, serum triiodothyronine remains close to normal values while the appearance of the thyroid varies, very marked hyperactivity being noted 7 days after commencement of treatment, this is less marked at 14 days, but even after 9 months treatment there is clear cut evidence for hyperactivity with colloid changes which indicate this has persisted for some time. The short-term in vivo hepatic effects of the three phthalate esters can be reproduced in hepatocytes in tissue culture. All three phthalate esters, as well as clofibrate, have early marked effects on the metabolism of fatty acids in isolated hepatocytes. A hypothesis is presented to explain the progress from these initial metabolic effects to the final formation of liver tumors

  4. Genetics Home Reference: glycogen storage disease type IX

    Science.gov (United States)

    ... or elevated levels of ketones in the blood (ketosis). Ketones are molecules produced during the breakdown of ... down glycogen for glucose contributes to hypoglycemia and ketosis. Reduced energy production in muscle cells leads to ...

  5. Human skeletal muscle glycogen utilization in exhaustive exercise

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Holmberg, Hans-Christer; Schrøder, Henrik Daa

    2011-01-01

    Although glycogen is known to be heterogeneously distributed within skeletal muscle cells, there is presently little information available about the role of fibre types, utilization and resynthesis during and after exercise with respect to glycogen localization. Here, we tested the hypothesis...... to be influenced by fibre type prior to exercise, as well as carbohydrate availability during the subsequent period of recovery. These findings provide insight into the significance of fibre type-specific compartmentalization of glycogen metabolism in skeletal muscle during exercise and subsequent recovery. ....... that utilization of glycogen with different subcellular localizations during exhaustive arm and leg exercise differs and examined the influence of fibre type and carbohydrate availability on its subsequent resynthesis. When 10 elite endurance athletes (22 ± 1 years, VO2 max = 68 ± 5 ml kg-1 min-1, mean ± SD...

  6. Genetics Home Reference: glycogen storage disease type V

    Science.gov (United States)

    ... with GSDV experience mild symptoms such as poor stamina; others do not experience any symptoms. Related Information ... myophosphorylase. This enzyme is found only in muscle cells, where it breaks down glycogen into a simpler ...

  7. Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle

    DEFF Research Database (Denmark)

    Højlund, Kurt; Beck-Nielsen, Henning

    2006-01-01

    Insulin resistance in skeletal muscle is a major hallmark of type 2 diabetes and an early detectable abnormality in the development of this disease. The cellular mechanisms of insulin resistance include impaired insulin-mediated muscle glycogen synthesis and increased intramyocellular lipid content......, whereas impaired insulin activation of muscle glycogen synthase represents a consistent, molecular defect found in both type 2 diabetic and high-risk individuals. Despite several studies of the insulin signaling pathway believed to mediate dephosphorylation and hence activation of glycogen synthase......, the molecular mechanisms responsible for this defect remain unknown. Recently, the use of phospho-specific antibodies in human diabetic muscle has revealed hyperphosphorylation of glycogen synthase at sites not regulated by the classical insulin signaling pathway. In addition, novel approaches such as gene...

  8. Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas

    2011-01-01

    The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... and insulin signalling transduction remain elusive. We believe that one of the reasons is that the role of intracellular compartmentalization as a regulator of metabolic pathways and signalling transduction has been rather ignored. This paper briefly reviews the literature to discuss the role of intracellular...... compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss...

  9. The effect of glycogen phosphorolysis on basal glutaminergic transmission.

    Science.gov (United States)

    Mozrzymas, Jerzy; Szczęsny, Tomasz; Rakus, Darek

    2011-01-14

    Astrocytic glycogen metabolism sustains neuronal activity but its impact on basal glutamatergic synaptic transmission is not clear. To address this issue, we have compared the effect of glycogen breakdown inhibition on miniature excitatory postsynaptic currents (mEPSCs) in rat hippocampal pure neuronal culture (PNC) and in astrocyte-neuronal co-cultures (ANCC). Amplitudes of mEPSC in ANCC were nearly twice as large as in PNC with no difference in current kinetics. Inhibition of glycogen phosphorylase reduced mEPSC amplitude by roughly 40% in ANCC being ineffective in PNC. Altogether, these data indicate that astrocyte-neuronal interaction enhances basal mEPSCs in ANCC mainly due to astrocytic glycogen metabolism. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Lipopolysaccharide derived from the rumen down-regulates stearoyl-CoA desaturase 1 expression and alters fatty acid composition in the liver of dairy cows fed a high-concentrate diet.

    Science.gov (United States)

    Xu, Tianle; Tao, Hui; Chang, Guangjun; Zhang, Kai; Xu, Lei; Shen, Xiangzhen

    2015-03-07

    Dairy cows are often fed a high-concentrate diet to meet lactating demands, yet long-term concentrate feeding induces subacute ruminal acidosis (SARA) and leads to a decrease in milk fat. Stearoyl-CoA desaturase1 (SCD1) participates in fatty acid biosynthesis in the liver of lactating ruminants. Here, we conducted this study to investigate the impact of lipopolysaccharide derived from the rumen on SCD1 expression and on fatty acid composition in the liver of dairy cows fed a high-concentrate diet. Eight multiparous mid-lactating Holstein cows (455 ± 28 kg) were randomly assigned into two groups in the experiment and were fed a low-concentrate diet (LC) or high-concentrate diet (HC) for 18 weeks. The results showed that the total volatile fatty acids and lactic acid accumulated in the rumen, leading to a decreased rumen pH and elevated lipopolysaccharides (LPSs) in the HC group. The long chain fatty acid profile in the rumen and hepatic vein was remarkably altered in the animals fed the HC diet. The triglyceride (TG), non-esterified fatty acid (NEFA) and total cholesterol (TCH) content in the plasma was significantly decreased, whereas plasma glucose and insulin levels were increased. The expression of SCD1 in the liver was significantly down-regulated in the HC group. In regards to transcriptional regulators, the expression of sterol regulatory element binding transcription factors (SREBF1c, SREBF2) and SREBP cleavage activating protein (SCAP) was down-regulated, while peroxisome proliferator-activated receptor α (PPARα) was up-regulated. These data indicate that lipopolysaccharide derived from the rumen down-regulates stearoyl-CoA desaturase 1 expression and alters fatty acid composition in the liver of dairy cows fed a high-concentrate diet.

  11. Glycogen-bound polyphosphate kinase from the archaebacterium Sulfolobus acidocaldarius.

    OpenAIRE

    Skórko, R; Osipiuk, J; Stetter, K O

    1989-01-01

    Glycogen-bound polyphosphate kinase has been isolated from a crude extract of Sulfolobus acidocaldarius by isopycnic centrifugation in CsCl. Divalent cations (Mn2+ greater than Mg2+) stimulated the reaction. The enzyme does not require the presence of histones for its activity; it is inhibited strongly by phosphate and slightly by fluoride. The protein from the glycogen complex migrated in a sodium dodecyl sulfate-polyacrylamide gel as a 57-kilodalton protein band; after isoelectric focusing ...

  12. Inadequate Brain Glycogen or Sleep Increases Spreading Depression Susceptibility

    KAUST Repository

    Kilic, Kivilcim; Karatas, Hulya; Donmez-Demir, Buket; Eren-Kocak, Emine; Gursoy-Ozdemir, Yasemin; Can, Alp; Petit, Jean-Marie; Magistretti, Pierre J.; Dalkara, Turgay

    2017-01-01

    Glycogen in astrocyte endfeet contributes to maintenance of low extracellular glutamate and K+ concentrations around synapses. Sleep deprivation (SD), a common migraine trigger induces transcriptional changes in astrocytes reducing glycogen breakdown. We hypothesize that when glycogen utilization cannot match synaptic energy demand, extracellular K+ can rise to levels that activate neuronal pannexin-1 channels and downstream inflammatory pathway, which might be one of the mechanisms initiating migraine headaches.We suppressed glycogen breakdown by inhibiting glycogen phosphorylation with 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) and by SD.DAB caused neuronal pannexin-1 large-pore opening and activation of the downstream inflammatory pathway as shown by procaspase-1 cleavage and HMGB1 release from neurons. Six-hour SD induced pannexin-1 mRNA. DAB and SD also lowered the cortical spreading depression (CSD) induction threshold, which was reversed by glucose or lactate supplement, suggesting that glycogen-derived energy substrates are needed to prevent CSD generation. Supporting this, knocking-down neuronal lactate transporter, MCT2 with an anti-sense oligonucleotide or inhibiting glucose transport from vessels to astrocytes with intracerebroventricularly given phloretin reduced the CSD threshold. In vivo recordings with a K+ -sensitive/selective fluoroprobe, APG-4 disclosed that DAB treatment or SD caused significant rise in extracellular K+ during whisker-stimulation, illustrating the critical role of glycogen in extracellular K+ clearance.Synaptic metabolic stress caused by insufficient glycogen-derived energy substrate supply can activate neuronal pannexin-1 channels as well as lowering the CSD threshold. Therefore, conditions that limit energy supply to synapse (e.g. SD) may predispose to migraine attacks as suggested by genetic studies associating glucose or lactate transporter deficiency with migraine. This article is protected by copyright. All rights reserved.

