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Sample records for alters liver glycogen

  1. Acrylamide alters glycogen content and enzyme activities in the liver of juvenile rat.

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    Kovac, Renata; Rajkovic, Vesna; Koledin, Ivana; Matavulj, Milica

    2015-10-01

    Acrylamide (AA) is spontaneously formed in carbohydrate-rich food during high-temperature processing. It is neurotoxic and potentially cancer causing chemical. Its harmful effects on the liver, especially in a young organism, are still to be elucidated. The study aimed to examine main liver histology, its glycogen content and enzyme activities in juvenile rats treated with 25 or 50mg/kg bw of AA for 3 weeks. Liver samples were fixed in formalin, routinely processed for paraffin embedding, sectioning and histochemical staining. Examination of haematoxylin and eosin (H&E)-stained sections showed an increase in the volume of hepatocytes, their nuclei and cytoplasm in both AA-treated groups compared to the control. In Periodic acid-Schiff (PAS)-stained sections in low-dose group was noticed glycogen reduction, while in high-dose group was present its accumulation compared to the control, respectively. Serum analysis showed increased activity of aspartate aminotransferase (AST), and decreased activity of alanine aminotransferase (ALT) in both AA-treated groups, while the activity of alkaline phosphatase (ALP) was increased in low-dose, but decreased in high-dose group compared to the control, respectively. Present results suggest a prominent hepatotoxic potential of AA which might alter the microstructural features and functional status in hepatocytes of immature liver.

  2. Dysfunctional muscle and liver glycogen metabolism in mdx dystrophic mice.

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    David I Stapleton

    Full Text Available 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.Dystrophic mdx mice had increased skeletal muscle glycogen (79%, (P<0.01. Skeletal muscle glycogen synthesis is initiated by glycogenin, the expression of which was increased by 50% in mdx mice (P<0.0001. Glycogen synthase activity was 12% higher (P<0.05 but glycogen branching enzyme activity was 70% lower (P<0.01 in mdx compared with wild-type mice. The rate-limiting enzyme for glycogen breakdown, glycogen phosphorylase, had 62% lower activity (P<0.01 in mdx mice resulting from a 24% reduction in PKA activity (P<0.01. In mdx mice glycogen debranching enzyme expression was 50% higher (P<0.001 together with starch-binding domain protein 1 (219% higher; P<0.01. In addition, mdx mice were glucose intolerant (P<0.01 and had 30% less liver glycogen (P<0.05 compared with control mice. Subsequent analysis of the enzymes dysregulated in skeletal muscle glycogen metabolism in mdx mice identified reduced glycogenin protein expression (46% less; P<0.05 as a possible cause of this phenotype.We identified that mdx mice were glucose intolerant, and had increased skeletal muscle glycogen but reduced amounts of liver glycogen.

  3. Garlic (Allium sativum) Extract Supplementation Alters the Glycogen Deposition in Liver and Protein Metabolism in Gonads of Female Albino Rats

    OpenAIRE

    Sashank Srivastava; P. H. Pathak

    2012-01-01

    Garlic is an ayurvedic herb that has been extensively used as medication and as the taste enhancer of the food. The present investigation was undertaken to provide data on the efficacy of garlic (Allium sativum Linn.) extract on glycogen deposition and protein metabolism in female albino rats that may further explore medicinal potential of garlic. The rats were divided into four groups A, B, C and D, keeping group A as a healthy control. The garlic extract was tried in three different doses, ...

  4. Garlic (Allium sativum Extract Supplementation Alters the Glycogen Deposition in Liver and Protein Metabolism in Gonads of Female Albino Rats

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    Sashank Srivastava

    2012-04-01

    Full Text Available Garlic is an ayurvedic herb that has been extensively used as medication and as the taste enhancer of the food. The present investigation was undertaken to provide data on the efficacy of garlic (Allium sativum Linn. extract on glycogen deposition and protein metabolism in female albino rats that may further explore medicinal potential of garlic. The rats were divided into four groups A, B, C and D, keeping group A as a healthy control. The garlic extract was tried in three different doses, 1ml, 2ml and 4ml/ kg body weight as low, medium and high dose respectively and given orally for the period of 7, 14, 21 and 28 days daily to the rats of group B, C and D as stated above. The significant (P<0.01 & P<0.05 increase in glycogen and protein level was observed when rats were fed with low and medium dose but when rats were fed with high dose of garlic extract there was significant (P<0.01 decrease in glycogen level and a not significant decrease in protein level was observed.

  5. Activity of glycogen synthase and glycogen phosphorylase in normal and cirrhotic rat liver during glycogen synthesis from glucose or fructose.

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    Bezborodkina, Natalia N; Chestnova, Anna Yu; Okovity, Sergey V; Kudryavtsev, Boris N

    2014-03-01

    Cirrhotic patients often demonstrate glucose intolerance, one of the possible causes being a decreased glycogen-synthesizing capacity of the liver. At the same time, information about the rates of glycogen synthesis in the cirrhotic liver is scanty and contradictory. We studied the dynamics of glycogen accumulation and the activity of glycogen synthase (GS) and glycogen phosphorylase (GP) in the course of 120min after per os administration of glucose or fructose to fasted rats with CCl4-cirrhosis or fasted normal rats. Blood serum and liver pieces were sampled for examinations. In the normal rat liver administration of glucose/fructose initiated a fast accumulation of glycogen, while in the cirrhotic liver glycogen was accumulated with a 20min delay and at a lower rate. In the normal liver GS activity rose sharply and GPa activity dropped in the beginning of glycogen synthesis, but 60min later a high synthesis rate was sustained at the background of a high GS and GPa activity. Contrariwise, in the cirrhotic liver glycogen was accumulated at the background of a decreased GS activity and a low GPa activity. Refeeding with fructose resulted in a faster increase in the GS activity in both the normal and the cirrhotic liver than refeeding with glucose. To conclude, the rate of glycogen synthesis in the cirrhotic liver is lower than in the normal one, the difference being probably associated with a low GS activity.

  6. Molecular Structure of Human-Liver Glycogen.

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    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.

  7. Molecular Structure of Human-Liver Glycogen

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    Deng, Bin; Sullivan, Mitchell A.; Chen, Cheng; Li, Jialun; Powell, Prudence O.; Hu, Zhenxia; Gilbert, Robert G.

    2016-01-01

    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. PMID:26934359

  8. A 13CO2 breath test for liver glycogen oxidation

    NARCIS (Netherlands)

    A.A. Tanis

    2003-01-01

    textabstractIn conclusion we developed a model to monitor the oxidation of liver glycogen. Our studies showed that it was possible to label the liver glycogen with naturally 13C-enriched carbohydrate and to monitor its oxidation. 13C-enriched muscle glycogen did not interfere with the test within th

  9. Reduced-size liver transplantation for glycogen storage disease

    Institute of Scientific and Technical Information of China (English)

    Hao-Feng Ji; Wei-Lin Wang; Yan Shen; Min Zhang; Ting-Bo Liang; Jian Wu; Xiao Xu; Sheng Yan; Shu-Sen Zheng

    2009-01-01

    BACKGROUND: Glycogen storage disease (GSD) is an inherited metabolic disorder in which the concentration and/or structure of glycogen in tissues is abnormal. Essentially, abnormalities in all known enzymes involved in the synthesis or degradation of glycogen and glucose have been found to cause some type of GSD. Liver and muscle have abundant quantities of glycogen and are the most common and seriously affected tissues. This study was to assess reduced-size liver transplantation for the treatment of GSD. METHODS: The clinical data from one case of GSD typeⅠ with hepatic adenoma was retrospectively analyzed. The clinical manifestations were hepatomegaly, delayed puberty, growth retardation, sexual immaturity, hypoglycemia, and lactic acidosis, which made the young female patient eligible for reduced-size liver transplantation. RESULTS: The patient recovered uneventfully with satisfactory outcome, including 12 cm growth in height and 5 kg increase in weight during 16 months after successful reduced-size liver transplantation. She has been living a normal life for 4 years so far. CONCLUSIONS: Reduced-size liver transplantation is an effective treatment for GSD with hepatomegaly and hepatic adenoma. Delayed puberty, growth retardation, hypoglycemia and lactic acidosis can be cured by surgery.

  10. Neonatally induced diabetes: liver glycogen storage in pregnant rats

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    Isabela Lovizutto Iessi

    2012-04-01

    Full Text Available The aim of this sstudy was to evaluate the liver glycogen storage in pregnant rats presenting neonatal streptozotocin-induced diabetes and to establish a relation with glycemia and insulin levels. Wistar rats were divided in to two groups: 1 Mild Diabetes (STZ - received streptozotocin (glycemia from 120 to 300 mg/dL, 2 Control - received vehicle (glycemia below 120 mg/dL. At days 0, 7, 14 and 21 of the pregnancy, body weight and glycemia were evaluated. At day 21 of the pregnancy, the rats were anesthetized for blood and liver collection so as to determine insulin and liver glycogen, which showed no changes in the STZ group as compared to the controls. In the STZ group, maternal weight gain were lower as compared to those in the control group. Significantly increased glycemia was observed at days 0 and 14 of the pregnancy in the STZ group. Therefore, neonatally induced diabetes in the rats did not cause metabolic changes that impaired insulin and liver glycogen relation in these rats.

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

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

    2016-08-01

    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. PMID:27358407

  12. Hepatic Glycogen Supercompensation Activates AMP-Activated Protein Kinase, Impairs Insulin Signaling, and Reduces Glycogen Deposition in the Liver

    OpenAIRE

    Winnick, Jason J.; An, Zhibo; Ramnanan, Christopher J.; Smith, Marta; Irimia, Jose M.; Neal, Doss W.; Moore, Mary Courtney; Peter J Roach; Cherrington, Alan D.

    2011-01-01

    OBJECTIVE The objective of this study was to determine how increasing the hepatic glycogen content would affect the liver’s ability to take up and metabolize glucose. RESEARCH DESIGN AND METHODS During the first 4 h of the study, liver glycogen deposition was stimulated by intraportal fructose infusion in the presence of hyperglycemic-normoinsulinemia. This was followed by a 2-h hyperglycemic-normoinsulinemic control period, during which the fructose infusion was stopped, and a 2-h experiment...

  13. 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.

  14. 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

  15. Hepatic glycogen can regulate hypoglycemic counterregulation via a liver-brain axis.

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    Winnick, Jason J; Kraft, Guillaume; Gregory, Justin M; Edgerton, Dale S; Williams, Phillip; Hajizadeh, Ian A; Kamal, Maahum Z; Smith, Marta; Farmer, Ben; Scott, Melanie; Neal, Doss; Donahue, E Patrick; Allen, Eric; Cherrington, Alan D

    2016-06-01

    Liver glycogen is important for the counterregulation of hypoglycemia and is reduced in individuals with type 1 diabetes (T1D). Here, we examined the effect of varying hepatic glycogen content on the counterregulatory response to low blood sugar in dogs. During the first 4 hours of each study, hepatic glycogen was increased by augmenting hepatic glucose uptake using hyperglycemia and a low-dose intraportal fructose infusion. After hepatic glycogen levels were increased, animals underwent a 2-hour control period with no fructose infusion followed by a 2-hour hyperinsulinemic/hypoglycemic clamp. Compared with control treatment, fructose infusion caused a large increase in liver glycogen that markedly elevated the response of epinephrine and glucagon to a given hypoglycemia and increased net hepatic glucose output (NHGO). Moreover, prior denervation of the liver abolished the improved counterregulatory responses that resulted from increased liver glycogen content. When hepatic glycogen content was lowered, glucagon and NHGO responses to insulin-induced hypoglycemia were reduced. We conclude that there is a liver-brain counterregulatory axis that is responsive to liver glycogen content. It remains to be determined whether the risk of iatrogenic hypoglycemia in T1D humans could be lessened by targeting metabolic pathway(s) associated with hepatic glycogen repletion. PMID:27140398

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

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    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. PMID:20127879

  17. 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

  18. Liver transplantation for glycogen storage disease types I, III, and IV

    NARCIS (Netherlands)

    Matern, D; Starzl, TE; Arnaout, W; Barnard, J; Bynon, JS; Dhawan, A; Emond, J; Haagsma, EB; Hug, G; Lachaux, A; Smit, GPA; Chen, YT

    1999-01-01

    Glycogen storage disease (GSD) types I, III, and IV can be associated with severe liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for liver transplantation. Early diagnosis and initiation of effective dietary therapy hav

  19. Methodologies of tissue preservation and analysis of the glycogen content of the broiler chick liver.

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    Bennett, L W; Keirs, R W; Peebles, E D; Gerard, P D

    2007-12-01

    The current study was performed to develop convenient, rapid, reliable, and pragmatic methodologies by which to harvest and preserve liver tissue glycogen and to analyze its levels within reasonable limits of quantification and with extended chromophore stability. Absorbance values decreased by 2 h and again by 24 h after preparation of the iodine-potassium iodide chromophore, whereas absorbance values of the phenol-sulfuric acid chromophore remained constant over the same time period. These absorbance trends for each chromophore followed full color development within 5 min after combining the analyte with the respective chromophore reagent. Use of the phenol-sulfuric acid reagent allowed for a 10-fold reduction in assay limits of detection and quantification when compared with the iodine-potassium iodide reagent. Furthermore, glycogen concentration-absorbance relationships were affected by the source (i.e., rabbit liver vs. bovine liver) of glycogen standards when the iodine-potassium iodide chromophore was used, but the source of the standards had no influence when the phenol-sulfuric acid chromophore was used. The indifference of the phenol-sulfuric acid method to the glycogen source, as exhibited by similar linear regressions of absorbance, may be attributed to actual determination of glucose subunit concentrations after complete glycogen hydrolysis by sulfuric acid. This is in contrast to the actual measurement of whole glycogen, which may exhibit source- or time-related molecular structural differences. The iodine-potassium iodide methodology is a test of whole glycogen concentrations; therefore, it may be influenced by glycogen structural differences. Liver tissue sample weight (between 0.16 and 0.36 g) and processing, which included mincing, immediate freezing, or refrigeration in 10% perchloric acid for 1 wk prior to tissue grinding, had no effect on glycogen concentrations that were analyzed by using the phenol-sulfuric acid reagent. These results

  20. Time sequence of changes in the responsiveness of glycogen breakdown to adrenergic agonists in perfused liver of rats with insulin-induced hypoglycemia

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    M. Vardanega-Peicher

    2000-07-01

    Full Text Available The time-course changes of the responsiveness of glycogen breakdown to a- and ß-adrenergic agonists during insulin-induced hypoglycemia (IIH were investigated. Blood glucose levels were decreased prior to the alteration in the hepatic responsiveness to adrenergic agonists. The activation of hepatic glucose production and glycogenolysis by phenylephrine (2 µM and isoproterenol (20 µM was decreased in IIH. The changes in the responsiveness of glycogen catabolism were first observed for isoproterenol and later for phenylephrine. Hepatic ß-adrenergic receptors showed a higher degree of adrenergic desensitization than did a-receptors. Liver glycogen synthase activity, glycogen content and the catabolic effect of dibutyryl cyclic AMP (the ß-receptor second messenger were not affected by IIH.

  1. Lipid and glycogen contents in liver of high-yield dairy cows in peripartal period

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    Đoković Radojica

    2004-01-01

    Full Text Available Liver tissue samples were taken by biopsy from Holstein cows in advanced stages of gravidity and in early lactation for pathological-histological examinations. Lipid content in hepatocytes was determined using the stereometric method by calculating volume density, and of glycogen using semi-quantitative microscopic examination of sections stained according to the method of Best. Pathological-histological examinations of liver tissue samples in healthy animals, gravid or peripartal cows did not reveal lipid infiltration or cell degeneration, and hepatocytes were completely or partly filled with glycogen. In ketotic cows, pathological-histological examinations of liver tissue samples showed lipid infiltration and hepatocyte degeneration of different intensity. In only one ketotic cow, we determined a slight degree of lipid infiltration, there was a medium degree of lipid infiltration and degeneration in six cows, and three cows were found to have a grave form of fatty liver. The quantity of glycogen in hepatocytes is in negative correlation with the degree of lipid infiltration and degeneration. In severe cases of fatty liver, glycogen is completely absent from hepatocyte cytoplasm.

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

    International Nuclear Information System (INIS)

    To investigate the relationship between liver glucose, glycogen, and plasma glucose in diabetic patients, in vivo liver carbon-13 magnetic resonance spectroscopy (13C 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), 13C 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 [1-13C]glucose, was administered. The MR signals of liver [1-13C]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 13C 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, 13C MRS has a potential to become a powerful tool in diagnosing diabetes multilaterally.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-06-01

    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-/sup 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-05-01

    The effect of fructose on glycogen degradation was examined by measuring flux of (/sup 14/C) from prelabeled glycogen in perfused rat livers. During 2 h refeeding of fasted rats hepatic glycogen was labeled by injection of (U /sup 14/C) galactose (0.1 mg and 0.02 ..mu..Ci/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 ..mu..moles/g of liver with 1, 2, and 10 mM fructose. Maximum inhibition of phosphorylase was 82%; FIP concentration for half inhibition was 0.57 ..mu..moles/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.

  5. Dynamical changing pattems of glycogen and enzyme histochemical activities in rat liver graft undergoing warm ischemia injury

    Institute of Scientific and Technical Information of China (English)

    Xiao-Shun He; Yi Ma; Lin-Wei Wu; Jin-Lang Wu; Rui-De Hu; Gui-Hua Chen; Jie-Fu Huang

    2005-01-01

    AIM: To investigate the changing patterns of glycogen and enzyme histochemical activities in rat liver graft under a dif ferent warm ischemia time (WIT) and to predict the tolerant time limitation of the liver graft to warm ischemia injury.METHODS: The rats were randomized into five groups, WTT was 0, 15, 30, 45, 60 min, respectively, and histochemical staining of liver graft specimens was observed. The recovery changes of glycogen and enzyme histochemistry activities were measured respectively 6 and 24 h following liver graft implantation.RESULTS: The activities of succinic dehydrogenase, cytochrome oxidase, apyrase (Mg++-ATPase) and content of glycogen were decreased gradually after different WIT in a time-dependent manner. The changes were significant when WIT was over 30 min.CONCLUSION: Hepatic injury is reversible within 30 min of warm ischemia injury. Glycogen and enzyme histochemistry activities of liver grafts and their recovery potency after reperfusion may serve as criteria to evaluate the quality of liver grafts.

  6. Differences in glycogen, lipids, and enzymes in livers from rats flown on Cosmos 2044

    Science.gov (United States)

    Merrill, Alfred H., Jr.; Wang, Elaine; Laroque, Regina; Mullins, Richard E.; Morgan, Edward T.; Hargrove, James L.; Bonkovsky, Herbert L.; Popova, Irina A.

    1992-01-01

    Livers from rats flown aboard Cosmos 2044 were analyzed for protein, carbohydrate (glycogen), and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. The major differences between the flight group and the synchronous control were elevations in microsomal protein, liver glycogen content, tyrosine aminotransferase, and tryptophan oxygenase and reductions in sphingolipids and the rate-limiting enzyme of heme biosynthesis delta-aminolevulinic acid synthase. These results provide further evidence that spaceflight has pronounced and diverse effects on liver function; however, some of the results with samples from Cosmos 2044 differed notably from those from previous spaceflights. This may be due to conditions of spaceflight and/or the postflight recovery period for Cosmos 2044.

  7. Differences in glycogen, lipids, and enzymes in livers from rats flown on COSMOS 2044.

    Science.gov (United States)

    Merrill, A H; Wang, E; LaRocque, R; Mullins, R E; Morgan, E T; Hargrove, J L; Bonkovsky, H L; Popova, I A

    1992-08-01

    Livers from rats flown aboard COSMOS 2044 were analyzed for protein, carbohydrate (glycogen), and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. The major differences between the flight group and the synchronous control were elevations in microsomal protein, liver glycogen content, tyrosine aminotransferase, and tryptophan oxygenase and reductions in sphingolipids and the rate-limiting enzyme of heme biosynthesis, delta-aminolevulinic acid synthase. These results provide further evidence that spaceflight has pronounced and diverse effects on liver function; however, some of the results with samples from COSMOS 2044 differed notably from those from previous spaceflights. This may be due to conditions of spaceflight and/or the postflight recovery period for COSMOS 2044.

  8. Attenuation of Helicteres isora L. bark extracts on streptozotocin-induced alterations in glycogen and carbohydrate metabolism in albino rats.

    Science.gov (United States)

    Kumar, G; Sharmila Banu, G; Murugesan, A G

    2009-11-01

    The present study was undertaken to assess the effect of Helicteres isora L. on four important enzymes of carbohydrate metabolism (glucokinase [GK], hexokinase [HK] phosphofructokinase [PFK] and fructose-1, 6-bisphosphatase [FBP]) along with glycogen content of insulin-dependent (skeletal muscle and liver) and insulin-independent tissues (kidneys and brain) in streptozotocin (STZ; 60 mg/kg)-induced model of diabetes for 30 days. Administration of bark extracts (100, 200 mg/kg) for 30 days led to decrease in plasma glucose levels by approximately 9.60% and 22.04% and 19.18% and 33.93% on 15th and 30th day, respectively, of the experiment. Liver and two-kidney weight expressed as percentage of body weight significantly increased in diabetics (P bark extract of H. isora partially corrected this alteration. The efficacy of the bark extract was comparable with Tolbutamide, a well-known hypoglycemic drug.

  9. Muscle and liver glycogen, protein, and triglyceride in the rat. Effect of exercise and of the sympatho-adrenal system

    DEFF Research Database (Denmark)

    Richter, E A; Sonne, B; Mikines, K J;

    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...

  10. 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.

  11. 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 exercise can be restored by selenium administration. It can be argued that physiological doses of selenium administration can contribute to performance. PMID:20340052

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-03-01

    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-/sup 3/H,U-/sup 14/C)glucose into liver glycogen. Labeled glucose was injected into the portal vein at the end of meal-feeding. The ratio of /sup 3/H//sup 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 (/sup 3/H) and (/sup 14/C)-glycogen in rats infused with (3-/sup 3/H,U-/sup 14/C)glucose. No significant difference was found between the RSA of (/sup 3/H)glycogen and (/sup 14/C)glycogen, indicating further that the pathway for glycogen synthesis in liver from exogenous glucose is from the direct pathway.

  13. In vivo portal-hepatic venous gradients of glycogenic precursors and incorporation of D-(3- sup 3 H)glucose into liver glycogen in the awake rat

    Energy Technology Data Exchange (ETDEWEB)

    Dobson, G.P.; Veech, R.L.; Passonneau, J.V.; Huang, M.T. (National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (USA))

    1990-09-25

    Male Wistar fed rats were chronically cannulated and fed ground chow for 2 h for 6 days. On the 7th post-operative day, blood was simultaneously drawn from the portal and hepatic veins over a 2-h feeding period. The position of the hepatic vein cannula was verified using a tritiated water washout technique. In separate experiments, 200 microCi of (3-3H)glucose was added to the food in order to determine the contribution of D-glucose and 3-C precursors to newly synthesized glycogen. The 22-h fasting plasma portal vein concentrations of D-glucose, L-lactate, and L-alanine were 4.8 +/- 0.03, 0.81 +/- 0.06, and 0.20 +/- 0.03 mM, respectively (n = 5). The fasting hepatic vein plasma concentrations were 5.1 +/- 0.2, 0.70 +/- 0.15 and 0.19 +/- 0.03 mM, respectively. The portal-hepatic vein gradients after 22 h were -0.24, +0.16, and +0.01 mM for D-glucose, L-lactate, and L-alanine, respectively. At 20 min after beginning the meal, the respective gradients were +2.2, +0.53, and +0.44 mM, indicating hepatic uptake of all glycogen precursors. Of the total carbon from the three major precursors entering the liver as C-6, D-glucose contributed 82%, while alanine and lactate contributed 18% at 20 min. As portal vein D-glucose and L-alanine levels exceeded 6.65 +/- 0.69 and 0.32 +/- 0.07 mM, respectively, the portal-hepatic venous gradient became positive and increased linearly with portal concentrations. The glycogen concentration in the liver increased from a 22-h fast value of 5 mumol of glucosyl units/g wet weight to 101 +/- 7 mumol/g 2 h after the meal. The mean specific activity of portal vein plasma of (3-3H)glucose was 11,490 +/- 1,180 dpm/mumol (+/- S.E.) and that in the glycogen isolated from liver was 8,175 +/- 785 dpm/mumol of glycosyl units 2 h after the meal. The specific activity of liver (3H)glycogen relative to glucose after the meal was 0.73 +/- 0.08.

  14. Effects of maternal starvation on some blood metabolites, liver glycogen, birth weight and survival of piglets.

    Science.gov (United States)

    Ezekwe, M O

    1981-12-01

    Pregnant crossbred sows were assigned to three treatments during the third trimester of gestation for an evaluation of the effects of maternal starvation on fetal development and piglet survival. Two groups of sows were taken off feed (water and trace mineralized salt only) on days 93 and 107 of gestation, respectively; the third group was fed 1.82 kg of complete sow diet/day and served as the control. Litter size, gestation length and pig birth weight in the 7-day and 21-day starvation groups were not different from those in the control group (P less than .05). Liver weight was depressed (P greater than .05) among the 7-day and 21-day progeny. However, liver glycogen concentrations and total liver glycogen were unaffected. Maternal blood glucose decreased to a fasting but steady level, while free fatty acid (FFA) increased in the two starved groups. Blood glucose and FFA at birth were similar for all treatment groups; however, FFA increased in the progeny of sows in the 7-day (P greater than .05) and 21-day (P greater than .01) starvation groups at 48 hr of age. Blood glucose at 48 hr did not vary (P less than .05), but the control progeny showed a faster glucose utilization, suggesting a greater dependence on carbohydrate metabolism than in the progeny of starved dams. Survival rate at 72 hr of age was higher among 21-day (43.8%) and 7-day (37.5%) progeny than among control progeny (8.5%). The increased plasma FFA level observed with fasting in the progeny of starved dams might indicate a shift toward lipid metabolism, which would account for the improved survival observed among the progeny of treated dams.

  15. Ursolic acid and luteolin-7-glucoside improves rat plasma lipid profile and increases liver glycogen content through glycogen synthase kinase-3

    OpenAIRE

    Azevedo, Marisa; Camsari, Çagri; Sá, Carla M.; Lima, Cristóvão F.; Ferreira, Manuel Fernandes; Wilson, Cristina Pereira

    2010-01-01

    Documento submetido para revisão pelos pares. A publicar em Phytotherapy Research. ISSN 0951-418X 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 profi le (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 glucos...

  16. 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. T

  17. The effect of 3-methylcholanthrene and butylated hydroxytoluene on glycogen levels of liver, muscle, testis, and tumor tissues of rats

    OpenAIRE

    POLAT, Fikriye; DERE, Egemen; GÜL, Eylem; YELKUVAN, İzzet; ÖZDEMİR, Öztürk; BİNGÖL, Günsel

    2013-01-01

    This study examined the effects of separate and combined applications of 3-methylcholanthrene, a polycyclic aromatic hydrocarbon and potent carcinogenic agent, and butylated hydroxytoluene, the antioxidant food additive, on the glycogen levels of liver, muscle, testis, and tumor tissues in rats. Adult male Wistar albino rats weighing 100-110 g at 8 weeks of age were used in this study. This study consisted of a control group (n = 9) and 3 different experiment groups in which rats were chronic...

  18. Responsiveness of glycogen breakdown to cyclic AMP in perfused liver from rats with insulin-induced hypoglycemia

    Directory of Open Access Journals (Sweden)

    M. Vardanega-Peicher

    2003-01-01

    Full Text Available The responsiveness of glycogen breakdown to cAMP was investigated in isolated perfused liver from male Wistar fed rats (200-220 g with insulin-induced hypoglycemia. The activation of glycogenolysis by 3 µM cAMP was decreased (P<0.05 in livers from rats with hypoglycemia induced by the administration of insulin or during the direct infusion of insulin into the isolated liver. The direct effect of insulin on glycogen catabolism promoted by 3 µM cAMP occurred as early as 3 min after starting insulin infusion. In contrast, the cAMP agonists resistant to phosphodiesterases, 8Br-cAMP and 6MB-cAMP, used at the same concentration as cAMP, i.e., 3 µM, did not modify the effect of insulin. The data suggest that the decreased hepatic responsiveness of glycogen breakdown during insulin-induced hypoglycemia is a direct effect of insulin decreasing the intracellular levels of cAMP.

  19. 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/

  20. 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.

  1. Glycogen metabolism in humans.

    Science.gov (United States)

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

    2016-06-01

    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 transporters, phosphorylation of glucose to glucose 6-phosphate, isomerization to glucose 1-phosphate, and formation of uridine 5'-diphosphate-glucose, which is the direct glucose donor for glycogen synthesis. Glycogenin catalyzes the formation of a short glucose polymer that is extended by the action of glycogen synthase. Glycogen branching enzyme introduces branch points in the glycogen particle at even intervals. Laforin and malin are proteins involved in glycogen assembly but their specific function remains elusive in humans. Glycogen is accumulated in the liver primarily during the postprandial period and in the skeletal muscle predominantly after exercise. In the cytosol, glycogen breakdown or glycogenolysis is carried out by two enzymes, glycogen phosphorylase which releases glucose 1-phosphate from the linear chains of glycogen, and glycogen debranching enzyme which untangles the branch points. In the lysosomes, glycogen degradation is catalyzed by α-glucosidase. The glucose 6-phosphatase system catalyzes the dephosphorylation of glucose 6-phosphate to glucose, a necessary step for free glucose to leave the cell. Mutations in the genes encoding the enzymes involved in glycogen metabolism cause glycogen storage diseases. PMID:27051594

  2. 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...

  3. Cinnamon increases liver glycogen in an animal model of insulin resistance

    Science.gov (United States)

    Cinnamon, and aqueous polyphenol extracts of cinnamon, improve insulin sensitivity in vitro, and in animal and human studies. Given the relationship between the glucose/insulin system and glycogen metabolism, the objective of this study was to determine the effects of cinnamon on glycogen synthesis...

  4. 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 sucrose (2.03 ± 0.43 g/min) vs. glucose (1.66 ± 0.36 g/min; P 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.

  5. Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice

    Science.gov (United States)

    Udoh, Uduak S.; Swain, Telisha M.; Filiano, Ashley N.; Gamble, Karen L.; Young, Martin E.

    2015-01-01

    Chronic ethanol consumption has been shown to significantly decrease hepatic glycogen content; however, the mechanisms responsible for this adverse metabolic effect are unknown. In this study, we examined the impact chronic ethanol consumption has on time-of-day-dependent oscillations (rhythms) in glycogen metabolism processes in the liver. For this, male C57BL/6J mice were fed either a control or ethanol-containing liquid diet for 5 wk, and livers were collected every 4 h for 24 h and analyzed for changes in various genes and proteins involved in hepatic glycogen metabolism. Glycogen displayed a robust diurnal rhythm in the livers of mice fed the control diet, with the peak occurring during the active (dark) period of the day. The diurnal glycogen rhythm was significantly altered in livers of ethanol-fed mice, with the glycogen peak shifted into the inactive (light) period and the overall content of glycogen decreased compared with controls. Chronic ethanol consumption further disrupted diurnal rhythms in gene expression (glycogen synthase 1 and 2, glycogenin, glucokinase, protein targeting to glycogen, and pyruvate kinase), total and phosphorylated glycogen synthase protein, and enzyme activities of glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes of glycogen metabolism. In summary, these results show for the first time that chronic ethanol consumption disrupts diurnal rhythms in hepatic glycogen metabolism at the gene and protein level. Chronic ethanol-induced disruption in these daily rhythms likely contributes to glycogen depletion and disruption of hepatic energy homeostasis, a recognized risk factor in the etiology of alcoholic liver disease. PMID:25857999

  6. A metabolic link between mitochondrial ATP synthesis and liver glycogen metabolism: NMR study in rats re-fed with butyrate and/or glucose

    Directory of Open Access Journals (Sweden)

    Beauvieux Marie-Christine

    2011-06-01

    Full Text Available Abstract Background Butyrate, end-product of intestinal fermentation, is known to impair oxidative phosphorylation in rat liver and could disturb glycogen synthesis depending on the ATP supplied by mitochondrial oxidative phosphorylation and cytosolic glycolysis. Methods In 48 hr-fasting rats, hepatic changes of glycogen and total ATP contents and unidirectional flux of mitochondrial ATP synthesis were evaluated by ex vivo 31P NMR immediately after perfusion and isolation of liver, from 0 to 10 hours after force-feeding with (butyrate 1.90 mg + glucose 14.0 mg.g-1 body weight or isocaloric glucose (18.2 mg.g-1 bw; measurements reflected in vivo situation at each time of liver excision. The contribution of energetic metabolism to glycogen metabolism was estimated. Results A net linear flux of glycogen synthesis (~11.10 ± 0.60 μmol glucosyl units.h-1.g-1 liver wet weight occurred until the 6th hr post-feeding in both groups, whereas butyrate delayed it until the 8th hr. A linear correlation between total ATP and glycogen contents was obtained (r2 = 0.99 only during net glycogen synthesis. Mitochondrial ATP turnover, calculated after specific inhibition of glycolysis, was stable (~0.70 ± 0.25 μmol.min-1.g-1 liver ww during the first two hr whatever the force-feeding, and increased transiently about two-fold at the 3rd hr in glucose. Butyrate delayed the transient increase (1.80 ± 0.33 μmol.min-1.g-1 liver ww to the 6th hr post-feeding. Net glycogenolysis always appeared after the 8th hr, whereas flux of mitochondrial ATP synthesis returned to near basal level (0.91 ± 0.19 μmol.min-1.g-1 liver ww. Conclusion In liver from 48 hr-starved rats, the energy need for net glycogen synthesis from exogenous glucose corresponds to ~50% of basal mitochondrial ATP turnover. The evidence of a late and transient increase in mitochondrial ATP turnover reflects an energetic need, probably linked to a glycogen cycling. Butyrate, known to reduce oxidative

  7. Glycogen levels and energy status of the liver of fasting rats with diabetes types 1 and 2

    Directory of Open Access Journals (Sweden)

    Denise Silva de Oliveira

    2007-09-01

    Full Text Available Glycogen levels and the energy status of livers from fasting rats with diabetes types 1 and 2 were measured. After a 24 h fast, the hepatic glycogen levels of rats with diabetes1 and diabetes2 were, 18.7 and 2.6 times higher, respectively, than those of livers from the normal rats. In diabetes1 rats, the glycogen levels decreased when the fasting period was extended to 48 and 72 h. The opposite occurred with the control and diabetes2 rats. Consistently, glucose release by the perfused livers from diabetes1 rats was considerably higher during at least 60 minutes after initiating perfusion. The hepatic ATP content of diabetes1 rats was similar to that of the control rats; in diabetes2 rats, the hepatic ATP content was increased. It could be concluded that regulation of glycogen deposition and degradation in rats with diabetes1 differed markedly from that of rats with diabetes2 which, in turn, behaved similarly to normal healthy rats.Teores de glicogênio e os estados energéticos de fígados de ratos com diabete dos tipos 1 e 2 foram medidos. Após um jejum de 24 horas os teores de glicogênio de ratos com diabete1 e diabete2 foram, respectivamente 18,7 e 2,6 vezes superiores àqueles de fígados de animais controle. Em ratos com diabete1 o conteúdo de glicogênio diminuiu quando o período de jejum foi prolongado para 48 e 72 horas. O oposto ocorreu em ratos controle e ratos com diabete2. Consistentemente, a liberação de glicose por fígados em perfusão isolada obtidos de ratos com diabete1 foi consideravelmente maior durante ao menos 60 minutos após o início da perfusão. O conteúdo hepático de ATP de ratos com diabete1 foi similar àquele de ratos controle; em ratos com diabete2 o conteúdo hepático de ATP foi maior. Pode-se concluir que a regulação da deposição e degradação do glicogênio em ratos com diabete1 difere marcadamente daquela de ratos com diabete2, os quais, por seu turno, comportam-se similarmente a ratos normais e

  8. Single valproic acid treatment inhibits glycogen and RNA ribose turnover while disrupting glucose-derived cholesterol synthesis in liver as revealed by the [U-C(6)]-d-glucose tracer in mice.

    Science.gov (United States)

    Beger, Richard D; Hansen, Deborah K; Schnackenberg, Laura K; Cross, Brandie M; Fatollahi, Javad J; Lagunero, F Tracy; Sarnyai, Zoltan; Boros, Laszlo G

    2009-09-01

    Previous genetic and proteomic studies identified altered activity of various enzymes such as those of fatty acid metabolism and glycogen synthesis after a single toxic dose of valproic acid (VPA) in rats. In this study, we demonstrate the effect of VPA on metabolite synthesis flux rates and the possible use of abnormal (13)C labeled glucose-derived metabolites in plasma or urine as early markers of toxicity. Female CD-1 mice were injected subcutaneously with saline or 600 mg/kg) VPA. Twelve hours later, the mice were injected with an intraperitoneal load of 1 g/kg [U-(13)C]-d-glucose. (13)C isotopomers of glycogen glucose and RNA ribose in liver, kidney and brain tissue, as well as glucose disposal via cholesterol and glucose in the plasma and urine were determined. The levels of all of the positional (13)C isotopomers of glucose were similar in plasma, suggesting that a single VPA dose does not disturb glucose absorption, uptake or hepatic glucose metabolism. Three-hour urine samples showed an increase in the injected tracer indicating a decreased glucose re-absorption via kidney tubules. (13)C labeled glucose deposited as liver glycogen or as ribose of RNA were decreased by VPA treatment; incorporation of (13)C via acetyl-CoA into plasma cholesterol was significantly lower at 60 min. The severe decreases in glucose-derived carbon flux into plasma and kidney-bound cholesterol, liver glycogen and RNA ribose synthesis, as well as decreased glucose re-absorption and an increased disposal via urine all serve as early flux markers of VPA-induced adverse metabolic effects in the host.

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

    OpenAIRE

    Andrew Specht; Laurie Fiske; Kirsten Erger; Travis Cossette; John Verstegen; Martha Campbell-Thompson; Struck, Maggie B.; Young Mok Lee; 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,...

  10. Intraorgan differences of blood flow, oxygen supply and glycogen content in the multilobular liver of normal and hemorrhagic rats.

    Science.gov (United States)

    Metzger, H P; Schywalsky, M

    1992-02-01

    In order to characterize intraorgan differences in blood supply of the rat liver, hepatic blood flow (HBF), surface oxygen tension (sPO2) and glycogen content of the largest and smallest lobi have been determined for normal and hemorrhagic rats (N = 68) in ketamin-xylazine anesthesia. 1. Mean HBF +/- SD of lobus sinister measured 1.07 +/- 0.23 ml/g min (n = 119 determinations, N = 9 rats); HBF of lob. caudatus dexter showed a left-shifted histogram (mean value = 0.77 ml/g.min, median = 0.72 ml/g.min, modul = 0.63 ml/g.min, p less than 0.005). 2. Mean sPO2 +/- SD of lob. sin. measured 23 +/- 6.8 mm Hg (n = 168, N = 16). The histograms of lob. caudat. dext. and sin. were left-shifted (mean value of l.c.d. = 9 mm Hg, median = 4 mm Hg, modul = 0 mm Hg, mean value of l.c.s. = 16 mm Hg, median = 17 mm Hg, modul = 0 mm Hg). Under hemorrhage sPO2 became almost zero in 91% of the measurements. 3. In response to an arterial bolus of fluorescence stained gamma-globulins, spreading of the dye showed a pronounced front and marked periportal area within lob. sin., while an irregular convective front and a much smaller area were detected within both of the lobi caudati. Under hemorrhage, intersinusoidal staining and undefined, irregular contours were observed within all lobes. 4. Compared with lob. sin. preferential glycogen depletion and partial centrilobular necrosis were detected within both of the lob. caudati while under hemorrhage the glycogen stores were empty and severe group necroses have been observed especially within the small lobi. From the data it is concluded that in comparison to lob. sin. an insufficient supply and pronounced vulnerability against hepatic ischemia exists within the small lobi caudati.

  11. Inhibition of glycogen synthase kinase 3β promotes autophagy to protect mice from acute liver failure mediated by peroxisome proliferator-activated receptor α

    OpenAIRE

    Ren, F.; Zhang, L; Zhang, X; Shi, H; T. Wen; Bai, L.; S. Zheng; Y. Chen; Chen, D.; Li, L.; Duan, Z

    2016-01-01

    Our previous studies have demonstrated that inhibition of glycogen synthase kinase 3β (GSK3β) activity protects mice from acute liver failure (ALF), whereas its protective and regulatory mechanism remains elusive. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of the present study was to test the hypothesis that inhibition of GSK3β mediates autophagy to inhibit liver inflammation and protect against ALF. In ALF mice model induced by d-gala...

  12. Factors Altering Pyruvate Excretion in a Glycogen Storage Mutant of the Cyanobacterium, Synechococcus PCC7942.

    Science.gov (United States)

    Benson, Phoebe J; Purcell-Meyerink, Diane; Hocart, Charles H; Truong, Thy T; James, Gabriel O; Rourke, Loraine; Djordjevic, Michael A; Blackburn, Susan I; Price, G D

    2016-01-01

    Interest in the production of carbon commodities from photosynthetically fixed CO2 has focused attention on cyanobacteria as a target for metabolic engineering and pathway investigation. We investigated the redirection of carbon flux in the model cyanobacterial species, Synechococcus elongatus PCC 7942, under nitrogen deprivation, for optimized production of the industrially desirable compound, pyruvate. Under nitrogen limited conditions, excess carbon is naturally stored as the multi-branched polysaccharide, glycogen, but a block in glycogen synthesis, via knockout mutation in the gene encoding ADP-glucose pyrophosphorylase (glgC), results in the accumulation of the organic acids, pyruvate and 2-oxoglutarate, as overflow excretions into the extracellular media. The ΔglgC strain, under 48 h of N-deprivation was shown to excrete pyruvate for the first time in this strain. Additionally, by increasing culture pH, to pH 10, it was possible to substantially elevate excretion of pyruvate, suggesting the involvement of an unknown substrate/proton symporter for export. The ΔglgC mutant was also engineered to express foreign transporters for glucose and sucrose, and then grown photomixotrophically with exogenous organic carbon supply, as added 5 mM glucose or sucrose during N- deprivation. Under these conditions we observed a fourfold increase in extracellular pyruvate excretion when glucose was added, and a smaller increase with added sucrose. Although the magnitude of pyruvate excretion did not correlate with the capacity of the ΔglgC strain for bicarbonate-dependent photosynthetic O2 evolution, or with light intensity, there was, however, a positive correlation observed between the density of the starter culture prior to N-deprivation and the final extracellular pyruvate concentration. The factors that contribute to enhancement of pyruvate excretion are discussed, as well as consideration of whether the source of carbon for pyruvate excretion might be derived from

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

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    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.

  14. 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

    Liver phosphorylase a activity in intact animals is mostly determined during anesthesia. The aim of this study was to investigate the effect of administering pentobarbital by different routes on activity of liver phosphorylase a. Rats had chronically implanted venous catheters and received pentob...... by differences in duration before the drug takes effect. It is proposed that intraperitoneal injection of pentobarbital may anesthetize hepatic sympathetic nerves or have a direct inhibiting effect on phosphorylase a activity....

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

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    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.

  16. Metformin protects the skeletal muscle glycogen stores against alterations inherent to functional limitation

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    Paula Lima Bosi

    2008-04-01

    Full Text Available The aim of this study was to evaluate the glycogen content (GC of the rat hind limb muscles submitted to joint immobilization, either associated with metformin treatment (M, 1,4mg.ml-1 or not. In the metformin group, there was a significant increase in the GC (soleus - S 65% , white gastrocnemius - WG 30.5%, red gastrocnemius- RG31.7%, extensor digitorum longus - EDL 44%, tibialis anterior- TA 77.4%. The immobilization significantly reduced the GC (S 31.6%, WG 56.6%, RG 39.1%, ELD 41.7%, TA 45.2% and weight (S 34.2% and ELD 27%, whereas in the group immobilized with the metformin, there was an increase in the GC of all the muscles (S 177%, WG 290%, RG 172%,ELD 47%, TA 217%, in addition to minimizing the weight loss of S (29.6% and ELD (27.8%.O objetivo deste estudo foi avaliar o conteúdo de glicogênio (GLI da musculatura da pata posterior de ratos submetidos à imobilização articular, associado ou não ao tratamento com metformina (MET, 1,4 mg.ml -1 no período de sete dias. No grupo metformina, houve elevação significativa nas RG (65% no sóleo - S, 30.5% no gastrocnêmio branco - GB, 31.7% no gastrocnêmio vermelho - GV , 44% no extensor longo dos dedos - EDL e de 77.4% no tibial anterior - TA . A imobilização reduziu significativamente as RG (S 31,6%, GB 56,6%, GV 39,1%, ELD 41,7%, TA 45,2% e peso (S 34,2% e ELD 27%, já no grupo imobilizado com metformina houve o aumento das RG de todos os músculos (S 177%, GB 290%, GV 172%,EDL 47%, TA 217%, além de minimizar a perda de peso do S (29,6% e ELD (27,8%.