  13. Inadequate Brain Glycogen or Sleep Increases Spreading Depression Susceptibility

    KAUST Repository

    Kilic, Kivilcim

    2017-12-16

    Glycogen in astrocyte endfeet contributes to maintenance of low extracellular glutamate and K+ concentrations around synapses. Sleep deprivation (SD), a common migraine trigger induces transcriptional changes in astrocytes reducing glycogen breakdown. We hypothesize that when glycogen utilization cannot match synaptic energy demand, extracellular K+ can rise to levels that activate neuronal pannexin-1 channels and downstream inflammatory pathway, which might be one of the mechanisms initiating migraine headaches.We suppressed glycogen breakdown by inhibiting glycogen phosphorylation with 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) and by SD.DAB caused neuronal pannexin-1 large-pore opening and activation of the downstream inflammatory pathway as shown by procaspase-1 cleavage and HMGB1 release from neurons. Six-hour SD induced pannexin-1 mRNA. DAB and SD also lowered the cortical spreading depression (CSD) induction threshold, which was reversed by glucose or lactate supplement, suggesting that glycogen-derived energy substrates are needed to prevent CSD generation. Supporting this, knocking-down neuronal lactate transporter, MCT2 with an anti-sense oligonucleotide or inhibiting glucose transport from vessels to astrocytes with intracerebroventricularly given phloretin reduced the CSD threshold. In vivo recordings with a K+ -sensitive/selective fluoroprobe, APG-4 disclosed that DAB treatment or SD caused significant rise in extracellular K+ during whisker-stimulation, illustrating the critical role of glycogen in extracellular K+ clearance.Synaptic metabolic stress caused by insufficient glycogen-derived energy substrate supply can activate neuronal pannexin-1 channels as well as lowering the CSD threshold. Therefore, conditions that limit energy supply to synapse (e.g. SD) may predispose to migraine attacks as suggested by genetic studies associating glucose or lactate transporter deficiency with migraine. This article is protected by copyright. All rights reserved.

  14. In vitro variation of glycogen content in three sheep nematodes.

    Science.gov (United States)

    Premvati, G; Chopra, A K

    1979-06-01

    In vitro variation of glycogen content under aerobic conditions was measured on fresh weight basis in 3 sheep nematodes inhabiting different niches; Haemonchus contortus, Oesophagostomum columbianum and Trichuris ovis. The parasites were saparated into species and then sexes and starved for varying periods of time up to 24 h in glucose-free physiological saline. The differences between females and males and among the species with respect to glycogen content and its rate of change with time are discussed.

  15. Humanizing π-class glutathione S-transferase regulation in a mouse model alters liver toxicity in response to acetaminophen overdose.

    Directory of Open Access Journals (Sweden)

    Matthew P Vaughn

    Full Text Available Glutathione S-transferases (GSTs metabolize drugs and xenobiotics. Yet despite high protein sequence homology, expression of π-class GSTs, the most abundant of the enzymes, varies significantly between species. In mouse liver, hepatocytes exhibit high mGstp expression, while in human liver, hepatocytes contain little or no hGSTP1 mRNA or hGSTP1 protein. π-class GSTs are known to be critical determinants of liver responses to drugs and toxins: when treated with high doses of acetaminophen, mGstp1/2+/+ mice suffer marked liver damage, while mGstp1/2-/- mice escape liver injury.To more faithfully model the contribution of π-class GSTs to human liver toxicology, we introduced hGSTP1, with its exons, introns, and flanking sequences, into the germline of mice carrying disrupted mGstp genes. In the resultant hGSTP1+mGstp1/2-/- strain, π-class GSTs were regulated differently than in wild-type mice. In the liver, enzyme expression was restricted to bile duct cells, Kupffer cells, macrophages, and endothelial cells, reminiscent of human liver, while in the prostate, enzyme production was limited to basal epithelial cells, reminiscent of human prostate. The human patterns of hGSTP1 transgene regulation were accompanied by human patterns of DNA methylation, with bisulfite genomic sequencing revealing establishment of an unmethylated CpG island sequence encompassing the gene promoter. Unlike wild-type or mGstp1/2-/- mice, when hGSTP1+mGstp1/2-/- mice were overdosed with acetaminophen, liver tissues showed limited centrilobular necrosis, suggesting that π-class GSTs may be critical determinants of toxin-induced hepatocyte injury even when not expressed by hepatocytes.By recapitulating human π-class GST expression, hGSTP1+mGstp1/2-/- mice may better model human drug and xenobiotic toxicology.

  16. Dietary saturated and monounsaturated fats protect against acute acetaminophen hepatotoxicity by altering fatty acid composition of liver microsomal membrane in rats

    Directory of Open Access Journals (Sweden)

    Shim Eugene

    2011-10-01

    Full Text Available Abstract Background Dietary polyunsaturated fats increase liver injury in response to ethanol feeding. We evaluated the effect of dietary corn oil (CO, olive oil (OO, and beef tallow (BT on fatty acid composition of liver microsomal membrane and acute acetaminophen hepatotoxicity. Methods Male Sprague-Dawley rats were fed 15% (wt/wt CO, OO or BT for 6 weeks. After treatment with acetaminophen (600 mg/kg, samples of plasma and liver were taken for analyses of the fatty acid composition and toxicity. Results Treatment with acetaminophen significantly elevated levels of plasma GOT and GPT as well as hepatic TBARS but reduced hepatic GSH levels in CO compared to OO and BT groups. Acetaminophen significantly induced protein expression of cytochrome P450 2E1 in the CO group. In comparison with the CO diet, lower levels of linoleic acid, higher levels of oleic acids and therefore much lower ratios of linoleic to oleic acid were detected in rats fed OO and BT diets. Conclusions Dietary OO and BT produces similar liver microsomal fatty acid composition and may account for less severe liver injury after acetaminophen treatment compared to animals fed diets with CO rich in linoleic acid. These findings imply that types of dietary fat may be important in the nutritional management of drug-induced hepatotoxicity.

  17. The protective of antox (vitamins A, C, E and selenium on some biochemical and histological alterations in liver of gamma irradiated rats

    International Nuclear Information System (INIS)

    Mohamed, S.K.; Abu Nour, S.M.; Abdel-AzEEm, M.G.

    2004-01-01

    present study has been performed to investigate the possible protective role of antox (vitamins A, C, E and selenium) in minimizing the radiation induced changes in certain biochemical and histological parameters as well as ultrastructural study of the liver of rats exposed to single dose of whole body gamma irradiation at 6 Gy. Antox was orally administered (0.4 gm/kg body wt) daily for 10 days before irradiation. Blood samples were collected from animals at time intervals (1 and 7 days) after irradiation. Serum AST, ALT, alkaline phosphatase, total protein, albumin, globulin and A/G ratio were assayed. In addition, histological and ultrastructural changes in the liver tissue were examined. The results demonstrated that whole body gamma irradiation induced significant elevations in the levels of all the measured parameters except total protein and globulin which showed significant depletion. Exposure to radiation induced also distortion in the architecture pattern of the liver. Concerning the ultrastructure studies, liver of gamma irradiated rats showed marked degenerative changes in the hepatocytes, dense mitochondria without cristae and fragmented rough endoplasmic reticulum. Also, the number of free ribosomes was found to be highly concentrated in damaged hepatocytes as compared to control liver. Oral administration of antox for 10 consecutive days before gamma irradiation (single dose of 6 Gy) exerted noticeable amelioration in the intensity of all the changes induced by radiation exposure

  18. Liver cancer oncogenomics

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Andersen, Jesper B

    2015-01-01

    Primary liver cancers are among the most rapidly evolving malignant tumors worldwide. An underlying chronic inflammatory liver disease, which precedes liver cancer development for several decades and frequently creates a pro-oncogenic microenvironment, impairs progress in therapeutic approaches....... Molecular heterogeneity of liver cancer is potentiated by a crosstalk between epithelial tumor and stromal cells that complicate translational efforts to unravel molecular mechanisms of hepatocarcinogenesis with a drugable intend. Next-generation sequencing has greatly advanced our understanding of cancer...... development. With regards to liver cancer, the unprecedented coverage of next-generation sequencing has created a detailed map of genetic alterations and identified key somatic changes such as CTNNB1 and TP53 as well as several previously unrecognized recurrent disease-causing alterations that could...

  19. Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling

    Science.gov (United States)

    Yang, Wei; Burkhardt, Britta; Fischer, Luise; Beirow, Maja; Bork, Nadja; Wönne, Eva C.; Wagner, Cornelia; Husen, Bettina; Zeilinger, Katrin; Liu, Liegang; Nussler, Andreas K.

    2015-01-01

    Aging is characterized by a progressive decrease of cellular functions, because cells gradually lose their capacity to respond to injury. Increased oxidative stress is considered to be one of the major contributors to age-related changes in all organs including the liver. Our study has focused on elucidating whether important antioxidative enzymes, the mTOR pathway, and MAPKs exhibit age-dependent changes in the liver of rats during aging. We found an age-dependent increase of GSH in the cytosol and mitochondria. The aged liver showed an increased SOD enzyme activity, while the CAT enzyme activity decreased. HO-1 and NOS-2 gene expression was lower in adult rats, but up-regulated in aged rats. Western blot analysis revealed that SOD1, SOD2, GPx, GR, γ-GCL, and GSS were age-dependent up-regulated, while CAT remained constant. We also demonstrated that the phosphorylation of Akt, JNK, p38, and TSC2Ser1254 decreased while ERK1/2 and TSC2Thr1462 increased age-dependently. Furthermore, our data show that the mTOR pathway seems to be activated in livers of aged rats, and hence stimulating cell proliferation/regeneration, as confirmed by an age-dependent increase of PCNA and p-eIF4ESer209 protein expression. Our data may help to explain the fact that liver cells only proliferate in cases of necessity, like injury and damage. In summary, we have demonstrated that, age-dependent changes of the antioxidant system and stress-related signaling pathways occur in the livers of rats, which may help to better understand organ aging. PMID:27004051

  20. Ultrastructural and cytochemical study of membrane alterations in x-irradiated liver tissue from normal and vitamin E-deficient ducklings

    International Nuclear Information System (INIS)

    Huijbers, W.A.R.; Oosterbaan, J.A.; Meskendorp-Haarsma, T.J.; Hardonk, M.J.; Molenaar, I.