  17. 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.

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    Kuralay Atageldiyeva

    Full Text Available 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.

  18. 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. PMID:27327650

  19. Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism.

    Science.gov (United States)

    Abruzzese, Giselle Adriana; Heber, Maria Florencia; Ferreira, Silvana Rocio; Velez, Leandro Martin; Reynoso, Roxana; Pignataro, Omar Pedro; Motta, Alicia Beatriz

    2016-07-01

    Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis. PMID:27179108

  20. Effects of /sup 45/Ca on murine skeletal muscle. 1. Alterations of glycogen, phosphorylase and phosphohexose isomerase levels

    Energy Technology Data Exchange (ETDEWEB)

    Asotra, K.; Katoch, S.S.; Krishan, K.; Malhotra, R.K. (Himachal Pradesh Univ., Simla (India). Dept. of Bio-sciences)

    1983-01-01

    Adult Swiss albino mice weighing 16+-1 g were injected with 3.7x10/sup 4/ Bq and 7.4x10/sup 4/ Bq/g body weight of /sup 45/Ca. Mice of both dose groups were autopsied on days 1, 3, 5, 7, 14 and 28 after /sup 45/Ca administration. Diaphragm and gastrocnemius in the /sup 45/Ca-treated and normal mice were analyzed for quantitation of glycogen as well as bioassay of phosphorylase and phosphohexose isomerase activities. Internal irradiation with the two doses of /sup 45/Ca resulted in glycogen accumulation in both the muscles. /sup 45/Ca-treated diaphragm showed greater radioresponse but a slower recovery than gastrocnemius with respect to glycogen accumulation. A decline in the rates of glycogenolysis and glycolysis indicated by decreased phosphorylase and phosphohexose isomerase activities appeared to be responsible for glycogen accumulation in skeletal muscle on account of /sup 45/Ca treatment.

  1. Quantifying hepatic glycogen synthesis by direct and indirect pathways in rats under normal ad libitum feeding conditions.

    Science.gov (United States)

    Soares, Ana F; Viega, Francisco J; Carvalho, Rui A; Jones, John G

    2009-01-01

    Hepatic glycogen synthesis from intact hexose (direct pathway) relative to that from gluconeogenic precursors (indirect pathway) was quantified in ad libitum-fed rats. Following (2)H(2)O administration and overnight feeding, the livers were removed and glycogen (2)H-enrichment was measured by (2)H NMR. Six controls and six rats rendered hyperglycemic by streptozotocin (STZ; fasting blood glucose = 385 +/- 31 mg/dl) were studied. The indirect pathway contribution, estimated as glycogen hydrogen 5 relative to hydrogen 2 enrichment, was 54% +/- 4% for control rats-similar to values from healthy, meal-fed humans. In STZ-treated rats, the indirect pathway contribution was significantly higher (68% +/- 4%, P diabetic (T1D) patients. In conclusion, sources of hepatic glycogen synthesis in rats during ad libitum nocturnal feeding were quantified by analysis of glycogen enrichment from (2)H(2)O. STZ caused alterations resembling the pathophysiology of hepatic glycogen synthesis in T1D patients.

  2. 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...

  3. Brain glycogen – new perspectives on its metabolic function and regulation at the subcellular level

    Directory of Open Access Journals (Sweden)

    Linea Frimodt Obel

    2012-03-01

    Full Text Available 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 underlying glycogen metabolism. Based on i the compartmentation of the interconnected second messenger pathways controlling glycogen metabolism (calcium and cAMP, ii alterations in the subcellular location of glycogen-associated enzymes and proteins induced by the metabolic status and iii a sequential component in the intermolecular mechanisms of glycogen metabolism, we suggest that glycogen metabolism in astrocytes is compartmentalized at the subcellular level. As a consequence, the meaning and importance of conventional terms used to describe glycogen metabolism (e.g. turnover is challenged. Overall, this review represents an overview of contemporary knowledge about brain glycogen and its metabolism and function. However, it also has a sharp focus on what we do not know, which is perhaps even more important for the future quest of uncovering the roles of glycogen in brain physiology and pathology.

  4. 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.

  5. Alteration of N-glycans and Expression of Their Related Glycogenes in the Epithelial-Mesenchymal Transition of HCV29 Bladder Epithelial Cells

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    Jia Guo

    2014-12-01

    Full Text Available The epithelial-mesenchymal transition (EMT is an essential step in the proliferation and metastasis of solid tumor cells, and glycosylation plays a crucial role in the EMT process. Certain aberrant glycans have been reported as biomarkers during bladder cancer progression, but global variation of N-glycans in this type of cancer has not been previously studied. We examined the profiles of N-glycan and glycogene expression in transforming growth factor-beta (TGFβ-induced EMT using non-malignant bladder transitional epithelium HCV29 cells. These expression profiles were analyzed by mass spectrometry, lectin microarray analysis, and GlycoV4 oligonucleotide microarray analysis, and confirmed by lectin histochemistry and real-time RT-PCR. The expression of 5 N-glycan-related genes were notably altered in TGFβ-induced EMT. In particular, reduced expression of glycogene man2a1, which encodes α-mannosidase 2, contributed to the decreased proportions of bi-, tri- and tetra-antennary complex N-glycans, and increased expression of hybrid-type N-glycans. Decreased expression of fuca1 gene, which encodes Type 1 α-L-fucosidase, contributed to increased expression of fucosylated N-glycans in TGFβ-induced EMT. Taken together, these findings clearly demonstrate the involvement of aberrant N-glycan synthesis in EMT in these cells. Integrated glycomic techniques as described here will facilitate discovery of glycan markers and development of novel diagnostic and therapeutic approaches to bladder cancer.

  6. 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

  7. Modeling function-perfusion behavior in liver lobules including tissue, blood, glucose, lactate and glycogen by use of a coupled two-scale PDE-ODE approach.

    Science.gov (United States)

    Ricken, T; Werner, D; Holzhütter, H G; König, M; Dahmen, U; Dirsch, O

    2015-06-01

    This study focuses on a two-scale, continuum multicomponent model for the description of blood perfusion and cell metabolism in the liver. The model accounts for a spatial and time depending hydro-diffusion-advection-reaction description. We consider a solid-phase (tissue) containing glycogen and a fluid-phase (blood) containing glucose as well as lactate. The five-component model is enhanced by a two-scale approach including a macroscale (sinusoidal level) and a microscale (cell level). The perfusion on the macroscale within the lobules is described by a homogenized multiphasic approach based on the theory of porous media (mixture theory combined with the concept of volume fraction). On macro level, we recall the basic mixture model, the governing equations as well as the constitutive framework including the solid (tissue) stress, blood pressure and solutes chemical potential. In view of the transport phenomena, we discuss the blood flow including transverse isotropic permeability, as well as the transport of solute concentrations including diffusion and advection. The continuum multicomponent model on the macroscale finally leads to a coupled system of partial differential equations (PDE). In contrast, the hepatic metabolism on the microscale (cell level) was modeled via a coupled system of ordinary differential equations (ODE). Again, we recall the constitutive relations for cell metabolism level. A finite element implementation of this framework is used to provide an illustrative example, describing the spatial and time-depending perfusion-metabolism processes in liver lobules that integrates perfusion and metabolism of the liver.

  8. Glycogen storage diseases: New perspectives

    Institute of Scientific and Technical Information of China (English)

    Hasan (O)zen

    2007-01-01

    Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism. Different hormones,including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20 000-43 000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle,or both. Type Ⅰ a involves the liver, kidney and intestine (and Ⅰ b also leukocytes), and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia,hyperlactatemia, hyperuricemia and hyperlipidemia. Type Ⅲa involves both the liver and muscle, and Ⅲb solely the liver. The liver symptoms generally improve with age.Type Ⅳ usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type Ⅵ and Ⅸ are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia.Type Ⅺ is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type Ⅱ is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types Ⅴ and Ⅶ involve only the muscle.

  9. Implication of altered proteasome function in alcoholic liver injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The proteasome is a major protein-degrading enzyme,which catalyzes degradation of oxidized and aged proteins, signal transduction factors and cleaves peptides for antigen presentation. Proteasome exists in the equilibrium of 26S and 20S particles. Proteasome function is altered by ethanol metabolism, depending on oxidative stress levels: low oxidative stress induces proteasome activity, while high oxidative stress reduces it. The proposed mechanisms for modulation of proteasome activity are related to oxidative modification of proteasomal proteins with primary and secondary products derived from ethanol oxidation.Decreased proteolysis by the proteasome results in the accumulation of insoluble protein aggregates, which cannot be degraded by proteasome and which further inhibit proteasome function. Mallory bodies, a common signature of alcoholic liver diseases, are formed by liver cells, when proteasome is unable to remove cytokeratins.Proteasome inhibition by ethanol also promotes the accumulation of pro-apoptotic factors in mitochondria of ethanol-metabolizing liver cells that are normally degraded by proteasome. In addition, decreased proteasome function also induces accumulation of the negative regulators of cytokine signaling (Ⅰ-κB and SOCS), thereby blocking cytokine signal transduction.Finally, ethanol-elicited blockade of interferon type 1 and 2 signaling and decreased proteasome function impairs generation of peptides for MHC class Ⅰ-restricted antigen presentation.

  10. Biomarker for Glycogen Storage Diseases

    Science.gov (United States)

    2016-08-25

    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

  11. Brain glycogen decreases during prolonged exercise

    Science.gov (United States)

    Matsui, Takashi; Soya, Shingo; Okamoto, Masahiro; Ichitani, Yukio; Kawanaka, Kentaro; Soya, Hideaki

    2011-01-01

    Abstract Brain glycogen could be a critical energy source for brain activity when the glucose supply from the blood is inadequate (hypoglycaemia). Although untested, it is hypothesized that during prolonged exhaustive exercise that induces hypoglycaemia and muscular glycogen depletion, the resultant hypoglycaemia may cause a decrease in brain glycogen. Here, we tested this hypothesis and also investigated the possible involvement of brain monoamines with the reduced levels of brain glycogen. For this purpose, we exercised male Wistar rats on a treadmill for different durations (30–120 min) at moderate intensity (20 m min−1) and measured their brain glycogen levels using high-power microwave irradiation (10 kW). At the end of 30 and 60 min of running, the brain glycogen levels remained unchanged from resting levels, but liver and muscle glycogen decreased. After 120 min of running, the glycogen levels decreased significantly by ∼37–60% in five discrete brain loci (the cerebellum 60%, cortex 48%, hippocampus 43%, brainstem 37% and hypothalamus 34%) compared to those of the sedentary control. The brain glycogen levels in all five regions after running were positively correlated with the respective blood and brain glucose levels. Further, in the cortex, the levels of methoxyhydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), potential involved in degradation of the brain glycogen, increased during prolonged exercise and negatively correlated with the glycogen levels. These results support the hypothesis that brain glycogen could decrease with prolonged exhaustive exercise. Increased monoamines together with hypoglycaemia should be associated with the development of decreased brain glycogen, suggesting a new clue towards the understanding of central fatigue during prolonged exercise. PMID:21521757

  12. Visceral adiposity influences glucose and glycogen metabolism in control and hyperlipidic-fed animals

    Directory of Open Access Journals (Sweden)

    Danielle Kaiser de Souza

    2013-04-01

    Full Text Available Introduction: Evidences suggest that fat intake, visceral obesity and intracellular lipids are related to insulin impairment. Objective: The objective of the present paper was correlate visceral obesity and metabolic alterations in control (CTR and hyperlipidic cafeteria diet (CFT fed animals. Methods: After 6 months of diet treatment, liver and muscle of the male rats were utilized to determined glucose uptake and glycogen metabolism after administration of 0.4I U/kg insulin in vivo, and correlate the visceral adiposity to these two parameters. Results: Ample range of physiologic answers to body composition in metabolic profile of the both diets was found. No differences were found in glycemia and triacylglycerol after insulin action in both groups, however CFT group accumulated higher adiposity, mostly visceral fat, and showed lower glycogen content in the liver. We also found an inverse correlation between visceral adiposity and glucose uptake and a decrease of the glycogen synthase active form in the liver. CTR animals demonstrated an inverse correlation between glucose uptake and visceral adiposity in the muscle. Discussion and conclusion: It was observed a variability of metabolic alterations in animals which can be related to degree of accumulation of abdominal adiposity and ingestion of diet fats. Further studies will be required to clarify the reasons for the observed liver alterations in CFT and muscle alterations in CTR animals.

  13. Csf2 Null Mutation Alters Placental Gene Expression and Trophoblast Glycogen Cell and Giant Cell Abundance in Mice1

    OpenAIRE

    Sferruzzi-Perri, Amanda N.; Macpherson, Anne M.; Roberts, Claire T.; Robertson, Sarah A.

    2009-01-01

    Genetic deficiency in granulocyte-macrophage colony-stimulating factor (CSF2, GM-CSF) results in altered placental structure in mice. To investigate the mechanism of action of CSF2 in placental morphogenesis, the placental gene expression and cell composition were examined in Csf2 null mutant and wild-type mice. Microarray and quantitative RT-PCR analyses on Embryonic Day (E) 13 placentae revealed that the Csf2 null mutation caused altered expression of 17 genes not previously known to be ass...

  14. Synthetic, enzyme kinetic, and protein crystallographic studies of C-β-d-glucopyranosyl pyrroles and imidazoles reveal and explain low nanomolar inhibition of human liver glycogen phosphorylase.

    Science.gov (United States)

    Kantsadi, Anastassia L; Bokor, Éva; Kun, Sándor; Stravodimos, George A; Chatzileontiadou, Demetra S M; Leonidas, Demetres D; Juhász-Tóth, Éva; Szakács, Andrea; Batta, Gyula; Docsa, Tibor; Gergely, Pál; Somsák, László

    2016-11-10

    C-β-d-Glucopyranosyl pyrrole derivatives were prepared in the reactions of pyrrole, 2-, and 3-aryl-pyrroles with O-peracetylated β-d-glucopyranosyl trichloroacetimidate, while 2-(β-d-glucopyranosyl) indole was obtained by a cross coupling of O-perbenzylated β-d-glucopyranosyl acetylene with N-tosyl-2-iodoaniline followed by spontaneous ring closure. An improved synthesis of O-perbenzoylated 2-(β-d-glucopyranosyl) imidazoles was achieved by reacting C-glucopyranosyl formimidates with α-aminoketones. The deprotected compounds were assayed with isoforms of glycogen phosphorylase (GP) to show no activity of the pyrroles against rabbit muscle GPb. The imidazoles proved to be the best known glucose derived inhibitors of not only the muscle enzymes (both a and b) but also of the pharmacologically relevant human liver GPa (Ki = 156 and 26 nM for the 4(5)-phenyl and -(2-naphthyl) derivatives, respectively). An X-ray crystallographic study of the rmGPb-imidazole complexes revealed structural features of the strong binding, and also allowed to explain the absence of inhibition for the pyrrole derivatives. PMID:27522507

  15. Radiation and cadmium induced histological alteration in the mice liver

    International Nuclear Information System (INIS)

    Healthy male Swiss albino mice (6-8 weeks old) were procured from CCS Agricultural University, Hissar and maintained at 20-25 degree celcius. The animals were housed in polypropylene cages and maintained on balanced mice feed and tap water ad libitum. Cobalt gamma radiotherapy source (Thearton, Canada) was used to irradiate the animals.The animals were irradiated at the dose rate of 0.97 Gy/Min. The aqueous solution of cadmium chloride (20 ppm) was administered orally in drinking water. For the purpose the animals were divided into the following groups. Group-I included sham irradiated animals and served as normal.The animal of Group-II were treated with cadmium chloride through out the experiment. The mice of group-Ill were irradiated with 1.25, 2.5 and 5.0 Gy of gamma rays. The animals of group-IV were treated with cadmium chloride and also exposed to 1.25, 2.5 and 5.0 Gy of gamma rays. Five animals were autopsied by cervical dislocation from every set of experiment and each post treatment interval of 1, 2, 4, 7, 14 and 28 days. The weight of animals was recorded. For histopathological studies pieces of liver were fixed in Bouins fixative for 24 hrs. The tissues were washed in water to remove excess of the fixative, dehydrated in graded series of alcohol, cleared in xylene and embedded in paraffin wax. Section were cut at 5 micrometer and stained in Harris heametoxylene and alcoholic eosin. The histopathological changes included cytoplasmic degranulation, vaculation, pycnotic nuclei, giant cells, binucleated cells and enucleation. Hyperaemia and leucocytic infilteration were also noticed. The changes were more marked on day 7 but on day 14 the sign of recovery were observed and on day 28 comparatively better hepatic architecture were observed. The synergistic additive changes were seen in the liver after the combined treatment of gamma radiation and cadmium chloride. From present finding it could de deduced that the liver of Swiss albino mice suffered with

  16. RENAL COMPLICATIONS IN GLYCOGEN-STORAGE-DISEASE TYPE-I

    NARCIS (Netherlands)

    REITSMABIERENS, WCC

    1993-01-01

    Deficiency of the enzyme glucose-6-phosphatase is the biochemical defect in glycogen storage disease type I (GSD I). Normally this enzyme is present in the liver, intestine and kidneys. The lack of the enzyme in the kidney makes it obvious that glycogen storage will not be restricted to the liver bu

  17. 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. PMID:26835382

  18. Resistin disrupts glycogen synthesis under high insulin and high glucose levels by down-regulating the hepatic levels of GSK3β.

    Science.gov (United States)

    Song, Rongjing; Wang, Xi; Mao, Yiqing; Li, Hui; Li, Zhixin; Xu, Wei; Wang, Rong; Guo, Tingting; Jin, Ling; Zhang, Xiaojing; Zhang, Yizhuang; Zhou, Na; Hu, Ruobi; Jia, Jianwei; Lei, Zhen; Irwin, David M; Niu, Gang; Tan, Huanran

    2013-10-15

    The effect of mouse resistin on hepatic insulin resistance in vivo and in vitro, and its possible molecular mechanism were examined. Focusing on liver glycogen metabolism and gluconeogenesis, which are important parts of glucose metabolism, in primary cultures of rat hepatocytes we found that glycogen content was significantly lower (Pchange observed being the level of phosphorylated (at Ser 9) glycogen synthase kinase-3β (GSK-3β) (Pforms were observed between control and resistin treated primary rat hepatocytes. In a mouse model with high liver-specific expression of resistin, fasting blood glucose levels and liver glycogen content changed. Fasting blood glucose levels were significantly higher (P<0.001) in the model mice, compared to the control mice, while the glycogen content of the liver tissue was about 60% of that of the control mice (P<0.05). The gluconeogenic response was not altered between the experimental and control mice. The level of phosphorylated GSK-3β in the liver tissue was also decreased (P<0.05) in the model mice, consistent with the results from the primary rat hepatocytes. Our results suggest that resistin reduces the levels of GSK-3β phosphorylated at Ser 9 leading to impaired hepatic insulin action in primary rat hepatocytes and in a mouse model with high liver-specific expression of resistin. PMID:23860320

  19. Liver autofluorescence properties in animal model under altered nutritional conditions.

    Science.gov (United States)

    Croce, Anna Cleta; De Simone, Uliana; Vairetti, Mariapia; Ferrigno, Andrea; Boncompagni, Eleonora; Freitas, Isabel; Bottiroli, Giovanni

    2008-09-01

    Autofluorescence spectroscopy is a promising and powerful approach for an in vivo, real time characterization of liver functional properties. In this work, preliminary results on the dependence of liver autofluorescence parameters on the nutritional status are reported, with particular attention to vitamin A and lipid accumulation in liver tissue. Normally fed and 24 h starving rats were used as animal models. Histochemical and autofluorescence analysis showed that lipids and vitamin A colocalize in the liver parenchyma. Fasting condition results in a parallel increase in both lipids and vitamin A. Autofluorescence imaging and microspectrofluorometric analysis carried out on unfixed, unstained tissue sections under 366 nm excitation, evidenced differences in both spectral shape and response to continuous irradiation between liver biopsies from fed and starving rats. As to photobleaching, in particular, fitting analysis evidenced a reduction of about 85% of the signal attributable solely to vitamin A during the first 10 s of irradiation. The tissue whole emission measured in fed and starving rat livers exhibited reductions of about 35% and 52%, respectively, that are closely related to vitamin A contents. The findings open interesting perspectives for the set up of an in situ, real time diagnostic procedure for the assessment of liver lipid accumulation, exploiting the photophysical properties of vitamin A. PMID:18754051

  20. 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

  1. Hypoxia and fatty liver

    OpenAIRE

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-01-01

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty li...

  2. The alterations in the extracellular matrix composition guide the repair of damaged liver tissue.

    Science.gov (United States)

    Klaas, Mariliis; Kangur, Triin; Viil, Janeli; Mäemets-Allas, Kristina; Minajeva, Ave; Vadi, Krista; Antsov, Mikk; Lapidus, Natalia; Järvekülg, Martin; Jaks, Viljar

    2016-01-01

    While the cellular mechanisms of liver regeneration have been thoroughly studied, the role of extracellular matrix (ECM) in liver regeneration is still poorly understood. We utilized a proteomics-based approach to identify the shifts in ECM composition after CCl4 or DDC treatment and studied their effect on the proliferation of liver cells by combining biophysical and cell culture methods. We identified notable alterations in the ECM structural components (eg collagens I, IV, V, fibronectin, elastin) as well as in non-structural proteins (eg olfactomedin-4, thrombospondin-4, armadillo repeat-containing x-linked protein 2 (Armcx2)). Comparable alterations in ECM composition were seen in damaged human livers. The increase in collagen content and decrease in elastic fibers resulted in rearrangement and increased stiffness of damaged liver ECM. Interestingly, the alterations in ECM components were nonhomogenous and differed between periportal and pericentral areas and thus our experiments demonstrated the differential ability of selected ECM components to regulate the proliferation of hepatocytes and biliary cells. We define for the first time the alterations in the ECM composition of livers recovering from damage and present functional evidence for a coordinated ECM remodelling that ensures an efficient restoration of liver tissue. PMID:27264108

  3. Liver cell adenoma showing sequential alteration of radiological findings suggestive of well-differentiated hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Takayuki Kogure; Yoshiyuki Ueno; Satoshi Sekiguchi; Kazuyuki Ishida; Takehiko Igarashi; Yuta Wakui; Takao Iwasaki; Tooru Shimosegawa

    2009-01-01

    A liver tumor 35 mm in diameter was found incidentally in a 40-year-old woman who had no history of liver diseases or the use of oral contraceptives. Radiological diagnostics showed the typical findings of liver cell adenoma (LCA). Dynamic computed tomography revealed that the tumor showed a homogenous enhancement in the arterial phase and almost the same enhancement as the surrounding liver parenchyma in the delayed phase. The tumor was found to contain fat on magnetic resonance imaging. A benign fat containing liver tumor was suggested. However, radiological findings altered, which caused us to suspect that a welldifferentiated hepatocellular carcinoma (HCC) containing fat was becoming dedifferentiated. Partial hepatectomy was performed and the pathological findings showed the typical findings of LCA. This case was an extremely rare LCA, which had no background of risk for LCA and developed the sequential alteration of the radiological findings to suspect well-differentiated HCC.

  4. Alteration of Brain Oxygenation During "Piggy Back" Liver Transplantation

    Science.gov (United States)

    Panzera, Piercarmine; Greco, Luigi; Carravetta, Giuseppe; Gentile, Antonella; Catalano, Giorgio; Cicco, Giuseppe; Memeo, Vincenzo

    Relevant changes in cerebral circulation occur during "Piggy Back" liver transplantation. Particularly at the washout-reperfusion time the cerebral perfusion suddenly changes from its lowest to its highest values. Further investigation is required to evaluate whether patients with the greatest change in cerebral oxygenation at this time point will suffer neurological complications after transplantation.

  5. Changes in the activity levels of glutamine synthetase, glutaminase and glycogen synthetase in rats subjected to hypoxic stress

    Science.gov (United States)

    Vats, P.; Mukherjee, A. K.; Kumria, M. M. L.; Singh, S. N.; Patil, S. K. B.; Rangnathan, S.; Sridharan, K.

    Exposure to high altitude causes loss of body mass and alterations in metabolic processes, especially carbohydrate and protein metabolism. The present study was conducted to elucidate the role of glutamine synthetase, glutaminase and glycogen synthetase under conditions of chronic intermittent hypoxia. Four groups, each consisting of 12 male albino rats (Wistar strain), were exposed to a simulated altitude of 7620 m in a hypobaric chamber for 6 h per day for 1, 7, 14 and 21 days, respectively. Blood haemoglobin, blood glucose, protein levels in the liver, muscle and plasma, glycogen content, and glutaminase, glutamine synthetase and glycogen synthetase activities in liver and muscle were determined in all groups of exposed and in a group of unexposed animals. Food intake and changes in body mass were also monitored. There was a significant reduction in body mass (28-30%) in hypoxia-exposed groups as compared to controls, with a corresponding decrease in food intake. There was rise in blood haemoglobin and plasma protein in response to acclimatisation. Over a three-fold increase in liver glycogen content was observed following 1 day of hypoxic exposure (4.76+/-0.78 mg.g-1 wet tissue in normal unexposed rats; 15.82+/-2.30 mg.g-1 wet tissue in rats exposed to hypoxia for 1 day). This returned to normal in later stages of exposure. However, there was no change in glycogen synthetase activity except for a decrease in the 21-days hypoxia-exposed group. There was a slight increase in muscle glycogen content in the 1-day exposed group which declined significantly by 56.5, 50.6 and 42% following 7, 14, and 21 days of exposure, respectively. Muscle glycogen synthetase activity was also decreased following 21 days of exposure. There was an increase in glutaminase activity in the liver and muscle in the 7-, 14- and 21-day exposed groups. Glutamine synthetase activity was higher in the liver in 7- and 14-day exposed groups; this returned to normal following 21 days of exposure

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

    International Nuclear Information System (INIS)

    The molecular order of synthesis and mobilization of glycogen in the perfused heart was studied by 13C NMR. By varying the glucose isotopomer ([1-13C]glucose or [2-13C]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 [1-13C]glucose was given initially in the perfusion and [2-13C]glucose was given second, [2-13C]lactate was detected first during ischemia and [3-13C]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 13C-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

  7. Skeletal-muscle glycogen synthesis during the starved-to-fed transition in the rat.

    Science.gov (United States)

    Holness, M J; Schuster-Bruce, M J; Sugden, M C

    1988-09-15

    The pattern of glycogen deposition in skeletal muscles of varying fibre composition was examined in rats during the starved-to-fed transition. In all the muscles studied, glycogen concentrations steadily increased during the first 8 h after chow re-feeding, and the fed value was exceeded. Rates of glycogen deposition varied, not with muscle fibre composition, but with the extent of glycogen depletion during starvation. There was no evidence for skeletal-muscle glycogen breakdown during the period of hepatic glycogenesis, making it unlikely that recycling of carbon from muscle glycogen to lactate is quantitatively important for the provision of glycogenic precursors to the liver, but moderate glycogen loss was observed from 8 to 24 h after re-feeding, when the liver is in the lipogenic mode. The factors influencing glucose disposal by skeletal muscle after re-feeding are discussed.

  8. 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.

  9. Hemostatic alterations in liver disease : A review on pathophysiology, clinical consequences, and treatment

    NARCIS (Netherlands)

    Lisman, Ton; Leebeek, Frank W. G.

    2007-01-01

    In most patients with acute or chronic liver failure, extensive changes in all pathways contributing to hemostasis are found. These hemostatic alterations concern both pro- and antihemostatic pathways, and therefore the net result of the hemostatic dysbalance is unclear. Although it is generally bel

  10. Interplay between viral infections and genetic alterations in liver cancer

    Directory of Open Access Journals (Sweden)

    Pierre Hainaut

    2007-02-01

    Full Text Available

    With over 500 000 annual deaths, Hepatocellular carcinoma (HCC is the fifth most common cancer worldwide and a leading cause of death in developing countries where about 80% of the cases arise. Risk factors include chronic hepatitis infections (hepatitis B, (HBV and hepatitis C (HCV viruses, alcohol, dietary contaminants such as falatoxins The incidence shows important geographic variations, accor In southern Asia, HCC development is mainly related to the endemic Hepatitis B Virus (HBV infection, cases with hot spot mutation in codon 249 (249ser of TP53 tumor suppressor gene were also described and associated to a low-intermediate exposure rate to Aflatoxin B1 (AFB1. Presence of Hepatitis C Virus (HCV infection was also detected in 12 - 17% of HCC cases. Despite the increasing number of studies identifying viral/host interactions in viro-induced HCC or describing potential pathways for hepatocarcinogenesis, precise mechanism has not been identified so far. HBV was demonstrated to enhance hepatocarcinogenesis by different manners; HBV chronic infection is associated to active hepatitis (CAH and cirrhosis which are hepatic complications considered as early stage for HCC development. These complications mobilise the host immune response, the resulting inflammation initiates and selects the first genetic alteration at the origin of loss of cell control. Moreover, HBV can also promote carcinogenesis through genetic instability generated by its common integration in host DNA. HBV proteins, as HBx, was proven to interact with a variety of targets in the host cell including protein or host transcription factor such as, in particular, the p53 protein or the transcription factor E4F, which is implicated in growth, differenciation and senescence. Specific HBV mutations or distinct HBV genotypes are associated to higher risks factors for HCC or hepatic complications leading

  11. Alterations of the gut microbiome and metabolome in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Wei; Zhong; Zhanxiang; Zhou

    2014-01-01

    Alcohol consumption is one of the leading causes of liver diseases and liver-related death worldwide. The gut is a habitat for billions of microorganisms which promotes metabolism and digestion in their symbiotic relationship with the host. Alterations of gut microbiome by alcohol consumption are referred to bacterial overgrowth, release of bacteria-derived products, and/or changed microbiota equilibrium. Alcohol consumption also perturbs the function of gastrointestinal mucosa and elicits a pathophysiological condition. These adverse effects caused by alcohol may ultimately result in a broad change of gastrointestinal luminal metabolites such as bile acids, short chain fatty acids, and branched chain amino acids. Gut microbiota alterations, metabolic changes produced in a dysbiotic intestinal environment, and the host factors are all critical contributors to the development and progression of alcoholic liver disease. This review summarizes recent findings of how alcohol-induced alterations of gut microbiota and metabolome, and discusses the mecha-nistic link between gastrointestinal dyshomeostasis and alcoholic liver injury.

  12. Liver function alterations after laparoscopy-assisted gastrectomy for gastric cancer and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Gui-Ae Jeong; Gyu-Seok Cho; Eung-Jin Shin; Moon-Soo Lee; Hyung-Chul Kim; Ok-Pyung Song

    2011-01-01

    AIM: To evaluate the factors associated with liver function alterations after laparoscopy-assisted gastrectomy(LAG) for gastric cancer.METHODS: We collected the data of gastrectomy patients with gastric cancer and divided them into 2 groups: open gastrectomy (OG) and LAG. We also collectedthe data of patients with colon cancer to evaluate the effect of liver manipulations during surgery on liver function alterations. Serum aspartate aminotransferase(AST), alanine aminotransferase (ALT), total bilirubin,and alkaline phosphatase were measured on the preoperative day and postoperative day 1 (POD1), POD3,POD5, and POD7.RESULTS: No changes in liver function were observed after the operation in patients with colon cancer (n =121). However, in gastric cancer patients (n = 215),AST and ALT levels increased until POD5 compared to those in colon cancer patients and these findings were observed both in the LAG and OG without a significantsignificant difference except at POD1. The mean hepatic enzyme levels at POD1 in the LAG group were significantly higher than those in the OG group (P = 0.047for AST and P = 0.039 for ALT). The factors associated with elevated ALT on POD1 in patients with gastric cancer were body mass index (P < 0.001), operationtime (P < 0.001), intraoperative hepatic injury (P =0.048), and ligation of an aberrant left hepatic artery(P = 0.052) but not type of operation (OG vs LAG, P =0.094).CONCLUSION: We conclude that the liver function alteration after LAG may have been caused by direct liver manipulation or aberrant hepatic artery ligation rather than the CO2 pneumoperitoneum.

  13. Predominant role of gluconeogenesis in the hepatic glycogen repletion of diabetic rats.

    OpenAIRE

    Giaccari, A; Rossetti, L.

    1992-01-01

    Liver glycogen formation can occur via the direct (glucose----glucose-6-phosphate----glycogen) or indirect (glucose----C3 compounds----glucose-6-phosphate----glycogen) pathways. In the present study we have examined the effect of hyperglycemia on the pathways of hepatic glycogenesis, estimated from liver uridine diphosphoglucose (UDPglucose) specific activities, and on peripheral (muscle) glucose metabolism in awake, unstressed control and 90% pancreatectomized, diabetic rats. Under identical...

  14. Glycogen shortage during fasting triggers liver–brain–adipose neurocircuitry to facilitate fat utilization

    Science.gov (United States)

    Izumida, Yoshihiko; Yahagi, Naoya; Takeuchi, Yoshinori; Nishi, Makiko; Shikama, Akito; Takarada, Ayako; Masuda, Yukari; Kubota, Midori; Matsuzaka, Takashi; Nakagawa, Yoshimi; Iizuka, Yoko; Itaka, Keiji; Kataoka, Kazunori; Shioda, Seiji; Niijima, Akira; Yamada, Tetsuya; Katagiri, Hideki; Nagai, Ryozo; Yamada, Nobuhiro; Kadowaki, Takashi; Shimano, Hitoshi

    2013-01-01

    During fasting, animals maintain their energy balance by shifting their energy source from carbohydrates to triglycerides. However, the trigger for this switch has not yet been entirely elucidated. Here we show that a selective hepatic vagotomy slows the speed of fat consumption by attenuating sympathetic nerve-mediated lipolysis in adipose tissue. Hepatic glycogen pre-loading by the adenoviral overexpression of glycogen synthase or the transcription factor TFE3 abolished this liver–brain–adipose axis activation. Moreover, the blockade of glycolysis through the knockdown of the glycogen phosphorylase gene and the resulting elevation in the glycogen content abolished the lipolytic signal from the liver, indicating that glycogen is the key to triggering this neurocircuitry. These results demonstrate that liver glycogen shortage activates a liver–brain–adipose neural axis that has an important role in switching the fuel source from glycogen to triglycerides under prolonged fasting conditions. PMID:23939267

  15. The role of aerobic training and Pistacia atlantica extract on the levels of protein carbonyl, heat shock protein 70, and glycogen in the liver tissue of diabetic rats

    Directory of Open Access Journals (Sweden)

    Fatemeh Mohammadi Karizno

    2014-05-01

    Conclusion: It was found that aerobic training and Pistacia atlantica extract consumption, either alone or together, led to a significant reduction in PC levels in the liver tissues of diabetic rats. Thus, Pistacia atlantica extract and aerobic training can be good remedies in reducing liver complications resulting from diabetes.

  16. Loss of liver FA binding protein significantly alters hepatocyte plasma membrane microdomains[S

    OpenAIRE

    McIntosh, Avery L.; Atshaves, Barbara P.; Storey, Stephen M.; Landrock, Kerstin K.; Landrock, Danilo; Martin, Gregory G.; Kier, Ann B.; Schroeder, Friedhelm

    2012-01-01

    Although lipid-rich microdomains of hepatocyte plasma membranes serve as the major scaffolding regions for cholesterol transport proteins important in cholesterol disposition, little is known regarding intracellular factors regulating cholesterol distribution therein. On the basis of its ability to bind cholesterol and alter hepatic cholesterol accumulation, the cytosolic liver type FA binding protein (L-FABP) was hypothesized to be a candidate protein regulating these microdomains. Compared ...

  17. 肝细胞内糖原拮抗肝脏缺血-再灌注损伤的临床初步研究%The clinical study on effect of intracellular glycogen on liver ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    汤礼军; 田伏洲; 胡建中; 闫勇; 邢庆蓉

    2001-01-01

    目的探讨临床上施行复杂的肝脏手术前增加肝细胞内糖原含量能否减轻术中因阻断肝血流所带来的肝脏缺血-再灌注损伤。方法将近3年我院收治的临床基本情况相近的17例患者分为实验组及对照组。实验组患者于术前24h内静脉滴注25%葡萄糖250 ml,共4次(1次/6h),对照组不作特殊处理。两组患者均采用阻断第一肝门方法行病变肝脏切除术。术中分别于肝脏缺血前、缺血后及再灌注1 h获取相对正常的肝组织测定组织中ATP含量,此外于术前及术后第1、5d,抽取血液标本,检测患者肝功能情况。结果两组患者于缺血后及再灌注1 h,实验组肝组织ATP含量显著高于对照组(P<0.01);术后第1、5 d,实验组肝功能改善程度均显著地优于对照组(P<0.01),而术前两组间则差异不显著。结论临床上在阻断肝脏血流施行复杂的肝脏手术之前,增加肝细胞内糖原含量可有效地减轻肝脏缺血-再灌注损伤程度,降低手术风险。%Objective To study the effect of intracellular glycogen on liver ischemia - reperfusion injury from hepatic vascular exclusion. Methods 17 patients were divided into experiment group( n-- 9)and control group(n = 8). The patients of experiment group were injected with 250 ml of 25% glucose via vein per 6 hours during pre - operative 24 hours. The pathological liver tissue were resected by using portal triad clamping in the two groups. Hepatic tissue were biopsied to measured hepatic tissue ATP contents at the point of pre - ischemia, post - is chemia and reperfusion 1 hour. Furthermore, liver function of all patients were investigated at the point of pre - operative and post - operative 1and 5 days. Results Hepatic tissue ATP contents of experiment group significantly were higher than that of control group at the point of postischemia or repeffusion 1 hour ( P < 0.01) .Besides,liver function of experiment group were

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-03-15

    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.

  19. Postpartal subclinical endometritis alters transcriptome profiles in liver and adipose tissue of dairy cows.

    Science.gov (United States)

    Akbar, Haji; Cardoso, Felipe C; Meier, Susanne; Burke, Christopher; McDougall, Scott; Mitchell, Murray; Walker, Caroline; Rodriguez-Zas, Sandra L; Everts, Robin E; Lewin, Harris A; Roche, John R; Loor, Juan J

    2014-01-01

    Transcriptome alterations in liver and adipose tissue of cows with subclinical endometritis (SCE) at 29 d postpartum were evaluated. Bioinformatics analysis was performed using the Dynamic Impact Approach by means of KEGG and DAVID databases. Milk production, blood metabolites (non-esterified fatty acids, magnesium), and disease biomarkers (albumin, aspartate aminotransferase) did not differ greatly between healthy and SCE cows. In liver tissue of cows with SCE, alterations in gene expression revealed an activation of complement and coagulation cascade, steroid hormone biosynthesis, apoptosis, inflammation, oxidative stress, MAPK signaling, and the formation of fibrinogen complex. Bioinformatics analysis also revealed an inhibition of vitamin B3 and B6 metabolism with SCE. In adipose, the most activated pathways by SCE were nicotinate and nicotinamide metabolism, long-chain fatty acid transport, oxidative phosphorylation, inflammation, T cell and B cell receptor signaling, and mTOR signaling. Results indicate that SCE in dairy cattle during early lactation induces molecular alterations in liver and adipose tissue indicative of immune activation and cellular stress.

  20. Postpartal subclinical endometritis alters transcriptome profiles in liver and adipose tissue of dairy cows.

    Science.gov (United States)

    Akbar, Haji; Cardoso, Felipe C; Meier, Susanne; Burke, Christopher; McDougall, Scott; Mitchell, Murray; Walker, Caroline; Rodriguez-Zas, Sandra L; Everts, Robin E; Lewin, Harris A; Roche, John R; Loor, Juan J

    2014-01-01

    Transcriptome alterations in liver and adipose tissue of cows with subclinical endometritis (SCE) at 29 d postpartum were evaluated. Bioinformatics analysis was performed using the Dynamic Impact Approach by means of KEGG and DAVID databases. Milk production, blood metabolites (non-esterified fatty acids, magnesium), and disease biomarkers (albumin, aspartate aminotransferase) did not differ greatly between healthy and SCE cows. In liver tissue of cows with SCE, alterations in gene expression revealed an activation of complement and coagulation cascade, steroid hormone biosynthesis, apoptosis, inflammation, oxidative stress, MAPK signaling, and the formation of fibrinogen complex. Bioinformatics analysis also revealed an inhibition of vitamin B3 and B6 metabolism with SCE. In adipose, the most activated pathways by SCE were nicotinate and nicotinamide metabolism, long-chain fatty acid transport, oxidative phosphorylation, inflammation, T cell and B cell receptor signaling, and mTOR signaling. Results indicate that SCE in dairy cattle during early lactation induces molecular alterations in liver and adipose tissue indicative of immune activation and cellular stress. PMID:24578603

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

    International Nuclear Information System (INIS)

    Hepatic glycogen was depleted rapidly in fasted mice treated with CCl4. Glycogen breakdown was slow when CCl4 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 CCl4 injection. The incorporation of glucose-U-14C into glycogen was higher in mice which were refed before CCl4 administration than in fasted mice treated with the hepatotoxin. The specific activity of lactate was higher in CCl4 treated mice. The data suggested differences in glycogen metabolism of fasted and refed mice in response to CCl4 treatment. (author)

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

    Science.gov (United States)

    Liu, Jie; Lu, Yuan-Fu; Zhang, Youcai; Wu, Kai Connie; Fan, Fang; Klaassen, Curtis D

    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.

  3. Chronic mild stress alters circadian expressions of molecular clock genes in the liver.

    Science.gov (United States)

    Takahashi, Kei; Yamada, Tetsuya; Tsukita, Sohei; Kaneko, Keizo; Shirai, Yuta; Munakata, Yuichiro; Ishigaki, Yasushi; Imai, Junta; Uno, Kenji; Hasegawa, Yutaka; Sawada, Shojiro; Oka, Yoshitomo; Katagiri, Hideki

    2013-02-01

    Chronic stress is well known to affect metabolic regulation. However, molecular mechanisms interconnecting stress response systems and metabolic regulations have yet to be elucidated. Various physiological processes, including glucose/lipid metabolism, are regulated by the circadian clock, and core clock gene dysregulation reportedly leads to metabolic disorders. Glucocorticoids, acting as end-effectors of the hypothalamus-pituitary-adrenal (HPA) axis, entrain the circadian rhythms of peripheral organs, including the liver, by phase-shifting core clock gene expressions. Therefore, we examined whether chronic stress affects circadian expressions of core clock genes and metabolism-related genes in the liver using the chronic mild stress (CMS) procedure. In BALB/c mice, CMS elevated and phase-shifted serum corticosterone levels, indicating overactivation of the HPA axis. The rhythmic expressions of core clock genes, e.g., Clock, Npas2, Bmal1, Per1, and Cry1, were altered in the liver while being completely preserved in the hypothalamic suprachiasmatic nuculeus (SCN), suggesting that the SCN is not involved in alterations in hepatic core clock gene expressions. In addition, circadian patterns of glucose and lipid metabolism-related genes, e.g., peroxisome proliferator activated receptor (Ppar) α, Pparγ-1, Pparγ-coactivator-1α, and phosphoenolepyruvate carboxykinase, were also disturbed by CMS. In contrast, in C57BL/6 mice, the same CMS procedure altered neither serum corticosterone levels nor rhythmic expressions of hepatic core clock genes and metabolism-related genes. Thus, chronic stress can interfere with the circadian expressions of both core clock genes and metabolism-related genes in the liver possibly involving HPA axis overactivation. This mechanism might contribute to metabolic disorders in stressful modern societies.

  4. Effect of α-Ketoglutarate on Cyanide-induced Biochemical Alterations in Rat Brain and Liver

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the biochemical changes in rat brain and liver following acute exposure to a lethal dose of cyanide, and its response to treatment of α-ketoglutarate (α-KG) in the absence or presence of sodium thiosulfate (STS). Methods Female rats were administered 2.0 LD50 potassium cyanide (KCN; oral) in the absence or presence of pre-treatment (-10 min), simultaneous treatment (0 min) or post-treatment (+2-3 min) of α-KG (2.0 g/kg, oral) and/or STS (1.0 g/kg,intraperitoneal, -15 min, 0 min or + 2-3 min). At the time of onset of signs and symptoms of KCN toxicity (2-4 min) and at the time of death (5-15 min), various parameters particularly akin to oxidative stress viz. Cytochrome oxidase (CYTOX),superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH) and oxidized glutathione (GSSG) in brain, and CYTOX, sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP), GSH and GSSG in liver homogenate were measured. Results At both time intervals brain CYTOX, SOD, GPx, and GSH significantly reduced (percent inhibition compared to control) to 24%, 56%, 77%, and 65%, and 44%, 46%, 78%, and 57%, respectively. At the corresponding time points liver CYTOX and GSH reduced to 74% and 63%, and 44% and 68%, respectively. The levels of GSSG in the brain and liver, and hepatic ALP and SDH were unchanged. Pre-treatment and simultaneous treatment of α-KG alone or with STS conferred significant protection on above variables. Post-treatment was effective in restoring the changes in liver but failed to normalize the changes in the brain. Conclusions Oral treatment with α-KG alone or in combination with STS has protective effects on cyanide-induced biochemical alterations in rat brain and liver.

  5. Hyperproliferative Hepatocellular Alterations after Intraportal Transplantation of Thyroid Follicles

    Science.gov (United States)

    Dombrowski, Frank; Klotz, Luisa; Hacker, Hans Jörg; Li, Yanhua; Klingmüller, Dietrich; Brix, Klaudia; Herzog, Volker; Bannasch, Peter

    2000-01-01

    The thyroid hormone 3,5,3′-triiodo-l-thyronine (T3) is a strong direct hepatocyte mitogen in vivo. The effects of T3 resemble those of peroxisome proliferators, which are known to induce hepatocellular tumors in rats. With the aim of studying long-term local effects of thyroid hormones on liver parenchyma, small pieces of thyroid tissue were transplanted via the portal veins into the livers of thyroidectomized male Lewis rats. At 1 week, 3 weeks, 3 months, and 18 months after transplantation, the transplants were found to proliferate, to synthesize thyroglobulin, and to release thyroxine and T3. At 3 and 18 months after transplantation, the hepatocytes of the liver acini downstream of the transplanted follicles showed an increase in cytoplasmic basophilia, a loss of glycogen, an enlargement and hyperchromasia of their nuclei, and a strong increase in cell turnover compared with unaltered liver acini. The altered hepatocytes exhibited an increase in the activities of glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, malic enzyme, mitochondrial glycerol-3-phosphate dehydrogenase, cytochrome-c-oxidase, and acid phosphatase; the activities of glycogen synthase and glycogen phosphorylase were strongly decreased. The hepatocytic alterations downstream of the transplanted follicles could be explained by effects of T3. On the other hand, they resembled alterations characteristic of amphophilic preneoplastic liver foci observed in different models of hepatocarcinogenesis. PMID:10623658

  6. Altered Wnt Signaling Pathway in Cognitive Impairment Caused by Chronic Intermittent Hypoxia: Focus on Glycogen Synthase Kinase-3β and β-catenin

    Institute of Scientific and Technical Information of China (English)

    Yue-Ying Pan; Yan Deng; Sheng Xie; Zhi-Hua Wang; Yu Wang; Jie Ren; Hui-Guo Liu

    2016-01-01

    Background:Cognitive impairment is a severe complication caused by obstructive sleep apnea (OSA).The mechanisms of causation are still unclear.The Wnt/β-catenin signaling pathway is involved in cognition,and abnormalities in it are implicated in neurological disorders.Here,we explored the Wnt/β-catenin signaling pathway abnormalities caused by chronic intermittent hypoxia (CIH),the most characteristic pathophysiological component of OSA.Methods:We divided 32 4-week-old male C57/BL mice into four groups of eight each:a CIH + normal saline (NS) group,CIH + LiC1 group,sham CIH + NS group,and a sham CIH + LiC1 group.The spatial learning performance of each group was assessed by using the Morris water maze (MWM).Protein expressions of glycogen synthase kinase-3β (GSK-3β) and β-catenin in the hippocampus were examined using the Western blotting test.EdU labeling and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining methods were used,respectively,to determine the proliferation and apoptosis of neurons in the hippocampal dentate gyrus region.Results:Mice exposed to CIH showed impaired spatial learning performance in the MWM,including increased mean escape latencies to reach the target platform,decreased mean times passing through the target platform and mean duration in the target quadrant.The GSK-3β activity increased,and expression of β-catenin decreased significantly in the hippocampus of the CIH-exposed mice.Besides,CIH significantly increased hippocampal neuronal apoptosis,with an elevated apoptosis index.Meanwhile,LiCl decreased the activity of GSK-3β and increased the expression of β-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH.Conclusions:Wnt/β-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCl might attenuate CIH-induced cognitive impairment via Wnt

  7. Chronic Intake of Japanese Sake Mediates Radiation-Induced Metabolic Alterations in Mouse Liver.

    Directory of Open Access Journals (Sweden)

    Tetsuo Nakajima

    Full Text Available Sake is a traditional Japanese alcoholic beverage that is gaining popularity worldwide. Although sake is reported to have beneficial health effects, it is not known whether chronic sake consumption modulates health risks due to radiation exposure or other factors. Here, the effects of chronic administration of sake on radiation-induced metabolic alterations in the livers of mice were evaluated. Sake (junmai-shu was administered daily to female mice (C3H/He for one month, and the mice were exposed to fractionated doses of X-rays (0.75 Gy/day for the last four days of the sake administration period. For comparative analysis, a group of mice were administered 15% (v/v ethanol in water instead of sake. Metabolites in the liver were analyzed by capillary electrophoresis-time-of-flight mass spectrometry one day following the last exposure to radiation. The metabolite profiles of mice chronically administered sake in combination with radiation showed marked changes in purine, pyrimidine, and glutathione (GSH metabolism, which were only partially altered by radiation or sake administration alone. Notably, the changes in GSH metabolism were not observed in mice treated with radiation following chronic administration of 15% ethanol in water. Changes in several metabolites, including methionine and valine, were induced by radiation alone, but were not detected in the livers of mice who received chronic administration of sake. In addition, the chronic administration of sake increased the level of serum triglycerides, although radiation exposure suppressed this increase. Taken together, the present findings suggest that chronic sake consumption promotes GSH metabolism and anti-oxidative activities in the liver, and thereby may contribute to minimizing the adverse effects associated with radiation.

  8. Genetic and histopathological alterations induced by cypermethrin in rat kidney and liver: Protection by sesame oil.

    Science.gov (United States)

    Soliman, Mohamed Mohamed; Attia, Hossam F; El-Ella, Ghada A Abou

    2015-12-01

    Pesticides are widespread synthesized substances used for public health protection and agricultural programs. However, they cause environmental pollution and health hazards. This study aimed to examine the protective effects of sesame oil (SO) on the genetic alterations induced by cypermethrin (CYP) in the liver and kidney of Wistar rats. Male rats were divided into four groups, each containing 10 rats: the control group received vehicle, SO group (5 mL/kg b.w), CYP group (12 mg/kg b.w), and protective group received SO (5 mL/kg b.w) plus CYP (12 mg/kg b.w). Biochemical analysis showed an increase in albumin, urea, creatinine, GPT, GOT, and lipid profiles in the CYP group. Co-administration of SO with CYP normalized such biochemical changes. CYP administration decreased both the activity and mRNA expression of the examined antioxidants. SO co-administration recovered CYP, downregulating the expression of glutathione-S-transferase (GST), catalase, and superoxide dismutase. Additionally, SO co-administration with CYP counteracted the CYP- altering the expression of renal interleukins (IL-1 and IL-6), tumor necrosis factor alpha (TNF-α), heme oxygenase-1 (HO-1), anigotensinogen (AGT), AGT receptors (AT1), and genes of hepatic glucose and fatty acids metabolism. CYP induced degenerative changes in the kidney and liver histology which are ameliorated by SO. In conclusion, SO has a protective effect against alterations and pathological changes induced by CYP in the liver and kidney at genetic and histological levels.

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

    International Nuclear Information System (INIS)

    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)

  10. Hepatitis C virus and ethanol alter antigen presentation in liver cells

    Institute of Scientific and Technical Information of China (English)

    Natalia A Osna

    2009-01-01

    Alcoholic patients have a high incidence of hepatitis Cvirus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCVinduced inability of the immune system to recognizeinfected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex (MHC) classⅠ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC classⅠand class Ⅱ in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 (IL-10) and transforming growth factor beta (TGFβ) predominance,preventing cell maturation and allostimulation capacity.The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC classⅠ-restricted antigen presentation.Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.

  11. FR258900, a potential anti-hyperglycemic drug, binds at the allosteric site of glycogen phosphorylase

    OpenAIRE

    Tiraidis, C.; Alexacou, K. M.; Zographos, Spyros E.; Leonidas, Demetres D.; Gimisis, T.; Oikonomakos, Nikos G.

    2007-01-01

    FR258900 has been discovered as a novel inhibitor of human liver glycogen phosphorylase a and proved to suppress hepatic glycogen breakdown and reduce plasma glucose concentrations in diabetic mice models. To elucidate the mechanism of inhibition, we have determined the crystal structure of the cocrystallized rabbit muscle glycogen phosphorylase b–FR258900 complex and refined it to 2.2 Å resolution. The structure demonstrates that the inhibitor binds at the allosteric activator site, where th...

  12. 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

    OpenAIRE

    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 (NCH...

  13. Chemically-induced alteration of UDP-glucuronic acid concentration in rat liver.

    Science.gov (United States)

    Watkins, J B; Klaassen, C D

    1983-01-01

    Since many xenobiotics alter hepatic UDP-glucuronosyltransferase activity, their effect on UDPGA concentration was determined. Rats were pretreated with: 1) microsomal enzyme inducers (7,8-benzoflavone, benzo(a)pyrene, butylated hydroxyanisole, isosafrole, 3-methylcholanthrene, phenobarbital, pregnenolone-16 alpha-carbonitrile (PCN), 2,3,7,8-tetrachlorodibenzo-p-dioxin, trans-stilbene oxide); 2) inhibitors of microsomal enzymes (cobaltous chloride, piperonyl butoxide, SKF 525-A, borneol, galactosamine); 3) hepatotoxins (allyl alcohol, aflatoxin B1, alpha-naphthylisothiocyanate, bromobenzene, cadmium chloride, carbon tetrachloride, 1,1-dichloroethylene), and 4) commonly used anesthetics (pentobarbital, urethane, diethyl ether, halothane, enflurane, methoxyflurane). Rats were decapitated before removal of the liver. All inducers except PCN and isosafrole increased UDPGA 36-85% above control. Mixed-function oxidase inhibitors had no effect whereas borneol and galactosamine reduced UDPGA 85-90%. Aflatoxin B1 and cadmium produced decreases of 59 and 25%, respectively. Hepatic UDPGA content was diminished 70-95% after exposure to the inhalation anesthetics, whereas the other anesthetics reduced UDPGA about 25%. Thus, numerous xenobiotics alter the concentration of UDPGA in rat liver, which may influence the rate of glucoronidation.

  14. Histological and biochemical alterations in early-stage lobar ischemia-reperfusion in rat liver

    Institute of Scientific and Technical Information of China (English)

    Hossein Ali Arab; Farhang Sasani; Mohammad Hossein Rafiee; Ahmad Fatemi; Abbas Javaheri

    2009-01-01

    AIM: To investigate the structural and biochemical changes in the early stage of reperfusion in the rat livers exposed to lobar ischemia-reperfusion (IR).METHODS: The median and left lobes of the liver were subjected to 60 min ischemia followed by 5, 10,30, 45, 60 and 120 min reperfusion. Blood samples were taken at different time intervals to test enzyme activities and biochemical alterations induced by reperfusion. At the end of each reperfusion period, the animals were killed by euthanasia and tissue samples were taken for histological examination and immunohistochemistry.RESULTS: Cell vacuolation, bleb formation and focal hepatitis were the most important changes occur during ischemia. While some changes including bleb formation were removed during reperfusion, other alterations including portal hepatitis, inflammation and the induction of apoptosis were seen during this stage. The occurrence of apoptosis, as demonstrated by apoptot i c cel l s and bodies , was the mos t important histological change during reperfusion. The severity of apoptosis was dependent on the time of reperfusion, and by increasing the time of reperfusion,the numbers of apoptotic bodies was significantly enhanced. The amounts of lactate dehydrogenase,alanine aminotransferase, aspartate aminotransferase,creatinine and urea were significantly increased in serum obtained from animals exposed to hepatic IR.

  15. Liver disease alters high-density lipoprotein composition, metabolism and function.

    Science.gov (United States)

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk.

  16. Liver disease alters high-density lipoprotein composition, metabolism and function.

    Science.gov (United States)

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk. PMID:27106140

  17. The role of skeletal muscle glycogen breakdown for regulation of insulin sensitivity by exercise

    Directory of Open Access Journals (Sweden)

    Jørgen eJensen

    2011-12-01

    Full Text Available Glycogen is the storage form of carbohydrates in mammals. In humans the majority of glycogen is stored in skeletal muscles (~500 g and the liver (~100 g. Food is supplied in larger meals, but the blood glucose concentration has to be kept within narrow limits to survive and stay healthy. Therefore, the body has to cope with periods of excess carbohydrates and periods without supplementation. Healthy persons remove blood glucose rapidly when glucose is in excess, but insulin-stimulated glucose disposal is reduced in insulin resistant and type 2 diabetic subjects. During a hyperinsulinemic euglycaemic clamp, 70-90 % of glucose disposal will be stored as muscle glycogen in healthy subjects. The glycogen stores in skeletal muscles are limited because an efficient feedback-mediated inhibition of glycogen synthase prevents accumulation. De novo lipid synthesis can contribute to glucose disposal when glycogen stores are filled. Exercise physiologists normally consider glycogen’s main function as energy substrate. Glycogen is the main energy substrate during exercise intensity above 70 % of maximal oxygen uptake (VO2max and fatigue develops when the glycogen stores are depleted in the active muscles. After exercise, the rate of glycogen synthesis is increased to replete glycogen stores, and blood glucose is the substrate. Indeed insulin-stimulated glucose uptake and glycogen synthesis is elevated after exercise, which, from an evolutional point of view, will favour glycogen repletion and preparation for new fight or flight events. In the modern society, the reduced glycogen stores in skeletal muscles after exercise allows carbohydrates to be stored as muscle glycogen and prevents that glucose is channelled to de novo lipid synthesis, which over time will causes ectopic fat accumulation and insulin resistance. The reduction of skeletal muscle glycogen after exercise allows a healthy storage of carbohydrates after meals and prevents development of type

  18. Characteristic Liver Manifestations of Glycogen Storage Disease Type Ⅰa:A Retrospective Study of 82 Cases%82例糖原累积症Ⅰa型肝脏受累特点

    Institute of Scientific and Technical Information of China (English)

    唐晓艳; 陈萌; 马明圣; 李明; 邱正庆

    2014-01-01

    目的:探讨糖原累积症( glycogen storage disease, GSD)Ⅰa型的肝脏受累特点。方法回顾性分析2006年1月至2013年12月在北京协和医院住院治疗的82例基因确诊为GSD Ⅰa型患儿的临床资料及肝脏影像学结果,并总结其肝脏受累特点。结果82例GSDⅠa型患儿中,男55例,女27例;出现症状平均年龄为(1.2±0.9)岁,其中42例(54.9%)以发现肝脏肿大为首要原因就诊。13.4%(11/82)患儿出现肝脏腺瘤,腺瘤出现年龄平均(15.7±3.0)岁(12~23岁);63.6%(7/11)为多发腺瘤,36.4%(4/11)为单发腺瘤。单发肝脏腺瘤均位于肝脏右叶,多发腺瘤均表现为左叶及右叶均有分布。1例患儿行肝动脉栓塞治疗,1例合并腺瘤癌变。结论 GSD Ⅰa型是小儿较常见的导致肝脏肿大的遗传代谢病之一,至青春期左右易发生肝脏腺瘤,部分癌变。定期随诊腹部超声意义重大。对年长儿不明原因的多发肝脏腺瘤要注意鉴别GSD Ⅰa型。%Objective To summarize the characteristic liver manifestations of glycogen storage disease typeⅠa (GSDⅠa).Methods We retrospectively analyzed the clinical data and liver image results of 82 genetically di-agnosed GSD Ⅰa patients hospitalized in Peking Union Medical College Hospital between January 2006 and De-cember 2013 , and summarized the characteristics of liver involvement of these patients .Results The 82 patients included 55 boys and 27 girls.Their symptoms developed at the mean age of (1.2 ±0.9 ) years.Forty-two pa-tients (54.9%) visited doctors because of hepatomegaly .Eleven (13.4%) had hepatic adenomas , which ap-peared at the age of (15.7 ±3.0 ) years (12-23 years).Among them, 63.6% (7/11) had multiple adeno-mas, and the other (36.4%, 4/11) had single ones.The single adenomas were all located in the right lobe of the liver , and the multiple adenomas all involved both left and right lobes of the liver .One child

  19. Defining Hepatic Dysfunction Parameters in Two Models of Fatty Liver Disease in Zebrafish Larvae

    OpenAIRE

    Howarth, Deanna L.; Yin, Chunyue; Yeh, Karen; Kirsten C. Sadler

    2013-01-01

    Fatty liver disease in humans can progress from steatosis to hepatocellular injury, fibrosis, cirrhosis, and liver failure. We developed a series of straightforward assays to determine whether zebrafish larvae with either tunicamycin- or ethanol-induced steatosis develop hepatic dysfunction. We found altered expression of genes involved in acute phase response and hepatic function, and impaired hepatocyte secretion and disruption of canaliculi in both models, but glycogen deficiency in hepato...

  20. Butachlor, a suspected carcinogen, alters growth and transformation characteristics of mouse liver cells.

    Science.gov (United States)

    Ou, Y H; Chung, P C; Chang, Y C; Ngo, F Q; Hsu, K Y; Chen, F D

    2000-12-01

    Butachlor is a widely used herbicide in Asia and South America. Previous investigations have indicated that it is a suspected carcinogen. To understand more about the biological effects of butachlor on cultured cells and the mechanism(s) of its carcinogenicity, we studied the alteration of the growth characteristics that was induced by butachlor in normal mouse liver cells (BNL CL2). This study demonstrates that butachlor decreases the population-doubling time of BNL CL2 cells, suggesting that it stimulates cell proliferation. To support this finding, a thymidine incorporation assay was conducted and a similar result that butachlor stimulates cell proliferation was elucidated. In addition, we show that butachlor increases the saturation density of the BNL CL2 cells. When combined with the tumor initiator N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), butachlor transforms cells efficiently, as demonstrated by loss of contact inhibition. These findings indicate that butachlor alters the growth characteristics of BNL CL2 cells and suggest that butachlor may induce malignant transformation through stimulation of cell proliferation, alteration of cell cycle regulation, and suppression of cell density-dependent inhibition of proliferation.

  1. Starvation alters the liver transcriptome of the innate immune response in Atlantic salmon (Salmo salar

    Directory of Open Access Journals (Sweden)

    Secombes Christopher J

    2010-07-01

    Full Text Available Abstract Background The immune response is an energy demanding process, which has effects in many physiological pathways in the body including protein and lipid metabolism. During an inflammatory response the liver is required to produce high levels of acute phase response proteins that attempt to neutralise an invading pathogen. Although this has been extensively studied in both mammals and fish, little is known about how high and low energy reserves modulate the response to an infection in fish which are ectothermic vertebrates. Food withdrawal in fish causes a decrease in metabolic rate so as to preserve protein and lipid energy reserves, which occurs naturally during the life cycle of many salmonids. Here we investigated how the feeding or fasting of Atlantic salmon affected the transcriptional response in the liver to an acute bacterial infection. Results Total liver RNA was extracted from four different groups of salmon. Two groups were fed or starved for 28 days. One of each of the fed or starved groups was then exposed to an acute bacterial infection. Twenty four hours later (day 29 the livers were isolated from all fish for RNA extraction. The transcriptional changes were examined by micro array analysis using a 17 K Atlantic salmon cDNA microarray. The expression profiling results showed major changes in gene transcription in each of the groups. Enrichment for particular biological pathways was examined by analysis of gene ontology. Those fish that were starved decreased immune gene transcription and reduced production of plasma protein genes, and upon infection there was a further decrease in genes encoding plasma proteins but a large increase in acute phase response proteins. The latter was greater in magnitude than in the fish that had been fed prior to infection. The expression of several genes that were found altered during microarray analysis was confirmed by real time PCR. Conclusions We demonstrate that both starvation and

  2. Garlic attenuates histological and histochemical alterations in livers of Schistosoma mansoni infected mice.

    Science.gov (United States)

    Mahmoud, Y I; Riad, N H; Taha, H

    2016-08-01

    Interest in screening for new anti-schistosomal agents is growing because of increased concerns about resistance to and safety of praziquantel. We investigated the anti-schistosomal action of prophylactic and therapeutic doses of garlic on the histological and histochemical alterations caused by Schistosoma mansoni infection. Livers of infected mice were characterized by granulomas, periportal inflammation and fibrosis, hepatocyte vacuolation, fatty degeneration and necrosis, and hypertrophy and pigmentation of Kupffer cells. Significant depletion of carbohydrates and increased lipid vacuoles also were observed. All garlic regimens caused suppression of granuloma formation and amelioration of histological and histochemical changes; the continuous treatment protocol produced the best results. Garlic appears to be a safe and economical anti-schistosomal adjuvant for attenuating the pathogenicity of schistosomiasis. PMID:27045197

  3. Alteration in substrate specificity of horse liver alcohol dehydrogenase by an acyclic nicotinamide analog of NAD(+).

    Science.gov (United States)

    Malver, Olaf; Sebastian, Mina J; Oppenheimer, Norman J

    2014-11-01

    A new, acyclic NAD-analog, acycloNAD(+) has been synthesized where the nicotinamide ribosyl moiety has been replaced by the nicotinamide (2-hydroxyethoxy)methyl moiety. The chemical properties of this analog are comparable to those of β-NAD(+) with a redox potential of -324mV and a 341nm λmax for the reduced form. Both yeast alcohol dehydrogenase (YADH) and horse liver alcohol dehydrogenase (HLADH) catalyze the reduction of acycloNAD(+) by primary alcohols. With HLADH 1-butanol has the highest Vmax at 49% that of β-NAD(+). The primary deuterium kinetic isotope effect is greater than 3 indicating a significant contribution to the rate limiting step from cleavage of the carbon-hydrogen bond. The stereochemistry of the hydride transfer in the oxidation of stereospecifically deuterium labeled n-butanol is identical to that for the reaction with β-NAD(+). In contrast to the activity toward primary alcohols there is no detectable reduction of acycloNAD(+) by secondary alcohols with HLADH although these alcohols serve as competitive inhibitors. The net effect is that acycloNAD(+) has converted horse liver ADH from a broad spectrum alcohol dehydrogenase, capable of utilizing either primary or secondary alcohols, into an exclusively primary alcohol dehydrogenase. This is the first example of an NAD analog that alters the substrate specificity of a dehydrogenase and, like site-directed mutagenesis of proteins, establishes that modifications of the coenzyme distance from the active site can be used to alter enzyme function and substrate specificity. These and other results, including the activity with α-NADH, clearly demonstrate the promiscuity of the binding interactions between dehydrogenases and the riboside phosphate of the nicotinamide moiety, thus greatly expanding the possibilities for the design of analogs and inhibitors of specific dehydrogenases.

  4. 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 being of key importance for SR Ca2+ release and thereby affecting muscle contractility and fatigability....

  5. 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.

  6. Development of a quantitative 96-well method to image glycogen storage in primary rat hepatocytes.

    Science.gov (United States)

    Pilling, James; Garside, Helen; Ainscow, Edward

    2010-08-01

    Within the liver, hormonal control of glycogen metabolism allows for rapid release and uptake of glucose from the circulation, providing a reserve of glucose that can be utilised by other organs. Traditionally, cellular glycogen storage has been detected using Periodic acid Schiff (PAS) staining of histopathology samples or a biochemical assay. Colorimetric measurement of glycogen content using PAS staining is hard to quantify whilst biochemical techniques give limited information about events such as cytotoxicity or allow analysis of hepatic heterogeneity. Here, we describe the development of an imaging based method to quantify glycogen storage in 96-well cultures of primary rat hepatocytes using the inherent fluorescence properties of the Schiff reagent. PAS-stained hepatocytes were imaged using an automated fluorescent microscope, with the amount of glycogen present in each cell being quantified. Using this technique, we found an increase in glycogen storage in response to insulin (EC50 = 0.31 nM) that was in agreement with that determined using biochemical quantification (EC50 = 0.32 nM). Furthermore, a dose dependent increase in glycogen storage was also seen in response to glycogen synthase kinase inhibitors and glycogen phosphorylase inhibitors. This technique allows rapid assessment of cellular glycogen storage in response to hormones and small molecule inhibitors.

  7. 锁阳煎剂对运动大鼠肝脏自由基代谢及肝糖原代谢的影响%Effects of cynomorium decoction upon the metabolism of free radical and liver glycogen of liver tissue of exercise rats

    Institute of Scientific and Technical Information of China (English)

    李东哲; 马维民

    2013-01-01

    目的 研究锁阳煎剂对大鼠肝脏自由基及肝糖原代谢的影响.方法 将48只雄性Wister大鼠随机分成A(安静组)、B(安静给药组)、C(运动组)、D(运动给药组)4组,每组12只,给药组大鼠灌胃服用锁阳煎剂,运动组进行递增负荷跑台运动,7周后对大鼠进行力竭处理,测定肝脏超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)和丙二醛(MDA)以及肝脏糖原等指标.结果 力竭后给药组大鼠肝脏超氧化物歧化酶(SOD)和总抗氧化能力(T-AOC)的活性及肝脏糖原含量均高于对照组(P<0.05),肝脏丙二醛(MDA)含量低于对照组(P<0.05);运动给药组SOD和T-AOC活性均高于安静给药组(P<0.01),MDA含量低于安静给药组(P<0.01);运动给药组肝糖原含量均高于安静给药组(P<0.01).结论 锁阳煎剂具有保护肝脏免受自由基损伤及提高运动能力的功能.%OBJECTIVE To explore effects of cynomorium decoction upon free radicals' metabolism of liver tissue and liver glycogen content of rats. METHODS 48 male Wister rats were divided into four groups (each group of 12) : A (the control group), B (the control group with cynomorium decoction), C (the exercise group) and D (the exercise group with cynomorium decoction). The exercise groups performed treadmill exercise with incremental intensity and rats were affused with cynomorium decoction by stomach. After seven weeks, the superoxide dismutase (SOD), theT-AOC, the MDA of liver tissue and hep-atin of liver and muscle tissues were measured by exhaustive treatment on rats. RESULTS The results indicated that the SOD, the T-AOC and hepatin of liver tissue and quadriceps improved remarkably (P < 0.05) , and the MDA of liver tissue reduced outstandingly (P < 0.05). Activity of SOD and T-AOC of the exercise group with cynomorium decoction was stronger than the control group with cynomorium decoction, and the quantity of MDA was less than the control group with cynomorium decoction; liver

  8. 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. PMID:27178921

  9. Quantitative relationship between hepatocytic neoplasms and islands of cellular alteration during hepatocarcinogenesis in the male F344 rat.

    OpenAIRE

    Kaufmann, W. K.; Mackenzie, S. A.; Kaufman, D G

    1985-01-01

    Hepatocytic neoplasms (nodules and carcinomas) and islands of cellular alteration which display abnormal retention of glycogen on fasting were quantified in F344 male rats at intervals after initiation of hepatocarcinogenesis by the combination of a two-thirds partial hepatectomy with a single treatment with methyl(acetoxymethyl)-nitrosamine during the subsequent peak of DNA synthesis in regenerating livers. In initiated rats fed the liver tumor promoter phenobarbital, yields of neoplasms and...

  10. 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

    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.......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...

  11. Refsum disease diagnostic marker phytanic acid alters the physical state of membrane proteins of liver mitochondria.

    Science.gov (United States)

    Schönfeld, P; Struy, H

    1999-08-27

    Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), a branched chain fatty acid accumulating in Refsum disease to high levels throughout the body, induces uncoupling of rat liver mitochondria similar to non-branched fatty acids (e.g. palmitic acid), but the contribution of the ADP/ATP carrier or the aspartate/glutamate carrier in phytanic acid-induced uncoupling is of minor importance. Possible deleterious effects of phytanic acid on membrane-linked energy coupling processes were studied by ESR spectroscopy using rat liver mitochondria and a membrane preparation labeled with the lipid-specific spin probe 5-doxylstearic acid (5-DSA) or the protein-specific spin probe MAL-TEMPO (4-maleimido-2,2,6, 6-tetramethyl-piperidine-1-oxyl). The effects of phytanic acid on phospholipid molecular dynamics and on the physical state of membrane proteins were quantified by estimation of the order parameter or the ratio of the amplitudes of the weakly to strongly immobilized MAL-TEMPO binding sites (W/S ratio), respectively. It was found, that phytanic acid (1) increased the mobility of phospholipid molecules (indicated by a decrease in the order parameter) and (2) altered the conformational state and/or the segmental mobility of membrane proteins (indicated by a drastic decrease in the W/S ratio). Unsaturated fatty acids with multiple cis-double bonds (e.g. linolenic or arachidonic acid), but not non-branched FFA (ranging from chain length C10:0 to C18:0), also decrease the W/S ratio. It is hypothesized that the interaction of phytanic acid with transmembrane proteins might stimulate the proton permeability through the mitochondrial inner membrane according to a mechanism, different to a protein-supported fatty acid cycling.

  12. Alteration in the fatty acid composition of liver, kidney and plasma from diethylhexyl phthalate-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Okita, J.R.; Okita, R.T. (Medical Coll. of Wisconsin, Milwaukee (United States))

    1990-02-26

    Cytochromes P-450 are induced in rat liver microsomes by a number of compounds which cause peroxisome proliferation. One such compound, diethylhexyl phthalate (DEHP), induces P-450 IVA1 which catalyzes {omega}- and ({omega}-1)-hydroxylation of fatty acids. In liver of rats fed DEHP, there is a 10-fold induction of {omega}-hydroxylation of laurate and ({omega}-1)-hydroxylation of palmitate, as compared to control rat liver. There is a 3-fold induction of other hydroxylations, such as W-hydroxylation of palmitate and {omega}- ({omega}-1)-hydroxylation of syristate. Despite these increases in hydroxylase activity, the authors have not been able to demonstrate increases in hydroxy fatty acids or dicarboxylic acids in liver or plasma of rats fed DEHP. However, alterations in the fatty acid composition of lipids in liver, kidney cortex and plasma were observed. They consistently observed increases in oleate (expressed as mol% of total fatty acid) in liver (11% in control increased to 24% in DEHP-treated), kidney cortex (12% to 16%) and plasma (13% to 24%). This increase in oleate was quite striking when expressed as ug/gm tissue or ug/al plasma. DEHP treatment resulted in increased oleate in mitochondrial, microsomal and cytosolic fractions of liver.

  13. 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. PMID:26908609

  14. Neither bovine somatotropin nor growth hormone-releasing factor alters expression of thyroid hormone receptors in liver and mammary tissues.

    Science.gov (United States)

    Capuco, A V; Binelli, M; Tucker, H A

    2011-10-01

    Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine to specific nuclear receptors. Organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, have been hypothesized to target the action of thyroid hormones on the mammary gland and play a role in mediating or augmenting a galactopoietic response to bovine somatotropin (bST). Additionally, tissue responsiveness to thyroid hormones may be altered by changes in the number or affinity of nuclear receptors for thyroid hormones. In the present study, effects of bST and bovine growth hormone-releasing factor (bGRF) on thyroid hormone receptors in liver and mammary gland were studied. Lactating Holstein cows received continuous infusions of bST or bGRF for 63 d or served as uninfused controls. Nuclei were isolated from harvested mammary and liver tissues and incubated with [(125)I]-triiodothyronine. Treatments did not alter the capacity or affinity of specific binding sites for triiodothyronine in liver or mammary nuclei. Evaluation of transcript abundance for thyroid hormone receptors showed that isoforms of thyroid hormone receptor or retinoid receptor (which may influence thyroid receptor action) expressed in the mammary gland were not altered by bST or bGRF treatment. Data do not support the hypothesis that administration of bST or bGRF alters sensitivity of mammary tissue by changing expression of thyroid hormone receptors.

  15. Non-alcoholic fatty liver disease in HIV infection associated with altered hepatic fatty acid composition.

    Science.gov (United States)

    Arendt, Bianca M; Mohammed, Saira S; Ma, David W L; Aghdassi, Elaheh; Salit, Irving E; Wong, David K H; Guindi, Maha; Sherman, Morris; Heathcote, E Jenny; Allard, Johane P

    2011-03-01

    Hepatic fatty acid (FA) composition, especially a reduction in n-3 polyunsaturated FA (PUFA) may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is common in HIV-infection.. In a cross-sectional study we compared hepatic FA composition between 20 HIV-infected men with NAFLD (HIV/NAFLD), 21 HIV-negative men with NAFLD (NAFLD), and 7 healthy controls. Within HIV/NAFLD we compared simple steatosis (HIV/SS) to steatohepatitis (HIV/NASH). FA composition in liver and erythrocytes, oxidative stress, diet, and exercise were assessed. Major findings (P<0.05) were: 1) higher hepatic n-6/n-3 ratio in HIV/NAFLD [median (range)] [8.08 (1.08-21.52)] compared to controls [5.83 (3.58-6.93)] and NAFLD [5.97 (1.46-10.40)], with higher n-6 PUFA in HIV/NAFLD compared to NAFLD; 2) lower n-3 PUFA in erythrocytes (mol%), a marker for dietary intake, in HIV/NAFLD [5.26 (1.04-11.75)] compared to controls [8.92 (4.79-12.67)]; 3) the ratios of long-chain PUFA products to essential FA precursors of the n-6 and n-3 series were lower in HIV/NAFLD and NAFLD compared to controls. In contrast, the ratio of oleic/stearic acid was higher in HIV/NAFLD compared to the other groups. These ratios are indirect markers of enzymatic FA desaturation and elongation. Hepatic PUFA, especially biologically active long-chain PUFA, were also lower in HIV/NASH compared to HIV/SS. Oxidative stress was not different among the groups. We conclude that HIV/NAFLD is associated with altered hepatic FA composition. Changes may be due to impaired FA metabolism or suboptimal n-3 PUFA intake. The potential role of n-3 PUFA (e.g. fish oil) to treat or prevent HIV/NAFLD warrants further investigation. PMID:21434863

  16. Dynamic alteration of telomerase expression and its diagnostic significance in liver or peripheral blood for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Deng-Fu Yao; Wei Wu; Min Yao; Li-Wei Qiu; Xin-Hua Wu; Xiao-Qin Su; Li Zou; Deng-Bing Yao; Xian-Yong Meng

    2006-01-01

    AIM: To investigate the dynamic alteration of telomerase expression during development of hepatocellular carcinoma (HCC) and its diagnostic implications in liver tissues or peripheral blood mononuclear cells for HCC.METHODS: Dynamic expressions of liver telomerase during malignant transformation of hepatocytes were observed in Sprague-Dawly (SD) rats fed with 0.05% of 2-fluoenyacetamide (2-FAA). Total RNA and telomerase were extracted from rat or human liver tissues. The telomerase activities in livers and in circulating blood were detected by a telomeric repeat amplification protocol-enzyme-linked immunosorbent assay (TRAPELISA), and its diagnostic value was investigated in patients with benign or malignant liver diseases.RESULTS: The hepatoma model displayed the dynamic expression of hepatic telomerase during HCC development. The telomerase activities were consistent with liver total RNA levels (r = 0.83, P<0.01) at the stages of degeneration, precancerosis, and cancerization of hepatocytes. In HCC patients, the telomerase levels in HCC tissues were significantly higher than in their adjacent non-cancerous tissues, but liver total RNA levels were lower in the former than in the latter. Although the circulating telomerase of HCC patients was abnormally expressed among patients with chronic liver diseases,the telomerase activity was a non-specific marker for HCC diagnosis, because the incidence was 15.7% in normal control, 25% in chronic hepatitis, 45.9% in liver cirrhosis, and 85.2% in HCC, respectively when absorbance value of telomerase activity was more than 0.2. If the value was over 0.6, the incidence was 60%in HCC group and 0% in any of the others (P<0.01)except in two cases with liver cirrhosis. However, the combination of circulating telomerase with serum alphafetoprotein level could increase the positive rate and the accuracy (92.6%, 125 of 135) of HCC diagnosis.CONCLUSION: The overexpression of telomerase is associated with HCC development, and its

  17. [Glycogen storage disease by amylo 1,6-glucosidase deficiency (author's transl)].

    Science.gov (United States)

    Méndez Aparicio, F M

    1980-10-01

    A case of liver glycogen storage disease with amylo 1,6-glucosidase deficiency is reported. Enlarged liver was found at birth, and it is now accompanied by splenomegaly, low fasting blood glucose with ketonuria, elevation of transaminase values and glycogen accumulation with connective periportal tissue in liver histological study. In this glucogenosis results of functional tests on carbohidrate metabolism and glycogen enzymatic assay showed a direct relationship between functional and biochemical behaviour of liver cells. Amylo 1,6-glucosidase deficiency is accompanied by absence of glucogenolysis when glucagon is administrated after a long fast, and an increase of blood glucose when glucagon is administrated after food ingestion. Glycolisis tests show blood lactate elevation when some hexose or alanine are administrated; glyconeogenesis tests show blood glucose elevation when hexose, alanine or glycerol are administrated. PMID:6937153

  18. Experimental Periodontitis Results in Prediabetes and Metabolic Alterations in Brain, Liver and Heart: Global Untargeted Metabolomic Analyses

    Science.gov (United States)

    Ilievski, Vladimir; Kinchen, Jason M; Prabhu, Ramya; Rim, Fadi; Leoni, Lara; Unterman, Terry G.; Watanabe, Keiko

    2016-01-01

    Results from epidemiological studies suggest that there is an association between periodontitis and prediabetes, however, causality is not known. The results from our previous studies suggest that induction of periodontitis leads to hyperinsulinemia glucose intolerance and insulin resistance, all hallmarks of prediabetes. However, global effects of periodontitis on critical organs in terms of metabolic alterations are unknown. We determined the metabolic effects of periodontitis on brain, liver, heart and plasma resulting from Porphyromonas gingivalis induced periodontitis in mice. Periodontitis was induced by oral application of the periodontal pathogen, Porphyromonas gingivalis for 22 weeks. Global untargeted biochemical profiles in samples from these organs/plasma were determined by liquid and gas chromatography/mass spectrometry and compared between controls and animals with periodontitis. Oral application of Porphyromonas gingivalis induced chronic periodontitis and hallmarks of prediabetes. The results of sample analyses indicated a number of changes in metabolic readouts, including changes in metabolites related to glucose and arginine metabolism, inflammation and redox homeostasis. Changes in biochemicals suggested subtle systemic effects related to periodontal disease, with increases in markers of inflammation and oxidative stress most prominent in the liver. Signs of changes in redox homeostasis were also seen in the brain and heart. Elevated bile acids in liver were suggestive of increased biosynthesis, which may reflect changes in liver function. Interestingly, signs of decreasing glucose availability were seen in the brain. In all three organs and plasma, there was a significant increase in the microbiome-derived bioactive metabolite 4-ethylphenylsulfate sulfate in animals with periodontitis. The results of metabolic profiling suggest that periodontitis/bacterial products alter metabolomic signatures of brain, heart, liver, and plasma in the

  19. Early maternal undernutrition programs increased feed intake, altered glucose metabolism and insulin secretion, and liver function in aged female offspring.

    Science.gov (United States)

    George, Lindsey A; Zhang, Liren; Tuersunjiang, Nuermaimaiti; Ma, Yan; Long, Nathan M; Uthlaut, Adam B; Smith, Derek T; Nathanielsz, Peter W; Ford, Stephen P

    2012-04-01

    Insulin resistance and obesity are components of the metabolic syndrome that includes development of cardiovascular disease and diabetes with advancing age. The thrifty phenotype hypothesis suggests that offspring of poorly nourished mothers are predisposed to the various components of the metabolic syndrome due to adaptations made during fetal development. We assessed the effects of maternal nutrient restriction in early gestation on feeding behavior, insulin and glucose dynamics, body composition, and liver function in aged female offspring of ewes fed either a nutrient-restricted [NR 50% National Research Council (NRC) recommendations] or control (C: 100% NRC) diet from 28 to 78 days of gestation, after which both groups were fed at 100% of NRC from day 79 to lambing and through lactation. Female lambs born to NR and C dams were reared as a single group from weaning, and thereafter, they were fed 100% NRC recommendations until assigned to this study at 6 yr of age. These female offspring were evaluated by a frequently sampled intravenous glucose tolerance test, followed by dual-energy X-ray absorptiometry for body composition analysis prior to and after ad libitum feeding of a highly palatable pelleted diet for 11 wk with automated monitoring of feed intake (GrowSafe Systems). Aged female offspring born to NR ewes demonstrated greater and more rapid feed intake, greater body weight gain, and efficiency of gain, lower insulin sensitivity, higher insulin secretion, and greater hepatic lipid and glycogen content than offspring from C ewes. These data confirm an increased metabolic "thriftiness" of offspring born to NR mothers, which continues into advanced age, possibly predisposing these offspring to metabolic disease. PMID:22277936

  20. 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.

  1. Altered microRNA expression induced by tumorigenic conazoles in mouse liver.

    Science.gov (United States)

    Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants ...

  2. Molecular Mechanism Responsible for Fibronectin-controlled Alterations in Matrix Stiffness in Advanced Chronic Liver Fibrogenesis.

    Science.gov (United States)

    Iwasaki, Ayumi; Sakai, Keiko; Moriya, Kei; Sasaki, Takako; Keene, Douglas R; Akhtar, Riaz; Miyazono, Takayoshi; Yasumura, Satoshi; Watanabe, Masatoshi; Morishita, Shin; Sakai, Takao

    2016-01-01

    Fibrosis is characterized by extracellular matrix (ECM) remodeling and stiffening. However, the functional contribution of tissue stiffening to noncancer pathogenesis remains largely unknown. Fibronectin (Fn) is an ECM glycoprotein substantially expressed during tissue repair. Here we show in advanced chronic liver fibrogenesis using a mouse model lacking Fn that, unexpectedly, Fn-null livers lead to more extensive liver cirrhosis, which is accompanied by increased liver matrix stiffness and deteriorated hepatic functions. Furthermore, Fn-null livers exhibit more myofibroblast phenotypes and accumulate highly disorganized/diffuse collagenous ECM networks composed of thinner and significantly increased number of collagen fibrils during advanced chronic liver damage. Mechanistically, mutant livers show elevated local TGF-β activity and lysyl oxidase expressions. A significant amount of active lysyl oxidase is released in Fn-null hepatic stellate cells in response to TGF-β1 through canonical and noncanonical Smad such as PI3 kinase-mediated pathways. TGF-β1-induced collagen fibril stiffness in Fn-null hepatic stellate cells is significantly higher compared with wild-type cells. Inhibition of lysyl oxidase significantly reduces collagen fibril stiffness, and treatment of Fn recovers collagen fibril stiffness to wild-type levels. Thus, our findings indicate an indispensable role for Fn in chronic liver fibrosis/cirrhosis in negatively regulating TGF-β bioavailability, which in turn modulates ECM remodeling and stiffening and consequently preserves adult organ functions. Furthermore, this regulatory mechanism by Fn could be translated for a potential therapeutic target in a broader variety of chronic fibrotic diseases.

  3. [Alterations of prooxidant-antioxidant system of rat liver at ethanol and tetracycline action].