    1979-01-01

    An investigation into the differential susceptibility of liver cellular membranes to peroxidative processes has been performed, using x irradiation on the liver surface, resulting in a a 3-mm penetrating gradient of membrane damage. Ultrastructural, cytochemical, and histochemical findings in this area point to a differential sensitivity of cellular membranes to x irradiation. The plasma membrane and the lysosomal membrane, containing much lipid and cholesterol and little membrane and the lysosomal membrane, containing much lipid and cholesterol and little vitamin E, are highly susceptible to x irradiation. Less sensitive are the membranes of mitochondria and endoplasmic reticulum, containing relatively much vitamin E and proteins and a lower amount of lipids and cholesterol

  1. Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme.

    Science.gov (United States)

    Bertone, V; Tarantola, E; Ferrigno, A; Gringeri, E; Barni, S; Vairetti, M; Freitas, I

    2011-02-08

    Biliary complications often lead to acute and chronic liver injury after orthotopic liver transplantation (OLT). Bile composition and secretion depend on the integrated action of all the components of the biliary tree, starting from hepatocytes. Fatty livers are often discarded as grafts for OLT, since they are extremely vulnerable to conventional cold storage (CS). However, the insufficiency of donors has stimulated research to improve the usage of such marginal organs as well as grafts. Our group has recently developed a machine perfusion system at subnormothermic temperature (20°C; MP20) that allows a marked improvement in preservation of fatty and even of normal rat livers as compared with CS. We sought to evaluate the response of the biliary tree of fatty liver to MP20, and a suitable marker was essential to this purpose. Alkaline phosphatase (AlkP, EC 3.1.3.1), frequently used as marker of membrane transport in hepatocytes and bile ducts, was our first choice. Since no histochemical data were available on AlkP distribution and activity in fatty liver, we have first settled to investigate AlkP activity in the steatotic liver of fatty Zucker rats (fa/fa), using as controls lean Zucker (fa/+) and normal Wistar rats. The AlkP reaction in Wistar rats was in accordance with the existing data and, in particular, was present in bile canaliculi of hepatocytes in the periportal region and midzone, in the canals of Hering and in small bile ducts but not in large bile ducts. In lean ZR liver the AlkP reaction in Hering canals and small bile ducts was similar to Wistar rat liver but hepatocytes had lower canalicular activity and besides presented moderate basolateral reaction. The difference between lean Zucker and Wistar rats, both phenotypically normal animals, could be related to the fact that lean Zucker rats are genotypically heterozygous for a recessive mutated allele. In fatty liver, the activity in ductules and small bile ducts was unchanged, but most hepatocytes

  2. Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme

    Directory of Open Access Journals (Sweden)

    V. Bertone

    2011-02-01

    Full Text Available Biliary complications often lead to acute and chronic liver injury after orthotopic liver transplantation (OLT. Bile composition and secretion depend on the integrated action of all the components of the biliary tree, starting from hepatocytes. Fatty livers are often discarded as grafts for OLT, since they are extremely vulnerable to conventional cold storage (CS. However, the insufficiency of donors has stimulated research to improve the usage of such marginal organs as well as grafts. Our group has recently developed a machine perfusion system at subnormothermic temperature (20°C; MP20 that allows a marked improvement in preservation of fatty and even of normal rat livers as compared with CS. We sought to evaluate the response of the biliary tree of fatty liver to MP20, and a suitable marker was essential to this purpose. Alkaline phosphatase (AlkP, EC 3.1.3.1, frequently used as marker of membrane transport in hepatocytes and bile ducts, was our first choice. Since no histochemical data were available on AlkP distribution and activity in fatty liver, we have first settled to investigate AlkP activity in the steatotic liver of fatty Zucker rats (fa/fa, using as controls lean Zucker (fa/+ and normal Wistar rats. The AlkP reaction in Wistar rats was in accordance with the existing data and, in particular, was present in bile canaliculi of hepatocytes in the periportal region and midzone, in the canals of Hering and in small bile ducts but not in large bile ducts. In lean ZR liver the AlkP reaction in Hering canals and small bile ducts was similar to Wistar rat liver but hepatocytes had lower canalicular activity and besides presented moderate basolateral reaction. The difference between lean Zucker and Wistar rats, both phenotypically normal animals, could be related to the fact that lean Zucker rats are genotypically heterozygous for a recessive mutated allele. In fatty liver, the activity in ductules and small bile ducts was unchanged, but

  3. Homogenization versus homogenization-free method to measure muscle glycogen fractions.

    Science.gov (United States)

    Mojibi, N; Rasouli, M

    2016-12-01

    The glycogen is extracted from animal tissues with or without homogenization using cold perchloric acid. Three methods were compared for determination of glycogen in rat muscle at different physiological states. Two groups of five rats were kept at rest or 45 minutes muscular activity. The glycogen fractions were extracted and measured by using three methods. The data of homogenization method shows that total glycogen decreased following 45 min physical activity and the change occurred entirely in acid soluble glycogen (ASG), while AIG did not change significantly. Similar results were obtained by using "total-glycogen-fractionation methods". The findings of "homogenization-free method" indicate that the acid insoluble fraction (AIG) was the main portion of muscle glycogen and the majority of changes occurred in AIG fraction. The results of "homogenization method" are identical with "total glycogen fractionation", but differ with "homogenization-free" protocol. The ASG fraction is the major portion of muscle glycogen and is more metabolically active form.

  4. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia

    Science.gov (United States)

    Saez, Isabel; Duran, Jordi; Sinadinos, Christopher; Beltran, Antoni; Yanes, Oscar; Tevy, María F; Martínez-Pons, Carlos; Milán, Marco; Guinovart, Joan J

    2014-01-01

    Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that—against general belief—neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress. PMID:24569689

  5. Glucose uptake and transport in contracting, perfused rat muscle with different pre-contraction glycogen concentrations

    DEFF Research Database (Denmark)

    Hespel, P; Richter, Erik

    1990-01-01

    1. Glucose uptake and transport, muscle glycogen, free glucose and glucose-6-phosphate concentrations were studied in perfused resting and contracting rat skeletal muscle with different pre-contraction glycogen concentrations. Rats were pre-conditioned by a combination of swimming exercise and diet......, resulting in either low (glycogen-depleted rats), normal (control rats) or high (supercompensated rats) muscle glycogen concentrations at the time their hindlimbs were perfused. 2. Compared with control rats, pre-contraction muscle glycogen concentration was approximately 40% lower in glycogen-depleted rats......, whereas it was 40% higher in supercompensated rats. Muscle glycogen break-down correlated positively (r = 0.76; P less than 0.001) with pre-contraction muscle glycogen concentration. 3. Glucose uptake during contractions was approximately 50% higher in glycogen-depleted hindquarters than in control...

  6. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia.

    Science.gov (United States)

    Saez, Isabel; Duran, Jordi; Sinadinos, Christopher; Beltran, Antoni; Yanes, Oscar; Tevy, María F; Martínez-Pons, Carlos; Milán, Marco; Guinovart, Joan J

    2014-06-01

    Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that-against general belief-neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress.

  7. Chronic intermittent hypoxia predisposes to liver injury.

    Science.gov (United States)

    Savransky, Vladimir; Nanayakkara, Ashika; Vivero, Angelica; Li, Jianguo; Bevans, Shannon; Smith, Philip L; Torbenson, Michael S; Polotsky, Vsevolod Y

    2007-04-01

    Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH). OSA is associated with nonalcoholic steatohepatitis (NASH) in obese subjects. The aim of this study was to investigate the effects of CIH on the liver in the absence of obesity. Lean C57BL/6J mice (n = 15) on a regular chow diet were exposed to CIH for 12 weeks and compared with pair-fed mice exposed to intermittent air (IA, n = 15). CIH caused liver injury with an increase in serum ALT (224 +/- 39 U/l versus 118 +/- 22 U/l in the IA group, P fasting serum insulin levels, and mild elevation of fasting serum total cholesterol and triglycerides (TG). Liver TG content was unchanged, whereas cholesterol content was decreased. Histology showed swelling of hepatocytes, no evidence of hepatic steatosis, and marked accumulation of glycogen in hepatocytes. CIH led to lipid peroxidation of liver tissue with a malondialdehyde (MDA)/free fatty acids (FFA) ratio of 0.54 +/- 0.07 mmol/mol versus 0.30 +/- 0.01 mmol/mol in control animals (P obesity, CIH leads to mild liver injury via oxidative stress and excessive glycogen accumulation in hepatocytes and sensitizes the liver to a second insult, whereas NASH does not develop.

  8. Short and Long Term Effects of High-Intensity Interval Training on Hormones, Metabolites, Antioxidant System, Glycogen Concentration, and Aerobic Performance Adaptations in Rats

    OpenAIRE

    de Araujo, Gustavo G.; Papoti, Marcelo; dos Reis, Ivan Gustavo Masselli; de Mello, Maria A. R.; Gobatto, Claudio A.

    2016-01-01

    The purpose of the study was to investigate the effects of short and long term High-Intensity Interval Training (HIIT) on anaerobic and aerobic performance, creatinine, uric acid, urea, creatine kinase, lactate dehydrogenase, catalase, superoxide dismutase, testosterone, corticosterone, and glycogen concentration (liver, soleus, and gastrocnemius). The Wistar rats were separated in two groups: HIIT and sedentary/control (CT). The lactate minimum (LM) was used to evaluate the aerobic and anaer...

  9. Long-term study of liver damage following subcutaneous injection of airborne particle extracts and polycyclic aromatic hydrocarbon fractions

    Energy Technology Data Exchange (ETDEWEB)

    Meiss, R.; Heinrich, U.; Offermann, M.; Themann, H.