    Science.gov (United States)

    Nedoshytko, Kh Iu

    2013-01-01

    The state of antioxidant system and fatty acid composition of lipids in the liver tissues of rats of different sex at the ethanol and tetracycline action and at the influence of biologically active additives (BAA) "Alpha + Omega" at a dose of 0.5 mg/kg b.w. per os was investigated. It was found that the contet of lipid peroxidation products in the liver was increased at the action of 40% ethanol at a dose of 7 ml/kg b.w. per os and tetracycline--500 mg/kg and more profound at their joint using. However, the content of diene conjugates was stronger increased in the liver of females at the action of ethanol, while in the liver of males at the action of tetracycline (P tetracycline and more profound at their joint usage (P tetracycline unidirectionally changed fatty acid composition of total lipids of rat liver, but at the ethanol action the changes were more expressed in females while at the tetracycline action in males. The application during 14 days of BAA "Alpha + Omega" to male and female rats with an acute tetracycline damage at subacute ethanol action led to partial normalization of prooxidant-antioxidant system and the relative content of total lipids fatty acids of the liver of both sexes animals. PMID:24479333

  4. Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the effects of resveratrol on liver ischemia/reperfusion (I/R) injury in rats. METHODS: A total of 40 male Sprague-Dawley rats weighing 240-290 g were randomized into four groups often: (1) controls: data from unmanipulated animals; (2) sham group: rats subjected to the surgical procedure, except for liver I/R, and given saline; (3) I/R group: rats underwent liver ischemia for 45 min followed by reperfu-sion for 45 min; (4) I-R/Resveratrol group: rats pretreat-ed with resveratrol (10 μmol/L, iv). Liver tissues were obtained to determine antioxidant enzyme levels and for biochemical and histological evaluation. RESULTS: Plasma aminotransferase activities were higher in the I/R group than in the I-R/Resveratrol group. Malondialdehyde levels and the hepatic injury score decreased, while superoxide dismutase, catalase, and glutathione peroxidase levels increased in group 4 compared to group 3. In group 4, histopathological changes were significantly attenuated in resveratrol-treated livers.CONCLUSION: These results suggest that resveratrol has protective effects against hepatic I/R injury, and is a potential therapeutic drug for ischemia reperfusion-related liver injury.

  5. Histological alterations in liver and testis of Astyanax aff. bimaculatus caused by acute exposition to zinc

    Directory of Open Access Journals (Sweden)

    Daiane Cristina Marques dos Santos*

    2015-04-01

    Full Text Available This study investigated the effect of acute exposition to zinc (Zn on histology of the liver and testes of yellow tail lambari (Astyanax aff. bimaculatus. The exposure consisted of six concentrations of Zn (0, 3, 5, 10, 15, and 20 mg/L for 96 hours of exposure. Fragments of liver and testis were routinely processed and embedded in plastic resin based on glycol methacrylate. Fragments of bones, muscles, liver and testis were dehydrated and digested to quantify the absorption levels of Zn in the tissue. Acute exposure to concentrations above 10mg/L has produced structural changes in the liver and gonads. The changes found in the liver were vascular congestion; decrease of cellular volume; displacement of the hepatocyte nucleus; necrosis; disarrangement of cordon structure; leukocyte infiltrate and vacuolization. The changes found in the gonads were ruptured cyst, delayed development of germ cells, pyknotic nucleus, cell cluster, displacement of cyst wall and vacuolization. The histological changes observed were compatible with the increasing concentration of zinc in environment, compromising liver and reproductive functions, because there was an increase in relative frequency of hepatocytes and reduced sperm production

  6. 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.

  7. Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Wang, Baohong; Jiang, Xiangyang; Cao, Min; Ge, Jianping; Bao, Qiongling; Tang, Lingling; Chen, Yu; Li, Lanjuan

    2016-01-01

    Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease (NAFLD). But it remains unknown in nonobese NAFLD. This prospective, cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression. A total of 126 nonobese subjects were enrolled: 43 NAFLD and 83 healthy controls (HC). The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region. Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD. Compared with HC, patients had 20% more phylum Bacteroidetes (p = 0.005) and 24% less Firmicutes (p = 0.002). Within Firmicutes, four families and their 8 genera, which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria, were significantly decreased. Moreover, Gram-negative (G-) bacteria were prevalent in NAFLD (p = 0.008). Furthermore, a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD. This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression. PMID:27550547

  8. Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease

    Science.gov (United States)

    Wang, Baohong; Jiang, Xiangyang; Cao, Min; Ge, Jianping; Bao, Qiongling; Tang, Lingling; Chen, Yu; Li, Lanjuan

    2016-01-01

    Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease (NAFLD). But it remains unknown in nonobese NAFLD. This prospective, cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression. A total of 126 nonobese subjects were enrolled: 43 NAFLD and 83 healthy controls (HC). The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region. Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD. Compared with HC, patients had 20% more phylum Bacteroidetes (p = 0.005) and 24% less Firmicutes (p = 0.002). Within Firmicutes, four families and their 8 genera, which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria, were significantly decreased. Moreover, Gram-negative (G−) bacteria were prevalent in NAFLD (p = 0.008). Furthermore, a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD. This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression. PMID:27550547

  9. Morphological alterations in the liver of yellow perch (Perca flavescens) from a biological mercury hotspot.

    Science.gov (United States)

    Müller, Anne-Katrin; Brinkmann, Markus; Baumann, Lisa; Stoffel, Michael H; Segner, Helmut; Kidd, Karen A; Hollert, Henner

    2015-11-01

    Mercury (Hg) contamination is a global issue due to its anthropogenic release, long-range transport, and deposition in remote areas. In Kejimkujik National Park and National Historic Site, Nova Scotia, Canada, high concentrations of total mercury (THg) were found in tissues of yellow perch (Perca flavescens). The aim of this study was to evaluate a possible relationship between THg concentrations and the morphology of perch liver as a main site of metal storage and toxicity. Yellow perch were sampled from five lakes known to contain fish representing a wide range in Hg concentrations in fall 2013. The ultrastructure of hepatocytes and the distribution of Hg within the liver parenchyma were analyzed by transmission electron microscopy (TEM) and electron energy loss spectrometry (EELS). The relative area of macrophage aggregates (MAs) in the liver was determined using image analysis software and fluorescence microscopy. No relation between general health indicators (Fulton's condition index) and THg was observed. In line with this, TEM examination of the liver ultrastructure revealed no prominent pathologies related to THg accumulation. However, a morphological parameter that appeared to increase with muscle THg was the relative area of MAs in the liver. The hepatic lysosomes appeared to be enlarged in samples with the highest THg concentrations. Interestingly, EELS analysis revealed that the MAs and hepatic lysosomes contained Hg. PMID:25936831

  10. Therapy with bone marrow cells reduces liver alterations in mice chronically infected by Schistosoma mansoni

    Institute of Scientific and Technical Information of China (English)

    Sheilla Andrade Oliveira; Bruno Solano Freitas Souza; Cada Adriana Guimar(a)es-Ferreira; Elton Sá Barreto; Siane Campos Souza; Luiz Antonio Rodrigues Freitas; Ricardo Ribeiro-dos-Santos; Milena Botelho Pereira Soares

    2008-01-01

    AIM: To investigate the potential of bone marrow mononuclear cells (BM-MCs) in the regeneration of hepatic lesions induced by Schistosoma mansoni (S.mansoni) chronic infection.METHODS: Female mice chronically infected with S.mansoni were treated with BM-MCs obtained from male green fluorescent protein (GFP) transgenic mice by intravenous or intralobular injections. Control mice received injections of saline in similar conditions. Enzyme-linked immunosorbent assay (ELISA) assay for transforming growth factor-beta (TGF-β), polymerase chain reaction (PCR) for GFP DNA, immunofluorescence and morphometric studies were performed.RESULTS: Transplanted GFP+ cells migrated to granuloma areas and reduced the percentage of liver fibrosis. The presence of donor-derived cells was confirmed by Fluorescence in situ hybridization (FISH) analysis for detection of cells bearing Y chromosome and by PCR analysis for detection of GFP DNA. The levels of TGF-β, a cytokine associated with fibrosis deposition, in liver fragments of mice submitted to therapy were reduced. The number of oval cells in liver sections of S.rnansoni-infected mice increased 3-4 fold after transplantation. A partial recovery in albumin expression, which is decreased upon infection with S.mansoni, was found in livers of infected mice after cellular therapy.CONCLUSION: In conclusion, transplanted BMCs migrate to and reduce the damage of chronic fibrotic liver lesions caused by S.mansoni.

  11. A Study on the dynamic alterations of serum HA in rats with carbontetrachloride-induced liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Lan Ma; Li Sheng Zhao; Chun Hua Li; Qi Lu; Ren Kuan Li; Shuang Sheng Deng

    2000-01-01

    AIM To study the clinical significance of alterations of serum hyaluronic acid in rats with carbontetrachioride-induced liver fibrosis.METHODS Rat liver fibrosis model was induced by carbon tetrachloride (CC14). The rats were divided intofive groups; group 1 (control): 0 week with no CCl4-inducing; group 2, 3, 4 and 5: 3, 6, 9 and 12 weeksafter CCl4-induction respectively. Serum HA level was analysed among various liver fibrosis groups andcontrol, and then compared the HA findings with the hepatic histopathology.RESULTS During rat liver fibrosis, serum HA levels of the liver fibrosis groups (group 2: 7.98ng/mL;group 3: 20.10 ng/mL; group 4:229.73 ng/mL; group 5:324,74 ng/mL) were significantly higher thanthat of control group (group 1:0.21 ng/mL) (P<0.01), in which group 4 and group 5 are much higher1094 times (229.73ng/mL/0.21 ng/mL) and 1546 times (324.74 ng/mL/0.21 ng/mL) than group 1respectively. When compared with each other, the serum HA levels are 38 times (7.98ng/mL/0.21 ng/mL; P<0.01, group 2 vs group 1); 2.5 times (20.10ng/mL/7.98 ng/mL; P<0.01, group 3 vsgroup 2); 11.4 times (229.73 ng/mL/20.10 ng/mL; P<0.01, group 4 vs group 3); 1.4 times (324.74 ng/mL/229.73 ng/mL; P<0.01, group 5 vs group 4) respectively.CONCLUSION The results demonstrated that the dynamic alterations of serum HA play an important rolein the early clinical diagnosis and staging of liver cirrhosis.

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

    Science.gov (United States)

    Shukla, Shivendra D; Aroor, Annayya R; Restrepo, Ricardo; Kharbanda, Kusum K; Ibdah, Jamal A

    2015-11-20

    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.

  13. 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. PMID:27372291

  14. Dichloroacetate Stimulates Glycogen Accumulation in Primary Hepatocytes through an Insulin-Independent Mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Lingohr, Melissa K.(Washington State University); Bull, Richard J.(SELF-EMPLOYED CONSULTANTS); Kato-Weinstein, Junko (UNIVERSITY PROGRAMS); Thrall, Brian D.(BATTELLE (PACIFIC NW LAB))

    2002-01-01

    Dichloroacetate (DCA), a by-product of water chlorination, causes liver cancer in B6C3F1 mice. A hallmark response observed in mice exposed to carcinogenic doses of DCA is an accumulation of hepatic glycogen content. To distinguish whether the in vivo glycogenic effect of DCA was dependent on insulin and insulin signaling proteins, experiments were conducted in isolated hepatocytes where insulin concentrations could be controlled. In hepatocytes isolated from male B6C3F1 mice, DCA increased glycogen levels in a dose-related manner, independently of insulin. The accumulation of hepatocellular glycogen induced by DCA was not the result of decreased glycogenolysis, since DCA had no effect on the rate of glucagon-stimulated glycogen breakdown. Glycogen accumulation caused by DCA treatment was not hindered by inhibitors of extracellular-regulated protein kinase kinase (Erk1/2 kinase or MEK) or p70 kDa S6 protein kinase (p70(S6K)), but was completely blocked by the phosphatidylinositol 3-kinase (PI3K) inhibitors, LY294002 and wortmannin. Similarly, insulin-stimulated glycogen deposition was not influenced by the Erk1/2 kinase inhibitor, PD098509, or the p70(S6K) inhibitor, rapamycin. Unlike DCA-stimulated glycogen deposition, PI3K-inhibition only partially blocked the glycogenic effect of insulin. DCA did not cause phosphorylation of the downstream PI3K target protein, protein kinase B (PKB/Akt). The phosphorylation of PKB/Akt did not correlate to insulin-stimulated glycogenesis either. Similar to insulin, DCA in the medium decreased IR expression in isolated hepatocytes. The results indicate DCA increases hepatocellular glycogen accumulation through a PI3K-dependent mechanism that does not involve PKB/Akt and is, at least in part, different from the classical insulin-stimulated glycogenesis pathway. Somewhat surprisingly, insulin-stimulated glycogenesis also appears not to involve PKB/Akt in isolated murine hepatocytes.

  15. 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.

  16. The use of microencapsulated hepatocytes transplantation reduces mortality and liver alterations in Schistosoma mansoni infected hamsters.

    Science.gov (United States)

    Sherif, Soad A; Moharib, Mona N; El-Lakkany, Naglaa M; Hammam, Olfat A; Salman, Fatma H; El-Naggar, Mohamed M

    2014-04-01

    Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotropic liver transplantation. The goal of this work was to study the adequacy of intrasplenic hepatocyte transplantation (HCTx) in fresh and microencapsulated forms, in a hamster model of liver fibrosis by Schistosoma mansoni infected hamsters were divided into 6 groups; untreated for 11 weeks (GI) and for 15 weeks (GII), treated with praziquantel (PZQ) 7 weeks PI, and killed 4 weeks (GIII) and 8 weeks (GIV) post-treatment. Treated with PZQ 7 weeks PI, and then treated orally with immunosuppressive drug "cyclosporine (4 weeks post PZQ treatment), 24 hr. before interasplenic injection with fresh hepatocytes (V). Treated with PZQ 7 weeks PI, and then injected interasplenically (4 weeks post-treatment) with microencapsulated hepatocytes (GVI). GI & GIII were killed 11 weeks PI for assessment the anti-schistosomal efficacy of PZQ. The other four groups were killed 15 weeks PI for investigation of liver and spleen histology, serum liver enzymes and hepatic oxidative markers before and after HCTx. Freshly isolated hepatocytes with a mean viability 92.97 +/- 1.2% were used for microencapsulation and transplantation. Histological study showed the presence of transplanted hepatocytes in spleen of recipient. PZQ accelerated healing of hepatic granulomatous lesions as evidenced parasitologically by the increase in the percentage of dead eggs and histologically showing more granuloma circumscription with more ova degeneration and less inflammatory cells. The 25-day survival rates in GII, GIV, GV& GVI were 5/15 (33.3%), 8/15 (53.3%), 10/15 (66.7%) and 9/15 (60%) respectively. In addition, there were significantly better outcomes in serum biochemical indexes such as ALT, AST, gamma-GT, ALP, and hepatic SOD and MDA in the fresh and microencapsulated groups than in PZQ-treated group, without great differences between the microencapsulated and the fresh transplanted groups

  17. 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...... synthase was determined during electro-stimulation. The activity of this enzyme was measured at low UDPG concentration with either high or low Glu-6-P content. Western blots were performed against glycogen synthase over a range of stimulation periods. Activation of this enzyme was maximum before the net...

  18. Association of diabetes and cigarette smoke exposure on the glycemia and liver glycogen of pregnant Wistar rats Associação entre diabetes e exposição à fumaça de cigarro sobre a glicemia e glicogênio hepático de ratas Wistar prenhes

    Directory of Open Access Journals (Sweden)

    Yuri Karen Sinzato

    2008-12-01

    Full Text Available PURPOSE: To evaluate cigarette smoke exposure and/or diabetes association effects on the glycemia and liver glycogen levels of pregnant Wistar rats. METHODS: 60 adult rats were randomly distributed into (n=10/group: non-diabetic exposed to filtered air (G1; non-diabetic exposed to cigarette smoke only before pregnancy (G2; non-diabetic exposed to cigarette smoke before and during pregnancy (G3; diabetic exposed to filtered air (G4; diabetic exposed to cigarette smoke only before pregnancy (G5, and diabetic exposed to cigarette smoke before and during pregnancy (G6. Glycemia was determined at days 0 and 21 of pregnancy. Liver samples were collected for liver glycogen determinations. RESULTS: At day 21 of pregnancy, glycemia was higher in G5 and G6 compared to G4 group. G2 (2.43±0.43, G3 (3.20±0.49, G4 (2.62±0.34, G5 (2.65±0.27 and G6 groups (1.94±0.35 presented decreased liver glycogen concentrations compared to G1 (4.20±0.18 mg/100mg liver tissue (pOBJETIVO: Avaliar a associação da exposição à fumaça de cigarro e/ou diabete sobre a glicemia e concentrações de glicogênio hepático em ratas Wistar prenhes. MÉTODOS: 60 ratas adultas foram distribuídas aleatoriamente em seis grupos (n=10/grupo: não-diabético exposto ao ar filtrado (G1; não-diabético exposto à fumaça de cigarro antes da prenhez (G2; não-diabético exposto à fumaça de cigarro antes e durante a prenhez (G3; diabético exposto ao ar filtrado (G4; diabético exposto à fumaça de cigarro antes da prenhez (G5; diabético exposto à fumaça de cigarro antes e durante a prenhez (G6. A glicemia foi determinada nos dias 0 e 21 de prenhez. Foram coletadas amostras de fígado para dosagens de glicogênio. RESULTADOS: No 21º dia de prenhez, a glicemia foi maior nos grupos G5 e G6 comparados ao grupo G4. Os grupos G2 (2,43±0,43, G3 (3,20±0,49, G4 (2,62±0,34, G5 (2,65±0,27 e G6 (1,94±0,35 apresentaram concentrações de glicogênio diminuídas comparados ao grupo G1

  19. Prenatal arsenic exposure alters gene expression in the adult liver to a proinflammatory state contributing to accelerated atherosclerosis.

    Directory of Open Access Journals (Sweden)

    J Christopher States

    Full Text Available The mechanisms by which environmental toxicants alter developmental processes predisposing individuals to adult onset chronic disease are not well-understood. Transplacental arsenic exposure promotes atherogenesis in apolipoprotein E-knockout (ApoE(-/- mice. Because the liver plays a central role in atherosclerosis, diabetes and metabolic syndrome, we hypothesized that accelerated atherosclerosis may be linked to altered hepatic development. This hypothesis was tested in ApoE(-/- mice exposed to 49 ppm arsenic in utero from gestational day (GD 8 to term. GD18 hepatic arsenic was 1.2 µg/g in dams and 350 ng/g in fetuses. The hepatic transcriptome was evaluated by microarray analysis to assess mRNA and microRNA abundance in control and exposed pups at postnatal day (PND 1 and PND70. Arsenic exposure altered postnatal developmental trajectory of mRNA and microRNA profiles. We identified an arsenic exposure related 51-gene signature at PND1 and PND70 with several hubs of interaction (Hspa8, IgM and Hnf4a. Gene ontology (GO annotation analyses indicated that pathways for gluconeogenesis and glycolysis were suppressed in exposed pups at PND1, and pathways for protein export, ribosome, antigen processing and presentation, and complement and coagulation cascades were induced by PND70. Promoter analysis of differentially-expressed transcripts identified enriched transcription factor binding sites and clustering to common regulatory sites. SREBP1 binding sites were identified in about 16% of PND70 differentially-expressed genes. Western blot analysis confirmed changes in the liver at PND70 that included increases of heat shock protein 70 (Hspa8 and active SREBP1. Plasma AST and ALT levels were increased at PND70. These results suggest that transplacental arsenic exposure alters developmental programming in fetal liver, leading to an enduring stress and proinflammatory response postnatally that may contribute to early onset of atherosclerosis. Genes

  20. Methionine-choline deprivation alters liver and brain acetylcholinesterase activity in C57BL6 mice.

    Science.gov (United States)

    Vučević, Danijela B; Cerović, Ivana B; Mladenović, Dušan R; Vesković, Milena N; Stevanović, Ivana; Jorgačević, Bojan Z; Ješić Vukićević, Rada; Radosavljević, Tatjana S

    2016-07-01

    Choline and methionine are precursors of acetylcholine, whose hydrolysis is catalyzed by acetylcholinesterase (AChE). Considering the possibility of their common deficiency, we investigated the influence of methionine-choline deprivation on AChE activity in liver and various brain regions (hypothalamus, hippocampus, cerebral cortex and striatum) in mice fed with methionine-choline deficient (MCD) diet. Male C57BL/6 mice (n = 28) were randomly and equally divided into following groups: control group fed with standard diet for 6 weeks (C) and groups fed with MCD diet for 2 weeks (MCD2), 4 weeks (MCD4) and for 6 weeks (MCD6). After the diet, mice were sacrificied and AChE activity in liver and brain was determined spectrophotometrically. Hepatic AChE activity was higher in MCD2, MCD4 and MCD6 compared to control (p methionine-choline deprivation.

  1. Altered gene expression in the brain and liver of female fathead minnows Pimephales promelas Rafinesque exposed to fadrozole

    Energy Technology Data Exchange (ETDEWEB)

    Villeneuve, Daniel L. [US EPA, Duluth, MN (United States); Knoebl, Iris [US EPA, Cincinnati, OH (United States); Larkin, Patrick [Sante Fe Community College, Gainesville, FL (United States); EcoArray, Alachua, FL (United States); Miracle, Ann L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Carter, Barbara J. [EcoArray, Alachua, FL (United States); Denslow, Nancy D. [Univ. of Florida, Gainesville, FL (United States); Ankley, Gerald T. [US EPA, Duluth, MN (United States)

    2008-06-01

    The fathead minnow (Pimephales promelas) is a small fish species widely used for ecotoxicology research and regulatory testing in North America. This study used a novel 2000 gene oligonucleotide microarray to evaluate the effects of the aromatase inhibitor, fadrozole, on gene expression in the liver and brain tissue of exposed females. Exposure to 60 μg 1-1 fadrozole/L for 7 d, resulted in the significant (p<0.05; high-moderate agreement among multiple probes spotted on the array) up-regulation of approximately 47 genes in brain and 188 in liver, and the significant down-regulation of 61 genes in brain and 162 in liver. In particular, fadrozole exposure elicited significant up-regulation of five genes in brain involved in the cholesterol synthesis pathway and altered the expression of over a dozen cytoskeleton-related genes. In the liver, there was notable down-regulation of genes coding for vitellogenin precursors, vigillin, and fibroin-like ovulatory proteins which were consistent with an expected reduction in plasma estradiol concentrations as a result of fadrozole exposure and an associated reduction in measured plasma vitellogenin concentrations. These changes coincided with a general down-regulation of genes coding for non-mitochondrial ribosomal proteins and proteins that play a role in translation. With the exception of the fibroin-like ovulatory proteins, real-time PCR results largely corroborated the microarray responses. Overall, results of this study demonstrate the utility of high density oligonucleotide microarrays for unsupervised, discovery-driven, ecotoxicogenomics research with the fathead minnow and helped inform the subsequent development of a 22,000 gene microarray for the species.

  2. Carcinogenic alterations in murine liver, lung, and uterine tumors induced by in utero exposure to ionizing radiation.

    Science.gov (United States)

    Lumniczky, K; Antal, S; Unger, E; Wunderlich, L; Hidvégi, E J; Sáfrány, G

    1998-02-01

    The atomic bombing of Hiroshima and Nagasaki and the nuclear accident at Chernobyl raised the question of prenatal sensitivity to ionizing radiation-induced cancer. In this study, mice were exposed to single doses of gamma-radiation (0.2-2.0 Gy) at different embryonic stages. The tumor incidence increased with dose from 15% in control mice to 35% in mice irradiated with 2.0 Gy on 18 d of prenatal life. Various oncogenic events were investigated in lymphoid, liver, lung, and uterine tumors. We observed threefold to fivefold increases in myc expression in 25% of the lymphomas, and the expression of Ha-ras and p53 genes decreased in 40% and 60% of the lung tumors by twofold to fivefold. Point mutations were tissue specific: Ha-ras codon 61 mutations were found in about 40% of the liver adenocarcinomas, Ki-ras codon 12 mutations in about 17% of lung tumors, and p53 mutations in about 15% of the lymphomas. Amplification and rearrangement of the p53, myc, and Ha-, Ki- and N-ras genes were not detected. Loss of heterozygosity on chromosome 4 at the multiple tumor suppressor 1 and 2 genes was observed in all types of malignancies. Allelic losses on chromosome 11 at the p53 locus were found in lymphoid, liver, and lung tumors, but they were absent from uterine tumors. Multiple oncogenic changes were often detected. The frequency of carcinogenic alterations was similar in spontaneous and radiation-induced lymphoid, liver, and uterine tumors. In radiation-induced lung adenocarcinomas, however, the incidences of many oncogenic changes were different from those found in their spontaneous counterparts. This suggests that different oncogenic pathways are activated during spontaneous and in utero gamma-radiation-induced murine lung carcinogenesis. PMID:9496910

  3. Subtle BBB alterations in brain edema associated with acute liver failure

    OpenAIRE

    Nguyen, Justin H

    2010-01-01

    Vasogenic mechanism of brain edema in acute liver failure (ALF) remains poorly understood. Recent work demonstrates that matrix metalloproteinase-9 (MMP-9) contributes to the development of brain edema in experimental ALF (J Hepatol 44:1105, 2006). Importantly, MMP-9 blockage with specific monoclonal antibodies and/or synthetic inhibitor, the edema is attenuated. Specifically, utrastructural evaluations demonstrate intact blood-brain barrier and its tight junction. These results suggest that ...

  4. Starvation alters the liver transcriptome of the innate immune response in Atlantic salmon (Salmo salar)

    OpenAIRE

    Secombes Christopher J; Houlihan Dominic F; Douglas Alex; Martin Samuel AM

    2010-01-01

    Abstract Background The immune response is an energy demanding process, which has effects in many physiological pathways in the body including protein and lipid metabolism. During an inflammatory response the liver is required to produce high levels of acute phase response proteins that attempt to neutralise an invading pathogen. Although this has been extensively studied in both mammals and fish, little is known about how high and low energy reserves modulate the response to an infection in ...

  5. Alterations in the Rat Serum Proteome During Liver Injury from Acetaminophen Exposure

    OpenAIRE

    Merrick, B. Alex; Bruno, Maribel E.; Madenspacher, Jennifer H.; Wetmore, Barbara A.; Foley, Julie; Pieper, Rembert; Zhao, Ming; Makusky, Anthony J.; McGrath, Andrew M.; ZHOU, JEFF X.; Taylor, John; Tomer, Kenneth B.

    2006-01-01

    Changes in the serum proteome were identified during early, fulminant and recovery phases of liver injury from acetaminophen in the rat. Male F344 rats received a single, non-injury dose or a high, injury-producing dose of acetaminophen for evaluation at 6 hr to 120 hr. Two-dimensional gel electrophoresis of immunodepleted serum separated about 800 stained proteins per sample from which differentially expressed proteins were identified by mass spectrometry. Serum ALT/AST levels and histopatho...

  6. Biochemical and histological alterations in liver following sub chronic exposure of arsenic

    Directory of Open Access Journals (Sweden)

    Madhuri Mehta

    2015-07-01

    Full Text Available Objective: Contamination of groundwater with arsenic is of global concern. The present work was aimed to evaluate the biochemical and histological changes in liver of female rats induced by sodium arsenite at doses naturally found in groundwater of Punjab. Method: Twenty four female rats were divided into four groups of 6 animals each. Group I animals received distilled water and served as control; Group II-IV received arsenic at the dose of 10, 30 and 50 ppb (μg/L dissolved in distilled water ad libitum for 30 days. At the end of experiment, animals were sacrificed and liver was collected for biochemical and histological evaluation. Results: Biochemical analysis showed an increase in the activity of hepatic marker enzymes including transferases, phosphatases and lactate dehydrogenase (LDH. Also, the levels of antioxidant enzymes (catalase, reduced glutathione and glutathione-S-transferase decreased significantly (P<0.05 in treated animals when compared to control. A significant (P<0.05 dose dependent increase in the levels of lipid peroxidation and arsenic concentration in liver tissue was observed. Histological examination showed the presence of pyknotic bodies (necrosis and sinusoidal dilation in hepatocytes of treated groups. Conclusion: Sub chronic exposure of arsenic at these doses induces hepatotoxicity leading to oxidative stress.

  7. Histone modifications and alcohol-induced liver disease: Are altered nutrients the missing link?

    Institute of Scientific and Technical Information of China (English)

    Akshata Moghe; Swati Joshi-Barve; Smita Ghare; Leila Gobejishvili; Irina Kirpich; Craig J McClain; Shirish Barve

    2011-01-01

    Alcoholism is a major health problem in the United States and worldwide, and alcohol remains the single most significant cause of liver-related diseases and deaths. Alcohol is known to influence nutritional status at many levels including nutrient intake, absorption, utilization, and excretion, and can lead to many nutritional disturbances and deficiencies. Nutrients can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease (ALD). There is growing interest regarding epigenetic changes, including histone modifications that regulate gene expression during disease pathogenesis. Notably, modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation, and control gene transcription. This review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to ALD. The review is focused on four critical metabolites, namely, acetate, S-adenosylmethionine, nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.

  8. Ethanol Metabolism Alters Major Histocompatibility Complex Class I-Restricted Antigen Presentation In Liver Cells

    Science.gov (United States)

    Osna, Natalia A.; White, Ronda L.; Thiele, Geoffrey M.; Donohue, Terrence M.

    2009-01-01

    The proteasome is a major enzyme that cleaves proteins for antigen presentation. Cleaved peptides traffic to the cell surface, where they are presented in the context of MHC class I. Recognition of these complexes by cytotoxic T lymphocytes is crucial for elimination of cells bearing “non-self” proteins. Our previous studies revealed that ethanol suppresses proteasome function in ethanol-metabolizing liver cells. We hypothesized that proteasome suppression reduces the hydrolysis of antigenic peptides, thereby decreasing the presentation of the peptide-MHC class I-complexes on the cell surface. To test this, we used the mouse hepatocyte cell line (CYP2E1/ADH-transfected HepB5 cells) or primary mouse hepatocytes, both derived from livers of C57Bl/6 mice, which present the ovalbumin peptide, SIINFEKL, complexed with H2Kb. To induce H2Kb expression, HepB5 cells were treated with interferon gamma (IFNγ) and then exposed to ethanol. In these cells, ethanol metabolism decreased not only proteasome activity, but also hydrolysis of the C-extended peptide, SIINFEKL-TE and the presentation of SIINFEKL-H2Kb complexes measured after the delivery of SIINFEKL-TE to cytoplasm. The suppressive effects of ethanol were, in part, attributed to ethanol-elicited impairment of IFNγ signaling. However, in primary hepatocytes, even in the absence of IFNγ, we observed a similar decline in proteasome activity and antigen presentation after ethanol exposure. We conclude that proteasome function is directly suppressed by ethanol metabolism and indirectly, by preventing the activating effects of IFNγ. Ethanol-elicited reduction in proteasome activity contributes to the suppression of SIINFEKL-H2Kb presentation on the surface of liver cells. Immune response to viral antigens plays a crucial role in the pathogenesis of hepatitis C or B viral infections (HCV and HBV, respectively). Professional antigen-presenting cells (dendritic cells and macrophages) are responsible for priming the

  9. Hematotesticular barrier is altered from early stages of liver cirrhosis:Effect of insulin-like growth factor 1

    Institute of Scientific and Technical Information of China (English)

    Inma Castilla-Cortázar; Isabel Varela-Nieto; Jesús Prieto; Salvador González-Barón; Nieves Diez; María García-Fernández; Juan Enrique Puche; Fernando Diez-Caballero; Jorge Quiroga; Matías Díaz-Sánchez; Alberto Castilla; Amelia Díaz Casares

    2004-01-01

    AIM: The pathogenesis of hypogonadism in liver cirrhosis is not well understood. Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis. The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis.The aim of this study was to establish the historical progression of the described alterations in the testes,explore testicular morphology, histopathology, cellular proliferation, integrity of testicular barrier and hypophysogonadal axis in rats with no ascitic cirrhosis.METHODS: Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride (CCl4) for 11 wk,were allocated into two groups (n = 12, each) to receive vehicle. Healthy rats receiving vehicle were used as control group (n = 12).RESULTS: Compared to controls, rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities.However, these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression. In addition, pituitary-gonadal axis was altered, with significant higher levels of FSH (P<0.001vs controls) and increased levels of LH in untreated cirrhotic animals. Interestingly, IGF-1 treatment normalized testicular transferrin expression and cellular proliferation and reduced serum levels of LH (P = ns vs controls, and P<0.01 vs untreated cirrhotic group).CONCLUSION: The testicular barrier is altered from an early stage of cirrhosis, shown by a reduction of transferrin expression in Sertoli cells, a diminished cellular proliferation and an altered gonadal axis. The treatment with IGF-1 could be also useful in this initial stage of testicular disorder associated with compensated cirrhosis.

  10. 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.

  11. Model steatogenic compounds (amiodarone, valproic acid, and tetracycline alter lipid metabolism by different mechanisms in mouse liver slices.

    Directory of Open Access Journals (Sweden)

    Ewa Szalowska

    Full Text Available Although drug induced steatosis represents a mild type of hepatotoxicity it can progress into more severe non-alcoholic steatohepatitis. Current models used for safety assessment in drug development and chemical risk assessment do not accurately predict steatosis in humans. Therefore, new models need to be developed to screen compounds for steatogenic properties. We have studied the usefulness of mouse precision-cut liver slices (PCLS as an alternative to animal testing to gain more insight into the mechanisms involved in the steatogenesis. To this end, PCLS were incubated 24 h with the model steatogenic compounds: amiodarone (AMI, valproic acid (VA, and tetracycline (TET. Transcriptome analysis using DNA microarrays was used to identify genes and processes affected by these compounds. AMI and VA upregulated lipid metabolism, whereas processes associated with extracellular matrix remodelling and inflammation were downregulated. TET downregulated mitochondrial functions, lipid metabolism, and fibrosis. Furthermore, on the basis of the transcriptomics data it was hypothesized that all three compounds affect peroxisome proliferator activated-receptor (PPAR signaling. Application of PPAR reporter assays classified AMI and VA as PPARγ and triple PPARα/(β/δ/γ agonist, respectively, whereas TET had no effect on any of the PPARs. Some of the differentially expressed genes were considered as potential candidate biomarkers to identify PPAR agonists (i.e. AMI and VA or compounds impairing mitochondrial functions (i.e. TET. Finally, comparison of our findings with publicly available transcriptomics data showed that a number of processes altered in the mouse PCLS was also affected in mouse livers and human primary hepatocytes exposed to known PPAR agonists. Thus mouse PCLS are a valuable model to identify early mechanisms of action of compounds altering lipid metabolism.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Alterations of rat liver mitochondrial oxidative phosphorylation and calcium uptake by benzo[a]pyrene

    International Nuclear Information System (INIS)

    We report that oxidative phosphorylation and Ca2+ uptake processes are enhanced in liver mitochondria isolated from benzo[a]pyrene (B[a]P)-treated rats. The carcinogen did not affect either the respiratory control index or the Ca2+ control ratio. B[a]P treatment increased the oxidation rate of several substrates that donate electrons at the level of all three coupling sites, either the ADP- or Ca2+-stimulated rates or those observed after ADP or Ca2+ exhaustion. However, the efficiency of energy coupling was maintained because both ADP/O and Ca2+/site ratios remained unchanged. The electron flow through NADH-oxidase, NADH-duroquinone reductase, NADH-juglone reductase, NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase was enhanced by B[a]P; however, succinate dehydrogenase activity was not affected. All these effects depended on the time post B[a]P administration, with a greater increase close to 48 h after administration of the carcinogen. The contents of cytochromes b, c1, and a + a3 from liver mitochondria, especially those isolated 48 h after B[a]P, were also significantly increased, although cytochrome c levels was just lightly increased 24 h after B[a]P treatment. These results suggest that B[a]P treatment stimulates mitochondrial respiration by increasing the level of several components of the mitochondrial respiratory chain. This may reflect mitochondrial adaptation to the cellular energy requirements of cell division in the neoplastic transformation process

  14. 霍山石斛多糖干预对力竭运动小鼠BUN、MDA、BLA、肝糖原影响的研究%Effects of Intervention of Dendrobium Huoshanness Polysaccharide on BUN,MDA,BLA and Liver Glycogen in Mice after Exhaustive Exercise Protocol

    Institute of Scientific and Technical Information of China (English)

    夏云建; 余刚

    2012-01-01

    研究目的:通过建立小鼠负重游泳模型,从负重游泳力竭时间、血乳酸、血清尿素氮、丙二醛、肝糖元等指标实验研究,探讨霍山石斛多糖抗疲劳作用机制,为运动饮料中增加霍山石斛多糖提高运动员抗疲劳能力提供依据。研究方法:将SD小鼠随机分为4组。阴性对照组:给予生理盐水灌胃;阳性对照组:给予葡萄糖2g/(kg.d)灌胃;高剂量实验组:给予霍山石斛多糖450 mg/(kg.d)灌胃;低剂量实验组:给予霍山石斛多糖150mg/(kg.d)灌胃,实验组小鼠连续14d进行负重游泳力竭运动和给药后,测量和分析其血乳酸、血清尿素氮、丙二醛、肝糖元等指标变化。研究结果:1.霍山石斛多糖能显著延长小鼠游泳时间,降低运动后小鼠的乳酸累积。2.霍山石斛多糖能降低血清尿素氮、丙二醛含量,增加运动后小鼠的肝糖原储备值。3.补充霍山石斛多糖可以有效的提高小鼠的运动能力。%Polysaccharide from Dendrobium huoshanense as anti-fatigue resistant composition studies has not been reported.From the angle of indicators changed as: the time of mouse to exhaust、BLA、BUN、MDA、Liver Glycogen,discussion on huoshanness polysaccharide anti-fatigue effect of intervention mechanisms provides a basis that sports drink which added Dendrobium huoshanense polysaccharides to improve the anti fatigue ability of athletes.METHODS: The SD mice were divided into four groups,each 8 mice(n=8) which are negative control group,given normal saline orally;positive control group,given Glucose 2g/(kg.d) orally;Polysaccharide huoshanness high-dose treatment group,given Polysaccharide huoshanness 450 mg/(kg.d) orally;Polysaccharide huoshanness low-dose treatment group,given Polysaccharide huoshanness 150 mg/(kg.d) orally,Continuous administration of 14d.From the angle of indicators changed as: the time of mouse to exhaust,BLA,BUN,MDA,Liver Glycogen,it discussed huoshanness

  15. Effects of water temperature on oxygen consumption rate, asphyxiant point, blood glucose content, and muscle and liver glycogen content of juvenile Coilia nasus%水温对刀鲚幼鱼耗氧率、窒息点、血糖及肌肝糖元指标的影响

    Institute of Scientific and Technical Information of China (English)

    徐钢春; 聂志娟; 薄其康; 徐跑; 顾若波

    2012-01-01

    In order to supply reference for the rational breeding and transportation of Coilia na-sus , a laboratory experiment was conducted to measure the oxygen consumption rate (OCR) and asphyxiation point ( AP) of juvenile C. nasus under different water temperature, and to study the diurnal variations of the OCR as well as the effects of water temperature on the blood glucose and muscle- and liver glycogen of the juveniles. At water temperature ( T, ℃) 16-28℃, the OCR (R, mg·L-1 ) of the juveniles increased with increasing temperature, and there was a linear re-lationship between the R and T (R = 0.988T2-32.36T+343. 7, R2 -0.96). The OCR revealed a diurnal rhythm, with the peak at 7:00 am and the bottom at 9:00 pm. The AP (A, mg·L-1) was significantly correlated to T (A =0. 9397T0.8001, R2 =0. 98). At water temperature 16-24 ℃, the blood glucose content of the juveniles kept relatively steady and ranged from 17. 24 to 19. 79 mmol·L-1, while the muscle- and liver glycogen content fluctuated. At water temperature 24-28℃, the blood glucose content increased significantly with increasing temperature, while the muscle- and liver glycogen content had a significant decrease.%实验测定了不同水温条件下刀鲚(Coilia nasus)幼鱼的耗氧率和窒息点,并对耗氧率的昼夜变化规律以及水温对刀鲚幼鱼血糖及肌肝糖元指标的影响进行了研究,旨在为刀鲚运输、养殖生产中制定合理的放养密度和养殖工艺提供参考依据.结果表明:在试验水温(16℃~28C)条件下,刀鲚幼鱼的耗氧率随水温的升高而增大,耗氧率(R)与水温(T)的回归方程为R=0.988T2-32.36T+343.7,相关系数为0.96;刀鲚幼鱼的耗氧率具有昼夜节律性,耗氧高峰出现在7:00,低谷在21:00;刀鲚幼鱼的窒息点与水温显著相关,窒息点A(mg·L-1)与水温T(℃)的回归关系为A=0.9397T0.8001,R2=0.98.刀鲚幼鱼血清中血糖含量在水温16℃~24℃阶段保持相对稳定,血糖含量在17.24

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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...

  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...

  19. Molecular characterization of hepatocellular adenomas developed in patients with glycogen storage disease type I

    NARCIS (Netherlands)

    Calderaro, Julien; Labrune, Philippe; Morcrette, Guillaume; Rebouissou, Sandra; Franco, Dominique; Prevot, Sophie; Quaglia, Alberto; Bedossa, Pierre; Libbrecht, Louis; Terracciano, Luigi; Smit, G. Peter A.; Bioulac-Sage, Paulette; Zucman-Rossi, Jessica

    2013-01-01

    Background & Aims: Hepatocellular adenomas (HCA) are benign liver tumors mainly related to oral contraception and classified into 4 molecular subgroups: inflammatory (IHCA), HNF1A-inactivated (H-HCA), beta-catenin-activated (bHCA) or unclassified (UHCA). Glycogen storage disease type I (GSD) is a ra

  20. Alterations in Arterial Blood Parameters in Patients with Liver Cirrhosis and Ascites

    Directory of Open Access Journals (Sweden)

    Konstantinos Charalabopoulos, Dimitrios Peschos, Leonidas Zoganas, George Bablekos, Christos Golias, Alexander Charalabopoulos, Dimitrios Stagikas, Angi Karakosta, Athanasios Papathanasopoulos, George Karachalios, Anna Batistatou

    2007-01-01

    Full Text Available In cirrhotic patients, in addition to hepatocytes and Kuppfer cells dysfunction circulatory anatomic shunt and ventilation/perfusion (VA/ Q ratio abnormalities can induce decrease in partial pressure of oxygen in arterial blood (PaO2, in oxygen saturation of hemoglobin (SaO2 as well as various acid-base disturbances. We studied 49 cases of liver cirrhosis (LC with ascites compared to 50 normal controls. Causes were: posthepatic 37 (75.51%, alcoholic 7 (14.24%, cardiac 2 (4.08%, and cryptogenic 3 (6.12%. Complications were: upper gastrointestinal bleeding 24 (48.97, hepatic encephalopathy 20 (40.81%, gastritis 28 (57.14%, hepatoma 5 (10.2%, renal hepatic syndrome 2 (4.01%, HbsAg (+ 24 (48.97%, and hepatic pleural effusions 7 (14.28%. Average PaO2 and SaO2 were 75.2 mmHg and 94.5 mmHg, respectively, compared to 94.2 mmHg and 97.1 mmHg of the control group, respectively (p value in both PaO2 and SaO2 was pA/Q inequality can induce a decrease in PaO2 and SaO2 as well as various acid-base disturbances. As a result, pulmonary resistance is impaired and patients more likely succumb to infections and adult respiratory distress syndrome.

  1. New inhibitors of glycogen phosphorylase as potential antidiabetic agents.

    Science.gov (United States)

    Somsák, L; Czifrák, K; Tóth, M; Bokor, E; Chrysina, E D; Alexacou, K-M; Hayes, J M; Tiraidis, C; Lazoura, E; Leonidas, D D; Zographos, S E; Oikonomakos, N G

    2008-01-01

    The protein glycogen phosphorylase has been linked to type 2 diabetes, indicating the importance of this target to human health. Hence, the search for potent and selective inhibitors of this enzyme, which may lead to antihyperglycaemic drugs, has received particular attention. Glycogen phosphorylase is a typical allosteric protein with five different ligand binding sites, thus offering multiple opportunities for modulation of enzyme activity. The present survey is focused on recent new molecules, potential inhibitors of the enzyme. The biological activity can be modified by these molecules through direct binding, allosteric effects or other structural changes. Progress in our understanding of the mechanism of action of these inhibitors has been made by the determination of high-resolution enzyme inhibitor structures (both muscle and liver). The knowledge of the three-dimensional structures of protein-ligand complexes allows analysis of how the ligands interact with the target and has the potential to facilitate structure-based drug design. In this review, the synthesis, structure determination and computational studies of the most recent inhibitors of glycogen phosphorylase at the different binding sites are presented and analyzed. PMID:19075645

  2. 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...... groups of rats. These changes may partly explain the demonstrated training-induced increase in glucose tolerance. None of the findings could be ascribed to differences in foold intake or body weight....

  3. Beneficial Effects of Montelukast Against Methotrexate-Induced Liver Toxicity: A Biochemical and Histological Study

    Directory of Open Access Journals (Sweden)

    Evren Kose

    2012-01-01

    Full Text Available The effects of montelukast against methotrexate-induced liver damage were investigated. 35 Wistar albino female rats were divided into 5 groups as follows: group I: control; group II: montelukast (ML; group III: methotrexate (Mtx; group IV: montelukast treatment after methotrexate application (Mtx + ML; group V: montelukast treatment before methotrexate application (ML + Mtx. At the end of the experiment, the liver tissues of rats were removed. Malondialdehyde (MDA, myeloperoxidase (MPO, and reduced glutathione levels were determined from liver tissues. In addition, the liver tissues were examined histologically. MDA and MPO levels of Mtx group were significantly increased when compared to control group. In Mtx + ML group, these parameters were decreased as compared to Mtx group. Mtx injection exhibited major histological alterations such as eosinophilic staining and swelling of hepatocytes. The glycogen storage in hepatocytes was observed as decreased by periodic acid schiff staining in Mtx group as compared to controls. ML treatment did not completely ameliorate the lesions and milder degenerative alterations as loss of the glycogen content was still present. It was showed that montelukast treatment after methotrexate application could reduce methotrexate-induced experimental liver damage.

  4. 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

    diabetic state. Also, our objective was to elucidate the contribution of glycogen to support neurotransmitter glutamate and GABA homeostasis. A glycogen phosphorylase (GP) inhibitor was administered to Sprague-Dawley (SprD) and Zucker Diabetic Fatty (ZDF) rats in vivo and after one day of treatment [1......-(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...

  5. Identification of mutations in Type IV glycogen storage disease

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Y.; Kishnani, P.; Chen, Y.T. [Duke Univ. Medical Center, Durham, NC (United States)] [and others

    1994-09-01

    Type IV glycogen storage disease (GSD IV, Andersen disease) is caused by a deficiency of glycogen branching enzyme (GBE) activity, which results in the accumulation of glycogen with unbranched, long, outer chains in the tissues. The molecular basis of the disease is not known. We studied four patients with the disease; three with typical presentation of progressive liver cirrhosis and failure, and one with severe and fatal neonatal hypotonia and cardiomyopathy. Southern blot analysis with EcoRI or MspI did not detect gross DNA rearrangement, deletion or duplication in patients` glycogen branching enzyme genes. Northern analysis with total cellular RNAs isolated from skin fibroblast MI strains of three patients with typical clinical presentation showed a normal level and size (2.95 kb) of GBE mRNA hybridization band in two and absent mRNA hybridization band in the remaining one. The patient with atypical severe neonatal hypotonia demonstrated a less intense and smaller size (2.75 kb) of mRNA hybridization band. A 210 hp deletion from nucleotide sequence 873 to 1082 which causes 70 amino acids missing from amino acid sequence 262 to 331 was detected in all 17 clones sequenced from the fatal hypotonia patient. This deletion is located in the region which is highly conserved between prokaryotic, yeast and human GBE polypeptide sequences, and also includes the first of the four regions which constitute the catalytic active sites of most of amylolytic enzymes. A point mutation C-T (1633) which changes the amino acid from Arginine to Cystine was found in 19 of 20 cDNA clones from a patient with classical clinical presentation. This point mutation was unique to this patient and was not observed in three other patients or normal controls. This is the first report on the molecular basis of GSD IV and our data indicated the presence of extensive genetic heterogeneity in the disease.

  6. Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells.

    Science.gov (United States)

    Sharma, Monika; Tuaine, Jo; McLaren, Blair; Waters, Debra L; Black, Katherine; Jones, Lynnette M; McCormick, Sally P A

    2016-01-01

    Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5'-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.

  7. Glycogen repletion and exercise endurance in rats adapted to a high fat diet.

    Science.gov (United States)

    Conlee, R K; Hammer, R L; Winder, W W; Bracken, M L; Nelson, A G; Barnett, D W

    1990-03-01

    It is well accepted that exercise endurance is directly related to the amount of carbohydrate stored in muscle and that a low carbohydrate diet reduces glycogen storage and exercise performance. However, more recent evidence has shown that when the organism adapts to a high fat diet endurance is not hindered. The present study was designed to test that claim and to further determine if animals adapted to a high fat diet could recover from exhausting exercise and exercise again in spite of carbohydrate deprivation. Fat-adapted (3 to 4 weeks, 78% fat, 1% carbohydrates) rats (FAT) ran (28 m/min, 10% grade) as long as carbohydrate-fed (69% carbohydrates) animals (CHO) (115 v 109 minutes, respectively) in spite of lower pre-exercise glycogen levels in red vastus muscle (36 v 54 mumols/g) and liver (164 v 313 mumols/g) in the FAT group. Following 72 hours of recovery on the FAT diet, glycogen in muscle had replenished to 42 mumols/g (v 52 for CHO) and liver glycogen to 238 mumols/g (v 335 for CHO). The animals were run to exhaustion a second time and run times were again similar (122 v 132 minutes FAT v CHO). When diets were switched after run 1, FAT-adapted animals, which received carbohydrates for 72 hours, restored muscle and liver glycogen (48 and 343 mumols/g, respectively) and then ran longer (144 minutes) than CHO-adapted animals (104 minutes) that ate fat for 72 hours and that had reduced glycogen repletion. We conclude that, in contrast to the classic CHO loading studies in humans that involved acute (72 hours) fat feedings and subsequently reduced endurance, rats adapted to a high fat diet do not have a decrease in endurance capacity even after recovery from previous exhausting work bouts. Part of this adaptation may involve the increased storage and utilization of intramuscular triglycerides (TG) as observed in the present experiment. PMID:2308519

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

    Directory of Open Access Journals (Sweden)

    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

  9. Role of liver functions on liver cell mitosis

    Directory of Open Access Journals (Sweden)

    Takata,Tameyuki

    1974-06-01

    Full Text Available The control mechanism of mitosis in the regenerating rat liver was studied in relation to the cell functions. Partial hepatec· tomy induces a series of changes prior to the initiation of mitosis, i. e. decrease in serum glucose and albumin levels, loss of glycogen from liver cells, and increased lipid mobilization to liver cells. Massive supplies of glucose and fructose suppressed significantly hepatocellu. lar mitosis with suppression of lipid accumulation and preservation of glycogen in the liver cells and of blood sugar level. Homologous serum administration also suppressed the rate of liver cell mitosis after hepatectomy preventing the decrease in serum albumin level, but did not suppress the lipid accumulation in the liver. Starvation, which would relieve the liver cell from the work of detoxication of intesti. nal toxic products, did not show any suppressive effect on the mitotic rate of liver cells after partial hepatectomy in single animals. But starvation induced severe hypoglycemia, moderate hypoalbuminemia and loss of glycogen content in the liver. These changes in metabo. lism by starvation and partial hepatectomy were suppressed by con· jugating the animals with nonhepatectomized fed.partners by aortic anastomosis, and mitosis was suppressed in the residual liver of the fasting animals in this parabiosis. The results indicate that all the major functions of parenchymal live cells tested, sugar metabolism, serum albumin production, and detoxication, are closely related to the control of liver cell mitosis. Accumulation of lipids in the liver remnant after partial hepatectomy is thought to be for the compensa. tion of reduced glycogen storage and not concerned directly with the liver cell mitosis. Discussion was made briefly on the humoral factor and portal blood factor in relation to excess load of functions on resi. dual liver cells.

  10. Brain glycogen supercompensation following exhaustive exercise.

    Science.gov (United States)

    Matsui, Takashi; Ishikawa, Taro; Ito, Hitoshi; Okamoto, Masahiro; Inoue, Koshiro; Lee, Min-Chul; Fujikawa, Takahiko; Ichitani, Yukio; Kawanaka, Kentaro; Soya, Hideaki

    2012-02-01

    Brain glycogen localized in astrocytes, a critical energy source for neurons, decreases during prolonged exhaustive exercise with hypoglycaemia. However, it is uncertain whether exhaustive exercise induces glycogen supercompensation in the brain as in skeletal muscle. To explore this question, we exercised adult male rats to exhaustion at moderate intensity (20 m min(-1)) by treadmill, and quantified glycogen levels in several brain loci and skeletal muscles using a high-power (10 kW) microwave irradiation method as a gold standard. Skeletal muscle glycogen was depleted by 82-90% with exhaustive exercise, and supercompensated by 43-46% at 24 h after exercise. Brain glycogen levels decreased by 50-64% with exhaustive exercise, and supercompensated by 29-63% (whole brain 46%, cortex 60%, hippocampus 33%, hypothalamus 29%, cerebellum 63% and brainstem 49%) at 6 h after exercise. The brain glycogen supercompensation rates after exercise positively correlated with their decrease rates during exercise. We also observed that cortical and hippocampal glycogen supercompensation were sustained until 24 h after exercise (long-lasting supercompensation), and their basal glycogen levels increased with 4 weeks of exercise training (60 min day(-1) at 20 m min(-1)). These results support the hypothesis that, like the effect in skeletal muscles, glycogen supercompensation also occurs in the brain following exhaustive exercise, and the extent of supercompensation is dependent on that of glycogen decrease during exercise across brain regions. However, supercompensation in the brain preceded that of skeletal muscles. Further, the long-lasting supercompensation of the cortex and hippocampus is probably a prerequisite for their training adaptation (increased basal levels), probably to meet the increased energy demands of the brain in exercising animals. PMID:22063629

  11. Altered distribution of regulatory lymphocytes by oral administration of soy-extracts exerts a hepatoprotective effect alleviating immune mediated liver injury, non-alcoholic steatohepatitis and insulin resistance

    Science.gov (United States)

    Khoury, Tawfik; Ben Ya'acov, Ami; Shabat, Yehudit; Zolotarovya, Lidya; Snir, Ram; Ilan, Yaron

    2015-01-01

    AIM: To determine the immune-modulatory and the hepatoprotective effects of oral administration of two soy extracts in immune mediated liver injury and non-alcoholic steatohepatitis (NASH). METHODS: Two soy extracts, M1 and OS, were orally administered to mice with concanavalin A (ConA) immune-mediated hepatitis, to high-fat diet (HFD) mice and to methionine and choline reduced diet combined with HFD mice. Animals were followed for disease and immune biomarkers. RESULTS: Oral administration of OS and M1 had an additive effect in alleviating ConA hepatitis manifested by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels. Oral administration of the OS and M1 soy derived fractions, ameliorated liver injury in the high fat diet model of NASH, manifested by a decrease in hepatic triglyceride levels, improvement in liver histology, decreased serum cholesterol and triglycerides and improved insulin resistance. In the methionine and choline reduced diet combined with the high fat diet model, we noted a decrease in hepatic triglycerides and improvement in blood glucose levels and liver histology. The effects were associated with reduced serum tumor necrosis factor alpha and alteration of regulatory T cell distribution. CONCLUSION: Oral administration of the combination of OS and M1 soy derived extracts exerted an adjuvant effect in the gut-immune system, altering the distribution of regulatory T cells, and alleviating immune mediated liver injury, hyperlipidemia and insulin resistance. PMID:26139990

  12. Lysophosphatidic Acid Alters the Expression Profiles of Angiogenic Factors, Cytokines, and Chemokines in Mouse Liver Sinusoidal Endothelial Cells

    OpenAIRE

    Chia-Hung Chou; Shou-Lun Lai; Cheng-Maw Ho; Wen-Hsi Lin; Chiung-Nien Chen; Po-Huang Lee; Fu-Chuo Peng; Sung-Hsin Kuo; Szu-Yuan Wu; Hong-Shiee Lai

    2015-01-01

    Background and Aims Lysophosphatidic acid (LPA) is a multi-function glycerophospholipid. LPA affects the proliferation of hepatocytes and stellate cells in vitro, and in a partial hepatectomy induced liver regeneration model, the circulating LPA levels and LPA receptor (LPAR) expression levels in liver tissue are significantly changed. Liver sinusoidal endothelial cells (Lsecs) play an important role during liver regeneration. However, the effects of LPA on Lsecs are not well known. Thus, we ...

  13. 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)

    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

  14. Distribution of electrophoretically separated serum high density lipoprotein subfraction levels among healthy students and its alteration in patients with liver diseases.

    Directory of Open Access Journals (Sweden)

    Ikeda,Satoru

    1986-06-01

    Full Text Available In an attempt to evaluate high density lipoprotein (HDL subfraction levels in liver diseases, HDL was separated by a precipitation method with dextran sulfate-Mg2+ from sera of 289 healthy adults and 50 patients with liver diseases. The HDL was subdivided into HDL2e and HDL3e by Utermann's polyacrylamide gel electrophoresis with lauric acid. Ultracentrifugally separated HDL2 and HDL3 roughly corresponded to HDL2e and HDL3e, respectively. Male and female groups had different distributions of HDL2e/HDL3e ratios. Among healthy males, 121 cases had ratios less than 1.0 (mean +/- SD = 0.72 +/- 0.39, n = 150, while among healthy females, the ratios were generally larger than those of males and varied widely from 0.2 to 6.6 (mean +/- SD = 1.77 +/- 1.05, n = 139. Low levels of HDL-cholesterol were found in patients with liver diseases, except those with mild alcoholic liver injury and intrahepatic cholestasis. Apparent decreases in HDL3e, but not in HDL2e, were found in all cases with liver diseases investigated, even in those who did not show decreases in the total HDL level, when male and female patients were analyzed separately. The analysis of HDL subfractions by the present method is simple and useful for the study on altered lipid metabolism in liver diseases.

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

    International Nuclear Information System (INIS)

    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 14C 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

  16. 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...... blood-lactate, and the fall in blood-pH were similar during N and CHR. In protocol 2, time to exhaustion was identical for N and CHR. It is concluded that during short-term intense exercise during which muscle glycogen availability exceeds glycogen demand, rate of glycogen breakdown, lactate...

  17. Altered fatty acid profile in the liver and serum of stroke-prone spontaneously hypertensive rats: reduced proportion of cis-vaccenic acid.

    Science.gov (United States)

    Tanaka, Shizuyo; Kojiguchi, Chiho; Yamazaki, Tohru; Mitsumoto, Atsushi; Kobayashi, Daisuke; Kudo, Naomi; Kawashima, Yoichi

    2013-01-01

    Stroke-prone spontaneously hypertensive rats (SHRSP) are utilized as models for study of the pathogenesis of not only stroke and cardiovascular disorders but also atherosclerosis and metabolic syndrome. Basic information on the profiles of fatty acids and lipid classes in the liver is indispensable to use SHRSP as a model of disorder of lipid metabolism; nevertheless, detailed information on the metabolism of triacylglycerols (TAGs) and fatty acids in the liver of SHRSP is lacking. This study aimed to characterize profiles of lipid classes and fatty acids and to explore the mechanism underlying the characteristic alterations in metabolism of TAGs and fatty acids in the liver of SHRSP, in comparison with spontaneously hypertensive rats (SHR). The characteristic changes observed in SHRSP were (1) markedly lower hepatic TAG contents; (2) altered expressions of genes encoding three enzymes responsible for the control of TAG level, namely, adipose triglyceride lipase (for TAG degradation; up-regulated), carnitine palmitoyltransferase 1a (for fatty acid β-oxidation; up-regulated) and long-chain acyl-CoA synthetase 3 (for glycerolipid synthesis; down-regulated); (3) evidently lower contents and proportions of monounsaturated fatty acids, in particular cis-vaccenic acid (18:1n-7), in the liver and serum; and (4) down-regulation of palmitoleoyl-CoA chain elongase, which is necessary for the biosynthesis of 18:1n-7, in the liver. From the above observations, we concluded that there are significant differences in profiles of lipid classes and fatty acids between SHRSP and SHR, and that altered characteristics in SHRSP are likely responsible for increases in TAG hydrolysis and β-oxidation, and decreases in TAG synthesis and 18:1n-7 synthesis.

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

    International Nuclear Information System (INIS)

    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

  19. 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)

    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)

  20. Role of 239Pu-induced chromosome alterations and mutated Ki-v-ras oncogene during liver-cancer induction in Chinese hamsters and mice

    International Nuclear Information System (INIS)

    Chromosome aberrations and mutated oncogenes can cause important changes during carcinogenesis. Model systems are being studied in which defined cellular and molecular changes can be quantitated and altered, and tumor frequency, type, and time of appearance can be evaluated. Dose-response relationships for Pu Citrate-induced chromosome aberrations and liver cancer were measured in Chinese hamsters. Chromosome aberrations increased linearly according to dose, with a slope of 4.8 x 10-1 aberrations/cell/Gy; liver-tumor incidence was 1.1 x 10-1 tumors/animal/Gy. The dose was calculated at the 50% survival time. The interaction between Pu and Ki-v-ras, an altered, dominant-acting oncogene, on the induction of liver cancer was measured in B6C3F1 mice. The neo oncogene was used as a negative control in these studies. The Ki-v-ras oncogene was inserted into a viral vector and incorporated into the livers of mice either 30 days before or after the incorporation of 239Pu. Compared with both the controls and the mice injected with a single insult, mortality increased in groups of animals that received combined exposure to oncogenes, CCl4, and 239Pu. The relationships between molecular and cellular damage and the induction of cancer is being defined in both mice and Chinese hamsters

  1. Ameliorating effect of black tea extract on cadmium chloride-induced alteration of serum lipid profile and liver histopathology in rats.

    Science.gov (United States)

    Mantur, Venkappa S; Somannavarib, Manjunath S; Yendigeri, Saeed; Das, Kusal K; Goudar, Shivaprasad S

    2014-01-01

    Cadmium is one among the most environmental pollutants that affects many organs like kidney, liver and testis. The present study was aimed to assess the simultaneous effects of black tea extracts (BTE) on cadmium chloride induced alterations in lipid profile and liver histology. Adult rats were divided into four groups (n=6/group), group I (normal saline), group II (CdCl2, 1.0 mg/kg, b.wt; i.p), group III (black tea extract, 2.5 gm tea leaf/dl of water that is 2.5% of aqueous BTE) and group IV (cadmium chloride + BTE). Cadmium chloride intoxicated rats showed significant increase in serum total cholesterol, triglycerides, and low density lipoprotein-cholesterol and there is a significant decrease in the serum high density lipoprotein-cholesterol. In the liver, cadmium chloride showed changes in normal architecture, swollen hepatocytes, kupffer cells hyperplasia, dilation and congestion of central vein. Oral administration of black tea extracts with cadmium chloride significantly improves lipid profile and liver architecture as compared to the cadmium chloride group. The results indicate that BTE is beneficial in preventing cadmium-induced lipid alterations and hepatocellular damage.

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

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    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.

  3. Malarial Infection of Female BWF1 Lupus Mice Alters the Redox State in Kidney and Liver Tissues and Confers Protection against Lupus Nephritis

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    Saleh Al-Quraishy

    2013-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototypic autoimmune disease characterized by an imbalanced redox state and increased apoptosis. Tropical infections, particularly malaria, may confer protection against SLE. Oxidative stress is a hallmark of SLE. We have measured changes in the levels of nitric oxide (NO, hydrogen peroxide (H2O2, malondialdehyde (MDA, and reduced glutathione (GSH in both kidney and liver tissues of female BWF1 lupus mice, an experimental model of SLE, after infection with either live or gamma-irradiated malaria. We observed a decrease in NO, H2O2, and MDA levels in kidney tissues after infection of lupus mice with live malaria. Similarly, the levels of NO and H2O2 were significantly decreased in the liver tissues of lupus mice after infection with live malaria. Conversely, GSH levels were obviously increased in both kidney and liver tissues after infection of lupus mice with either live or gamma-irradiated malaria. Liver and kidney functions were significantly altered after infection of lupus mice with live malaria. We further investigated the ultrastructural changes and detected the number of apoptotic cells in kidney and liver tissues in situ by electron microscopy and TUNEL assays. Our data reveal that infection of lupus mice with malaria confers protection against lupus nephritis.

  4. Radiation-Induced Glycogen Accumulation Detected by Single Cell Raman Spectroscopy Is Associated with Radioresistance that Can Be Reversed by Metformin.

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    Quinn Matthews

    Full Text Available Altered cellular metabolism is a hallmark of tumor cells and contributes to a host of properties associated with resistance to radiotherapy. Detection of radiation-induced biochemical changes can reveal unique metabolic pathways affecting radiosensitivity that may serve as attractive therapeutic targets. Using clinically relevant doses of radiation, we performed label-free single cell Raman spectroscopy on a series of human cancer cell lines and detected radiation-induced accumulation of intracellular glycogen. The increase in glycogen post-irradiation was highest in lung (H460 and breast (MCF7 tumor cells compared to prostate (LNCaP tumor cells. In response to radiation, the appearance of this glycogen signature correlated with radiation resistance. Moreover, the buildup of glycogen was linked to the phosphorylation of GSK-3β, a canonical modulator of cell survival following radiation exposure and a key regulator of glycogen metabolism. When MCF7 cells were irradiated in the presence of the anti-diabetic drug metformin, there was a significant decrease in the amount of radiation-induced glycogen. The suppression of glycogen by metformin following radiation was associated with increased radiosensitivity. In contrast to MCF7 cells, metformin had minimal effects on both the level of glycogen in H460 cells following radiation and radiosensitivity. Our data demonstrate a novel approach of spectral monitoring by Raman spectroscopy to assess changes in the levels of intracellular glycogen as a potential marker and resistance mechanism to radiation therapy.

  5. Radiation-Induced Glycogen Accumulation Detected by Single Cell Raman Spectroscopy Is Associated with Radioresistance that Can Be Reversed by Metformin.

    Science.gov (United States)

    Matthews, Quinn; Isabelle, Martin; Harder, Samantha J; Smazynski, Julian; Beckham, Wayne; Brolo, Alexandre G; Jirasek, Andrew; Lum, Julian J

    2015-01-01

    Altered cellular metabolism is a hallmark of tumor cells and contributes to a host of properties associated with resistance to radiotherapy. Detection of radiation-induced biochemical changes can reveal unique metabolic pathways affecting radiosensitivity that may serve as attractive therapeutic targets. Using clinically relevant doses of radiation, we performed label-free single cell Raman spectroscopy on a series of human cancer cell lines and detected radiation-induced accumulation of intracellular glycogen. The increase in glycogen post-irradiation was highest in lung (H460) and breast (MCF7) tumor cells compared to prostate (LNCaP) tumor cells. In response to radiation, the appearance of this glycogen signature correlated with radiation resistance. Moreover, the buildup of glycogen was linked to the phosphorylation of GSK-3β, a canonical modulator of cell survival following radiation exposure and a key regulator of glycogen metabolism. When MCF7 cells were irradiated in the presence of the anti-diabetic drug metformin, there was a significant decrease in the amount of radiation-induced glycogen. The suppression of glycogen by metformin following radiation was associated with increased radiosensitivity. In contrast to MCF7 cells, metformin had minimal effects on both the level of glycogen in H460 cells following radiation and radiosensitivity. Our data demonstrate a novel approach of spectral monitoring by Raman spectroscopy to assess changes in the levels of intracellular glycogen as a potential marker and resistance mechanism to radiation therapy. PMID:26280348

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

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    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

  7. EFFECTS OF 10‰SALINITY TO THE PLASMA OSMOTIC PRESSURE, CORTISOL, GLUCOSE AND LIVER GLYCOGEN IN COLILIA NASUS STRESSED DURING LOADING AND TRANSPORTATION%10‰盐度对长江刀鲚幼鱼装载和运输胁迫中应激指标的影响

    Institute of Scientific and Technical Information of China (English)

    徐钢春; 杜富宽; 聂志娟; 殷文健; 徐跑; 顾若波

    2015-01-01

    time points—before loading (BL), after loading (AL), 2h, 4h, 6h, and 8h after the beginning of transportation, 24h recovery, and 96h recovery. We tested the plasma osmotic pressure, cortisol, glucose and the liver glycogen of these samples. The result showed that after the 96h recovery, the survival rates of the normal stress group and the salt stress group were 20% and 100% re-spectively. The blood osmotic pressure was reduced in the normal stress group after transportation. In contrast it was significantly elevated in the salt stress group, and reached to the peak value [(0.348±0.002) mOsm/kg] 8h after the be-ginning of transportation. The plasma cortisol rapidly climbed to the peak 2h after the beginning of transportation in the normal stress group, whereas, it reached to the peak [(574.71±64.75) ng/mL] 4h after the beginning of transportation in the salt stress group. The level of glucose in the normal stress group was significantly elevated after the transportation, but its change in the salt stress group was much milder and the concentration was stabilized 6h after the beginning of transportation. Moreover, the glucose concentration in the salt stress group was significantly lower than that in the nor-mal stress group. The change in the liver glycogen was consistent with the change in glucose level, so we speculated that the increase in glucose resulted from the glycogenolysis of the liver glycogen. These results suggested that 10‰salinity could significantly improve the level of plasma osmotic pressure, reduce the energy consumption of material, and avoid strong stress reactions such as walling and rawing, therefore effectively raise the survival rate.

  8. A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0

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    Pereira Maria

    2010-01-01

    Full Text Available Abstract Background Glycogen storage disease type 0 is an autosomal recessive disease presenting in infancy or early childhood and characterized by ketotic hypoglycemia after prolonged fasting and postprandial hyperglycemia and hyperlactatemia. Sixteen different mutations have been identified to date in the gene which encodes hepatic glycogen synthase, resulting in reduction of glycogen storage in the liver. Case Presentation Biochemical evaluation as well as direct sequencing of exons and exon-intron boundary regions of the GYS2 gene were performed in a patient presenting fasting hypoglycemia and postprandial hyperglycemia and her parents. The patient was found to be compound heterozygous for one previously reported nonsense mutation (c.736 C>T; R243X and a novel frameshift mutation (966_967delGA/insC which introduces a stop codon 21 aminoacids downstream from the site of the mutation that presumably leads to loss of 51% of the COOH-terminal part of the protein. The glycemia and lactatemia of the parents after an oral glucose tolerance test were evaluated to investigate a possible impact of the carrier status on the metabolic profile. The mother, who presented a positive family history of type 2 diabetes, was classified as glucose intolerant and the father, who did not exhibit metabolic changes after the glucose overload, had an antecedent history of hypoglycemia after moderate alcohol ingestion. Conclusion The current results expand the spectrum of known mutations in GYS2 and suggest that haploinsufficiency could explain metabolic abnormalities in heterozygous carriers in presence of predisposing conditions.

  9. 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

  10. Stress and inflammatory gene networks in bovine liver are altered by plane of dietary energy during late pregnancy.

    Science.gov (United States)

    Khan, M Jawad; Jacometo, Carolina B; Riboni, Mario Vailati; Trevisi, Erminio; Graugnard, Daniel E; Corrêa, Marcio N; Loor, Juan J

    2015-09-01

    The prepartal dietary energy level is tightly correlated with the degree of tissue mobilization that the animal experiences around parturition (giving birth). To better understand the link between the dry period dietary energy management and the inflammatory status around parturition, 12 multiparous Holstein cows were fed for the entire dry period either a high-wheat straw/lower-energy diet to supply at least 100% of the calculated net energy for lactation (NEL) (control, CON) or a higher-energy diet to supply >140% of NEL (overfed, OVE). The blood was sampled throughout the transition period for biomarker analyses. Liver tissue samples were taken on days -14, 7, 14, and 30 relative to parturition for triacylglycerol (TAG) composition and gene expression analysis. Fifty genes involved in inflammation, endoplasmic reticulum (ER), and oxidative stress, and cell cycle and growth were evaluated. Although blood biomarkers did not reveal signs of a greater inflammatory status compared with OVE, CON cows had a greater activation of the intrahepatic unfolded protein response prepartum. However, postpartum mRNA profiling indicated that the OVE group experienced a mild but sustained level of ER stress, with higher oxidative stress and impairment of antioxidant mechanisms. After parturition, inflammation-related genes were upregulated in OVE cows compared with CON. However, CON cows experienced a gradual increase in expression of key inflammatory transcription regulators up to 30 days postpartum which agreed with the lower plasma albumin and cholesterol, suggesting an inflammatory state. Data underscored that ER stress is not necessarily linked with inflammation during the peripartal period. Gene expression data also suggest that prepartum overnutrition could have negative effects on normal cell cycle activity. Overall, allowing cows to overconsume energy prepartum increased the hepatic pro-inflammatory response prepartum and up to the point of parturition. Subsequently, cows

  11. Butyrate ingestion improves hepatic glycogen storage in the re-fed rat

    Directory of Open Access Journals (Sweden)

    Rigalleau Vincent

    2008-10-01

    Full Text Available Abstract Background Butyrate naturally produced by intestinal fiber fermentation is the main nutrient for colonocytes, but the metabolic effect of the fraction reaching the liver is not totally known. After glycogen hepatic depletion in the 48-hour fasting rat, we monitored the effect of (butyrate 1.90 mg + glucose 14.0 mg/g body weight versus isocaloric (glucose 18.2 mg/g or isoglucidic (glucose 14.0 mg/g control force-feeding on in vivo changes in hepatic glycogen and ATP contents evaluated ex vivo by NMR in the isolated and perfused liver. Results The change in glycogen was biphasic with (i an initial linear period where presence of butyrate in the diet increased (P = 0.05 the net synthesis rate (0.20 ± 0.01 μmol/min.g-1 liver wet weight, n = 15 versus glucose 14.0 mg/g only (0.16 ± 0.01 μmol/min.g-1 liver ww, n = 14, and (ii a plateau of glycogen store followed by a depletion. Butyrate delayed the establishment of the equilibrium between glycogenosynthetic and glycogenolytic fluxes from the 6th to 8th hour post-feeding. The maximal glycogen content was then 97.27 ± 10.59 μmol/g liver ww (n = 7 at the 8th hour, which was significantly higher than with the isocaloric control diet (64.34 ± 8.49 μmol/g, n = 12, P = 0.03 and the isoglucidic control one (49.11 ± 6.35 μmol/g liver ww, n = 6, P = 0.003. After butyrate ingestion, ATP content increased from 0.95 ± 0.29 to a plateau of 2.14 ± 0.23 μmol/g liver ww at the 8th hour post-feeding (n = 8 [P = 0.04 versus isoglucidic control diet (1.45 ± 0.19 μmol/g, n = 8 but was not different from the isocaloric control diet (1.70 ± 0.18 μmol/g, n = 12]. Conclusion The main hepatic effect of butyrate is a sparing effect on glycogen storage explained (i by competition between butyrate and glucose oxidation, glucose being preferentially directed to glycogenosynthesis during the post-prandial state; and (ii by a likely reduced glycogenolysis from the newly synthesized glycogen. This first

  12. 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

  13. 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. PMID:26569044

  14. 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.

  15. 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)

    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

  16. Systemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo.

    Science.gov (United States)

    Principi, Elisa; Girardello, Rossana; Bruno, Antonino; Manni, Isabella; Gini, Elisabetta; Pagani, Arianna; Grimaldi, Annalisa; Ivaldi, Federico; Congiu, Terenzio; De Stefano, Daniela; Piaggio, Giulia; de Eguileor, Magda; Noonan, Douglas M; Albini, Adriana

    2016-01-01

    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 microscopy) methods. We observed a transient accumulation of SWCNTs in the lungs, spleen, and kidneys of CD1 mice exposed to SWCNTs. A dose- and time-dependent accumulation was found in the liver, associated with increases in levels of aspartate aminotransferase, alanine aminotransferase and bilirubinemia, which are metabolic markers associated with liver damage. Our data suggest that hepatic accumulation of SWCNTs associated with liver damage results in an M1 macrophage-driven inflammation. PMID:27621623

  17. 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.

  18. 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...

  19. Liver metastases

    Science.gov (United States)

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver ...

  20. Different alterations of cytochrome P450 3A4 isoform and its gene expression in livers of patients with chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Li-Qun Yang; Shen-Jing Li; Yun-Fei Cao; Xiao-Bo Man; Wei-Feng Yu; Hong-Yang Wang; Meng-Chao Wu

    2003-01-01

    AIM: To determine whether parenchymal cells or hepaticcytochrome P450 protein was changed in chronic liverdiseases, and to compare the difference of CYP3A4 enzymeand its gene expression between patients with hepaticcirrhosis and obstructive jaundice, and to investigate thepharmacologic significance behind this difference.METHODS: Liver samples were obtained from patientsundergoing hepatic surgery with hepatic cirrhosis (n=6) andobstructive jaundice (n=6) and hepatic angeioma (controls,n=6). CYP3A4 activity and protein were determined by Nashand western bloting using specific polychonal antibody,respectively. Total hepatic RNA was extracted andCYP3A4cDNA probe was prepared according the methodof random primer marking, and difference of cyp3a4expression was compared among those patients byNorthern blotting.RESULTS: Compared to control group, the CYP3A4 activityand protein in liver tissue among patients with cirrhosis wereevidently reduced. (P<0.01) Northern blot showed the samechange in its mRNA levels. In contrast, the isoenzyme andits gene expression were not changed among patients withobstructive jaundice.CONCLUSION: Hepatic levels of P450s and its CYP3A4isoform activity were selectively changed in different chronicliver diseases. CYP3A4 isoenzyme and its activity declinedamong patients with hepatic cirrhosis as expression of cyp3a4gene was significantly reduced. Liver's ability to eliminatemany clinical therateutic drug substrates would declineconsequently, These findings may have practical implicationsfor the use of drugs in patients with cirrhosis and emphasizethe need to understand the metabolic fate of therapeuticcompounds. Elucidation of the reasons for these differentchanges in hepatic CYP3A4 may provide insight into morefundamental aspects and mechanisms of imparied liverfunction.

  1. Genetics Home Reference: glycogen storage disease type VII

    Science.gov (United States)

    ... storage disease type VII glycogen storage disease type VII Enable Javascript to view the expand/collapse boxes. ... All Close All Description Glycogen storage disease type VII (GSDVII) is an inherited disorder caused by an ...

  2. Genetics Home Reference: glycogen storage disease type V

    Science.gov (United States)

    ... storage disease type V glycogen storage disease type V Enable Javascript to view the expand/collapse boxes. ... All Close All Description Glycogen storage disease type V (also known as GSDV or McArdle disease) is ...

  3. Genetics Home Reference: glycogen storage disease type I

    Science.gov (United States)

    ... storage disease type I glycogen storage disease type I Enable Javascript to view the expand/collapse boxes. ... All Close All Description Glycogen storage disease type I (also known as GSDI or von Gierke disease) ...

  4. 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.

  5. Glutathione peroxidase 1 expression, malondialdehyde levels and histological alterations in the liver of Acrossocheilus fasciatus exposed to cadmium chloride.

    Science.gov (United States)

    Liu, Guo-Di; Sheng, Zhang; Wang, You-Fa; Han, Ying-Li; Zhou, Yang; Zhu, Jun-Quan

    2016-03-10

    Cadmium (Cd) is known as a widespread pollutant in aquatic environment. The accumulation of reactive oxygen species (ROS) is attributed to Cd exposure, which may affect the growth, development and physiological metabolism of aquatic organisms. In response to these unfavorable damages, antioxidant systems have been developed to protect against oxidative stress. In this study, we investigated the expression pattern of glutathione peroxidase 1 genes (GPx-1a and GPx-1b) in the liver of Acrossocheilus fasciatus after Cd administration. Total RNA extraction, reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) were performed in order to clone the A. fasciatus GPx-1a and GPx-1b full-length cDNA sequences and partial fragment of β-actin cDNA from the liver for the first time. Tissue-specific expression analysis proved that GPx-1 genes were widely expressed in the liver, kidney, gill, testis, muscle, spleen, heart and brain. The changes of GPx-1 mRNA and malondialdehyde (MDA) levels in the liver treated with Cd were measured. In addition, the acute toxic effects of Cd on the microstructure of the liver were studied using light microscopy. These results suggest that GPx-1, MDA and liver histology which represent molecular, biochemical and histological levels, can be used as potential biomarkers to monitor Cd pollution. The overall findings also highlight the potential use of those three bio-indicators combined together as a multi-level tool (molecular, biochemical and histological levels) when monitoring Cd contamination and other possible exogenetic pollutants in aquatic environment.

  6. Reduced Muscle Glycogen Differentially Affects Exercise Performance and Muscle Fatigue

    OpenAIRE

    Simon Lees; Williams, Jay H; Batts, Timothy W.

    2013-01-01

    This investigation examined the effects of reduced muscle glycogen on exercise performance and muscle fatigue. Male rats were assigned to a low glycogen group (LG) that participated in a protocol of exercise and fasting, a high glycogen group (HG) that exercised but were allowed free access to food, or control group (CON) that did not exercise but were allowed free access to food. Following the protocol, muscle glycogen content of the LG animals was reduced by 45%. The LG animals also perform...

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

    Energy Technology Data Exchange (ETDEWEB)

    Ritchie, D.G. (Shriners Burns Institute, Galveston, TX (USA))

    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 ({sup 14}C)glucose for 24 h, a procedure that resulted in the labeling of hepatic glycogen pools that subsequently could be depleted (with concomitant ({sup 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, ({sup 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.

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

    International Nuclear Information System (INIS)

    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 [14C]glucose for 24 h, a procedure that resulted in the labeling of hepatic glycogen pools that subsequently could be depleted (with concomitant [14C]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, [14C]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

  9. FR258900, a potential anti-hyperglycemic drug, binds at the allosteric site of glycogen phosphorylase.

    Science.gov (United States)

    Tiraidis, Costas; Alexacou, Kyra-Melinda; Zographos, Spyros E; Leonidas, Demetres D; Gimisis, Thanasis; Oikonomakos, Nikos G

    2007-08-01

    FR258900 has been discovered as a novel inhibitor of human liver glycogen phosphorylase a and proved to suppress hepatic glycogen breakdown and reduce plasma glucose concentrations in diabetic mice models. To elucidate the mechanism of inhibition, we have determined the crystal structure of the cocrystallized rabbit muscle glycogen phosphorylase b-FR258900 complex and refined it to 2.2 A resolution. The structure demonstrates that the inhibitor binds at the allosteric activator site, where the physiological activator AMP binds. The contacts from FR258900 to glycogen phosphorylase are dominated by nonpolar van der Waals interactions with Gln71, Gln72, Phe196, and Val45' (from the symmetry-related subunit), and also by ionic interactions from the carboxylate groups to the three arginine residues (Arg242, Arg309, and Arg310) that form the allosteric phosphate-recognition subsite. The binding of FR258900 to the protein promotes conformational changes that stabilize an inactive T-state quaternary conformation of the enzyme. The ligand-binding mode is different from those of the potent phenoxy-phthalate and acyl urea inhibitors, previously described, illustrating the broad specificity of the allosteric site. PMID:17600143

  10. Glycogen storage disease: report of two cases in the city of Cartagena

    Directory of Open Access Journals (Sweden)

    Ciro C. Alvear

    2010-09-01

    Full Text Available Objective: to report two cases of children with type Ia glycogen storage disease compatible with Von Gierke disease, suspected in the presence of findings such as hepatomegaly, nephromegaly, hypoglycemia, and stunted growth. Method: Presentation of the clinical records of two patients referred to the diagnostic unit of innate errors of metabolism of the Faculty of Medicine in Universidad de Cartagena. Results: The first case reported was a child who debuted with acute cyanosis without widespread neurological deficit when he was eleven months old, followed by hepatomegaly at two years of age. At 4 years of age, symptoms reappeared with similar characteristics: hypoglycemia, growth failure, and persistent hepatomegaly detected on physical examination. With the precedent that an older brother that presented similar symptoms was suspected of glycogen storage disease, a biopsy was performed and confirmed liver glycogen storage with normal structure. The patient’s treatment was modification of dietary habits (small, frequent feedings during the day and cornstarch. The second event was the older brother who consulted for the first time when he was 18 months old due to prolonged diarrhea. Hepatomegaly was documented by ultrasound study without kidney compromise and no hypoglycemia was found. Recommendations: It is necessary for the entire health team to be trained to detect rare diseases such as glycogen storage disease. If they make early diagnoses and establish support groups for interdisciplinary management of such diseases, they may change the prognosis and quality of life of these children.

  11. Glycogen storage disease: report of two cases in the city of Cartagena

    Directory of Open Access Journals (Sweden)

    Ciro C. Alvear

    2010-03-01

    Full Text Available Objective: to report two cases of children with type Ia glycogen storage disease compatible with Von Gierke disease, suspected in the presence of findings such as hepatomegaly, nephromegaly, hypoglycemia, and stunted growth.Method: Presentation of the clinical records of two patients referred to the diagnostic unit of innate errors of metabolism of the Faculty of Medicine in Universidad de Cartagena.Results: The first case reported was a child who debuted with acute cyanosis without widespread neurological deficit when he was eleven months old, followed by hepatomegaly at two years of age. At 4 years of age, symptoms reappeared with similar characteristics: hypoglycemia, growth failure, and persistent hepatomegaly detected on physical examination. With the precedent that an older brother that presented similar symptoms was suspected of glycogen storage disease, a biopsy was performed and confirmed liver glycogen storage with normal structure. The patient’s treatment was modification of dietary habits (small, frequent feedings during the day and cornstarch. The second event was the older brother who consulted for the first time when he was 18 months old due to prolonged diarrhea. Hepatomegaly was documented by ultrasound study without kidney compromise and no hypoglycemia was found.Recommendations: It is necessary for the entire health team to be trained to detect rare diseases such as glycogen storage disease. If they make early diagnoses and establish support groups for interdisciplinary management of such diseases, they may change the prognosis and quality of life of these children.

  12. Muscle and liver-specific alterations in lipid and acylcarnitine metabolism after a single bout of exercise in mice.

    Science.gov (United States)

    Hoene, Miriam; Li, Jia; Li, Yanjie; Runge, Heike; Zhao, Xinjie; Häring, Hans-Ulrich; Lehmann, Rainer; Xu, Guowang; Weigert, Cora

    2016-01-01

    Intracellular lipid pools are highly dynamic and tissue-specific. Physical exercise is a strong physiologic modulator of lipid metabolism, but most studies focus on changes induced by long-term training. To assess the acute effects of endurance exercise, mice were subjected to one hour of treadmill running, and (13)C16-palmitate was applied to trace fatty acid incorporation in soleus and gastrocnemius muscle and liver. The amounts of carnitine, FFA, lysophospholipids and diacylglycerol and the post-exercise increase in acetylcarnitine were pronouncedly higher in soleus than in gastrocnemius. In the liver, exercise increased the content of lysophospholipids, plasmalogens and carnitine as well as transcript levels of the carnitine transporter. (13)C16-palmitate was detectable in several lipid and acylcarnitine species, with pronounced levels of tracer-derived palmitoylcarnitine in both muscles and a strikingly high incorporation into triacylglycerol and phosphatidylcholine in the liver. These data illustrate the high lipid storing activity of the liver immediately after exercise whereas in muscle, fatty acids are directed towards oxidation. The observed muscle-specific differences accentuate the need for single-muscle analyses as well as careful consideration of the particular muscle employed when studying lipid metabolism in mice. In addition, our results reveal that lysophospholipids and plasmalogens, potential lipid signalling molecules, are acutely regulated by physical exercise. PMID:26916151

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

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    hindquarters than in controls, and glycogenolysis correlated significantly with precontraction glycogen concentrations. In slow-twitch fibers, electrical stimulation did not elicit glycogenolysis in either group. Glucose uptake and lactate release were decreased and increased, respectively, in supercompensated...