    1982-02-01

    Female NMRI mice aged 9-12 weeks were each given a single subcutaneous injection of 0.5 ml of a suspension containing either the total extracts or the polycyclic aromatic hydrocarbon (PAH) fraction of airborne particles. Both the total extracts and PAH fractions contain 3 microgram benzopyrene. After about 15 months the livers were removed from the animals, which had by that time developed tumors at the injection site, and were subjected to electron-microscopical study. The essential alterations were observed in the nucleoli and the cell nuclei, which had greatly proliferated and exhibited irregular nuclear membranes. Advanced fibrosis was observed in central liver specimens of all groups. Marked alterations were also observed in the mitochondria and the mitochondrial cristae as well as in the bile canaliculi, Intracytoplasmic glycogen usually occurred densely clustered along the periphery of the cell. It may be concluded from the observations that both the total extract of atmospheric suspended particulate matter and the PAH fraction cause hematogenic damage to the liver following subcutaneous injection, a finding which cannot be interpreted as metastatic carcinoma.

  10. Long-term study of liver damage following subcutaneous injection of airborne particle extracts and polycyclic aromatic hydrocarbon fractions

    Energy Technology Data Exchange (ETDEWEB)

    Meiss, R.; Heinrich, U.; Offermann, M.; Themann, H.

    1982-02-01

    Female NMRI mice aged 9-12 weeks were each given a single subcutaneous injection of 0.5 ml of a suspension containing either the total extracts or the polycyclic aromatic hydrocarbon (PAH) fraction of airborne particles. Both the total extracts and PAH fractions contain 3 ..mu..g benzopyrene. After about 15 months the livers were removed from the animals, which had by that time developed tumors at the injection site, and were subjected to electron-microscopical study. The essential alterations were observed in the nucleoli and the cell nuclei, which had greatly proliferated and exhibited irregular nuclear membranes. Advanced fibrosis was observed in central liver specimens of all groups. Marked alterations were also observed in the mitochondria and the mitochondrial cristae as well as in the bile canaliculi. Intracytoplasmic glycogen usually occurred densely clustered along the periphery of the cell. It may be concluded from the observations that both the total extract of atmospheric suspended particulate matter and the PAH fraction cause hematogenic damage to the liver following subcutaneous injection, a finding which cannot be interpreted as metastatic carcinoma.

  11. Obese mice fed a diet supplemented with enzyme-treated wheat bran display marked shifts in the liver metabolome concurrent with altered gut bacteria

    Science.gov (United States)

    Enzyme-treated wheat bran (ETWB) is a fermentable dietary fiber previously shown to decrease liver triglycerides and modify the gut microbiome in mice. It is not clear which mechanisms explain how ETWB feeding impacts hepatic metabolism, but factors (i.e., metabolites) associated with specific micro...

  12. Soapwort extract supplementation alters antioxidant status of serum, liver and heart tissues in growing Japanese quails reared under chronic intermittent cold stress

    Directory of Open Access Journals (Sweden)

    Bestami Dalkilic

    2017-01-01

    Full Text Available Antioxidant effect of dietary soapwort extract supplementation was studied in growing Japanese quails suffering from chronic intermittent cold stress. For this purpose, a total of ninety 15-d-old quails were divided into three groups with three replicates. Chronic intermittent cold stress was applied every night between 22.00 to 06.00 h; starting at 14 °C for the first week, and gradually weekly lowered to 8 °C. Three groups were fed with corn-soy based standard diets supplemented with 0, 50, and 100 ppm soapwort extract for four weeks. At the end of the study, three males and three females were slaughtered to determine total antioxidant and oxidant status of serum, malondialdehyde, glutathione, glutathione peroxidase activity, superoxide dismutase of liver and heart tissues. Although the dietary soapwort extract had no effect on serum total antioxidant capacity, it significantly lowered the total oxidant status of serum in cold stressed quails. Glutathione and superoxide dismutase enzyme activity of liver and heart tissues were similar among groups. While the dietary soapwort extract had no effect on glutathione peroxidase activity of the heart tissue, it significantly increased glutathione peroxidase activity in the liver tissue. In relation to the control group, malondialdehyde concentrations in the liver and heart tissues were significantly lower in soapwort extract groups. These data suggest that dietary soapwort extract could alleviate the detrimental effects of oxidative stress in growing Japanese quails exposed to cold stress.

  13. Estradiol stimulates glycogen synthesis whereas progesterone promotes glycogen catabolism in the uterus of the American mink (Neovison vison).

    Science.gov (United States)

    Bowman, Kole; Rose, Jack

    2017-01-01

    Glycogen synthesis by mink uterine glandular and luminal epithelia (GE and LE) is stimulated by estradiol (E 2 ) during estrus. Subsequently, the glycogen deposits are mobilized to near completion to meet the energy requirements of pre-embryonic development and implantation by as yet undetermined mechanisms. We hypothesized that progesterone (P 4 ) was responsible for catabolism of uterine glycogen reserves as one of its actions to ensure reproductive success. Mink were treated with E 2 , P 4 or vehicle (controls) for 3 days and uteri collected 24 h (E 2 , P 4 and vehicle) and 96 h (E 2 ) later. To evaluate E 2 priming, mink were treated with E 2 for 3 days, then P 4 for an additional 3 days (E 2 →P 4 ) and uteri collected 24 h later. Percent glycogen content of uterine epithelia was greater at E 2 + 96 h (GE = 5.71 ± 0.55; LE = 11.54 ± 2.32) than E 2 +24 h (GE = 3.63 ± 0.71; LE = 2.82 ± 1.03), and both were higher than controls (GE = 0.27 ± 0.15; LE = 0.54 ± 0.30; P glycogen content (GE = 0.61 ± 0.16; LE = 0.51 ± 0.13), to levels not different from controls, while concomitantly increasing catabolic enzyme (glycogen phosphorylase m and glucose-6-phosphatase) gene expression and amount of phospho-glycogen synthase protein (inactive) in uterine homogenates. Interestingly, E 2 →P 4 increased glycogen synthase 1 messenger RNA (mRNA) and hexokinase 1mRNA and protein. Our findings suggest to us that while E 2 promotes glycogen accumulation by the mink uterus during estrus and pregnancy, it is P 4 that induces uterine glycogen catabolism, releasing the glucose that is essential to support pre-embryonic survival and implantation. © 2016 Japanese Society of Animal Science.

  14. Histopathological alterations of white seabass, Lates calcarifer, in acute and subchronic cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Thophon, S.; Kruatrachue, M.; Upatham, E.S.; Pokethitiyook, P.; Sahaphong, S.; Jaritkhuan, S

    2003-03-01

    White seabass responded differently to cadmium at chronic and subchronic levels. - Histopathological alterations to white seabass, Lates calcarifer aged 3 months in acute and subchronic cadmium exposure were studied by light and scanning electron microscopy. The 96-h LC{sub 50} values of cadmium to L. calcarifer was found to be 20.12{+-}0.61 mg/l and the maximum acceptable toxicant concentration (MATC) was 7.79 mg/l. Fish were exposed to 10 and 0.8 mg/l of Cd (as CdCl{sub 2}H{sub 2}O) for 96 h and 90 days, respectively. The study showed that gill lamellae and kidney tubules were the primary target organs for the acute toxic effect of cadmium while in the subchronic exposure, the toxic effect to gills was less than that of kidney and liver. Gill alterations included edema of the epithelial cells with the breakdown of pillar cell system, aneurisms with some ruptures, hypertrophy and hyperplasia of epithelial and chloride cells. The liver showed blood congestion in sinusoids and hydropic swelling of hepatocytes, vacuolation and dark granule accumulation. Lipid droplets and glycogen content were observed in hepatocytes at the second and third month of subchronic exposure. The kidney showed hydropic swelling of tubular cell vacuolation and numerous dark granule accumulation in many tubules. Tubular degeneration and necrosis were seen in some areas.

  15. Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.

    LENUS (Irish Health Repository)

    Luo, Xiaoyan

    2011-11-01

    Glycogen storage disease type Ia (GSD-Ia) is caused by the deficiency of glucose-6-phosphatase (G6Pase). Long-term complications of GSD-Ia include life-threatening hypoglycemia and proteinuria progressing to renal failure. A double-stranded (ds) adeno-associated virus serotype 2 (AAV2) vector encoding human G6Pase was pseudotyped with four serotypes, AAV2, AAV7, AAV8, and AAV9, and we evaluated efficacy in 12-day-old G6pase (-\\/-) mice. Hypoglycemia during fasting (plasma glucose <100 mg\\/dl) was prevented for >6 months by the dsAAV2\\/7, dsAAV2\\/8, and dsAAV2\\/9 vectors. Prolonged fasting for 8 hours revealed normalization of blood glucose following dsAAV2\\/9 vector administration at the higher dose. The glycogen content of kidney was reduced by >65% with both the dsAAV2\\/7 and dsAAV2\\/9 vectors, and renal glycogen content was stably reduced between 7 and 12 months of age for the dsAAV2\\/9 vector-treated mice. Every vector-treated group had significantly reduced glycogen content in the liver, in comparison with untreated G6pase (-\\/-) mice. G6Pase was expressed in many renal epithelial cells of with the dsAAV2\\/9 vector for up to 12 months. Albuminuria and renal fibrosis were reduced by the dsAAV2\\/9 vector. Hepatorenal correction in G6pase (-\\/-) mice demonstrates the potential of AAV vectors for the correction of inherited diseases of metabolism.

  16. Obese Mice Fed a Diet Supplemented with Enzyme-Treated Wheat Bran Display Marked Shifts in the Liver Metabolome Concurrent with Altered Gut Bacteria

    DEFF Research Database (Denmark)

    Kieffer, Dorothy A.; Piccolo, Brian D.; Marco, Maria L.