  14. Effect of fasting on the metabolic response of liver to experimental burn injury.

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    Mehmet A Orman

    Full Text Available Liver metabolism is altered after systemic injuries such as burns and trauma. These changes have been elucidated in rat models of experimental burn injury where the liver was isolated and perfused ex vivo. Because these studies were performed in fasted animals to deplete glycogen stores, thus simplifying quantification of gluconeogenesis, these observations reflect the combined impact of fasting and injury on liver metabolism. Herein we asked whether the metabolic response to experimental burn injury is different in fed vs. fasted animals. Rats were subjected to a cutaneous burn covering 20% of the total body surface area, or to similar procedures without administering the burn, hence a sham-burn. Half of the animals in the burn and sham-burn groups were fasted starting on postburn day 3, and the others allowed to continue ad libitum. On postburn day 4, livers were isolated and perfused for 1 hour in physiological medium supplemented with 10% hematocrit red blood cells. The uptake/release rates of major carbon and nitrogen sources, oxygen, and carbon dioxide were measured during the perfusion and the data fed into a mass balance model to estimate intracellular fluxes. The data show that in fed animals, injury increased glucose output mainly from glycogen breakdown and minimally impacted amino acid metabolism. In fasted animals, injury did not increase glucose output but increased urea production and the uptake of several amino acids, namely glutamine, arginine, glycine, and methionine. Furthermore, sham-burn animals responded to fasting by triggering gluconeogenesis from lactate; however, in burned animals the preferred gluconeogenic substrate was amino acids. Taken together, these results suggest that the fed state prevents the burn-induced increase in hepatic amino acid utilization for gluconeogenesis. The role of glycogen stores and means to increase and/or maintain internal sources of glucose to prevent increased hepatic amino acid

  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 maintenan...

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

    OpenAIRE

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

    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 pati...

  17. 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.

  18. 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.

  19. Characterization of the highly branched glycogen from the thermoacidophilic red microalga Galdieria sulphuraria and comparison with other glycogens

    NARCIS (Netherlands)

    Martinez-Garcia, Marta; Stuart, Marc C A; van der Maarel, Marc J E C

    2016-01-01

    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 fro

  20. Lysophosphatidic acid alters the expression profiles of angiogenic factors, cytokines, and chemokines in mouse liver sinusoidal endothelial cells.

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    Chia-Hung Chou

    Full Text Available Lysophosphatidic acid (LPA is a multi-function glycerophospholipid. LPA affects the proliferation of hepatocytes and stellate cells in vitro, and in a partial hepatectomy induced liver regeneration model, the circulating LPA levels and LPA receptor (LPAR expression levels in liver tissue are significantly changed. Liver sinusoidal endothelial cells (Lsecs play an important role during liver regeneration. However, the effects of LPA on Lsecs are not well known. Thus, we investigated the effects of LPA on the expression profiles of angiogenic factors, cytokines, and chemokines in Lsecs.Mouse Lsecs were isolated using CD31-coated magnetic beads. The mRNA expression levels of LPAR's and other target genes were determined by quantitative RT-PCR. The protein levels of angiogenesis factors, cytokines, and chemokines were determined using protein arrays and enzyme immunoassay (EIA. Critical LPAR related signal transduction was verified by using an appropriate chemical inhibitor.LPAR1 and LPAR3 mRNA's were expressed in mouse LPA-treated Lsecs. Treating Lsecs with a physiological level of LPA significantly enhanced the protein levels of angiogenesis related proteins (cyr61 and TIMP-1, cytokines (C5/C5a, M-CSF, and SDF-1, and chemokines (MCP-5, gp130, CCL28, and CXCL16. The LPAR1 and LPAR3 antagonist ki16425 significantly inhibited the LPA-enhanced expression of cyr61, TIMP-1, SDF-1, MCP-5, gp130, CCL28, and CXCL16, but not that of C5/C5a or M-CSF. LPA-induced C5/C5a and M-CSF expression may have been through an indirect regulation mechanism.LPA regulated the expression profiles of angiogenic factors, cytokines, and chemokines in Lsecs that was mediated via LPAR1 and LPAR3 signaling. Most of the factors that were enhanced by LPA have been found to play critical roles during liver regeneration. Thus, these results may prove useful for manipulating LPA effects on liver regeneration.

  1. Lysophosphatidic Acid Alters the Expression Profiles of Angiogenic Factors, Cytokines, and Chemokines in Mouse Liver Sinusoidal Endothelial Cells

    Science.gov (United States)

    Chou, Chia-Hung; Lai, Shou-Lun; Ho, Cheng-Maw; Lin, Wen-Hsi; Chen, Chiung-Nien; Lee, Po-Huang; Peng, Fu-Chuo; Kuo, Sung-Hsin; Wu, Szu-Yuan; Lai, Hong-Shiee

    2015-01-01

    Background and Aims Lysophosphatidic acid (LPA) is a multi-function glycerophospholipid. LPA affects the proliferation of hepatocytes and stellate cells in vitro, and in a partial hepatectomy induced liver regeneration model, the circulating LPA levels and LPA receptor (LPAR) expression levels in liver tissue are significantly changed. Liver sinusoidal endothelial cells (Lsecs) play an important role during liver regeneration. However, the effects of LPA on Lsecs are not well known. Thus, we investigated the effects of LPA on the expression profiles of angiogenic factors, cytokines, and chemokines in Lsecs. Methods Mouse Lsecs were isolated using CD31-coated magnetic beads. The mRNA expression levels of LPAR’s and other target genes were determined by quantitative RT-PCR. The protein levels of angiogenesis factors, cytokines, and chemokines were determined using protein arrays and enzyme immunoassay (EIA). Critical LPAR related signal transduction was verified by using an appropriate chemical inhibitor. Results LPAR1 and LPAR3 mRNA’s were expressed in mouse LPA-treated Lsecs. Treating Lsecs with a physiological level of LPA significantly enhanced the protein levels of angiogenesis related proteins (cyr61 and TIMP-1), cytokines (C5/C5a, M-CSF, and SDF-1), and chemokines (MCP-5, gp130, CCL28, and CXCL16). The LPAR1 and LPAR3 antagonist ki16425 significantly inhibited the LPA-enhanced expression of cyr61, TIMP-1, SDF-1, MCP-5, gp130, CCL28, and CXCL16, but not that of C5/C5a or M-CSF. LPA-induced C5/C5a and M-CSF expression may have been through an indirect regulation mechanism. Conclusion LPA regulated the expression profiles of angiogenic factors, cytokines, and chemokines in Lsecs that was mediated via LPAR1 and LPAR3 signaling. Most of the factors that were enhanced by LPA have been found to play critical roles during liver regeneration. Thus, these results may prove useful for manipulating LPA effects on liver regeneration. PMID:25822713

  2. Contributions of Glycogen to Astrocytic Energetics during Brain Activation

    OpenAIRE

    Dienel, Gerald A.; Nancy F Cruz

    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 g...

  3. Diet-induced alterations in intestinal and extrahepatic lipid metabolism in liver fatty acid binding protein knockout mice

    OpenAIRE

    Newberry, Elizabeth P.; Kennedy, Susan M; Xie, Yan; Luo, Jianyang; Davidson, Nicholas O.

    2008-01-01

    Liver fatty acid binding protein (L-FABP) is highly expressed in both enterocytes and hepatocytes and binds multiple ligands, including saturated (SFA), unsaturated fatty acids (PUFA), and cholesterol. L-fabp−/− mice were protected against obesity and hepatic steatosis on a high saturated fat (SF), high cholesterol “Western” diet and manifested a similar phenotype when fed with a high SF, low cholesterol diet. There were no significant differences in fecal fat content or food consumption betw...

  4. ABHRAK BHASMA MEDIATED ALTERATIONS IN LIVER AND KIDNEY FUNCTIONS IN MALE ALBINO RATS DURING CARBON TETRACHLORIDE INDUCED TOXICITY

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    Teli Parashuram

    2013-10-01

    Full Text Available Abhrak bhasma, an Ayurvedic drug used against many diseases including hepatitis. In present study various doses of abhrak bhasma (10, 20, 30 and 40 mg/kg body wt were tested for hepatoprotective efficacy against carbon tetrachloride (CCl4 intoxicated liver and kidney functions in male albino rat. Administration of CCl4 to the normal rat increased serum levels of AST, ALT, ALP and bilirubin indicated acute damage. Abhrak bhasma treatment counteracted the action of CCl4 on liver and kidney functions. With the administration of increasing doses of abhrak bhasma all activities were dropped progressively and significantly at 40 mg dose as compared with silicate control. Conjugation metabolism and excretion of bilirubin were improved with increasing doses of abhrak bhasma suggesting dose dependent protection of all metabolic steps in bilirubin metabolism. Also CCl4 induced acute toxicity increased serum urea and creatinine content, which was progressively controlled by increasing abhrak bhasma doses. The findings of this study indicated that abhrak bhasma exert dose dependent protective effects in liver and kidneys functions against CCl4 induced toxicity in albino rat.

  5. Effect of oat bran on time to exhaustion, glycogen content and serum cytokine profile following exhaustive exercise.

    Science.gov (United States)

    Donatto, Felipe F; Prestes, Jonato; Frollini, Anelena B; Palanch, Adrianne C; Verlengia, Rozangela; Cavaglieri, Claudia Regina

    2010-01-01

    The aim of this study was to evaluate the effect of oat bran supplementation on time to exhaustion, glycogen stores and cytokines in rats submitted to training. The animals were divided into 3 groups: sedentary control group (C), an exercise group that received a control chow (EX) and an exercise group that received a chow supplemented with oat bran (EX-O). Exercised groups were submitted to an eight weeks swimming training protocol. In the last training session, the animals performed exercise to exhaustion, (e.g. incapable to continue the exercise). After the euthanasia of the animals, blood, muscle and hepatic tissue were collected. Plasma cytokines and corticosterone were evaluated. Glycogen concentrations was measured in the soleus and gastrocnemius muscles, and liver. Glycogen synthetase-α gene expression was evaluated in the soleus muscle. Statistical analysis was performed using a factorial ANOVA. Time to exhaustion of the EX-O group was 20% higher (515 ± 3 minutes) when compared with EX group (425 ± 3 minutes) (p = 0.034). For hepatic glycogen, the EX-O group had a 67% higher concentrations when compared with EX (p = 0.022). In the soleus muscle, EX-O group presented a 59.4% higher glycogen concentrations when compared with EX group (p = 0.021). TNF-α was decreased, IL-6, IL-10 and corticosterone increased after exercise, and EX-O presented lower levels of IL-6, IL-10 and corticosterone levels in comparison with EX group. It was concluded that the chow rich in oat bran increase muscle and hepatic glycogen concentrations. The higher glycogen storage may improve endurance performance during training and competitions, and a lower post-exercise inflammatory response can accelerate recovery. PMID:20955601

  6. Effect of oat bran on time to exhaustion, glycogen content and serum cytokine profile following exhaustive exercise

    Directory of Open Access Journals (Sweden)

    Frollini Anelena B

    2010-10-01

    Full Text Available Abstract The aim of this study was to evaluate the effect of oat bran supplementation on time to exhaustion, glycogen stores and cytokines in rats submitted to training. The animals were divided into 3 groups: sedentary control group (C, an exercise group that received a control chow (EX and an exercise group that received a chow supplemented with oat bran (EX-O. Exercised groups were submitted to an eight weeks swimming training protocol. In the last training session, the animals performed exercise to exhaustion, (e.g. incapable to continue the exercise. After the euthanasia of the animals, blood, muscle and hepatic tissue were collected. Plasma cytokines and corticosterone were evaluated. Glycogen concentrations was measured in the soleus and gastrocnemius muscles, and liver. Glycogen synthetase-α gene expression was evaluated in the soleus muscle. Statistical analysis was performed using a factorial ANOVA. Time to exhaustion of the EX-O group was 20% higher (515 ± 3 minutes when compared with EX group (425 ± 3 minutes (p = 0.034. For hepatic glycogen, the EX-O group had a 67% higher concentrations when compared with EX (p = 0.022. In the soleus muscle, EX-O group presented a 59.4% higher glycogen concentrations when compared with EX group (p = 0.021. TNF-α was decreased, IL-6, IL-10 and corticosterone increased after exercise, and EX-O presented lower levels of IL-6, IL-10 and corticosterone levels in comparison with EX group. It was concluded that the chow rich in oat bran increase muscle and hepatic glycogen concentrations. The higher glycogen storage may improve endurance performance during training and competitions, and a lower post-exercise inflammatory response can accelerate recovery.

  7. Glycogen Fuels Survival During Hyposmotic-Anoxic Stress in Caenorhabditis elegans.

    Science.gov (United States)

    LaMacchia, John C; Frazier, Harold N; Roth, Mark B

    2015-09-01

    Oxygen is an absolute requirement for multicellular life. Animals that are deprived of oxygen for sufficient periods of time eventually become injured and die. This is largely due to the fact that, without oxygen, animals are unable to generate sufficient quantities of energy. In human diseases triggered by oxygen deprivation, such as heart attack and stroke, hyposmotic stress and cell swelling (edema) arise in affected tissues as a direct result of energetic failure. Edema independently enhances tissue injury in these diseases by incompletely understood mechanisms, resulting in poor clinical outcomes. Here, we present investigations into the effects of osmotic stress during complete oxygen deprivation (anoxia) in the genetically tractable nematode Caenorhabditis elegans. Our findings demonstrate that nematode survival of a hyposmotic environment during anoxia (hyposmotic anoxia) depends on the nematode's ability to engage in glycogen metabolism. We also present results of a genome-wide screen for genes affecting glycogen content and localization in the nematode, showing that nematode survival of hyposmotic anoxia depends on a large number of these genes. Finally, we show that an inability to engage in glycogen synthesis results in suppression of the enhanced survival phenotype observed in daf-2 insulin-like pathway mutants, suggesting that alterations in glycogen metabolism may serve as a basis for these mutants' resistance to hyposmotic anoxia.

  8. Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation.

    Directory of Open Access Journals (Sweden)

    Victoria L Gadd

    Full Text Available Liver and systemic inflammatory factors influence monocyte phenotype and function, which has implications for hepatic recruitment and subsequent inflammatory and fibrogenic responses, as well as host defence.Peripheral blood monocyte surface marker (CD14, CD16, CD163, CSF1R, CCR2, CCR4, CCR5, CXCR3, CXCR4, CX3CR1, HLA-DR, CD62L, SIGLEC-1 expression and capacity for phagocytosis, oxidative burst and LPS-stimulated TNF production were assessed in patients with hepatitis C (HCV (n = 39 or non-alcoholic fatty liver disease (NAFLD (n = 34 (classified as non-advanced disease, compensated cirrhosis and decompensated cirrhosis and healthy controls (n = 11 by flow cytometry.The selected markers exhibited similar monocyte-subset-specific expression patterns between patients and controls. Monocyte phenotypic signatures differed between NAFLD and HCV patients, with an increased proportion of CD16+ non-classical monocytes in NAFLD, but increased expression of CXCR3 and CXCR4 in HCV. In both cohorts, monocyte CCR2 expression was reduced and CCR4 elevated over controls. CD62L expression was specifically elevated in patients with decompensated cirrhosis and positively correlated with the model-for-end-stage-liver-disease score. Functionally, monocytes from patients with decompensated cirrhosis had equal phagocytic capacity, but displayed features of dysfunction, characterised by lower HLA-DR expression and blunted oxidative responses. Lower monocyte TNF production in response to LPS stimulation correlated with time to death in 7 (46% of the decompensated patients who died within 8 months of recruitment.Chronic HCV and NAFLD differentially affect circulating monocyte phenotype, suggesting specific injury-induced signals may contribute to hepatic monocyte recruitment and systemic activation state. Monocyte function, however, was similarly impaired in patients with both HCV and NAFLD, particularly in advanced disease, which likely contributes to the increased

  9. 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); p

  10. Defining hepatic dysfunction parameters in two models of fatty liver disease in zebrafish larvae.

    Science.gov (United States)

    Howarth, Deanna L; Yin, Chunyue; Yeh, Karen; Sadler, Kirsten C

    2013-06-01

    Fatty liver disease in humans can progress from steatosis to hepatocellular injury, fibrosis, cirrhosis, and liver failure. We developed a series of straightforward assays to determine whether zebrafish larvae with either tunicamycin- or ethanol-induced steatosis develop hepatic dysfunction. We found altered expression of genes involved in acute phase response and hepatic function, and impaired hepatocyte secretion and disruption of canaliculi in both models, but glycogen deficiency in hepatocytes and dilation of hepatic vasculature occurred only in ethanol-treated larvae. Hepatic stellate cells (HSCs) become activated during liver injury and HSC numbers increased in both models. Whether the excess lipids in hepatocytes are a direct cause of hepatocyte dysfunction in fatty liver disease has not been defined. We prevented ethanol-induced steatosis by blocking activation of the sterol response element binding proteins (Srebps) using gonzo(mbtps1) mutants and scap morphants and found that hepatocyte dysfunction persisted even in the absence of lipid accumulation. This suggests that lipotoxicity is not the primary cause of hepatic injury in these models of fatty liver disease. This study provides a panel of parameters to assess liver disease that can be easily applied to zebrafish mutants, transgenics, and for drug screening in which liver function is an important consideration. PMID:23697887

  11. 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.

  12. 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.

  13. Distinct alterations in ATP-binding cassette transporter expression in liver, kidney, small intestine, and brain in adjuvant-induced arthritic rats.

    Science.gov (United States)

    Kawase, Atsushi; Norikane, Sari; Okada, Ayaka; Adachi, Mamiko; Kato, Yukio; Iwaki, Masahiro

    2014-08-01

    Pathophysiological changes of infection or inflammation are associated with alterations in the production of numerous absorption, distribution, metabolism and excretion-related proteins. However, little information is available on the effects of inflammation on the expression levels and activities of ATP-binding cassette (ABC) transporters. We examined the effect of acute (on day 7) and chronic (on day 21) inflammation on the expression of ABC transporters in some major tissues in rat. Adjuvant-induced arthritis (AA) in rats was used as an animal model for inflammation. The mRNA levels of mdr1a and mdr1b encoding P-glycoprotein (P-gp) decreased significantly in livers of AA rats on day 21. Hepatic protein levels of P-gp, Mrp2, and Bcrp decreased significantly in membranes but not homogenates of AA rats after 7 days and after 21 days of treatment with adjuvant. Contrary to liver, protein levels of P-gp and Mrp2, but not Bcrp in kidney, increased significantly in membranes. The biliary excretion of rhodamine 123 was decreased in rats with chronic inflammation owing to decreases in efflux activities of P-gp. Our results showed that the expression of transporters in response to inflammation was organ dependent. In particular, hepatic and renal P-gp and Mrp2 exhibited opposite changes in membrane protein levels.

  14. 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...... 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...

  15. 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

  16. Grape Seed Procyanidins and Cholestyramine Differentially Alter Bile Acid and Cholesterol Homeostatic Gene Expression in Mouse Intestine and Liver.

    Science.gov (United States)

    Heidker, Rebecca M; Caiozzi, Gianella C; Ricketts, Marie-Louise

    2016-01-01

    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 complementary

  17. The 3T3-L1 adipocyte glycogen proteome

    OpenAIRE

    Stapleton, David; Nelson, Chad; Parsawar, Krishna; Flores-Opazo, Marcelo; McClain, Donald; Parker, Glendon

    2013-01-01

    Background Glycogen is a branched polysaccharide of glucose residues, consisting of α-1-4 glycosidic linkages with α-1-6 branches that together form multi-layered particles ranging in size from 30 nm to 300 nm. Glycogen spatial conformation and intracellular organization are highly regulated processes. Glycogen particles interact with their metabolizing enzymes and are associated with a variety of proteins that intervene in its biology, controlling its structure, particle size and sub-cellula...

  18. 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.

  19. Cadmium sulfate and CdTe-quantum dots alter DNA repair in zebrafish (Danio rerio) liver cells

    International Nuclear Information System (INIS)

    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 CdSO4 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 CdSO4 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 CdSO4 and CdTe QDs lead to cell death and Cd accumulation. • Both CdSO4 and CdTe QDs induce cellular ROS generation and DNA strand breaks. • Both CdSO4 and CdTe QDs induce the expressions of stress defense and DNA repair genes. • NER repair capacity was inhibited with CdSO4 but not with CdTe QDs

  20. 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.

  1. Protective Effect of Ceratonia siliqua L. Against a Dextran Sulfate Sodium-Induced Alterations in Liver and Kidney in Rat.

    Science.gov (United States)

    Rtibi, Kaïs; Selmi, Slimen; Jabri, Mohammed-Amine; El-Benna, Jamel; Amri, Mohamed; Marzouki, Lamjed; Sebai, Hichem

    2016-09-01

    The aim of the present study is to investigate the potential protective role of Ceratonia siliqua L. against dextran sodium sulfate (DSS)-induced oxidative damage and inflammation in liver and kidney of rats. The hepatotoxicity and nephrotoxicity were induced in rats by oral administration of synthetic DSS (5%) in the drinking water for over 7 days. However, carob pods aqueous extract (CPAE; 50 and 100 mg/kg body weight) was given by oral administration for 21 days. Myeloperoxidase (MPO) activity, malondialdehyde, H2O2 content, as well as the levels of antioxidant enzymes in organs were measured to observe the possible mechanisms. As a result, the CPAE counteracted DSS-induced increase of MPO activity, lipoperoxidation, and the activity of antioxidant enzymes, such as superoxide dismutase and catalase (CAT). DSS administration increased also in the organs hydrogen peroxide (H2O2) and free iron levels, whereas the CPAE pretreatment reversed all intracellular mediator perturbations. It was concluded that the CPAE exerted a potential protective effect against DSS-induced inflammation and oxidative stress in the rat organs. Consequently, it is essential that adequate care is taken when we use carob pods for patients with hepatotoxicity and nephrotoxicity.

  2. 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...

  3. 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...... 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...... the role of skeletal muscle transverse tubules as potential modulators of tissue insulin responsiveness....

  4. Iminosugars as potential inhibitors of glycogenolysis: structural insights into the molecular basis of glycogen phosphorylase inhibition.

    Science.gov (United States)

    Oikonomakos, Nikos G; Tiraidis, Costas; Leonidas, Demetres D; Zographos, Spyros E; Kristiansen, Marit; Jessen, Claus U; Nørskov-Lauritsen, Leif; Agius, Loranne

    2006-09-21

    Iminosugars DAB (5), isofagomine (9), and several N-substituted derivatives have been identified as potent inhibitors of liver glycogen phosphorylase a (IC(50) = 0.4-1.2 microM) and of basal and glucagon-stimulated glycogenolysis (IC(50) = 1-3 microM). The X-ray structures of 5, 9, and its N-3-phenylpropyl analogue 8 in complex with rabbit muscle glycogen phosphorylase (GPb) shows that iminosugars bind tightly at the catalytic site in the presence of the substrate phosphate and induce conformational changes that characterize the R-state conformation of the enzyme. Charged nitrogen N1 is within hydrogen-bonding distance with the carbonyl oxygen of His377 (5) and in ionic contact with the substrate phosphate oxygen (8 and 9). Our findings suggest that the inhibitors function as oxocarbenium ion transition-state analogues. The conformational change to the R state provides an explanation for previous findings that 5, unlike inhibitors that favor the T state, promotes phosphorylation of GPb in hepatocytes with sequential inactivation of glycogen synthase. PMID:16970395

  5. 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

    Three female and three male highly trained endurance runners with mean maximal oxygen uptake (VO2max) values of 60.5 and 71.5 ml.kg-1.min-1, respectively, ran to exhaustion at 75%-80% of VO2max on two occasions after an overnight fast. One experiment was performed after a normal diet and training...... (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...... of the gastrocnemius muscle is unlikely to be the cause of fatigue during exhaustive running at 75%-80% of VO2max in highly trained endurance runners. Furthermore, diet- and training-induced carbohydrate super-compensation does not appear to improve endurance capacity in such individuals....

  6. Effects of Reduced Muscle Glycogen on Sarcoplasmic Reticulum (SR), Muscle and Exercise Performance

    OpenAIRE

    Batts, Timothy W.

    2002-01-01

    Fatigue during exercise is associated with reduced muscle glycogen. However, evidence linking glycogen content to fatigue is lacking. In this study we examined whether reduced muscle glycogen content limited SR function or muscle performance. Two groups of female Sprague-Dawley rats were fasted for 24 hr and exercised for 90 min to reduce muscle glycogen; rats fasted after exercise formed the low glycogen (LG) group. Rats in the high glycogen (HG) group were allowed free access to food and...

  7. Kalpaamruthaa ameliorates mitochondrial and metabolic alterations in diabetes mellitus induced cardiovascular damage.

    Science.gov (United States)

    Latha, Raja; Shanthi, Palanivelu; Sachdanandam, Panchanadham

    2014-12-01

    Efficacy of Kalpaamruthaa on the activities of lipid and carbohydrate metabolic enzymes, electron transport chain complexes and mitochondrial ATPases were studied in heart and liver of experimental rats. Cardiovascular damage (CVD) was developed in 8 weeks after type 2 diabetes mellitus induction with high fat diet (2 weeks) and low dose of streptozotocin (2 × 35 mg/kg b.w. i.p. in 24 hr interval). In CVD-induced rats, the activities of total lipase, cholesterol ester hydrolase and cholesterol ester synthetase were increased, while lipoprotein lipase and lecithin-cholesterol acyltransferase activities were decreased. The activities of lipid-metabolizing enzymes were altered by Kalpaamruthaa in CVD-induced rats towards normal. Kalpaamruthaa modulated the activities of glycolytic enzymes (hexokinase, phosphogluco-isomerase, aldolase and glucose-6-phosphate dehydrogenase), gluconeogenic enzymes (glucose-6-phosphatase and fructose-1, 6-bisphosphatase) and glycogenolytic enzyme (glycogen phosphorylase) along with increased glycogen content in the liver of CVD-induced rats. The activities of isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, α-ketoglutarate dehydrogenase, Complexes and ATPases (Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase) were decreased in CVD-induced rats, which were ameliorated by the treatment with Kalpaamruthaa. This study ascertained the efficacy of Kalpaamruthaa for the treatment of CVD in diabetes through the modulation of metabolizing enzymes and mitochondrial dysfunction.

  8. Liver lipid content and inflammometabolic indices in peripartal dairy cows are altered in response to prepartal energy intake and postpartal intramammary inflammatory challenge.

    Science.gov (United States)

    Graugnard, D E; Moyes, K M; Trevisi, E; Khan, M J; Keisler, D; Drackley, J K; Bertoni, G; Loor, J J

    2013-02-01

    -LPS at 14 and 30 d postpartum. Several inflammation-related genes (TNF, IRAK1, NFKB1, ANGPTL4) showed markedly decreased expression between 7 and 14 d, after which expression remained unchanged. No differences were observed in several genes of the growth-hormone/insulin-like growth factor-1 axis, except for SOCS2, expression of which decreased markedly between 7 and 14 d in OVE-LPS but not in CON-LPS. These data suggest that overfeeding a moderate-energy diet prepartum alters the response of the cow to an intramammary challenge after calving and may predispose it to sustained liver lipidosis.

  9. 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 tha...

  10. 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...

  11. 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

    1994-01-01

    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

  12. Hepatic histological alterations and biochemical changes induced by sildenafil overdoses.

    Science.gov (United States)

    Jarrar, Bashir Mahmoud; Almansour, Mansour Ibrahim

    2015-11-01

    Sildenafil is used for the treatment of erectile dysfunction and is helping millions of men around the world to achieve and maintain a long lasting erection. Fifty healthy male rabbits (Oryctolagus cuniculus) were used in the present study and exposed daily to sildenafil (0, 1, 3, 6, 9 mg/kg) for 5 days per week for 7 weeks to investigate the biochemical changes and alterations in the hepatic tissues induced by this drug overdosing. In comparison with respective control rabbits, sildenafil overdoses elevated significantly (p-value<0.05, ANOVA test) alanine aminotransferase (ALT), aspartate aminotransferase (AST), testosterone, follicular stimulating hormone and total protein, while creatinine and urea were lowered with no significant alteration was observed in uric acid and luteinizing hormone concentration. Also sildenafil provoked hepatocytes nuclear alterations, necrosis, hydropic degeneration, bile duct hyperplasia, Kupffer cells hyperplasia, inflammatory cells infiltration, hepatic vessels congestion and evident partial depletion of glycogen content. The results show that subchronic exposure to sildenafil overdoses exhibits significant biochemical and alterations in the hepatic tissues that might affect the functions of the liver and other vital organs. PMID:26639481

  13. Effect of 3 amino 1,2,4 triazole administration on the early CCl4-induced ultrastructural alterations in rat liver.

    Science.gov (United States)

    Bernacchi, A. S.; de Castro, C. R.; de Ferreyra, E. C.; de Fenos, O. M.; Castro, J. A.

    1982-01-01

    CCl4 administration to rats caused at 3 and 6 h intense effects on the liver-cell endoplasmic reticulum such as dilatation, disorganization, detachment of ribosomes, development of extensive areas of smooth component (SER) and formation of myelin figures. 3 Amino 1,2,4 triazole administration (AT) at 3 and 6 h led to the formation of round small vesicles from the rough endoplasmic reticulum (RER), detachment of ribosomes, appearance of extensive areas of SER, appearance of elongated and distorted mitochondria with an increase in the number of peroxisomes. The administration of CCl4 to AT-pretreated animals led to a mutual cancellation of the effects on the RER, particularly remarkable at 3 h but still evident at 6 h; also, the formation of myelin figures was prevented. The other effects on cell ultrastructure exerted either by CCl4 or by AT were also observed with the combination of both chemicals. These observations reinforce the hypothesis about the need of either covalent binding of CCl4 metabolites to cellular constituents or lipid peroxidation, or both, in the origin of CCl4-induced alterations. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:7066182

  14. Alterations to proteome and tissue recovery responses in fish liver caused by a short-term combination treatment with cadmium and benzo[a]pyrene

    Energy Technology Data Exchange (ETDEWEB)

    Costa, P.M., E-mail: pmcosta@fct.unl.p [IMAR-Instituto do Mar, Departamento de Ciencias e Engenharia do Ambiente, Faculdade de Ciencias e Tecnologia da Universidade Nova de Lisboa, 2829-516 Monte de Caparica (Portugal); Chicano-Galvez, E.; Lopez Barea, J. [Departamento de Bioquimica y Biologia Molecular, Universidad de Cordoba, Campus de Rabanales, Edificio Severo Ochoa, 14071 Cordoba (Spain); DelValls, T.A. [UNESCO/UNITWIN/WiCop Chair-Departamento de Quimica Fisica, Facultad de Ciencias del Mar y Ambientales, Universidad de Cadiz, Poligono rio San Pedro s/n, 11510 Puerto Real, Cadiz (Spain); Costa, M.H. [IMAR-Instituto do Mar, Departamento de Ciencias e Engenharia do Ambiente, Faculdade de Ciencias e Tecnologia da Universidade Nova de Lisboa, 2829-516 Monte de Caparica (Portugal)

    2010-10-15

    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, {beta}-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.

  15. 抑制糖原合成酶激酶3活性对Toll样受体4介导肝脏炎症反应的调节作用%Inhibition of glycogen synthase kinase 3β activity regulates Toll-like receptor 4-mediated liver inflammation

    Institute of Scientific and Technical Information of China (English)

    任锋; 张海燕; 朴正福; 郑素军; 陈煜; 陈德喜; 段钟平

    2012-01-01

    抗炎和促炎因子的表达从而引起肝脏缺血再灌注损伤的改善,随着促炎细胞因子被抑制,使得炎症反应所诱导的肝细胞凋亡也间接地受到有效控制.%Objective To determine the mechanism underlying the therapeutic activities of glycogen synthase kinase 3β (GSK3β) against hepatic ischemia-reperfusion (H-IR) injury by investigating the inhibitive effects of GSK3β on inflammation mediated by Toll-like receptor 4 (TLR4).Methods 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 GSK3β-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.Results 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,GSK3β activity was found to promote the gene expression of

  16. Liver Transplant

    Science.gov (United States)

    ... Home > Your Liver > Liver Disease Information > Liver Transplant Liver Transplant Explore this section to learn more about liver ... harmful substances from your blood. What is a liver transplant? A liver transplant is the process of replacing ...

  17. Effects of diabetes on brain metabolism - is brain glycogen a significant player?

    DEFF Research Database (Denmark)

    Sickmann, Helle M; Waagepetersen, Helle S.

    2015-01-01

    Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose to the br......Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose...... to the brain may be affected and have important impacts on brain metabolism and neurotransmission. This also implies that brain glycogen may serve an essential role in the diabetic state to sustain appropriate brain function. There are two main types of diabetes; type 1 and type 2 diabetes and both types may...... be associated with brain impairments e.g. cognitive decline and dementia. It is however, not clear how these impairments on brain function are linked to alterations in brain energy and neurotransmitter metabolism. In this review, we will illuminate how rodent diabetes models have contributed to a better...

  18. Glycogen synthase isoforms in Synechocystis sp. PCC6803: identification of different roles to produce glycogen by targeted mutagenesis.

    Directory of Open Access Journals (Sweden)

    Sang-Ho Yoo

    Full Text Available Synechocystis sp. PCC6803 belongs to cyanobacteria which carry out photosynthesis and has recently become of interest due to the evolutionary link between bacteria and plant species. Similar to other bacteria, the primary carbohydrate storage source of Synechocystis sp. PCC6803 is glycogen. While most bacteria are not known to have any isoforms of glycogen synthase, analysis of the genomic DNA sequence of Synechocystis sp. PCC6803 predicts that this strain encodes two isoforms of glycogen synthase (GS for synthesizing glycogen structure. To examine the functions of the putative GS genes, each gene (sll1393 or sll0945 was disrupted by double cross-over homologous recombination. Zymogram analysis of the two GS disruption mutants allowed the identification of a protein band corresponding to each GS isoform. Results showed that two GS isoforms (GSI and GSII are present in Synechocystis sp. PCC6803, and both are involved in glycogen biosynthesis with different elongation properties: GSI is processive and GSII is distributive. Total GS activities in the mutant strains were not affected and were compensated by the remaining isoform. Analysis of the branch-structure of glycogen revealed that the sll1393- mutant (GSI- produced glycogen containing more intermediate-length chains (DP 8-18 at the expense of shorter and longer chains compared with the wild-type strain. The sll0945- mutant (GSII- produced glycogen similar to the wild-type, with only a slightly higher proportion of short chains (DP 4-11. The current study suggests that GS isoforms in Synechocystis sp. PCC6803 have different elongation specificities in the biosynthesis of glycogen, combined with ADP-glucose pyrophosphorylase and glycogen branching enzyme.

  19. A fermented soy permeate improves the skeletal muscle glucose level without restoring the glycogen content in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Malardé, Ludivine; Vincent, Sophie; Lefeuvre-Orfila, Luz; Efstathiou, Théo; Groussard, Carole; Gratas-Delamarche, Arlette

    2013-02-01

    Exercise is essential into the therapeutic management of diabetic patients, but their level of exercise tolerance is lowered due to alterations of glucose metabolism. As soy isoflavones have been shown to improve glucose metabolism, this study aimed to assess the effects of a dietary supplement containing soy isoflavones and alpha-galactooligosaccharides on muscular glucose, glycogen synthase (GSase), and glycogen content in a type 1 diabetic animal model. The dietary supplement tested was a patented compound, Fermented Soy Permeate (FSP), developed by the French Company Sojasun Technologies. Forty male Wistar rats were randomly assigned to control or diabetic groups (streptozotocin, 45 mg/kg). Each group was then divided into placebo or FSP-supplemented groups. Both groups received by oral gavage, respectively, water or diluted FSP (0.1 g/day), daily for a period of 3 weeks. At the end of the protocol, glycemia was noticed after a 24-h fasting period. Glucose, total GSase, and the glycogen content were determined in the skeletal muscle (gastrocnemius). Diabetic animals showed a higher blood glucose concentration, but a lower glucose and glycogen muscle content than controls. Three weeks of FSP consumption allowed to restore the muscle glucose concentration, but failed to reduce glycemia and to normalize the glycogen content in diabetic rats. Furthermore, the glycogen content was increased in FSP-supplemented controls compared to placebo controls. Our results demonstrated that diabetic rats exhibited a depleted muscle glycogen content (-25%). FSP-supplementation normalized the muscle glucose level without restoring the glycogen content in diabetic rats. However, it succeeded to increase it in the control group (+20%). PMID:23356441

  20. Heteropoly acid catalyzed hydrolysis of glycogen to glucose

    International Nuclear Information System (INIS)

    Complete conversion of glycogen to glucose is achieved by using H3PW12O40·nH2O (HPW) and H4SiW12O40·nH2O (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

  1. 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.

  2. The 1.76 A resolution crystal structure of glycogen phosphorylase B complexed with glucose, and CP320626, a potential antidiabetic drug.

    Science.gov (United States)

    Oikonomakos, Nikos G; Zographos, Spyros E; Skamnaki, Vicky T; Archontis, Georgios

    2002-05-01

    CP320626, a potential antidiabetic drug, inhibits glycogen phosphorylase in synergism with glucose. To elucidate the structural basis of synergistic inhibition, we determined the structure of muscle glycogen phosphorylase b (MGPb) complexed with both glucose and CP320626 at 1.76 A resolution, and refined to a crystallographic R value of 0.211 (R(free)=0.235). CP320626 binds at a novel allosteric site, which is some 33 A from the catalytic site, where glucose binds. The high resolution structure allows unambiguous definition of the conformation of the 1-acetyl-4-hydroxy-piperidine ring supported by theoretical energy calculations. Both CP320626 and glucose promote the less active T-state, thereby explaining their synergistic inhibition. Structural comparison of MGPb--glucose--CP320626 complex with liver glycogen phosphorylase a (LGPa) complexed with a related compound (CP403700) show that the ligand binding site is conserved in LGPa. PMID:11886794

  3. Infantile Onset Glycogen Storage Disease Type 2: Case Report

    Directory of Open Access Journals (Sweden)

    Serkan Bilge Koca

    2014-08-01

    Full Text Available Glycogen storage disease type 2 (Pompe’s disease is an autosomal recessive, fatal glycogen storage disease presenting with hypotonia and muscle weakness. It is known that deficiency of lysosomal acid alpha-glucosidase (acid maltase leads to progressive generalised myopathy, cardiomyopathy and death in early infancy because of respiratory muscle weakness. Excessive undegradable intracellular glycogen deposition plays a role in the pathogenesis of the disease. Here we report a 3.5 month-old girl presenting with respiratory failure due to pneumonia and hypotonia, who was later diagnosed as Pompe disease.

  4. Role of glycogen availability in sarcoplasmic reticulum Ca2+ kinetics in human skeletal muscle

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Nielsen, Joachim; Saltin, Bengt;

    2011-01-01

    Glucose is stored as glycogen in skeletal muscle. The importance of glycogen as a fuel during exercise has been recognized since the 1960s; however, little is known about the precise mechanism that relates skeletal muscle glycogen to muscle fatigue. We show that low muscle glycogen is associated ...

  5. Carbohydrate metabolism alterations in Biomphalaria glabrata infected with Schistosoma mansoni and exposed to Euphorbia splendens var. hislopii latex

    OpenAIRE

    Clélia Christina Mello-Silva; Mônica Magno Vilar; Maurício Carvalho Vasconcellos; Jairo Pinheiro; Maria de Lurdes de A Rodrigues

    2010-01-01

    This paper evaluates the alterations in the glycogen content of tissues (digestive gland and cephalopedal mass) and glucose in the haemolymph of Biomphalaria glabrata BH strain infected with Schistosoma mansoni BH strain and exposed to the latex of Euphorbia splendens var. hislopii. A reduction in the glycogen deposits was observed in infected snails exposed and not exposed to latex. However, the exposure to latex caused a greater depletion of the glycogen levels in both sites analysed, espec...

  6. 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.

  7. Glycogen synthase kinase 3: more than a namesake

    OpenAIRE

    Rayasam, Geetha Vani; Tulasi, Vamshi Krishna; Sodhi, Reena; Davis, Joseph Alex; Ray, Abhijit

    2009-01-01

    Glycogen synthase kinase 3 (GSK3), a constitutively acting multi-functional serine threonine kinase is involved in diverse physiological pathways ranging from metabolism, cell cycle, gene expression, development and oncogenesis to neuroprotection. These diverse multiple functions attributed to GSK3 can be explained by variety of substrates like glycogen synthase, τ protein and β catenin that are phosphorylated leading to their inactivation. GSK3 has been implicated in various diseases such as...

  8. 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.

  9. Period2 gene mutant mice show compromised insulin-mediated endothelial nitric oxide release and altered glucose homeostasis

    Directory of Open Access Journals (Sweden)

    João Miguel Carvas

    2012-08-01

    Full Text Available Period2 (Per2 is an important component of the circadian clock. Mutation of this gene is associated with vascular endothelial dysfunction and altered glucose metabolism. The aim of this study is to further characterize whole body glucose homeostasis and endothelial NO production in response to insulin in the mPer2Brdm1 mice. We show that mPer2Brdm1 mice exhibit compromised insulin receptor activation and Akt signaling in various tissues including liver, fat, heart, and aortas with a tissue-specific heterogeneous diurnal pattern, and decreased insulin-stimulated endothelial NO release in the aortas in both active and inactive phases of the animals. As compared to wild type mice, the mPer2Brdm1 mice reveal hyperinsulinemia, hypoglycemia with lower fasting hepatic glycogen content and glycogen synthase level, no difference in glucose tolerance and insulin tolerance. The mPer2Brdm1 mice do not show increased predisposition to obesity either on normal chow or high fat diet compared to wild type controls. Thus, mice with Per2 gene mutation show altered glucose homeostasis and compromised insulin-stimulated endothelial NO release, independently of obesity.

  10. 饥饿小鼠和饱食小鼠肝糖原含量及血糖的比较%Hungry Mice and Sated Mice Hepatic Glycogen Content and Glucose Comparison

    Institute of Scientific and Technical Information of China (English)

    罗永会; 张翠香; 徐春萍

    2012-01-01

    Objective: Hunger and satiation on mouse Liver glycogen and Blood glucose determination, Awareness of hunger and satiation on blood glucose and glycogen in the original effect.. Method: Taking the weight above 25g health mice 60, Were randomly divided into two groups: The hungry group 30, Before the experiment strict fasting to restrain water 30h ; Repletion group, Free feeding, drinking water. Then by anthrone colorimetric method for determination of mouse liver glycogen, Using Folin- Wu method for the determination of blood glucose in mice. Result: Hunger and satiety were compared with blood glucose and hepatic glycogen in mice showed significantly decreased or increased trend ( That hungry mice blood glucose and liver glycogen reduction, Sated mice blood glucose and liver glycogen increases ) , And the P〈0.05 has statistical significance. Conclusion: Repletion after liver glycogen increases, Hunger reduced liver glycogen; Blood glucose was significantly elevated after feeding, Blood glucose was significantly reduced, hunger.%目的:通过对饥饿小鼠和饱食小鼠血糖及肝糖原测定,了解饥饿及饱食对血糖和肝糖原有影响。方法:取体重在25g以上的健康小鼠60只,随机分成两组:饥饿组30只,实验前严格禁食不禁水30h;饱食组30只:自由摄食,饮水。然后采用蒽酮显色法测定小鼠肝糖原,用Folin-吴法测定小鼠血糖。结果:饥饿与饱食进行比较小鼠血糖及肝糖原都表现为明显的降低或升高趋势(即饥饿小鼠血糖及肝糖原降低,饱食小鼠血糖及肝糖原升高),且P〈0.05具有统计学意义。结论:饱食后肝糖原增加,饥饿肝糖原逐渐降低;饱食后血糖明显升高,饥饿则血糖明显降低。

  11. Effect of fipronil on energy metabolism in the perfused rat liver.

    Science.gov (United States)

    de Medeiros, Hyllana Catarine Dias; Constantin, Jorgete; Ishii-Iwamoto, Emy Luiza; Mingatto, Fábio Erminio

    2015-07-01

    Fipronil is an insecticide used to control pests in animals and plants that can causes hepatotoxicity in animals and humans, and it is hepatically metabolized to fipronil sulfone by cytochrome P-450. The present study aimed to characterize the effects of fipronil (10-50μM) on energy metabolism in isolated perfused rat livers. In fed animals, there was increased glucose and lactate release from glycogen catabolism, indicating the stimulation of glycogenolysis and glycolysis. In the livers of fasted animals, fipronil inhibited glucose and urea production from exogenous l-alanine, whereas ammonia and lactate production were increased. In addition, fipronil at 50μM concentration inhibited the oxygen uptake and increased the cytosolic NADH/NAD⁺ ratio under glycolytic conditions. The metabolic alterations were found both in livers from normal or proadifen-pretreated rats revealing that fipronil and its reactive metabolites contributed for the observed activity. The effects on oxygen uptake indicated that the possible mechanism of toxicity of fipronil involves impairment on mitochondrial respiratory activity, and therefore, interference with energy metabolism. The inhibitory effects on oxygen uptake observed at the highest concentration of 50μM was abolished by pretreatment of the rats with proadifen indicating that the metabolites of fipronil, including fipronil sulfone, acted predominantly as inhibitors of respiratory chain. The hepatoxicity of both the parent compound and its reactive metabolites was corroborated by the increase in the activity of lactate dehydrogenase in the effluent perfusate in livers from normal or proadifen-pretreated rats. PMID:25943759

  12. Effect of fipronil on energy metabolism in the perfused rat liver.

    Science.gov (United States)

    de Medeiros, Hyllana Catarine Dias; Constantin, Jorgete; Ishii-Iwamoto, Emy Luiza; Mingatto, Fábio Erminio

    2015-07-01

    Fipronil is an insecticide used to control pests in animals and plants that can causes hepatotoxicity in animals and humans, and it is hepatically metabolized to fipronil sulfone by cytochrome P-450. The present study aimed to characterize the effects of fipronil (10-50μM) on energy metabolism in isolated perfused rat livers. In fed animals, there was increased glucose and lactate release from glycogen catabolism, indicating the stimulation of glycogenolysis and glycolysis. In the livers of fasted animals, fipronil inhibited glucose and urea production from exogenous l-alanine, whereas ammonia and lactate production were increased. In addition, fipronil at 50μM concentration inhibited the oxygen uptake and increased the cytosolic NADH/NAD⁺ ratio under glycolytic conditions. The metabolic alterations were found both in livers from normal or proadifen-pretreated rats revealing that fipronil and its reactive metabolites contributed for the observed activity. The effects on oxygen uptake indicated that the possible mechanism of toxicity of fipronil involves impairment on mitochondrial respiratory activity, and therefore, interference with energy metabolism. The inhibitory effects on oxygen uptake observed at the highest concentration of 50μM was abolished by pretreatment of the rats with proadifen indicating that the metabolites of fipronil, including fipronil sulfone, acted predominantly as inhibitors of respiratory chain. The hepatoxicity of both the parent compound and its reactive metabolites was corroborated by the increase in the activity of lactate dehydrogenase in the effluent perfusate in livers from normal or proadifen-pretreated rats.

  13. Digestion of glycogen by a glucosidase released by Trichomonas vaginalis.

    Science.gov (United States)

    Huffman, Ryan D; Nawrocki, Lauren D; Wilson, Wayne A; Brittingham, Andrew

    2015-12-01

    Trichomonas vaginalis is a protozoan parasite that is the causative agent of trichomoniasis, a widespread sexually transmitted disease. In vitro culture of T. vaginalis typically employs a medium supplemented with either maltose or glucose and carbohydrates are considered essential for growth. Although the nature of the carbohydrates utilized by T. vaginalis in vivo is undefined, the vaginal epithelium is rich in glycogen, which appears to provide a source of carbon for the vaginal microbiota. Here, we show that T. vaginalis grows equally well in growth media supplemented with simple sugars or with glycogen. Analysis of conditioned growth medium by thin layer chromatography indicates that growth on glycogen is accompanied by glycogen breakdown to a mixture of products including maltose, glucose, and oligosaccharides. Enzymatic assays with conditioned growth medium show that glycogen breakdown is accomplished via the release of a glucosidase activity having the properties of an α-amylase into the growth medium. Furthermore, we find that released glucosidase activity increases upon removal of carbohydrate from the growth medium, indicating regulation of synthesis and/or secretion in response to environmental cues. Lastly, we show that addition of T. vaginalis glucosidase activity to a growth medium containing glycogen generates sufficient simple sugar to support the growth of lactobacilli which, themselves, are unable to degrade glycogen. Thus, not only does the glucosidase activity likely play an important role in allowing T. vaginalis to secure simple sugars for its own use, it has the potential to impact the growth of other members of the vaginal microbiome.

  14. Fetal liver glycogen production and glycogenic transcript expression during prenatal development from pig breeds differing in preweaning survivability

    Science.gov (United States)

    Sow productivity is influenced by a number of factors including preweaning piglet mortality. In commercial pigs, low birth weight piglets exhibit the greatest susceptibility to preweaning mortality. In contrast, Meishan (MS) piglets have naturally occurring lower birth weight and also improved prewe...

  15. Changes in uridylic nucleotides and glycogen amount in animals tissue at exposure to ionizing radiation and physical exertion and some ways of their correction

    International Nuclear Information System (INIS)

    We have studied the amount of uridylic nucleoside phosphates and glycogen in the tissues of the rats exposed to ionizing radiation (6 Gy) and maximum physical exertion (running along a tredbahn till complete exhaustion). It has been shown that the amount of glycogen in the skeletal muscles decreases considerably 1 hour after combined action of ionizing radiation and physical exertion, 1 - 3 days after it decreased in the liver. Decrease of uridine diphosphate and uridine triphosphate polyphosphates amount as well as increase of uridine monophosphate in the tissue of the brain and liver are natural for uridylic nucleotides after combined action of ionizing radiation and physical exertion. These changes are more marked with increase of the period after the exposure

  16. Total body irradiation of donors can alter the course of tolerance and induce acute rejection in a spontaneous tolerance rat liver transplantation model.

    Science.gov (United States)

    Zhang, YeWei; Zhao, HeWei; Bo, Lin; Yang, YinXue; Lu, Xiang; Sun, JingFeng; Wen, JianFei; He, Xia; Yin, GuoWen

    2012-09-01

    Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of acute rejection of liver allografts in rats pre-treated with total body irradiation to eliminate passenger lymphocytes and to define the role of CD4(+)CD25(+) regulatory T cells in the induction of immunotolerance in the recipient. Male Lewis rats were used as donors and male DA rats were recipients. Rats were randomly assigned to the following four groups: control group, homogeneity liver transplantation group, idio-immunotolerance group and acute rejection group. After transplantation, the survival time of each group, serum alanine aminotransferase, total bilirubin levels, number of Foxp3(+)CD4(+)CD25(+) regulatory T cells, expression of glucocorticoid-induced tumor necrosis factor receptor on T cell subgroups, histopathology of the hepatic graft and spleen cytotoxic T lymphocyte lytic activity were measured. In the acute rejection group, where donors were preconditioned with total body irradiation before liver transplantation, all recipients died between day 17 and day 21. On day 14, serum alanine aminotransferase increased significantly to (459.2±76.9) U L(-1), total bilirubin increased to (124.1±33.7) μmol L(-1) (Pliver graft, and thus affected the course of tolerance and induced acute rejection after liver transplantation.

  17. Ethanol diversely alters palmitate, stearate and oleate metabolism in the liver and pancreas of rats using the deuterium oxide single tracer

    Science.gov (United States)

    Boros, Laszlo G.; Deng, Qinggao; Pandol, Stephen J.; Tsukamoto, Hidekazu; Go, Vay Liang W.; Lee, Wai-Nang Paul

    2015-01-01

    Objective To determine tissue specific effects of alcohol on fatty acid synthesis and distribution as related to functional changes in triglyceride transport and membrane formation. Methods Tissue fatty acid profile, and de novo lipogenesis were determined in adult male Wistar rats after 5 weeks of ethanol feeding using deuterated water and GC/MS. Liver and pancreas fatty acid profiles and new synthesis fractions were compared with those from control rats on an isocaloric diet. Results Fatty acid ratios in the liver indicated that there was an over two-fold accumulation of stearate to that of palmitate, with an apparent decrease in oleate content. On the other hand, in the pancreas there was a 17% decrease in the stearate to palmitate ratio, while oleate to palmitate ratio was increased by 30%. The fractions of deuterium labeled palmitate and stearate were substantially reduced in the liver and pancreas of the alcohol treated animals. Deuterium labeling of oleate was reduced in the liver but not in the pancreas consistent with the oleate/stearate ratios in these tissues. Conclusions Long-term alcohol exposure results in opposite effects on the desaturase activity in the liver and pancreas limiting fatty acid transport in the liver but promoting the exocrine function of the pancreas. PMID:19248221

  18. Thiamethoxam causes histochemical changes in the liver of Aristichthys nobilis Rich., 1845

    Directory of Open Access Journals (Sweden)

    STELA STOYANOVA

    2015-12-01

    Full Text Available In the present study, we aimed to investigate the effects of the neonicotinoid insecticide thiamethoxam on the hepatic glycogen in bighead carp (Aristichthys nobilis Rich.. Fish were exposed to 6.6 mg/L, 10 mg/L and 20 mg/L of the insecticide under laboratory conditions for 96 hours. The PAS-reaction was applied to liver cryostat sections in order to indicate the amount of glycogen. The results showed that the hepatic glycogen amount increased with increasing the insecticide concentrations. On the other hand, we observed glycogen conglomerates in certain hepatocytes. Hence, our results demonstrated an enhanced process of glyconeogenesis in the fish liver under the influence of thiamethoxam.

  19. Effects of different mitogens on intrasplenic liver tissue transplants in comparison to orthotopic liver.

    Science.gov (United States)

    Lupp, Amelie; Lucas, Norma; Tralls, Manuela; Fuchs, Udo; Danz, Manfred

    2003-06-01

    Ectopic liver cell transplants, when compared to orthotopic liver, can serve as a tool to study topic influences on liver cell differentiation, multiplication, function and responsiveness to xenobiotics. The aim of the present study was to evaluate, if characteristic effects of mitogens are exerted in both liver and intrasplenic liver cell transplants in a similar manner. Fetal liver tissue suspensions were transplanted into the spleens of adult male syngenic rats. Four months later, transplant recipients and controls were treated with fluorene (FEN), fluorenone (FON), 2-acetylaminofluorene (AAF), N-nitrosodibenzylamine (NDBA) or the solvent 48 hours before sacrifice. The following parameters were assessed within livers and spleens: mitotic activity of hepatocytes, glycogen content, cytochrome P450 (P450) isoforms expression, P450 mediated monooxygenase functions, tissue content of lipid peroxides (LPO) and of reduced and oxidized glutathione (GSH; GSSG). In both orthotopic livers and intrasplenic transplants FEN, FON or NDBA administration increased the mitotic activity of the hepatocytes. Treatment with the mitogens caused a distinct and characteristic induction of the P450 isoforms expression and of the respective monooxygenase functions in the livers and (with certain differences) also in the transplants. FEN and FON slightly increased, AAF and NDBA reduced liver glycogen content. The latter effect was also seen in the transplants. NDBA administration caused a slight increase in tissue LPO content in livers, but not in spleens. Additionally, AAF or NDBA treatment led to an elevation of liver (but not of spleen) GSH and GSSG concentrations. The results of the present investigation show that characteristic effects of mitogens on orthotopic liver occur with certain differences also in ectopic liver cell transplants.

  20. 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 BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: By recapitulating human π-class GST expression, hGSTP1+mGstp1/2-/- mice may better model human drug and xenobiotic toxicology.

  1. 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.

  2. Alterations of epigenetic signatures in hepatocyte nuclear factor 4α deficient mouse liver determined by improved ChIP-qPCR and (h)MeDIP-qPCR assays.

    Science.gov (United States)

    Zhang, Qinghao; Lei, Xiaohong; Lu, Hong

    2014-01-01

    Hepatocyte nuclear factor 4α (HNF4α) is a liver-enriched transcription factor essential for liver development and function. In hepatocytes, HNF4α regulates a large number of genes important for nutrient/xenobiotic metabolism and cell differentiation and proliferation. Currently, little is known about the epigenetic mechanism of gene regulation by HNF4α. In this study, the global and specific alterations at the selected gene loci of representative histone modifications and DNA methylations were investigated in Hnf4a-deficient female mouse livers using the improved MeDIP-, hMeDIP- and ChIP-qPCR assay. Hnf4a deficiency significantly increased hepatic total IPed DNA fragments for histone H3 lysine-4 dimethylation (H3K4me2), H3K4me3, H3K9me2, H3K27me3 and H3K4 acetylation, but not for H3K9me3, 5-methylcytosine,or 5-hydroxymethylcytosine. At specific gene loci, the relative enrichments of histone and DNA modifications were changed to different degree in Hnf4a-deficient mouse liver. Among the epigenetic signatures investigated, changes in H3K4me3 correlated the best with mRNA expression. Additionally, Hnf4a-deficient livers had increased mRNA expression of histone H1.2 and H3.3 as well as epigenetic modifiers Dnmt1, Tet3, Setd7, Kmt2c, Ehmt2, and Ezh2. In conclusion, the present study provides convenient improved (h)MeDIP- and ChIP-qPCR assays for epigenetic study. Hnf4a deficiency in young-adult mouse liver markedly alters histone methylation and acetylation, with fewer effects on DNA methylation and 5-hydroxymethylation. The underlying mechanism may be the induction of epigenetic enzymes responsible for the addition/removal of the epigenetic signatures, and/or the loss of HNF4α per se as a key coordinator for epigenetic modifiers.

  3. 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.

  4. Metabolic alterations and increased liver mTOR expression precede the development of autoimmune disease in a murine model of lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Laia Vilà

    Full Text Available Although metabolic syndrome (MS and systemic lupus erythematosus (SLE are often associated, a common link has not been identified. Using the BWF1 mouse, which develops MS and SLE, we sought a molecular connection to explain the prevalence of these two diseases in the same individuals. We determined SLE- markers (plasma anti-ds-DNA antibodies, splenic regulatory T cells (Tregs and cytokines, proteinuria and renal histology and MS-markers (plasma glucose, non-esterified fatty acids, triglycerides, insulin and leptin, liver triglycerides, visceral adipose tissue, liver and adipose tissue expression of 86 insulin signaling-related genes in 8-, 16-, 24-, and 36-week old BWF1 and control New-Zealand-White female mice. Up to week 16, BWF1 mice showed MS-markers (hyperleptinemia, hyperinsulinemia, fatty liver and visceral adipose tissue that disappeared at week 36, when plasma anti-dsDNA antibodies, lupus nephritis and a pro-autoimmune cytokine profile were detected. BWF1 mice had hyperleptinemia and high splenic Tregs till week 16, thereby pointing to leptin resistance, as confirmed by the lack of increased liver P-Tyr-STAT-3. Hyperinsulinemia was associated with a down-regulation of insulin related-genes only in adipose tissue, whereas expression of liver mammalian target of rapamicyn (mTOR was increased. Although leptin resistance presented early in BWF1 mice can slow-down the progression of autoimmunity, our results suggest that sustained insulin stimulation of organs, such as liver and probably kidneys, facilitates the over-expression and activity of mTOR and the development of SLE.

  5. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M

    1987-01-01

    cells were stained by antisera to carcinoembryonic antigen, keratin and epithelial membrane antigen, but not by antisera to alpha-lactalbumin, desmin or vimentin. Ultrastructurally, the epithelial derivation of the tumour was confirmed. Only a few intracytoplasmic lumina were demonstrated. The tumour......The light microscopic, immunohistochemical and ultrastructural features of a clear cell carcinoma of the breast have been studied. Both intraductal and invasive components were found. Histochemistry showed large amounts of intracytoplasmic glycogen and sparse neutral mucin in the tumour. The tumour...... was classified as a mucin-containing variant of glycogen-rich, clear cell carcinoma of the breast....

  6. Liver Metabolite Concentrations Measured with 1H MR Spectroscopy

    OpenAIRE

    Ouwerkerk, Ronald; PETTIGREW, RODERIC I.; Gharib, Ahmed M.

    2012-01-01

    In vivo measurement of liver choline concentrations in healthy humans is feasible, and even measurement of glycogen can be achieved in some patients at 3.0 T with point-resolved 1H MR spectroscopy by using navigator-guided synchronization to respiratory motion and state-of-the-art B0 field shimming techniques.

  7. 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 glyc

  8. Liver angioscintigraphy: clinical applications.

    Science.gov (United States)

    Dragoteanu, Mircea; Cotul, Sabin O; Pîgleşan, Cecilia; Tamaş, Stefan

    2004-03-01

    Liver angioscintigraphy (LAS) is a radio-isotope method for the investigation of liver perfusion and its alteration in various hepatic diseases. It measures the arterial and portal venous fractions of total liver blood flow. The percentage of liver blood flow supplied by hepatic artery is estimated mathematically by the hepatic perfusion index (HPI), normally between 25 % and 40 %. The decrease of portal blood flow in liver cirrhosis is compensated ("buffer" mechanisms) by increased arterial supply, with higher HPI value. For a patient with chronic liver disease, HPI over 50% suggests arterialization of hepatic perfusion, guiding the diagnose to liver cirrhosis. Splenic curve is completing the diagnostic information of the hepatic curve. Corroborated with per rectal scintigraphy and liver SPECT, LAS offers a good hemodynamic staging of chronic inflammatory liver diseases. Malignant tumors (primitive or metastases) increase the arterial supply of the liver and decrease the portal flow, HPI being over 50% (currently 65 % - 90 %). Benign tumors do not change portal/arterial liver blood flow ratio. SPECT or non-scintigraphic morphological investigations increase the diagnostic value of LAS for primitive liver tumors. Liver cancer occurring on cirrhosis is a limitative factor for LAS. Hepatic metastases increase the arterial perfusion (and HPI value) very quickly, before their size allows morphologic imaging diagnosis. LAS is therefore an early method to diagnose liver metastases being especially used in colorectal cancer. Other clinical applications of LAS are: follow up of liver toxicity of drugs, evaluation of portal vein permeability, post surgery follow up of the liver tumor patients. PMID:15054528

  9. 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

  10. The Liver X Receptor (LXR) and its Target Gene ABCA1 are Regulated Upon Low Oxygen in Human Trophoblast Cells : A Reason for Alterations in Preeclampsia?

    NARCIS (Netherlands)

    Plosch, T.; Gellhaus, A.; van Straten, E. M. E.; Wolf, N.; Huijkman, N. C. A.; Schmidt, M.; Dunk, C. E.; Kuipers, F.; Winterhager, E.

    2010-01-01

    Objectives: The Liver X receptors (LXR) alpha and beta and their target genes such as the ATP-binding cassette (ABC) transporters have been shown to be crucially involved in the regulation of cellular cholesterol homeostasis. The aim of this study was to characterize the role of LXR alpha/beta in th

  11. Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition

    Science.gov (United States)

    This study was designed to determine if the fatty acid composition of the diet affects the development and progression of nonalcoholic fatty liver disease (NAFLD). Male Sprague-Dawley rats (n = 5-6/group) were overfed low (5%) or high (70%) fat diets with different fatty acid sources: olive oil (OO,...

  12. Soft texture of atlantic salmon fillets is associated with glycogen accumulation.

    Directory of Open Access Journals (Sweden)

    Jacob S Torgersen

    Full Text Available Atlantic salmon (Salmo salar L. with soft fillets are not suited for manufacturing high quality products. Therefore fillets with insufficient firmness are downgraded, leading to severe economic losses to the farming and processing industries. In the current study, morphological characteristics of salmon fillets ranging from soft to hard were analysed. Different microscopic techniques were applied, including novel methods in this field of research: morphometric image analysis, periodic acid Schiff staining, immunofluorescence microscopy, transmission electron microscopy and fourier transform infrared microscopy. The results showed that the myocytes of soft muscle had detached cells with mitochondrial dysfunctions, large glycogen aggregates and enlarged inter cellular areas, void of extracellular matrix proteins, including lower amounts of sulfated glycoproteins. Myofibre-myofibre detachment and disappearance of the endomysium in soft muscles coincided with deterioration of important connective tissue constituents such as Collagen type I (Col I, Perlecan and Aggrecan. In summary our investigations show for the first time an association between soft flesh of Atlantic salmon and massive intracellular glycogen accumulation coinciding with degenerated mitochondria, myocyte detachment and altered extracellular matrix protein distribution. The results are important for further understanding the etiology of soft salmon.

  13. 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...

  14. Distal Splenorenal Shunt for Portal Vein Thrombosis after Liver Transplantation

    OpenAIRE

    Marino, Ignazio R.; Esquivel, Carlos O.; Zajko, Albert B.; Malatack, Jeffrey; Scantlebury, Velma P.; Shaw, Byers W.; Starzl, Thomas E.

    1989-01-01

    A 17-yr-old female received a liver transplant for type I glycogen storage disease. A year later, when she experienced variceal gastrointestinal hemorrhage, an angiogram revealed thrombosis of the portal vein with hepatopetal collateral channels. A distal splenorenal shunt was performed because of failure of sclerotherapy to control subsequent bleeding episodes and the fact that the liver function was normal. This patient continues to have normal hepatic function with a patent splenorenal shu...

  15. 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...

  16. Glycogen metabolism in Schistosoma mansoni worms after their isolation from the host

    NARCIS (Netherlands)

    Tiolens, A.G.M.; Bergh, S.G. van den

    1987-01-01

    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

  17. The utilization of glycogen and accumulation of some intermediates during anaerobiosis in Mytilus edulis L.

    NARCIS (Netherlands)

    Zwaan, A.; Zandee, D.I.

    1972-01-01

    1. 1. Glycogen degradation in the mussel under anaerobic conditions was measured at two temperatures. Glycogen decrease at 6·6°C was about 3 mg and at 20°C about 6 mg/24 hr per mussel. A Pasteur effect was observed. 2. 2. The decrease of glycogen was almost entirely restricted to muscles, including

  18. ALTERATIONS IN A11 TRANS RETINOIC ACID METABOLISM IN LIVER MICROSOMES FROM MICE TREATED WITH HEPATOTUMORIGENIC AND NON-HEPATOTUMORIGENIC CONAZOLES

    Science.gov (United States)

    Conazoles are fungicides used in crop protection and as pharmaceuticals. Triadimefon and propiconazole are hepatotumorigenic in mice, while myclobutanil is not. Previous toxicogenomic studies suggest that alteration of the retinoic acid metabolism pathway may be a key event in co...

  19. Pathway-level acceleration of glycogen catabolism by a response regulator in the cyanobacterium Synechocystis species PCC 6803.

    Science.gov (United States)

    Osanai, Takashi; Oikawa, Akira; Numata, Keiji; Kuwahara, Ayuko; Iijima, Hiroko; Doi, Yoshiharu; Saito, Kazuki; Hirai, Masami Yokota

    2014-04-01

    Response regulators of two-component systems play pivotal roles in the transcriptional regulation of responses to environmental signals in bacteria. Rre37, an OmpR-type response regulator, is induced by nitrogen depletion in the unicellular cyanobacterium Synechocystis species PCC 6803. Microarray and quantitative real-time polymerase chain reaction analyses revealed that genes related to sugar catabolism and nitrogen metabolism were up-regulated by rre37 overexpression. Protein levels of GlgP(slr1367), one of the two glycogen phosphorylases, in the rre37-overexpressing strain were higher than those of the parental wild-type strain under both nitrogen-replete and nitrogen-depleted conditions. Glycogen amounts decreased to less than one-tenth by rre37 overexpression under nitrogen-replete conditions. Metabolome analysis revealed that metabolites of the sugar catabolic pathway and amino acids were altered in the rre37-overexpressing strain after nitrogen depletion. These results demonstrate that Rre37 is a pathway-level regulator that activates the metabolic flow from glycogen to polyhydroxybutyrate and the hybrid tricarboxylic acid and ornithine cycle, unraveling the mechanism of the transcriptional regulation of primary metabolism in this unicellular cyanobacterium.

  20. Fat balance in obese subjects: role of glycogen stores.

    NARCIS (Netherlands)

    Schrauwen, P.; van Marken Lichtenbelt, W.D.; Westerterp, K.R.

    1998-01-01

    Department of Human Biology, Maastricht University, 6200 MD Maastricht, The Netherlands. In a previous study, we showed that lean subjects are capable of rapidly adjusting fat oxidation to fat intake on a high-fat (HF) diet when glycogen stores are lowered by exhaustive exercise. However, it has bee

  1. L-FABP T94A decreased fatty acid uptake and altered hepatic triglyceride and cholesterol accumulation in Chang liver cells stably transfected with L-FABP.

    Science.gov (United States)

    Gao, Na; Qu, Xia; Yan, Jin; Huang, Qi; Yuan, Hao-Yong; Ouyang, Dong-Sheng

    2010-12-01

    Liver fatty acid-binding protein (L-FABP, FABP1) is a highly conserved key factor in lipid metabolism. This study was undertaken to verify whether the T94A mutation in the L-FABP gene affects fatty acid uptake and intracellular esterification into specific lipid pools. Candidate SNPs were recreated using site-directed mutagenesis and tested for physical function in stably transfected Chang liver cell lines. We found that the T94A mutant of L-FABP lowered FFA uptake but had no effect on FFA efflux. L-FABP T94A-expressing cells showed decreased triglyceride content and increased cholesterol accumulation compared to the wild-type control for cells incubated with an FFA mixture (oleate: palmitate, 2:1 ratio). In conclusion, our study provided additional indications of the functional relevance of the L-FABP T94A SNP in hepatic fatty acid and lipid metabolism in humans.

  2. Alteration of Drug Sensitivity in Human Colon Cancer Cells after Exposure to Heat: Implications for Liver Metastasis Therapy using RFA and Chemotherapy

    OpenAIRE

    Makizumi, Ryouji; Yang, Weng-Lang; Owen, Randall P.; Sharma, Rohit R.; Ravikumar, T S

    2008-01-01

    Radiofrequency ablation (RFA) is gaining popularity for treating colorectal liver metastases by inducing image guided tumor hyperthermia. In order to reduce tumor recurrence, adjuvant therapies have been administered post-RFA. We hypothesized that tumor cells escaping RFA cytotoxicity by being in the sublethal zones of tumor might develop differential behavior toward cytotoxic drugs. Here, we used cultured human colorectal cancer cells to evaluate the interaction between heat treatment and ch...

  3. Effect of 3 amino 1,2,4 triazole administration on the early CCl4-induced ultrastructural alterations in rat liver.

    OpenAIRE

    Bernacchi, A. S.; de Castro, C. R.; de Ferreyra, E. C.; de Fenos, O. M.; Castro, J.A.

    1982-01-01

    CCl4 administration to rats caused at 3 and 6 h intense effects on the liver-cell endoplasmic reticulum such as dilatation, disorganization, detachment of ribosomes, development of extensive areas of smooth component (SER) and formation of myelin figures. 3 Amino 1,2,4 triazole administration (AT) at 3 and 6 h led to the formation of round small vesicles from the rough endoplasmic reticulum (RER), detachment of ribosomes, appearance of extensive areas of SER, appearance of elongated and disto...

  4. Fipronil induced oxidative stress involves alterations in SOD1 and catalase gene expression in male mice liver: Protection by vitamins E and C.

    Science.gov (United States)

    Badgujar, Prarabdh C; Chandratre, Gauri A; Pawar, Nitin N; Telang, A G; Kurade, N P

    2016-09-01

    In the present investigation, hepatic oxidative stress induced by fipronil was evaluated in male mice. We also investigated whether pretreatment with antioxidant vitamins E and C could protect mice against these effects. Several studies conducted in cell lines have shown fipronil as a potent oxidant; however, no information is available regarding its oxidative stress inducing potential in an animal model. Out of 8 mice groups, fipronil was administered to three groups at low, medium, and high dose based on its oral LD50 (2.5, 5, and 10 mg/kg). All three doses of fipronil caused a significant increase in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level with concomitant increase in the absolute and relative weight of liver. High dose of fipronil caused significant down-regulation in the hepatic mRNA expression of superoxide dismutase 1 (SOD1) and catalase (0.412 ± 0.01 and 0.376 ± 0.05-fold, respectively) as well as an increase in the lipid peroxidation (LPO). Also, decrease in the activity of antioxidant enzymes; SOD, catalase, and glutathione-S-transferase (GST) and the content of nonantioxidant enzymes; glutathione and total thiol were recorded. Histopathological examination of liver revealed dose dependant changes such as severe fatty degeneration and vacuolation leading to hepatocellular necrosis. Prior administration of vitamin E or vitamin C against fipronil high dose caused decrease in lipid peroxidation and increased activity of antioxidant enzymes. Severe reduction observed in functional activities of antioxidant enzymes was aptly substantiated by down-regulation seen in their relative mRNA expression. Thus results of the present study imply that liver is an important target organ for fipronil and similar to in vitro reports, it induces oxidative stress in the mice liver, which in turn could be responsible for its hepatotoxic nature. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1147-1158, 2016. PMID

  5. Biochemical aspects of overtraining in endurance sports : the metabolism alteration process syndrome.

    Science.gov (United States)

    Petibois, Cyril; Cazorla, Georges; Poortmans, Jacques-Rémi; Déléris, Gérard

    2003-01-01

    Recent studies have shown that endurance overtraining could result from successive and cumulative alterations in metabolism, which become chronic during training. The onset of this process is a biochemical alteration in carbohydrate (saccharide) metabolism. During endurance exercises, the amount of saccharide chains from two blood glycoproteins (alpha(2)-macroglobulin and alpha(1)-acid glycoprotein) was found to have decreased, i.e. concentrations of these proteins remained unchanged but their quality changed. These saccharide chains were probably used for burning liver glycogen stores during exercise. This step was followed by alterations in lipid metabolism. The most relevant aspect of this step was that the mean chain length of blood fatty acids decreased, i.e. the same amount of fatty acids were found within the blood, but overtrained individuals presented shorter fatty acids than well-trained individuals. This suggests that alterations appeared in the liver synthesis of long-chain fatty acids or that higher peroxidation of blood lipoparticles occurred. For the final step of this overtraining process, it was found that these dysfunctions in carbohydrate/lipid metabolism led to the higher use of amino acids, which probably resulted from protein catabolism. The evolution of three protein concentrations (alpha(1)-acid glycoprotein, alpha(2)-macroglobulin and IgG(3)) correlated with this amino acid concentration increase, suggesting a specific catabolism of these proteins. At this time only, overtraining was clinically diagnosed through conventional symptoms. Therefore, this process described successive alterations in exercise metabolism that shifted from the main energetic stores of exercise (carbohydrates and lipids) towards molecular pools (proteins) normally not substantially used for the energetic supply of skeletal muscles. Now, a general biochemical model of the overtraining process may be proposed which includes most of the previously identified metabolic

  6. Progression of Liver Disease

    Science.gov (United States)

    ... Browse Related Terms Progression of Liver Disease , Family History of Liver Disease , Liver Wellness , Liver Failure , Liver Biopsy Home > Your Liver > Liver Disease Information > The Progression ...

  7. Glycogen distribution in the microwave-fixed mouse brain reveals heterogeneous astrocytic patterns.

    Science.gov (United States)

    Oe, Yuki; Baba, Otto; Ashida, Hitoshi; Nakamura, Kouichi C; Hirase, Hajime

    2016-09-01

    In the brain, glycogen metabolism has been implied in synaptic plasticity and learning, yet the distribution of this molecule has not been fully described. We investigated cerebral glycogen of the mouse by immunohistochemistry (IHC) using two monoclonal antibodies that have different affinities depending on the glycogen size. The use of focused microwave irradiation yielded well-defined glycogen immunoreactive signals compared with the conventional periodic acid-Schiff method. The IHC signals displayed a punctate distribution localized predominantly in astrocytic processes. Glycogen immunoreactivity (IR) was high in the hippocampus, striatum, cortex, and cerebellar molecular layer, whereas it was low in the white matter and most of the subcortical structures. Additionally, glycogen distribution in the hippocampal CA3-CA1 and striatum had a 'patchy' appearance with glycogen-rich and glycogen-poor astrocytes appearing in alternation. The glycogen patches were more evident with large-molecule glycogen in young adult mice but they were hardly observable in aged mice (1-2 years old). Our results reveal brain region-dependent glycogen accumulation and possibly metabolic heterogeneity of astrocytes. GLIA 2016;64:1532-1545. PMID:27353480

  8. Glycogen in the Nervous System. I; Methods for Light and Electron Microscopy

    Science.gov (United States)

    Estable, Rosita F. De; Estable-Puig, J. F.; Miquel, J.

    1964-01-01

    'l'he relative value of different methods for combined light and electron microscopical studies of glycogen in the nervous tissue was investigated. Picroalcoholic fixatives preserve glycogen in a considerable amount but give an inadequate morphological image of glycogen distribution and are unsuitable for ultrastructural studies. Fixation by perfusion, with Dalton's chromeosmic fluid seems adequate for ultrastructural cytochemistry of glycogen. Furthermore it permits routine paraffin embedding of brain slices adjacent to those used for electron microscopy. Dimedone blocking is a necessary step for a selective staining of glycogen with PAS after osmic fixation. Enzymatic removal of glycogen in osmic fixed nervous tissue can be done In paraffin-embedded tissue. It can also be performed in glycolmethacrylate-embedded tissue without removal of the embedding medium. Paraphenylenediamine stains glycogen following periodic acid oxidation.

  9. 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)

    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

  10. Oral administration of immunoglobulin G-enhanced colostrum alleviates insulin resistance and liver injury and is associated with alterations in natural killer T cells.

    Science.gov (United States)

    Adar, T; Ben Ya'acov, A; Lalazar, G; Lichtenstein, Y; Nahman, D; Mizrahi, M; Wong, V; Muller, B; Rawlin, G; Ilan, Y

    2012-02-01

    Insulin resistance and metabolic syndrome are chronic inflammatory conditions that lead to hepatic injury and non-alcoholic steatohepatitis (NASH). Bovine colostrum has therapeutic effects in a variety of chronic infections. However its effectiveness in NASH was never studied. Natural killer T (NKT) cells have been shown to be associated with some of the pathological and metabolic abnormalities accompanying NASH in leptin-deficient (ob/ob) mice. In the present study, we used hyperimmune bovine colostrum to treat hepatic injury and insulin resistance and we also assessed the effects on NKT cells. We used ob/ob mice that were fed for 6 weeks with either 0·1 mg bovine colostrum prepared from non-immunized cows, 0·1 mg hyperimmune colostrum raised against a bacterial lipopolysaccharide (LPS) extract or 0·001, 0·1 or 1 mg of immunoglobulin (Ig)G purified from hyperimmune colostrum (IgG-LPS). NKT cells were phenotyped by flow cytometry, and hepatic injury and insulin resistance were assessed by measuring fasting glucose levels, glucose tolerance tests and liver enzymes. Fat accumulation was measured in the liver and plasma. Oral administration of hyperimmune colostrums decreased alanine aminotransferase (ALT) serum levels and serum triglycerides compared to controls. Glucose intolerance was also improved by the hyperimmune colostrum preparations. These results were accompanied by a decrease in serum tumour necrosis factor (TNF)-α levels following oral treatment with 0·1 or 1 mg of IgG-LPS. The beneficial effects of hyperimmune colostrums were associated with an increase in the number of splenic NKT cells. These data suggest that oral administration of hyperimmune colostrum preparations can alleviate chronic inflammation, liver injury and insulin resistance associated with NASH. PMID:22236001

  11. Reduction of liver function delays resumption of postpartum ovarian activity and alters the synthesis of acute phase proteins in dairy cows.

    Science.gov (United States)

    Montagner, Paula; Krause, Ana Rita Tavares; Schwegler, Elizabeth; Weschenfelder, Marina Menoncin; Rabassa, Viviane Rohrig; Schneider, Augusto; Pereira, Rubens Alves; Brauner, Cássio Cassal; Del Pino, Francisco Augusto Burkert; Gonçalves, Fernanda Medeiros; Corrêa, Marcio Nunes

    2016-06-01

    The aim of this study was to evaluate the concentration of acute phase proteins, milk production, and resumption of postpartum ovarian activity of clinically healthy dairy cows in a semi-extensive system with different Liver Functionality Index (LFI) values. The animals were divided into two groups: Low LFI (LLFI: -7 to -12; n: 10) and High LFI (HLFI: -7 to -4; n: 10). Animals with LLFI had lower paraoxonase activity and lower albumin concentration in the pre- and postpartum periods (Pacute phase proteins and the first ovulation interval, and it can be used to improve the production and reproductive performance. PMID:27234541

  12. Dietary fat source affects metabolism of fatty acids in pigs as evaluated by altered expression of lipogenic genes in liver and adipose tissues

    DEFF Research Database (Denmark)

    Duran-Montge, P; Theil, Peter Kappel; Lauridsen, Charlotte;

    2009-01-01

    of seven dietary treatments (eight animals per treatment): a semi-synthetic diet containing a very low level of fat (no fat (NF)) and six fat-supplemented diets (ca. 10%) based on barley and soybean meal. The supplemental fat sources were tallow (T), high-oleic sunflower oil (HOSF), sunflower oil (SFO......), linseed oil (LO), blend (FB) (55% T, 35% SFO and 10% LO) and fish oil (FO) blend (40% FO and 60% LO). Pigs were slaughtered at 100 kg BW and autopsies from liver, adipose tissue and muscle semimembranousus were collected for qPCR. The messenger ribonucleic acid (mRNA) abundances of genes related...

  13. Long-term fatty liver-induced insulin resistance in orotic acid-induced nonalcoholic fatty liver rats.

    Science.gov (United States)

    Han, Xiuqing; Liu, Chunhua; Xue, Yong; Wang, Jingfeng; Xue, Changhu; Yanagita, Teruyoshi; Gao, Xiang; Wang, Yuming

    2016-01-01

    We investigated whether fatty liver preceded insulin resistance or vice versa using a long-term orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model without the confounding effects of obesity and hyperlipidemia and explored the role of the liver in insulin resistance. Male Wistar rats were fed with or without OA supplementation for 30, 60, and 90 days. The NAFLD group showed increased liver lipid at 30, 60, and 90 days; glucose intolerance was noted at 60 and 90 days. Furthermore, partial liver proteins and gene expressions related to upstream signaling of insulin were decreased. However, the liver glycogen content was elevated, and gluconeogenesis genes expressions were obviously decreased at 90 days. The occurrence of fatty liver preceded insulin resistance in OA-induced NAFLD without the interference of obesity and hyperlipidemia, and hepatic insulin resistance may not play a conclusive role in insulin resistance in this model. PMID:26775542

  14. 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...... experience exercise intolerance due to insufficient carbohydrate oxidation in skeletal muscle. Six patients aged 17-36-years were studied. We determined VO 2peak (peak oxygen consumption), the response to forearm exercise, and the metabolic and cardiovascular responses to cycle exercise at 70% of VO 2peak...... capacity was significantly reduced, and our results indicate that this was due to a block in muscle glycogenolytic capacity. Our findings suggest that the general classification of GSD III as a glycogenosis characterized by fixed symptoms related to muscle wasting should be modified to include dynamic...

  15. Alterations of pyrimidine and nucleic acid synthesis during adaptive growth of liver induced by nafenopin, a peroxisome proliferator. An in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Seifert, J.; Mostecka, H. (Institute of Pharmacology, Prague (Czechoslovakia))

    1989-08-01

    The de novo synthesis of pyrimidine nucleotides in the rat liver after administration of nafenopin (NFP) was studied with the aid of (14C)orotic acid; the utilization of preformed nucleosides (salvage pathways) was followed using the (14C)cytidine and (14C)thymidine. A single dose (400 mg/kg) as well as repeated doses (100 mg/kg/day) of NFP increased the concentration of the cytidine and uridine components of the acid-soluble extract (ASE) of rat liver. Increase in the concentration of the cytidine components preceded the increase in the uridine components. The uptake of (14C)cytidine by the liver of rats that had been given a single dose of NFP was observed 24 h after the administration of the drug and a decrease followed after this period. The specific activity of RNA and DNA cytosine paralleled the changes of the specific activity of ASE. A single dose of NFP had no marked effect on the uptake of (14C)orotic acid. The specific activity of the uridine components of ASE remained unaltered for 2 days. After this period it decreased because of an increase in the amount of the soluble uridine components. A mild drop of the specific activity of cytidine components of ASE occurred on the second day, the total radioactivity of cytidine components increased 24 h after the administration of NFP. The specific activity of DNA pyrimidines was markedly increased 24 h after administration of the drug. On the fourth day the specific activity of DNA cytosine in the experimental group was the same as in the control group, whereas the activity of DNA thymine was lower. Following repeated administration of NFP (100 mg/kg/day) a decreased uptake of (14C)orotic acid was observed; its utilization for the synthesis of the uridine components of ASE, expressed as total radioactivity of soluble uridine components, was continuously suppressed. No changes in the specific activity of cytidine components were observed.

  16. Alterations of pyrimidine and nucleic acid synthesis during adaptive growth of liver induced by nafenopin, a peroxisome proliferator. An in vivo study.

    Science.gov (United States)

    Seifert, J; Mostecká, H

    1989-08-01

    The de novo synthesis of pyrimidine nucleotides in the rat liver after administration of nafenopin (NFP) was studied with the aid of [14C]orotic acid; the utilization of preformed nucleosides (salvage pathways) was followed using the [14C]cytidine and [14C]thymidine. A single dose (400 mg/kg) as well as repeated doses (100 mg/kg/day) of NFP increased the concentration of the cytidine and uridine components of the acid-soluble extract (ASE) of rat liver. Increase in the concentration of the cytidine components preceded the increase in the uridine components. The uptake of [14C]cytidine by the liver of rats that had been given a single dose of NFP was observed 24 h after the administration of the drug and a decrease followed after this period. The specific activity of RNA and DNA cytosine paralleled the changes of the specific activity of ASE. A single dose of NFP had no marked effect on the uptake of [14C]orotic acid. The specific activity of the uridine components of ASE remained unaltered for 2 days. After this period it decreased because of an increase in the amount of the soluble uridine components. A mild drop of the specific activity of cytidine components of ASE occurred on the second day, the total radioactivity of cytidine components increased 24 h after the administration of NFP. The specific activity of DNA pyrimidines was markedly increased 24 h after administration of the drug. On the fourth day the specific activity of DNA cytosine in the experimental group was the same as in the control group, whereas the activity of DNA thymine was lower. Following repeated administration of NFP (100 mg/kg/day) a decreased uptake of [14C]orotic acid was observed; its utilization for the synthesis of the uridine components of ASE, expressed as total radioactivity of soluble uridine components, was continuously suppressed. No changes in the specific activity of cytidine components were observed. The specific activity of DNA cytosine and thymine was distributed unevenly

  17. In vivo MRS assessment of altered fatty acyl unsaturation in liver tumor formation of a TGFα/c-myc transgenic mouse model*

    OpenAIRE

    Griffitts, J.; Tesiram, Y.; Reid, G. E.; Saunders, D; Floyd, R A; Towner, R. A.

    2009-01-01

    Current detection methods (computed tomography, ultrasound, and MRI) for hepatocarcinogenesis in humans rely on visual confirmation of neoplastic formations. A more effective early detection method is needed. Using in vivo magnetic resonance spectroscopy (MRS), we show that alterations in the integral ratios of the bis-allyl to vinyl hydrogen protons in unsaturated lipid fatty acyl groups correlate with the development of neoplastic formations in vivo in a TGFα/c-myc mouse hepatocellular carc...

  18. Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle

    DEFF Research Database (Denmark)

    Højlund, Kurt; Beck-Nielsen, Henning

    2006-01-01

    expression analysis and proteomics have pointed to abnormalities in mitochondrial oxidative phosphorylation and cellular stress in muscle of type 2 diabetic subjects, and recent work suggests that impaired mitochondrial activity is another early defect in the pathogenesis of type 2 diabetes. This review...... will discuss the latest advances in the understanding of the molecular mechanisms underlying insulin resistance in human skeletal muscle in type 2 diabetes with focus on possible links between impaired glycogen synthase activity and mitochondrial dysfunction....

  19. 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.

  20. 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......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 microU/ml insulin and 11-13 mM glucose...... 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-[14C]methyl-D-glucose was also markedly decreased after 5 and 7 h of perfusion...