    2016-01-01

    ) associated with specific microbes may be involved. Objective: The objective of this study was to characterize ETWB-driven shifts in the cecal microbiome and to identify correlates between microbial changes and diet-related differences in liver metabolism in diet-induced obese mice that typically display......Background: Enzyme-treated wheat bran (ETWB) contains a fermentable dietary fiber previously shown to decrease liver triglycerides (TGs) and modify the gut microbiome in mice. It is not clear which mechanisms explain how ETWB feeding affects hepatic metabolism, but factors (i.e., xenometabolites...... steatosis. Methods: Five-week-old male C57BL/6J mice fed a 45%-lard based fat diet supplemented with ETWB (20% wt:wt) or rapidly digestible starch (control) (n = 15/group) for 10 wk were characterized by using a multi-omics approach. Multivariate statistical analysis was used to identify variables that were...

  17. A functional glycogen biosynthesis pathway in Lactobacillus acidophilus: expression and analysis of the glg operon

    Science.gov (United States)

    Goh, Yong Jun; Klaenhammer, Todd R

    2013-01-01

    Glycogen metabolism contributes to energy storage and various physiological functions in some prokaryotes, including colonization persistence. A role for glycogen metabolism is proposed on the survival and fitness of Lactobacillus acidophilus, a probiotic microbe, in the human gastrointestinal environment. L. acidophilus NCFM possesses a glycogen metabolism (glg) operon consisting of glgBCDAP-amy-pgm genes. Expression of the glg operon and glycogen accumulation were carbon source- and growth phase-dependent, and were repressed by glucose. The highest intracellular glycogen content was observed in early log-phase cells grown on trehalose, which was followed by a drastic decrease of glycogen content prior to entering stationary phase. In raffinose-grown cells, however, glycogen accumulation gradually declined following early log phase and was maintained at stable levels throughout stationary phase. Raffinose also induced an overall higher temporal glg expression throughout growth compared with trehalose. Isogenic ΔglgA (glycogen synthase) and ΔglgB (glycogen-branching enzyme) mutants are glycogen-deficient and exhibited growth defects on raffinose. The latter observation suggests a reciprocal relationship between glycogen synthesis and raffinose metabolism. Deletion of glgB or glgP (glycogen phosphorylase) resulted in defective growth and increased bile sensitivity. The data indicate that glycogen metabolism is involved in growth maintenance, bile tolerance and complex carbohydrate utilization in L. acidophilus. PMID:23879596

  18. A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation.

    Science.gov (United States)

    Bjørndal, Bodil; Berge, Christ; Ramsvik, Marie Sannes; Svardal, Asbjørn; Bohov, Pavol; Skorve, Jon; Berge, Rolf K

    2013-10-07

    There is growing evidence that fish protein hydrolysate (FPH) diets affect mitochondrial fatty acid metabolism in animals. The aim of the study was to determine if FPH could influence fatty acid metabolism and inflammation in transgene mice expressing human tumor necrosis factor alpha (hTNFα). hTNFα mice (C57BL/6 hTNFα) were given a high-fat (23%, w/w) diet containing 20% casein (control group) or 15% FPH and 5% casein (FPH group) for two weeks. After an overnight fast, blood, adipose tissue, and liver samples were collected. Gene expression and enzyme activity was analysed in liver, fatty acid composition was analyzed in liver and ovarian white adipose tissue, and inflammatory parameters, carnitine, and acylcarnitines were analyzed in plasma. The n-3/n-6 fatty acid ratio was higher in mice fed the FPH diet than in mice fed the control diet in both adipose tissue and liver, and the FPH diet affected the gene expression of ∆6 and ∆9 desaturases. Mice fed this diet also demonstrated lower hepatic activity of fatty acid synthase. Concomitantly, a lower plasma INF-γ level was observed. Plasma carnitine and the carnitine precursor γ-butyrobetaine was higher in the FPH-group compared to control, as was plasma short-chained and medium-chained acylcarnitine esters. The higher level of plasma acetylcarnitine may reflect a stimulated mitochondrial and peroxisomal β-oxidation of fatty acids, as the hepatic activities of peroxisomal acyl-CoA oxidase 1 and mitochondrial carnitine palmitoyltransferase-II were higher in the FPH-fed mice. The FPH diet was shown to influence hepatic fatty acid metabolism and fatty acid composition. This indicates that effects on fatty acid metabolism are important for the bioactivity of protein hydrolysates of marine origin.

  19. Ageing sensitized by iPLA2β deficiency induces liver fibrosis and intestinal atrophy involving suppression of homeostatic genes and alteration of intestinal lipids and bile acids.

    Science.gov (United States)

    Jiao, Li; Gan-Schreier, Hongying; Zhu, Xingya; Wei, Wang; Tuma-Kellner, Sabine; Liebisch, Gerhard; Stremmel, Wolfgang; Chamulitrat, Walee

    2017-12-01

    Ageing is a major risk factor for various forms of liver and gastrointestinal (GI) disease and genetic background may contribute to the pathogenesis of these diseases. Group VIA phospholipase A2 or iPLA 2 β is a homeostatic PLA 2 by playing a role in phospholipid metabolism and remodeling. Global iPLA 2 β -/- mice exhibit aged-dependent phenotypes with body weight loss and abnormalities in the bone and brain. We have previously reported the abnormalities in these mutant mice showing susceptibility for chemical-induced liver injury and colitis. We hypothesize that iPLA 2 β deficiency may sensitize with ageing for an induction of GI injury. Male wild-type and iPLA 2 β -/- mice at 4 and 20-22months of age were studied. Aged, but not young, iPLA 2 β -/- mice showed increased hepatic fibrosis and biliary ductular expansion as well as severe intestinal atrophy associated with increased apoptosis, pro-inflammation, disrupted tight junction, and reduced number of mucin-containing globlet cells. This damage was associated with decreased expression of intestinal endoplasmic stress XBP1 and its regulator HNF1α, FATP4, ACSL5, bile-acid transport genes as well as nuclear receptors LXRα and FXR. By LC/MS-MS profiling, iPLA 2 β deficiency in aged mice caused an increase of intestinal arachidonate-containing phospholipids concomitant with a decrease in ceramides. By the suppression of intestinal FXR/FGF-15 signaling, hepatic bile-acid synthesis gene expression was increased leading to an elevation of secondary and hydrophobic bile acids in liver, bile, and intestine. In conclusions, ageing sensitized by iPLA 2 β deficiency caused a decline of key intestinal homeostatic genes resulting in the development of GI disease in a gut-to-liver manner. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Adenosine diphosphate sugar pyrophosphatase prevents glycogen biosynthesis in Escherichia coli

    Science.gov (United States)

    Moreno-Bruna, Beatriz; Baroja-Fernández, Edurne; Muñoz, Francisco José; Bastarrica-Berasategui, Ainara; Zandueta-Criado, Aitor; Rodríguez-López, Milagros; Lasa, Iñigo; Akazawa, Takashi; Pozueta-Romero, Javier

    2001-01-01

    An adenosine diphosphate sugar pyrophosphatase (ASPPase, EC 3.6.1.21) has been characterized by using Escherichia coli. This enzyme, whose activities in the cell are inversely correlated with the intracellular glycogen content and the glucose concentration in the culture medium, hydrolyzes ADP-glucose, the precursor molecule of glycogen biosynthesis. ASPPase was purified to apparent homogeneity (over 3,000-fold), and sequence analyses revealed that it is a member of the ubiquitously distributed group of nucleotide pyrophosphatases designated as “nudix” hydrolases. Insertional mutagenesis experiments leading to the inactivation of the ASPPase encoding gene, aspP, produced cells with marginally low enzymatic activities and higher glycogen content than wild-type bacteria. aspP was cloned into an expression vector and introduced into E. coli. Transformed cells were shown to contain a dramatically reduced amount of glycogen, as compared with the untransformed bacteria. No pleiotropic changes in the bacterial growth occurred in both the aspP-overexpressing and aspP-deficient strains. The overall results pinpoint the reaction catalyzed by ASPPase as a potential step of regulating glycogen biosynthesis in E. coli. PMID:11416161

  1. Mechanisms limiting glycogen storage in muscle during prolonged insulin stimulation

    International Nuclear Information System (INIS)

    Richter, E.A.; Hansen, S.A.; Hansen, B.F.

    1988-01-01

    The extent to which muscle glycogen concentrations can be increased during exposure to maximal insulin concentrations and abundant glucose was investigated in the isolated perfused rat hindquarter preparation. Perfusion for 7 h in the presence of 20,000 μU/ml insulin and 11-13 mM glucose increased muscle glycogen concentrations to maximal values 2, 3, and 3.5 times above normal fed levels in fast-twitch white, slow-twitch red, and fast-twitch red fibers, respectively. Glucose uptake decreased from 34.9 μmol·g -1 ·h -1 at 0 h to 7.5 after 7 h of perfusion. During the perfusion muscle glycogen synthase activity decreased and free intracellular glucose and glucose 6-phosphate increased indicating that glucose disposal was impaired. However, glucose transport as measured by the uptake of 3-O-[ 14 C]methyl-D-glucose was also markedly decreased after 5 and 7 h of perfusion compared with initial values. Total muscle water concentration decreased during glycogen loading of the muscles. Mechanisms limiting glycogen storage under maximal insulin stimulation include impaired insulin-stimulated membrane transport of glucose as well as impaired intracellular glucose disposal

  2. Livers from fasted rats acquire resistance to warm and cold ischemia injury.

    Science.gov (United States)

    Sumimoto, R; Southard, J H; Belzer, F O

    1993-04-01

    Successful liver transplantation is dependent upon many factors, one of which is the quality of the donor organ. Previous studies have suggested that the donor nutritional status may affect the outcome of liver transplantation and starvation, due to prolonged stay in the intensive care unit, may adversely affect the liver. In this study we have used the orthotopic rat liver transplant model to measure how fasting the donor affects the outcome of liver transplantation. Rat livers were preserved with UW solution either at 37 degrees C (warm ischemia for 45-60 min) or at 4 degrees C (cold ischemia for 30 or 44 hr). After preservation the livers were orthotopically transplanted and survival (for 7 days) was measured, as well as liver functions 6 hr after transplantation. After 45 min of warm ischemia 50% (3 of 6) animals survived when the liver was obtained from a fed donor about 80% (4 of 5) survived when the liver was obtained from a three-day-fasted donor. After 60 min warm ischemia no animal survived (0 of 8, fed group). However, if the donor was fasted for 3 days 89% (8 of 9) of the animals survived for 7 days. Livers cold-stored for 30 hr were 50% viable (3 of 6) and fasting for 1-3 days did not affect this outcome. However, if the donor was fasted for 4 days 100% (9 of 9) survival was obtained. After 44-hr preservation only 29% (2/7) of the recipients survived for 7 days. If the donor was fasted for 4 days, survival increased to 83% (5/6). Liver functions, bile production, and serum enzymes were better in livers from the fasted rats than from the fed rats. Fasting caused a 95% decrease in liver glycogen content. Even with this low concentration of glycogen, liver viability (animal survival) after warm or cold ischemia was not affected, and livers with a low glycogen content were fully viable. Thus liver glycogen does not appear to be important in liver preservation. This study shows that fasting the donor does not cause injury to the liver after warm or cold

  3. Glycogen availability and skeletal muscle adaptations with endurance and resistance exercise

    NARCIS (Netherlands)

    Knuiman, Pim; Hopman, Maria T.E.; Mensink, Marco

    2015-01-01

    It is well established that glycogen depletion affects endurance exercise performance negatively. Moreover, numerous studies have demonstrated that post-exercise carbohydrate ingestion improves exercise recovery by increasing glycogen resynthesis. However, recent research into the effects of

  4. Mountain-bike racing – the influence of prior glycogen- reducing ...

    African Journals Online (AJOL)

    bout of glycogen-reducing exercise on the general stress and immune response to ..... interaction effect of glutamine supplementation and glycogen reduction on the .... Hammarqvist F, Ejesson B, Wernerman J. Stress hormones initiate pro-.

  5. Structural mechanism of laforin function in glycogen dephosphorylation and lafora disease.

    Science.gov (United States)

    Raththagala, Madushi; Brewer, M Kathryn; Parker, Matthew W; Sherwood, Amanda R; Wong, Brian K; Hsu, Simon; Bridges, Travis M; Paasch, Bradley C; Hellman, Lance M; Husodo, Satrio; Meekins, David A; Taylor, Adam O; Turner, Benjamin D; Auger, Kyle D; Dukhande, Vikas V; Chakravarthy, Srinivas; Sanz, Pascual; Woods, Virgil L; Li, Sheng; Vander Kooi, Craig W; Gentry, Matthew S

    2015-01-22

    Glycogen is the major mammalian glucose storage cache and is critical for energy homeostasis. Glycogen synthesis in neurons must be tightly controlled due to neuronal sensitivity to perturbations in glycogen metabolism. Lafora disease (LD) is a fatal, congenital, neurodegenerative epilepsy. Mutations in the gene encoding the glycogen phosphatase laforin result in hyperphosphorylated glycogen that forms water-insoluble inclusions called Lafora bodies (LBs). LBs induce neuronal apoptosis and are the causative agent of LD. The mechanism of glycogen dephosphorylation by laforin and dysfunction in LD is unknown. We report the crystal structure of laforin bound to phosphoglucan product, revealing its unique integrated tertiary and quaternary structure. Structure-guided mutagenesis combined with biophysical and biochemical analyses reveal the basis for normal function of laforin in glycogen metabolism. Analyses of LD patient mutations define the mechanism by which subsets of mutations disrupt laforin function. These data provide fundamental insights connecting glycogen metabolism to neurodegenerative disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Deleterious effects of neuronal accumulation of glycogen in flies and mice.

    Science.gov (United States)

    Duran, Jordi; Tevy, María Florencia; Garcia-Rocha, Mar; Calbó, Joaquim; Milán, Marco; Guinovart, Joan J

    2012-08-01

    Under physiological conditions, most neurons keep glycogen synthase (GS) in an inactive form and do not show detectable levels of glycogen. Nevertheless, aberrant glycogen accumulation in neurons is a hallmark of patients suffering from Lafora disease or other polyglucosan disorders. Although these diseases are associated with mutations in genes involved in glycogen metabolism, the role of glycogen accumulation remains elusive. Here, we generated mouse and fly models expressing an active form of GS to force neuronal accumulation of glycogen. We present evidence that the progressive accumulation of glycogen in mouse and Drosophila neurons leads to neuronal loss, locomotion defects and reduced lifespan. Our results highlight glycogen accumulation in neurons as a direct cause of neurodegeneration. Copyright © 2012 EMBO Molecular Medicine.

  7. Modified glycogen as construction material for functional biomimetic microfibers.

    Science.gov (United States)

    Rabyk, Mariia; Hruby, Martin; Vetrik, Miroslav; Kucka, Jan; Proks, Vladimir; Parizek, Martin; Konefal, Rafal; Krist, Pavel; Chvatil, David; Bacakova, Lucie; Slouf, Miroslav; Stepanek, Petr

    2016-11-05

    We describe a conceptually new, microfibrous, biodegradable functional material prepared from a modified storage polysaccharide also present in humans (glycogen) showing strong potential as direct-contact dressing/interface material for wound healing. Double bonds were introduced into glycogen via allylation and were further exploited for crosslinking of the microfibers. Triple bonds were introduced by propargylation and served for further click functionalization of the microfibers with bioactive peptide. A simple solvent-free method allowing the preparation of thick layers was used to produce microfibers (diameter ca 2μm) from allylated and/or propargylated glycogen. Crosslinking of the samples was performed by microtron beta-irradiation, and the irradiation dose was optimized to 2kGy. The results from biological testing showed that these highly porous, hydrophilic, readily functionalizable materials were completely nontoxic to cells growing in their presence. The fibers were gradually degraded in the presence of cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Muscle glycogen depletion and lactate concentration during downhill skiing.

    Science.gov (United States)

    Tesch, P; Larsson, L; Eriksson, A; Karlsson, J

    1978-01-01

    Skilled and unskilled skiers were studied during downhill skiing. Muscle glycogen and muscle lactate concentrations in the vastus lateralis muscle were determined following different skiing conditions. Heavy glycogen utilization was found in the groups studied during a day of skiing. The skilled and unskilled skiers differed with respect to selective glycogen depletion pattern and the skilled subjects demonstrated greater depletion of slow twitch fibers than the unskilled subjects. Lactate concentrations ranged from approximately 5-26 mmoles x kg-1 wet muscle after approximately one minute of maximal skiing. This wide range was not found to be related to the level of skiing proficiency. However, skiing with varyingly angled boots, resulting in different knee angles, did affect lactate concentration. Lactate concentration was positively correlated to individual muscle fiber composition expressed as a percent of fast twitch fibers. The results suggest more pronounced involvement of aerobic energy metabolism in skilled skiers than in unskilled skiers.

  9. Chlordecone altered hepatic disposition of [14C]cholesterol and plasma cholesterol distribution but not SR-BI or ABCG8 proteins in livers of C57BL/6 mice

    International Nuclear Information System (INIS)

    Lee, Junga; Scheri, Richard C.; Curtis, Lawrence R.

    2008-01-01

    Organochlorine (OC) insecticides continue to occur in tissues of humans and wildlife throughout the world although they were banned in the United States a few decades ago. Low doses of the OC insecticide chlordecone (CD) alter hepatic disposition of lipophilic xenobiotics and perturb lipid homeostasis in rainbow trout, mice and rats. CD pretreatment altered tissue and hepatic subcellular distribution of exogenous [ 14 C]cholesterol (CH) equivalents 4 and 16 h after a bolus intraperitoneal (ip) injection of 5 ml corn oil/kg that contained 10 mg CH/kg. CD pretreatment altered tissue distribution of exogenously administered [ 14 C]CH by decreased hepatic and renal accumulation, and increased biliary excretion up to 300%. Biliary excretion of polar [ 14 C]CH metabolites was not altered by CD. CD pretreatment decreased subcellular distribution of [ 14 C]CH equivalents in hepatic cytosol and microsomes and lipoprotein-rich fraction-to-homogenate ratio. CD pretreatment increased the ratio of [ 14 C]CH equivalents in high density lipoprotein (HDL) to that in plasma and reduced [ 14 C]CH equivalents in the non-HDL fraction 4 h after a bolus lipid dose. CD pretreatment increased plasma non-HDL total CH by 80% 4 h after a bolus lipid dose. Scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter G8 (ABCG8) proteins were quantified by western blotting in hepatic membranes from control and CD treated mice. Liver membrane contents of SR-BI and ABCG8 proteins were unchanged by CD pretreatment. The data demonstrated that a single dose of CD altered CH homeostasis and lipoprotein metabolism

  10. Chlordecone altered hepatic disposition of [14C]cholesterol and plasma cholesterol distribution but not SR-BI or ABCG8 proteins in livers of C57BL/6 mice.

    Science.gov (United States)

    Lee, Junga; Scheri, Richard C; Curtis, Lawrence R

    2008-06-15

    Organochlorine (OC) insecticides continue to occur in tissues of humans and wildlife throughout the world although they were banned in the United States a few decades ago. Low doses of the OC insecticide chlordecone (CD) alter hepatic disposition of lipophilic xenobiotics and perturb lipid homeostasis in rainbow trout, mice and rats. CD pretreatment altered tissue and hepatic subcellular distribution of exogenous [(14)C]cholesterol (CH) equivalents 4 and 16 h after a bolus intraperitoneal (ip) injection of 5 ml corn oil/kg that contained 10 mg CH/kg. CD pretreatment altered tissue distribution of exogenously administered [(14)C]CH by decreased hepatic and renal accumulation, and increased biliary excretion up to 300%. Biliary excretion of polar [(14)C]CH metabolites was not altered by CD. CD pretreatment decreased subcellular distribution of [(14)C]CH equivalents in hepatic cytosol and microsomes and lipoprotein-rich fraction-to-homogenate ratio. CD pretreatment increased the ratio of [(14)C]CH equivalents in high density lipoprotein (HDL) to that in plasma and reduced [(14)C]CH equivalents in the non-HDL fraction 4 h after a bolus lipid dose. CD pretreatment increased plasma non-HDL total CH by 80% 4 h after a bolus lipid dose. Scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter G8 (ABCG8) proteins were quantified by western blotting in hepatic membranes from control and CD treated mice. Liver membrane contents of SR-BI and ABCG8 proteins were unchanged by CD pretreatment. The data demonstrated that a single dose of CD altered CH homeostasis and lipoprotein metabolism.

  11. PPAR-gamma activation is associated with reduced liver ischemia-reperfusion injury and altered tissue-resident macrophages polarization in a mouse model.

    Science.gov (United States)

    Linares, Ivan; Farrokhi, Kaveh; Echeverri, Juan; Kaths, Johan Moritz; Kollmann, Dagmar; Hamar, Matyas; Urbanellis, Peter; Ganesh, Sujani; Adeyi, Oyedele A; Yip, Paul; Selzner, Markus; Selzner, Nazia

    2018-01-01

    PPAR-gamma (γ) is highly expressed in macrophages and its activation affects their polarization. The effect of PPAR-γ activation on Kupffer cells (KCs) and liver ischemia-reperfusion injury (IRI) has not yet been evaluated. We investigated the effect of PPAR-γ activation on KC-polarization and IRI. Seventy percent (70%) liver ischemia was induced for 60mins. PPAR-γ-agonist or vehicle was administrated before reperfusion. PPAR-γ-antagonist was used to block PPAR-γ activation. Liver injury, necrosis, and apoptosis were assessed post-reperfusion. Flow-cytometry determined KC-phenotypes (pro-inflammatory Nitric Oxide +, anti-inflammatory CD206+ and anti-inflammatory IL-10+). Liver injury assessed by serum AST was significantly decreased in PPAR-γ-agonist versus control group at all time points post reperfusion (1hr: 3092±105 vs 4469±551; p = 0.042; 6hr: 7041±1160 vs 12193±1143; p = 0.015; 12hr: 5746±328 vs 8608±1259; p = 0.049). Furthermore, liver apoptosis measured by TUNEL-staining was significantly reduced in PPAR-γ-agonist versus control group post reperfusion (1hr:2.46±0.49 vs 6.90±0.85%;p = 0.001; 6hr:26.40±2.93 vs 50.13±8.29%; p = 0.048). H&E staining demonstrated less necrosis in PPAR-γ-agonist versus control group (24hr:26.66±4.78 vs 45.62±4.57%; p = 0.032). The percentage of pro-inflammatory NO+ KCs was significantly lower at all post reperfusion time points in the PPAR-γ-agonist versus control group (1hr:28.49±4.99 vs 53.54±9.15%; p = 0.040; 6hr:5.51±0.54 vs 31.12±9.58%; p = 0.009; 24hr:4.15±1.50 vs 17.10±4.77%; p = 0.043). In contrast, percentage of anti-inflammatory CD206+ KCs was significantly higher in PPAR-γ-agonist versus control group prior to IRI (8.62±0.96 vs 4.88 ±0.50%; p = 0.04). Administration of PPAR-γ-antagonist reversed the beneficial effects on AST, apoptosis, and pro-inflammatory NO+ KCs. PPAR-γ activation reduces IRI and decreases the pro-inflammatory NO+ Kupffer cells. PPAR-γ activation can become an

  12. A functional glycogen biosynthesis pathway in Lactobacillus acidophilus: expression and analysis of the glg operon

    OpenAIRE

    Goh, Yong Jun; Klaenhammer, Todd R

    2013-01-01

    Glycogen metabolism contributes to energy storage and various physiological functions in some prokaryotes, including colonization persistence. A role for glycogen metabolism is proposed on the survival and fitness of Lactobacillus acidophilus, a probiotic microbe, in the human gastrointestinal environment. L.?acidophilus?NCFM possesses a glycogen metabolism (glg) operon consisting of glgBCDAP - amy - pgm genes. Expression of the glg operon and glycogen accumulation were carbon source- and gro...

  13. Gamma Amino Butyric Acid Attenuates Liver and Kidney Damage Associated with Insulin Alteration in γ-Irradiated and Streptozotocin-Treated Rats

    International Nuclear Information System (INIS)

    Saada, H.N.; Eltahawy, N.A.; Hammad, A.S.; Morcos, N.Y.S.

    2016-01-01

    Gamma aminobutyric acid (GABA) is one of the inhibitory neurotransmitters that may have the ability to relive the intensity of stress. The aim of the current study was to evaluate the role of γ-amino butyric acid (GABA) in modulating insulin disturbance associated with liver and kidney damage in γ-irradiated and streptozotocin-treated rats. Irradiation was performed by whole body exposure to 6 Gy from a Cs-137 source. Streptozotocin (STZ) was administered in a single intraperitoneal dose (60 mg/kg body weight). GABA (200 mg/Kg body weight/day) was administered daily via gavages during 3 weeks to γ-irradiated and STZ-treated-rats. The results obtained showed that γ-irradiation induced hyperglycemia, hyperinsulinaemia and insulin resistance (similar to type 2 Diabetes), while STZ-treatment produced hyperglycemia, insulin deficiency with no insulin resistance detected (similar to type 1 Diabetes). In both cases, significant increases of alanine amino transferase (ALT) and aspartate amino transferase (AST) activities, urea and creatinine levels were recorded in the serum. These changes were associated with oxidative damage to the liver and kidney tissues notified by significant decreases of superoxide dismutase (SOD ), catalase and glutathione peroxidase ( GSH-Px) activities in parallel to significant increases of malondialdehyde (MDA) and advanced oxidation protein products ( AOPP) levels. The administration of GABA to irradiated as well as STZ-treated rats regulated insulin and glucose levels, minimized oxidative stress and reduced the severity of liver and kidney damage. It could be concluded that GABA could be a useful adjunct to reduce some metabolic complications associated with insulin deficiency and insulin resistance

  14. Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver.

    Science.gov (United States)

    Cavin, C; Marin-Kuan, M; Langouët, S; Bezençon, C; Guignard, G; Verguet, C; Piguet, D; Holzhäuser, D; Cornaz, R; Schilter, B

    2008-04-01

    Coffee consumption has been associated with a significant decrease in the risk of developing chronic diseases such as Parkinson disease, diabetes type-2 and several types of cancers (e.g. colon, liver). In the present study, a coffee-dependent induction of enzymes involved in xenobiotic detoxification processes was observed in rat liver and primary hepatocytes. In addition, coffee was found to induce the mRNA and protein expression of enzymes involved in cellular antioxidant defenses. These inductions were correlated with the activation of the Nrf2 transcription factor as shown using an ARE-reporter luciferase assay. The induction of detoxifying enzymes GSTs and AKR is compatible with a protection against both genotoxicity and cytotoxicity of aflatoxin B1 (AFB1). This hypothesis was confirmed in in vitro and ex vivo test systems, where coffee reduced both AFB1-DNA and protein adducts. Interestingly, coffee was also found to inhibit cytochrome CYP1A1/2, indicating that other mechanisms different from a stimulation of detoxification may also play a significant role in the chemoprotective effects of coffee. Further investigations in either human liver cell line and primary hepatocytes indicated that the chemoprotective effects of coffee against AFB1 genotoxicity are likely to be of relevance for humans. These data strongly suggest that coffee may protect against the adverse effects of AFB1. In addition, the coffee-mediated stimulation of the Nrf2-ARE pathway resulting in increased endogenous defense mechanisms against electrophilic but also oxidative insults further support that coffee may be associated with a protection against various types of chemical stresses.

  15. Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver.

    Science.gov (United States)

    Hinrichs, Arne; Kessler, Barbara; Kurome, Mayuko; Blutke, Andreas; Kemter, Elisabeth; Bernau, Maren; Scholz, Armin M; Rathkolb, Birgit; Renner, Simone; Bultmann, Sebastian; Leonhardt, Heinrich; de Angelis, Martin Hrabĕ; Nagashima, Hiroshi; Hoeflich, Andreas; Blum, Werner F; Bidlingmaier, Martin; Wanke, Rüdiger; Dahlhoff, Maik; Wolf, Eckhard

    2018-05-01

    Laron syndrome (LS) is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR) gene. To establish a large animal model for LS, pigs with GHR knockout (KO) mutations were generated and characterized. CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs. Since the latter two groups were not significantly different in any parameter investigated, they were pooled as the GHR expressing control group. The characterization program included body and organ growth, body composition, endocrine and clinical-chemical parameters, as well as signaling studies in liver tissue. GHR-KO pigs lacked GHR and had markedly reduced serum insulin-like growth factor 1 (IGF1) levels and reduced IGF-binding protein 3 (IGFBP3) activity but increased IGFBP2 levels. Serum GH concentrations were significantly elevated compared with control pigs. GHR-KO pigs had a normal birth weight. Growth retardation became significant at the age of five weeks. At the age of six months, the body weight of GHR-KO pigs was reduced by 60% compared with controls. Most organ weights of GHR-KO pigs were reduced proportionally to body weight. However, the weights of liver, kidneys, and heart were disproportionately reduced, while the relative brain weight was almost doubled. GHR-KO pigs had a markedly increased percentage of total body fat relative to body weight and displayed transient juvenile hypoglycemia along with decreased serum triglyceride and cholesterol levels. Analysis of insulin receptor related signaling in the liver of adult fasted pigs revealed increased phosphorylation of IRS1 and PI3K. In agreement with the loss of GHR, phosphorylation of STAT5 was significantly reduced. In contrast, phosphorylation

  16. Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver

    Directory of Open Access Journals (Sweden)

    Arne Hinrichs

    2018-05-01

    Full Text Available Objective: Laron syndrome (LS is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR gene. To establish a large animal model for LS, pigs with GHR knockout (KO mutations were generated and characterized. Methods: CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs. Since the latter two groups were not significantly different in any parameter investigated, they were pooled as the GHR expressing control group. The characterization program included body and organ growth, body composition, endocrine and clinical-chemical parameters, as well as signaling studies in liver tissue. Results: GHR-KO pigs lacked GHR and had markedly reduced serum insulin-like growth factor 1 (IGF1 levels and reduced IGF-binding protein 3 (IGFBP3 activity but increased IGFBP2 levels. Serum GH concentrations were significantly elevated compared with control pigs. GHR-KO pigs had a normal birth weight. Growth retardation became significant at the age of five weeks. At the age of six months, the body weight of GHR-KO pigs was reduced by 60% compared with controls. Most organ weights of GHR-KO pigs were reduced proportionally to body weight. However, the weights of liver, kidneys, and heart were disproportionately reduced, while the relative brain weight was almost doubled. GHR-KO pigs had a markedly increased percentage of total body fat relative to body weight and displayed transient juvenile hypoglycemia along with decreased serum triglyceride and cholesterol levels. Analysis of insulin receptor related signaling in the liver of adult fasted pigs revealed increased phosphorylation of IRS1 and PI3K. In agreement with the loss of GHR, phosphorylation of STAT5 was

  17. Glycogen-bound polyphosphate kinase from the archaebacterium Sulfolobus acidocaldarius.

    Science.gov (United States)

    Skórko, R; Osipiuk, J; Stetter, K O

    1989-09-01

    Glycogen-bound polyphosphate kinase has been isolated from a crude extract of Sulfolobus acidocaldarius by isopycnic centrifugation in CsCl. Divalent cations (Mn2+ greater than Mg2+) stimulated the reaction. The enzyme does not require the presence of histones for its activity; it is inhibited strongly by phosphate and slightly by fluoride. The protein from the glycogen complex migrated in a sodium dodecyl sulfate-polyacrylamide gel as a 57-kilodalton protein band; after isoelectric focusing it separated into several spots in the pH range of 5.6 to 6.7.

  18. Enzymatic description of the anhydrofructose pathway of glycogen degradation. I

    DEFF Research Database (Denmark)

    Yu, Shukun; Refdahl, Charlotte; Lundt, Inge

    2004-01-01

    The anhydrofructose pathway describes the degradation of glycogen and starch to metabolites via 1,5-anhydro-D-fructose (1,5AnFru). The enzyme catalyzing the first reaction step of this pathway, i.e., a-1,4-glucan lyase (EC 4.2.1.13), has been purified, cloned and characterized from fungi and red...... possessed all enzymes needed for conversion of glycogen to APP, an a-1,4-glucan lyase from this fungus was isolated and partially sequenced. Based on this work, a scheme of the enzymatic description of the anhydrofructose pathway in A. melaloma was proposed. Keywords: Anhydrofructose pathway; Anthracobia...

  19. Liver Hemangioma

    Science.gov (United States)

    Liver hemangioma Overview A liver hemangioma (he-man-jee-O-muh) is a noncancerous (benign) mass in the liver. A liver hemangioma is made up of a tangle of blood vessels. Other terms for a liver hemangioma are hepatic hemangioma and cavernous hemangioma. Most ...

  20. Differences between glycogen biogenesis in fast- and slow-twitch rabbit muscle

    DEFF Research Database (Denmark)

    Cussó, R; Lerner, L R; Cadefau, J

    2003-01-01

    Skeletal muscle glycogen is an essential energy substrate for muscular activity. The biochemical properties of the enzymes involved in de novo synthesis of glycogen were analysed in two types of rabbit skeletal muscle fiber (fast- and slow-twitch). Glycogen concentration was higher in fast...

  1. Glycogen metabolism in Schistosoma mansoni worms after their isolation from the host

    NARCIS (Netherlands)

    Tiolens, A.G.M.; Bergh, S.G. van den

    Adult Schistosoma mansoni worms rapidly degrade their endogenous glycogen stores immediately after isolation from the host. In NCTC 109 or in a diphasic culture medium the glycogen levels slowly recovered again after the initial decrease. The rapid degradation of glycogen could be prevented, even in

  2. Mice fed a high-fat diet supplemented with resistant starch display marked shifts in the liver metabolome concurrent with altered gut bacteria

    Science.gov (United States)

    High-amylose maize resistant starch type 2 (HAMRS2) is a fermentable dietary fiber known to alter the gut milieu, including the gut microbiota, which may explain reported effects of resistant starch to ameliorate obesity-associated metabolic dysfunction. Our working hypothesis is that HAMRS2-induced...

  3. Liver biopsy

    Science.gov (United States)

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  4. Energy metabolism and memory processing: role of glucose transport and glycogen in responses to adrenoceptor activation in the chicken.

    Science.gov (United States)

    Hutchinson, Dana S; Summers, Roger J; Gibbs, Marie E

    2008-06-15

    From experiments using a discriminated bead task in young chicks, we have defined when and where adrenoceptors (ARs) are involved in memory modulation. All three ARs subtypes (alpha(1)-, alpha(2)- and beta-ARs) are found in the chick brain and in regions associated with memory. Glucose and glycogen are important in the role of memory consolidation in the chick since increasing glucose levels improves memory consolidation while inhibiting glucose transporters (GLUTs) or glycogen breakdown inhibits memory consolidation. The selective beta(3)-AR agonist CL316243 enhances memory consolidation by a glucose-dependent mechanism and the administration of the non-metabolized glucose analogue 2-deoxyglucose reduces the ability of CL316243 to enhance memory. Agents that reduce glucose uptake by GLUTs and its incorporation into the glycolytic pathway also reduce the effectiveness of CL316243, but do not alter the dose-response relationship to the beta(2)-AR agonist zinterol. However, beta(2)-ARs do have a role in memory related to glycogen breakdown and inhibition of glycogenolysis reduces the ability of zinterol to enhance memory. Both beta(2)- and beta(3)-ARs are found on astrocytes from chick forebrain, and the actions of beta(3)-ARs on glucose uptake, and beta(2)-ARs on the breakdown of glycogen is consistent with an effect on astrocytic metabolism at the time of memory consolidation 30 min after training. We have shown that both beta(2)- and beta(3)-ARs can increase glucose uptake in chick astrocytes but do so by different mechanisms. This review will focus on the role of ARs on memory consolidation and specifically the role of energy metabolism on AR modulation of memory.

  5. Energy Metabolism in the Liver

    Science.gov (United States)

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

  6. Keap1-knockdown decreases fasting-induced fatty liver via altered lipid metabolism and decreased fatty acid mobilization from adipose tissue.

    Directory of Open Access Journals (Sweden)

    Jialin Xu

    Full Text Available AIMS: The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD, regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting. METHODS AND RESULTS: Male C57BL/6 (WT and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36 and Fatty acid transport protein (FATP 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar α signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters--CD36 and FATP1, via a PPARα-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. CONCLUSION: Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation.

  7. Altered composition of liver proteasome assemblies contributes to enhanced proteasome activity in the exceptionally long-lived naked mole-rat.

    Science.gov (United States)

    Rodriguez, Karl A; Edrey, Yael H; Osmulski, Pawel; Gaczynska, Maria; Buffenstein, Rochelle

    2012-01-01

    The longest-lived rodent, the naked mole-rat (Bathyergidae; Heterocephalus glaber), maintains robust health for at least 75% of its 32 year lifespan, suggesting that the decline in genomic integrity or protein homeostasis routinely observed during aging, is either attenuated or delayed in this extraordinarily long-lived species. The ubiquitin proteasome system (UPS) plays an integral role in protein homeostasis by degrading oxidatively-damaged and misfolded proteins. In this study, we examined proteasome activity in naked mole-rats and mice in whole liver lysates as well as three subcellular fractions to probe the mechanisms behind the apparently enhanced effectiveness of UPS. We found that when compared with mouse samples, naked mole-rats had significantly higher chymotrypsin-like (ChT-L) activity and a two-fold increase in trypsin-like (T-L) in both whole lysates as well as cytosolic fractions. Native gel electrophoresis of the whole tissue lysates showed that the 20S proteasome was more active in the longer-lived species and that 26S proteasome was both more active and more populous. Western blot analyses revealed that both 19S subunits and immunoproteasome catalytic subunits are present in greater amounts in the naked mole-rat suggesting that the observed higher specific activity may be due to the greater proportion of immunoproteasomes in livers of healthy young adults. It thus appears that proteasomes in this species are primed for the efficient removal of stress-damaged proteins. Further characterization of the naked mole-rat proteasome and its regulation could lead to important insights on how the cells in these animals handle increased stress and protein damage to maintain a longer health in their tissues and ultimately a longer life.

  8. Altered composition of