  1. Glycogen synthesis after road cycling in the fed state.

    Science.gov (United States)

    Reinert, A; Slivka, D; Cuddy, J; Ruby, B

    2009-07-01

    The purpose of this study was to determine the effects of a recovery beverage immediately after exercise on rates of muscle glycogen resynthesis in response to road cycling when nutritional supplementation was supplied during exercise and a solid meal was served two hours after exercise. Eight trained male cyclists, (25+/-4 years, 69.3+/-5.2 kg, VO2 peak=4.5+/-0.4 L.min(-1)) performed two 62 km outdoor training rides in a double-blind, randomized cross-over experiment. Subjects received a food bar and a commercial sport drink during each ride. A recovery beverage (40 g CHO+20 g PRO) or a placebo (PL) was administered 30 min post-exercise. At 2 h post-exercise, a solid meal was provided for both trials. There was no difference between trials at any time point for glycogen (140+/-9, 56+/-8, and 70+/-8 mmol.kg(-1)wet wt.(-1).hr.(-1) for pre, post, and 4 h post, respectively). The addition of a supplemental recovery beverage ingested soon after exercise did not significantly increase the rate of muscle glycogen resynthesis after 4 h of recovery when nutritional supplementation is provided during exercise and a meal is consumed 2 h after exercise.

  2. REPEATED ACUTE STRESS INDUCED ALTERATIONS IN CARBOHYDRATE METABOLISM IN RAT

    Directory of Open Access Journals (Sweden)

    Nirupama R.

    2010-09-01

    Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

  3. Acute phenanthrene toxicity to juvenile diploid and triploid African catfish (Clarias gariepinus): Molecular, biochemical, and histopathological alterations.

    Science.gov (United States)

    Karami, Ali; Romano, Nicholas; Hamzah, Hazilawati; Simpson, Stuart L; Yap, Chee Kong

    2016-05-01

    Information on the biological responses of polyploid animals towards environmental contaminants is scarce. This study aimed to compare reproductive axis-related gene expressions in the brain, plasma biochemical responses, and the liver and gill histopathological alterations in diploid and triploid full-sibling juvenile African catfish (Clarias gariepinus). Fish were exposed for 96 h to one of the two waterborne phenanthrene (Phe) concentrations [mean measured (SD): 6.2 (2.4) and 76 (4.2) μg/L]. In triploids, exposure to 76 μg/L Phe increased mRNA level of fushi tarazu-factor 1 (ftz-f1). Expression of tryptophan hydroxylase2 (tph2) was also elevated in both ploidies following the exposure to 76 μg/L Phe compared to the solvent control. In triploids, 76 μg/L Phe increased plasma alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels compared to the other Phe-exposed group. It also elevated lactate and glucose contents relative to the other groups. In diploids, however, biochemical biomarkers did not change. Phenanthrene exposures elevated glycogen contents and the prevalence of histopathological lesions in the liver and gills of both ploidies. This study showed substantial differences between diploids and triploids on biochemical and molecular biomarker responses, but similar histopathological alterations following acute Phe exposures. PMID:26845363

  4. Fat metabolism is regulated by altered gene expression of lipogenic enzymes and regulatory factors in liver and adipose tissue but not in semimembranosus muscle of pigs during the fattening period.

    Science.gov (United States)

    Duran-Montgé, P; Theil, P K; Lauridsen, C; Esteve-Garcia, E

    2009-11-01

    It has been shown previously that lipid metabolism is regulated by fatty acids (FA) and that thyroid hormones are important regulators of energy metabolism. The effects of weight, dietary fat level and dietary FA profile on thyroid hormone levels and expression of lipogenic genes and tissue FA composition were studied. Sixty-one crossbred gilts weighing 62 ± 5.2 kg BW average were either slaughtered at the beginning of the trial (n = 5) or fed one of seven diets (n = 8 pigs per diet): a semi-synthetic diet formulated to contain a very low level of fat (NF) and six diets based on barley-soybean meal supplemented with approximately 10% fat of different origin and slaughtered at 100 kg BW. The supplemental fats were tallow, high-oleic sunflower oil, sunflower oil (SFO), linseed oil, fat blend (55% tallow, 35% sunflower oil, 10% linseed oil) and fish oil blend (40% fish oil, 60% linseed oil). In general, the dietary FA profiles altered the FA composition of liver, semimembranosus muscle and adipose tissues. Pigs fed the NF diet had the highest free and total triiodothyronine (T3) values followed by pigs fed SFO. Total T3 levels were higher in pigs at 60 kg than in pigs at 100 kg. Correlations between thyroid hormones and genes encoding enzymes of fat synthesis in adipose tissue (acetyl CoA carboxylase (ACACA), fatty acid synthase and stearoyl CoA desaturase (SCD)) and the large differences in expression of lipogenic genes at different weights (60 and 100 kg BW), suggest a role for thyroid hormones and for T3, in particular, in regulating whole animal fat metabolism, with effects brought about by altered expression of lipogenic genes. Liver sterol receptor element binding protein-1 (SREBP1) mRNA content was affected by dietary treatment (P influence on mRNA abundance of genes related with lipid metabolism than diet and tissue FA composition. In the pig, FA synthesis appear to be of greater magnitude in adipose tissue than in the liver as suggested by the higher

  5. Liver Panel

    Science.gov (United States)

    ... liver damage. Alpha-feto protein (AFP) – associated with regeneration or proliferation of liver cell Autoimmune antibodies (e. ... the body – such as in the skeletal muscles, pancreas, or heart. It may also indicate early liver ...

  6. 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 ...

  7. Liver Diseases

    Science.gov (United States)

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  8. BOVINE CATTLE FED WITH ANDROPOGON AND BRACHIARIA GRASS: HISTOLOGICAL ALTERATIONS OF LIVER AND LYMPH NODES BOVINOS ALIMENTADOS COM CAPIM BRACHIARIA E ANDROPOGON: ALTERAÇÕES HISTOLÓGICAS DO FÍGADO E LINFONODOS

    Directory of Open Access Journals (Sweden)

    Eugênio Gonçalves de Araújo

    2009-04-01

    Full Text Available Numerous papers report hepatic alterations in ruminants fed with Brachiaria spp. The aim of this study was to verify whether the ingestion of Andropogon gayanus or Brachiaria (B. brizantha and B. decumbens produces microscopic alterations in the liver of cattle. By histological examination was characterized the hepatic injury, and determined the amount and localization of foamy macrophages in the liver and mesenteric and scapular lymphonodes. Those changes were correlated with live weight gains of the animals. Forty bulls divided into two groups of twenty were grazing, from weaning to slaughter, in Brachiaria spp or A. gayanus pastures. In the slaughterhouse, fragments of liver and mesenteric and scapular lymphonodes were collected. Results showed, in both groups, macro and microvacuolar degeneration of hepatocytes, mainly in the periacinar region. The animals fed on Brachiaria spp pastures revealed larger quantity of foamy macrophages in the hepatic parenchyma and mesenteric lymphonodes. There was a negative correlation between the number of foamy macrophages in the liver and in mesenteric lymphonodes with the live weight gain, regardless of the type of ingested grass. In the lymph nodes, the highest macrophage concentrations were in the cortical zone, followed by the paracortical zone. The mesenteric lymphonodes showed a higher amount of foam cells than the liver.

    KEY WORDS: Colangiohepatitis, foamy cells, saponins, sporidesmin, tropical grasses.

    Diversos trabalhos relatam a presença de alterações hepáticas em ruminantes alimentados com Brachiaria spp, em casos espontâneos e/ou induzidos de fotossensibilização hepatógena. O objetivo deste trabalho foi verificar se o tipo de capim ingerido provoca alteração microscópica no fígado de bovinos. Foi caracterizada a lesão hepática, quantificados e localizados os macrófagos espumosos no fígado e linfonodos e as alterações correlacionadas com o peso dos

  9. Effects of naphthenic acid exposure on development and liver metabolic processes in anuran tadpoles

    International Nuclear Information System (INIS)

    Naphthenic acids (NA) are used in a variety of commercial and industrial applications, and are primary toxic components of oil sands wastewater. We investigated developmental and metabolic responses of tadpoles exposed to sub-lethal concentrations of a commercial NA blend throughout development. We exposed Lithobates pipiens tadpoles to 1 and 2 mg/L NA for 75 days and monitored growth and development, condition factor, gonad and liver sizes, and levels of liver glucose, glycogen, lipids and cholesterol following exposure. NA decreased growth and development, significantly reduced glycogen stores and increased triglycerides, indicating disruption to processes associated with energy metabolism and hepatic glycolysis. Effects on liver function may explain reduced growth and delayed development observed in this and previous studies. Our data highlight the need for greater understanding of the mechanisms leading to hepatotoxicity in NA-exposed organisms, and indicate that strict guidelines may be needed for the release of NA into aquatic environments. -- Highlights: ► We exposed Lithobates pipiens tadpoles to 1–2 mg/L NA in the laboratory. ► We monitored survival, growth and development for 75 days. ► We measured liver glycogen, glucose, triglycerides, and cholesterol levels. ► NA significantly reduced growth and development compared to controls. ► NA significantly reduced glycogen levels and increased triglycerides. -- Leopard frog (Lithobates pipiens) tadpoles chronically exposed to sub-lethal NA concentrations (1–2 mg/L) suffered decreased growth and development and disruption to liver metabolic processes

  10. Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis.

    Science.gov (United States)

    Rato, L; Alves, M G; Dias, T R; Cavaco, J E; Oliveira, Pedro F

    2015-01-01

    Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by (1)H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters. PMID:26064993

  11. Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis

    Directory of Open Access Journals (Sweden)

    L. Rato

    2015-01-01

    Full Text Available Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by 1H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters.

  12. Histopathological alterations in the liver and intestine of Nile tilapia Oreochromis niloticus exposed to long-term sublethal concentrations of cadmium chloride

    Science.gov (United States)

    Younis, Elsayed; Abdel-Warith, Abdel-Wahab; Al-Asgah, Nasser; Ebaid, Hossam

    2015-07-01

    Fingerlings of Nile tilapia Oreochromis niloticus were exposed to 1.68, 3.36, and 5.04 mg/L cadmium (as CdCl2), which represent 10%, 20%, and 30% of their previously determined 96-h LC50. After exposure for 20 days, sections of the liver and intestine of treated fish were examined histologically. Histopathological changes varied from slight to severe structural modification, depending on the exposure concentration. The hepatic tissues of fish exposed to 10% LC50 showed markedly increased vacuolation of the hepatocytes and coarse granulation of their cytoplasm. Abundant erythrocytic infiltration among the hepatocytes was observed in fish exposed to 20% LC50. In the intestinal tissues of fish exposed to all doses, goblet cells proliferated and were greatly increased in size, the longitudinal muscularis mucosa was disturbed and, in the crypts of the sub-mucosal layer, apoptosis increased, indicated by large numbers of degenerated nuclei. Large numbers of inflammatory cells and dilated blood vessels were observed in the intestine of the group treated with 30% LC50.

  13. Free glycogen in vaginal fluids is associated with Lactobacillus colonization and low vaginal pH.

    Directory of Open Access Journals (Sweden)

    Paria Mirmonsef

    Full Text Available Lactobacillus dominates the lower genital tract microbiota of many women, producing a low vaginal pH, and is important for healthy pregnancy outcomes and protection against several sexually transmitted pathogens. Yet, factors that promote Lactobacillus remain poorly understood. We hypothesized that the amount of free glycogen in the lumen of the lower genital tract is an important determinant of Lactobacillus colonization and a low vaginal pH.Free glycogen in lavage samples was quantified. Pyrosequencing of the 16S rRNA gene was used to identify microbiota from 21 African American women collected over 8-11 years.Free glycogen levels varied greatly between women and even in the same woman. Samples with the highest free glycogen had a corresponding median genital pH that was significantly lower (pH 4.4 than those with low glycogen (pH 5.8; p<0.001. The fraction of the microbiota consisting of Lactobacillus was highest in samples with high glycogen versus those with low glycogen (median = 0.97 vs. 0.05, p<0.001. In multivariable analysis, having 1 vs. 0 male sexual partner in the past 6 months was negatively associated, while BMI ≥30 was positively associated with glycogen. High concentrations of glycogen corresponded to higher levels of L. crispatus and L. jensenii, but not L. iners.These findings show that free glycogen in genital fluid is associated with a genital microbiota dominated by Lactobacillus, suggesting glycogen is important for maintaining genital health. Treatments aimed at increasing genital free glycogen might impact Lactobacillus colonization.

  14. Cecropia peltata accumulates starch or soluble glycogen by differentially regulating starch biosynthetic genes

    OpenAIRE

    Bischof, Sylvain; Umhang, Martin; Eicke, Simona; Streb, Sebastian; Qi, Weihong; Zeeman, Samuel C.

    2013-01-01

    The branched glucans glycogen and starch are the most widespread storage carbohydrates in living organisms. The production of semicrystalline starch granules in plants is more complex than that of small, soluble glycogen particles in microbes and animals. However, the factors determining whether glycogen or starch is formed are not fully understood. The tropical tree Cecropia peltata is a rare example of an organism able to make either polymer type. Electron micrographs and quantitative measu...

  15. Creatine supplementation spares muscle glycogen during high intensity intermittent exercise in rats

    OpenAIRE

    Costa André; Marquezi Marcelo; Gualano Bruno; Roschel Hamilton; Lancha Antonio H

    2010-01-01

    Abstract Background The effects of creatine (CR) supplementation on glycogen content are still debatable. Thus, due to the current lack of clarity, we investigated the effects of CR supplementation on muscle glycogen content after high intensity intermittent exercise in rats. Methods First, the animals were submitted to a high intensity intermittent maximal swimming exercise protocol to ensure that CR-supplementation was able to delay fatigue (experiment 1). Then, the CR-mediated glycogen spa...

  16. Hibiscus rosa sinensis Linn. Petals Modulates Glycogen Metabolism and Glucose Homeostasis Signalling Pathway in Streptozotocin-Induced Experimental Diabetes.

    Science.gov (United States)

    Pillai, Sneha S; Mini, S

    2016-03-01

    The prevalence of diabetes mellitus is becoming more and more serious and reaches epidemic proportions worldwide. Scientific research is constantly looking for new agents that could be used as dietary functional ingredients in the fight against diabetes. The objective of the present study was to evaluate the effect of ethyl acetate fraction of Hibiscus rosa sinensis Linn. petals on experimental diabetes at a dose of 25 mg/kg body weight and it was compared with standard anti-diabetic drug metformin. The elevated levels of serum glucose (398.56 ± 35.78) and glycated haemoglobin (12.89 ± 1.89) in diabetic rats were significantly decreased (156.89 ± 14.45 and 6.12 ± 0.49, respectively) by Hibiscus rosa sinensis petals (EHRS) administration. Hepatotoxicity marker enzyme levels in serum were normalized. The fraction supplementation restored the glycogen content by regulating the activities of glycogen metabolizing enzymes. It significantly modulated the expressions of marker genes involved in glucose homeostasis signalling pathway. Histopathological analysis of liver and pancreas supported our findings. The overall effect was comparable with metformin. Hence, our study reveals the role of hibiscus petals for alleviation of diabetes complications, thus it can be propagated as a nutraceutical agent. PMID:26590603

  17. The transcriptomic signature of fasting murine liver

    Directory of Open Access Journals (Sweden)

    Gilhuijs-Pederson Lisa A

    2008-11-01

    Full Text Available Abstract Background The contribution of individual organs to the whole-body adaptive response to fasting has not been established. Hence, gene-expression profiling, pathway, network and gene-set enrichment analysis and immunohistochemistry were carried out on mouse liver after 0, 12, 24 and 72 hours of fasting. Results Liver wet weight had declined ~44, ~5, ~11 and ~10% per day after 12, 24, 48 and 72 hours of fasting, respectively. Liver structure and metabolic zonation were preserved. Supervised hierarchical clustering showed separation between the fed, 12–24 h-fasted and 72 h-fasted conditions. Expression profiling and pathway analysis revealed that genes involved in amino-acid, lipid, carbohydrate and energy metabolism responded most significantly to fasting, that the response peaked at 24 hours, and had largely abated by 72 hours. The strong induction of the urea cycle, in combination with increased expression of enzymes of the tricarboxylic-acid cycle and oxidative phosphorylation, indicated a strong stimulation of amino-acid oxidation peaking at 24 hours. At this time point, fatty-acid oxidation and ketone-body formation were also induced. The induction of genes involved in the unfolded-protein response underscored the cell stress due to enhanced energy metabolism. The continuous high expression of enzymes of the urea cycle, malate-aspartate shuttle, and the gluconeogenic enzyme Pepck and the re-appearance of glycogen in the pericentral hepatocytes indicate that amino-acid oxidation yields to glucose and glycogen synthesis during prolonged fasting. Conclusion The changes in liver gene expression during fasting indicate that, in the mouse, energy production predominates during early fasting and that glucose production and glycogen synthesis become predominant during prolonged fasting.

  18. Pediatric liver transplantation in 31 consecutive children

    Institute of Scientific and Technical Information of China (English)

    SHEN Zhong-yang; WANG Zi-fa; ZHU Zhi-jun; ZANG Yun-jin; ZHENG Hong; DENG Yong-lin; PAN Cheng; CHEN Xin-guo

    2008-01-01

    Background Although liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements. Methods Thirty-one children (≤18 years old) underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old (ranged from 5 months to 18 years) with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson's disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard (without venovenous bypass), 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug (FK506, steroid, and mycophenolate mofetil) immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months. Results Five of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively.Conclusions The most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients' age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher

  19. Glycogen content relative to expression of glycogen phosphorylase (GPH) and hexokinase (HK) during the reproductive cycle in the Fujian Oyster,Crassostrea angulata

    Institute of Scientific and Technical Information of China (English)

    ZENG Zhen; NI Jianbin; KE Caihuan

    2015-01-01

    Glycogen, a polymer of glucose, is an important means of storing energy. It is degraded by glycogen phosphorylase (GPH) and hexokinase (HK), glycogen phosphorylase, and hexokinase cDNAs (Ca-GPH andCa-HK, respectively), which encode the primary enzymes involved in glycogen use, cloned and characterized and used to investigate the regulation of glycogen metabolism at the mRNA level inCrassostrea angulata. Their expression profiles were examined in different tissues and during different reproductive stages. Full-length cDNA ofGPH was 3 078 bp in length with a 2 607 bp open reading frame (ORF) predicted to encode a protein of 868 amino acids (aa). The full-lengthHK cDNA was 3 088 bp long, with an ORF of 1 433 bp, predicted to encode a protein of 505 aa. Expression levels of both genes were found to be significantly higher in the gonads and adductor muscle than in the mantle, gill, and visceral mass. They were especially high in the adductor muscle, which suggested that these oysters can use glycogen to produce a readily available supply of glucose to support adductor muscle activity. The regulation of both genes was also found to be correlated with glycogen content via qRT-PCR andin situ hybridization and was dependent upon the stage of the reproductive cycle (initiation, maturation, ripeness). In this way, it appears that the expression ofCa-GPH andCa-HK is driven by the reproductive cycle of the oyster, reflecting the central role played by glycogen in energy use and gametogenic development inC. angulata. It is here suggested thatCa-GPH andCa-HK can be used as useful molecular markers for identifying the stages of glycogen metabolism and reproduction inC. angulata.

  20. Carbohydrate metabolism alterations in Biomphalaria glabrata infected with Schistosoma mansoni and exposed to Euphorbia splendens var. hislopii latex

    Directory of Open Access Journals (Sweden)

    Clélia Christina Mello-Silva

    2010-07-01

    Full Text Available This paper evaluates the alterations in the glycogen content of tissues (digestive gland and cephalopedal mass and glucose in the haemolymph of Biomphalaria glabrata BH strain infected with Schistosoma mansoni BH strain and exposed to the latex of Euphorbia splendens var. hislopii. A reduction in the glycogen deposits was observed in infected snails exposed and not exposed to latex. However, the exposure to latex caused a greater depletion of the glycogen levels in both sites analysed, especially from the third week onward. The utilisation of latex as a molluscicide to control the population of infected B. glabrata selectively is proposed.

  1. Sodium valproate increases the brain isoform of glycogen phosphorylase: looking for a compensation mechanism in McArdle disease using a mouse primary skeletal-muscle culture in vitro

    Directory of Open Access Journals (Sweden)

    Noemí de Luna

    2015-05-01

    Full Text Available McArdle disease, also termed ‘glycogen storage disease type V’, is a disorder of skeletal muscle carbohydrate metabolism caused by inherited deficiency of the muscle-specific isoform of glycogen phosphorylase (GP-MM. It is an autosomic recessive disorder that is caused by mutations in the PYGM gene and typically presents with exercise intolerance, i.e. episodes of early exertional fatigue frequently accompanied by rhabdomyolysis and myoglobinuria. Muscle biopsies from affected individuals contain subsarcolemmal deposits of glycogen. Besides GP-MM, two other GP isoforms have been described: the liver (GP-LL and brain (GP-BB isoforms, which are encoded by the PYGL and PYGB genes, respectively; GP-BB is the main GP isoform found in human and rat foetal tissues, including the muscle, although its postnatal expression is dramatically reduced in the vast majority of differentiated tissues with the exception of brain and heart, where it remains as the major isoform. We developed a cell culture model from knock-in McArdle mice that mimics the glycogen accumulation and GP-MM deficiency observed in skeletal muscle from individuals with McArdle disease. We treated mouse primary skeletal muscle cultures in vitro with sodium valproate (VPA, a histone deacetylase inhibitor. After VPA treatment, myotubes expressed GP-BB and a dose-dependent decrease in glycogen accumulation was also observed. Thus, this in vitro model could be useful for high-throughput screening of new drugs to treat this disease. The immortalization of these primary skeletal muscle cultures could provide a never-ending source of cells for this experimental model. Furthermore, VPA could be considered as a gene-expression modulator, allowing compensatory expression of GP-BB and decreased glycogen accumulation in skeletal muscle of individuals with McArdle disease.

  2. Rumen papillae keratinization, cell glycogen and chemical composition of the meat from young bulls fed different levels of concentrate and babassu mesocarp bran

    OpenAIRE

    Simone Santos Barros; Rossini Sôffa da Cruz; Lázaro Moreira de Melo Junior; Domenica Palomaris Mariano de Souza; Sandro Estevan Moron; Emerson Alexandrino; Regis Luis Missio; José Neuman Miranda Neiva; João Restle; Viviane Mayumi Maruo; Luciano Fernandes Sousa; Adriano Tony Ramos

    2015-01-01

    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. Fra...

  3. Further studies on the late preventive effects of the anticalmodulin trifluoperazine on carbon tetrachloride-induced liver necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Castro, J.; Bernacchi, A.; Fernandez, G.; Villarruel, M.C.; Ferreyra, E.; Castro, C.; Fenos, O.

    1986-03-01

    The authors previously reported that trifluorperazine (TFP) administration 6 or 10 hr after CCl/sub 4/ is able to partially prevent liver necrosis by the hepatotoxin at 24 hr. Preventive effect is not due to interference by TFP on CCl/sub 4/ metabolic activation to CCl/sub 3/ or its covalent binding to cellular components or of lipid peroxidation. Now the authors report that TFP administration 10 hr after CCl/sub 4/ does not prevent calcium accumulation but increases glycogen content. Increases in glycogen are more marked in livers of animals receiving only TFP. Administration slightly stimulates /sup 14/C-leucine incorporation in liver proteins but it does not modify decay of radioactivity in (/sup 14/C-guanidino) arginine prelabelled liver protein. TFP does not modify decay of radioactivity in /sup 32/P prelabelled phospholipid. Electron microscopy studies of livers from CCl/sub 4/ poisoned rats receiving TFP 10 hr after the hepatoto toxin and sacrificed at 24 hr revealed the presence of glycogen granules in otherwise glycogen-depleted preparations. These preparations showed only slight dilatation of the endoplasmic reticulum or the perinuclear membrane and intact mitochondria. Results might suggest that TFP interaction with calmodulin might interfere with a process of propagation of CCl/sub 4/-induced liver damage sparked by calcium accumulation and requiring the hormone for operation.

  4. A glycogene mutation map for discovery of diseases of glycosylation

    DEFF Research Database (Denmark)

    Hansen, Lars; Lind-Thomsen, Allan; Joshi, Hiren J;

    2015-01-01

    that effects glycosylation globally. Many glycosyltransferases are members of homologous isoenzyme families and deficiencies in individual isoenzymes may not affect glycosylation globally. In line with this there appears to be an underrepresentation of disease-causing glycogenes among these larger isoenzyme...... homologous families. However, Genome-Wide-Association Studies (GWAS) have identified such isoenzyme genes as candidates for different diseases, but validation is not straightforward without biomarkers. Large-scale whole exome sequencing (WES) provides access to mutations in e.g. glycosyltransferase genes...

  5. Enzymatic description of the anhydrofructose pathway of glycogen degradation. I

    DEFF Research Database (Denmark)

    Yu, Shukun; Refdahl, Charlotte; Lundt, Inge

    2004-01-01

    algae in our laboratory earlier. In the present study, two 1,5AnFru metabolizing enzymes were discovered in the fungus Anthracobia melaloma for the formation of ascopyrone P (APP), a fungal secondary metabolite exhibiting antibacterial and antioxidant activity. These are 1,5AnFru dehydratase (AFDH...... 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...

  6. POST-EXERCISE MUSCLE GLYCOGEN REPLETION IN THE EXTREME: EFFECT OF FOOD ABSENCE AND ACTIVE RECOVERY

    Directory of Open Access Journals (Sweden)

    Paul A. Fournier

    2004-09-01

    Full Text Available Glycogen plays a major role in supporting the energy demands of skeletal muscles during high intensity exercise. Despite its importance, the amount of glycogen stored in skeletal muscles is so small that a large fraction of it can be depleted in response to a single bout of high intensity exercise. For this reason, it is generally recommended to ingest food after exercise to replenish rapidly muscle glycogen stores, otherwise one's ability to engage in high intensity activity might be compromised. But what if food is not available? It is now well established that, even in the absence of food intake, skeletal muscles have the capacity to replenish some of their glycogen at the expense of endogenous carbon sources such as lactate. This is facilitated, in part, by the transient dephosphorylation-mediated activation of glycogen synthase and inhibition of glycogen phosphorylase. There is also evidence that muscle glycogen synthesis occurs even under conditions conducive to an increased oxidation of lactate post-exercise, such as during active recovery from high intensity exercise. Indeed, although during active recovery glycogen resynthesis is impaired in skeletal muscle as a whole because of increased lactate oxidation, muscle glycogen stores are replenished in Type IIa and IIb fibers while being broken down in Type I fibers of active muscles. This unique ability of Type II fibers to replenish their glycogen stores during exercise should not come as a surprise given the advantages in maintaining adequate muscle glycogen stores in those fibers that play a major role in fight or flight responses

  7. Liver regeneration.

    Science.gov (United States)

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-04-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

  8. Semecarpus anacardium (Bhallataka Alters the Glucose Metabolism and Energy Production in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Jaya Aseervatham

    2011-01-01

    Full Text Available Glucose produced by gluconeogenesis and glycogenolysis plays an important role in aggravating hyperglycemia in diabetes, and altered mitochondrial function is associated with impaired energy production. The present study focuses on the effect of Semecarpus anacardium on carbohydrate metabolism and energy production in diabetic rats. Diabetes was induced by the administration of Streptozotocin at a dose of 50 mg/kg.b.wt. Three days after the induction, Semecarpus anacardium at a dose of 300 mg/kg.b.wt was administered for 21 days. After the experimental duration, the activities of the enzymes involved in Glycolysis, TCA cycle, gluconeogenesis, and glycogen were assayed in the liver and kidney of the experimental animals. In addition, to the complexes the protein expression of AKT and PI3K were assayed. The levels of the enzymes involved in Glycolysis and TCA cycle increased, while that of gluconeogensis decreased. The activities of the mitochondrial complexes were also favorably modulated. The expressions of PI3K and AKT also increased in the skeletal muscle. These effects may be attributed to the hypoglycemic and the antioxidative activity of Semecarpus anacardium. The results of the study revealed that Semecarpus anacardium was able to restore the altered activities of the enzymes involved in carbohydrate metabolism and energy production.

  9. Early alterations of systemic and splanchnic hemodynamics after orthotopic liver transplantation in cirrhotic rats%肝硬化鼠肝移植后早期全身和内脏血流动力学的变化

    Institute of Scientific and Technical Information of China (English)

    曹晖; 吴志勇; 张效杰; 张海婴; 陈治平; 邝耀麟

    2001-01-01

    Objective The purpose of this study was to investigate early alterations of systemic and splanchnic hemodynamics after orthotopic liver transplantation (OLT) in normal and cirrhotic rats.Methods Male SD rats were divided into 4 groups: normal controls (NL,n=10),intrahepatic portal hypertension (IHPH,n=10) induced by CCl4,normal rats with OLT (NL-OLT,n=9) and IHPH rats with OLT (IHPH-OLT,n=16).Radioactive microsphere method was used for hemodynamic study.Results Increased cardiac output and splanchnic blood flow,decreased mean arterial blood pressure,total peripheral vascular resistance and splanchnic vascular resistance were found in IHPH,IHPH-OLT at day 3,and IHPH-OLT at day 7 in cirrhotic rats.The magnitude of hyperhemodynamic alterations was in the order of IHPH>IHPH-OLT (day 3) >IHPH-OLT (day 7) rats.Moreover,the derangement of splanchnic hyperhemodynamics was more significant than that of systemic hyperhemodynamics.Conclusions The results demonstrated that systemic and splanchnic hyperkinetic abnormalities seen in early liver transplantation may come from the pretransplant pathophysiologic status in cirrhotic rats.%目的观察正常鼠肝移植以及肝硬化鼠肝移植术后早期全身和内脏血流动力学的变化。方法实验动物随机分为正常鼠(NL,10只)、肝硬化鼠(IHPH,10只)、正常鼠肝移植(NL-OLT,9只)、肝硬化鼠肝移植(IHPH-OLT,16只)组。分别采用放射性微球法行血流动力学研究。结果 NL-OLT鼠绝大多数血流动力学参数与NL鼠比较差异无显著意义。IHPH及IHPH-OLT 3d,7d 组心输出量和内脏血流量增加,平均动脉压、周围血管总阻力和内脏血管阻力降低。内脏血流动力学紊乱较全身明显。结论肝硬化鼠肝移植后的血流动力学紊乱可能与移植前已存在的病理生理因素有关。

  10. Proteoglycans in liver cancer

    Science.gov (United States)

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-01

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects. PMID:26755884

  11. Isoform-selective regulation of glycogen phosphorylase by energy deprivation and phosphorylation in astrocytes

    DEFF Research Database (Denmark)

    Müller, Margit S; Pedersen, Sofie E; Walls, Anne B;

    2015-01-01

    by determination of glycogen content showing an increase in glycogen levels following knockdown of either GPMM or GPBB. NE triggered glycogenolysis within 15 min in control cells and after GPBB knockdown. However, astrocytes in which expression of GPMM had been silenced showed a delay in response to NE...

  12. Dual regulation of muscle glycogen synthase during exercise by activation and compartmentalization

    DEFF Research Database (Denmark)

    Prats, Clara; Helge, Jørn W; Nordby, Pernille;

    2009-01-01

    lateralis muscle of the previously reported mechanism of glycogen metabolism regulation in rabbit tibialis anterior muscle. After overnight low muscle glycogen level and/or in response to exhausting exercise-induced glycogenolysis, GS is associated with spherical structures at the I-band of sarcomeres....

  13. Body distribution and seasonal changes in the glycogen content of the common sea mussel Mytilus edulis

    NARCIS (Netherlands)

    Zwaan, Albertus de; Zandee, D.I.

    1972-01-01

    1. Glycogen content was measured in the sea musselMytilus edulis, and found to be present in amounts ranging from 10 to 35 per cent dry weight of the soft parts. 2. The annual glycogen cycle was followed for five different fractions: the digestive gland, muscles (including those of the foot), gills

  14. Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle

    DEFF Research Database (Denmark)

    Hunter, Roger W; Treebak, Jonas Thue; Wojtaszewski, Jørgen;

    2011-01-01

    OBJECTIVE During energy stress, AMP-activated protein kinase (AMPK) promotes glucose transport and glycolysis for ATP production, while it is thought to inhibit anabolic glycogen synthesis by suppressing the activity of glycogen synthase (GS) to maintain the energy balance in muscle. Paradoxicall...... and subsequent rise in cellular [G6P]....

  15. Muscle Glycogen Content Modifies SR Ca2 + Release Rate in Elite Endurance Athletes

    DEFF Research Database (Denmark)

    Gejl, Kasper Degn; Hvid, Lars G; Frandsen, Ulrik;

    2014-01-01

    The aim of the present study was to investigate the influence of muscle glycogen content on sarcoplasmic reticulum (SR) function and peak power output (Wpeak) in elite endurance athletes.......The aim of the present study was to investigate the influence of muscle glycogen content on sarcoplasmic reticulum (SR) function and peak power output (Wpeak) in elite endurance athletes....

  16. Increases in glycogenin and glycogenin mRNA accompany glycogen resynthesis in human skeletal muscle

    DEFF Research Database (Denmark)

    Shearer, Jane; Wilson, Rhonda J.; Battram, Danielle S.;

    2005-01-01

    300 min postexercise. Together, these results show that, during recovery from prolonged exhaustive exercise, glycogenin mRNA and protein content and activity increase in muscle. This may facilitate rapid glycogen resynthesis by providing the glycogenin backbone of proglycogen, the major component of......Glycogenin is the self-glycosylating protein primer that initiates glycogen granule formation. To examine the role of this protein during glycogen resynthesis, eight male subjects exercised to exhaustion on a cycle ergometer at 75% VO2 max followed by five 30-s sprints at maximal capacity to...... further deplete glycogen stores. During recovery, carbohydrate (75 g/h) was supplied to promote rapid glycogen repletion, and muscle biopsies were obtained from the vastus lateralis at 0, 30, 120, and 300 min postexercise. At time 0, no free (deglycosylated) glycogenin was detected in muscle, indicating...

  17. Insulin resistance is associated with reduced fasting and insulin-stimulated glycogen synthase phosphatase activity in human skeletal muscle.

    OpenAIRE

    Kida, Y; Esposito-Del Puente, A; Bogardus, C; Mott, D M

    1990-01-01

    Insulin-stimulated glycogen synthase activity in human skeletal muscle correlates with insulin-mediated glucose disposal rate (M) and is reduced in insulin-resistant subjects. We have previously reported reduced insulin-stimulated glycogen synthase activity associated with reduced fasting glycogen synthase phosphatase activity in skeletal muscle of insulin-resistant Pima Indians. In this study we investigated the time course for insulin stimulation of glycogen synthase and synthase phosphatas...

  18. Uterine glycogen metabolism in mink during estrus, embryonic diapause and pregnancy.

    Science.gov (United States)

    Dean, Matthew; Hunt, Jason; McDougall, Lisa; Rose, Jack

    2014-01-01

    We have determined uterine glycogen content, metabolizing enzyme expression and activity in the mink, a species that exhibits obligatory embryonic diapause, resulting in delayed implantation. Gross uterine glycogen concentrations were highest in estrus, decreased 50% by diapause and 90% in pregnancy (P ≤ 0.05). Endometrial glycogen deposits, which localized primarily to glandular and luminal epithelia, decreased 99% between estrus and diapause (P ≤ 0.05) and were nearly undetectable in pregnancy. Glycogen synthase and phosphorylase proteins were most abundant in the glandular epithelia. Glycogen phosphorylase activity (total) in uterine homogenates was higher during estrus and diapause, than pregnancy. While glycogen phosphorylase protein was detected during estrus and diapause, glycogen synthase was almost undetectable after estrus, which probably contributed to a higher glycogenolysis/glycogenesis ratio during diapause. Uterine glucose-6-phosphatase 3 gene expression was greater during diapause, when compared to estrus (P ≤ 0.05) and supports the hypothesis that glucose-6-phosphate resulting from phosphorylase activity was dephosphorylated in preparation for export into the uterine lumen. The relatively high amount of hexokinase-1 protein detected in the luminal epithelia during estrus and diapause may have contributed to glucose trapping after endometrial glycogen reserves were depleted. Collectively, our findings suggest to us that endometrial glycogen reserves may be an important source of energy, supporting uterine and conceptus metabolism up to the diapausing blastocyst stage. As a result, the size of uterine glycogen reserves accumulated prior to mating may in part, determine the number of embryos that survive to the blastocyst stage, and ultimately litter size. PMID:25225159

  19. The nutritional status of Methanosarcina acetivorans regulates glycogen metabolism and gluconeogenesis and glycolysis fluxes.

    Science.gov (United States)

    Santiago-Martínez, Michel Geovanni; Encalada, Rusely; Lira-Silva, Elizabeth; Pineda, Erika; Gallardo-Pérez, Juan Carlos; Reyes-García, Marco Antonio; Saavedra, Emma; Moreno-Sánchez, Rafael; Marín-Hernández, Alvaro; Jasso-Chávez, Ricardo

    2016-05-01

    Gluconeogenesis is an essential pathway in methanogens because they are unable to use exogenous hexoses as carbon source for cell growth. With the aim of understanding the regulatory mechanisms of central carbon metabolism in Methanosarcina acetivorans, the present study investigated gene expression, the activities and metabolic regulation of key enzymes, metabolite contents and fluxes of gluconeogenesis, as well as glycolysis and glycogen synthesis/degradation pathways. Cells were grown with methanol as a carbon source. Key enzymes were kinetically characterized at physiological pH/temperature. Active consumption of methanol during exponential cell growth correlated with significant methanogenesis, gluconeogenic flux and steady glycogen synthesis. After methanol exhaustion, cells reached the stationary growth phase, which correlated with the rise in glycogen consumption and glycolytic flux, decreased methanogenesis, negligible acetate production and an absence of gluconeogenesis. Elevated activities of carbon monoxide dehydrogenase/acetyl-CoA synthetase complex and pyruvate: ferredoxin oxidoreductase suggested the generation of acetyl-CoA and pyruvate for glycogen synthesis. In the early stationary growth phase, the transcript contents and activities of pyruvate phosphate dikinase, fructose 1,6-bisphosphatase and glycogen synthase decreased, whereas those of glycogen phosphorylase, ADP-phosphofructokinase and pyruvate kinase increased. Therefore, glycogen and gluconeogenic metabolites were synthesized when an external carbon source was provided. Once such a carbon source became depleted, glycolysis and methanogenesis fed by glycogen degradation provided the ATP supply. Weak inhibition of key enzymes by metabolites suggested that the pathways evaluated were mainly transcriptionally regulated. Because glycogen metabolism and glycolysis/gluconeogenesis are not present in all methanogens, the overall data suggest that glycogen storage might represent an environmental

  20. Enhanced Glycogen Storage of a Subcellular Hot Spot in Human Skeletal Muscle during Early Recovery from Eccentric Contractions

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Farup, Jean; Rahbek, Stine Klejs;

    2015-01-01

    Unaccustomed eccentric exercise is accompanied by muscle damage and impaired glucose uptake and glycogen synthesis during subsequent recovery. Recently, it was shown that the role and regulation of glycogen in skeletal muscle are dependent on its subcellular localization, and that glycogen synthe...

  1. Liver transplant

    Science.gov (United States)

    ... transplant - series References Keefe EB. Hepatic failure and liver transplantation. In: Goldman L, Schafer AI, eds. Goldman's Cecil ... Elsevier; 2011:chap 157. Martin P, Rosen HR. Liver transplantation. In: Feldman M, Friedman LS, Brandt LJ, eds. ...

  2. The Effect of Monosodium Glutamate (MSG On Rat Liver And The Ameliorating Effect Of "Guanidino Ethane Sulfonic acid (GES" (Histological, Histochemical and Electron Microscopy Studies

    Directory of Open Access Journals (Sweden)

    Hanaa F. Waer and *Saleh Edress

    2006-09-01

    Full Text Available Food additives are chemical substances added intentionally to food stuffs to preserve, color, sweeten and flavor food. Monosodium glutamate (MSG is used as a flavor enhancer and found in most soups, salad dressing and processed meat. The use of MSG in food is growing. Irrational fear had increased in the last few years due to the adverse reactions and toxicity of MSG. The present study was designed to investigate the effect of MSG on the rat liver and the ameliorating effect of taurine analog "Guanidinoethane sulfonic acid (GES". Sixty albino rats (2-3 months old were used in the present study. MSG was given orally at a daily dose of 60 mg/1000 g for one month, two months and was given at a daily dose of 100mg/1000gm for one month. The results revealed that the deleterious effects of MSG were dose related and cumulative. In MSG treated rats, the examined sections showed remarkable alterations varied considerably from moderate structural changes to cytoplasmic lysis and signs of degeneration of cellular organelles. The histological changes showed disturbed liver architecture, hemorrhage in the central veins, areas of necrosis, vacuolation and increased inflammatory cells infiltration. The glycogen granules increased as well as the collagen fibers in the liver cells. Ultrastructural changes showed loss of cytoplasmic differentiation, vacuolation, pyknotic nuclei with irregular nuclear membranes and elongated electron dense mitochondria. Conversely, treatment of rats with taurine analog (GES significantly attenuated the cellular toxicity of MSG.

  3. 大蒜素促进运动后大鼠糖原合成实验研究%The Experimental Research of Garlicin on Glycogen Synthesis after Exhaustive Exercise

    Institute of Scientific and Technical Information of China (English)

    蔡建光; 易乐; 王立文; 蒋小辉; 朱佩文

    2013-01-01

      To investigate the effects of garlicin on the content of glycogen in muscle and liver of rats. A total 52 rats were randomly allocated into 5 groups:control, training, training+sugar supplement, training+garlicin supplement and training+sugar+garlicin supplement. The sugar and garlicin were fed on gavage administration. The content of muscle glycogen and liver glycogen were determined by Anthranone method after 2 weeks of swimming exhaustive exercise. The experimental results displayed that, the supplement of garlicin, it was not significant effects on the content of liver glycogen, but the muscle glycogen was significant increased following the supplement of the sugar. It was implied that it was necessay to supplement the sugar to increase the content of glycogen for the swimming exhaustive rats.%  研究大蒜素在大鼠游泳力竭运动后大蒜素对机体糖原合成的影响。52只大鼠分成对照组(4只),训练组(12只),训练组+补糖组(12只),训练组+补大蒜素组(12只)和训练组+补糖+不大蒜素组(12只)后,采用灌胃法对大鼠进行糖和/或大蒜素的补充,进行为期2周游泳力竭训练后用蒽酮法测定大鼠肝糖原和肌糖原的水平。结果表明,补充大蒜素对大鼠肝糖原的影响不显著,但可以显著提高肌糖原的含量,且肌糖原含量的提高有赖于糖的补充。大蒜素促进大鼠游泳力竭运动后糖原的合成应在补糖的基础上才能实现。

  4. [Liver cirrhosis in metabolic disorders].

    Science.gov (United States)

    Tazawa, Y

    1994-01-01

    The most early cirrhosis is observed in newborns with neonatal hemachromatosis. Early cirrhosis occurs in hereditary tyrosinemia type I, peroxisomal diseases and glycogen storage disease (type IV). In Wilson's disease, a case complicated with cirrhosis was reported in a 4-year-old patient. Slowly progressive cirrhosis is seen in patients with familial progressive intrahepatic cholestasis. Focal biliary cirrhosis is found in cystic fibrosis of the pancreas. Moreover, many other metabolic disorders, except for urea cycle disorders, are occasionally or rarely complicated with cirrhosis. Early diagnosis and proper management could prevent the development of cirrhosis in patients with galactosemia, hereditary fructose intolerance, etc. The occurrence of hepatoma must be monitored in these patients. Liver transplantation is indicated in a part of the patients with cirrhosis. PMID:8114297

  5. Obesity, inflammation, and liver cancer.

    Science.gov (United States)

    Sun, Beicheng; Karin, Michael

    2012-03-01

    Obesity has become a universal and major public health problem with increasing prevalence in both adults and children in the 21st century, even in developing countries. Extensive epidemiological studies reveal a strong link between obesity and development and progression of various types of cancers. The connection between obesity and liver cancer is particularly strong and obesity often results in liver diseases such as non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH). NASH is characterized by fatty liver inflammation and is believed to cause fibrosis and cirrhosis. The latter is a known liver cancer risk factor. In fact due to its much higher prevalence obesity may be a more substantial contributor to overall hepatocellular carcinoma burden than infection with hepatitis viruses. Here we review and discuss recent advances in elucidation of cellular and molecular alterations and signaling pathways associated with obesity and liver inflammation and their contribution to hepatocarcinogenesis.

  6. Flavopiridol inhibits glycogen phosphorylase by binding at the inhibitor site.

    Science.gov (United States)

    Oikonomakos, N G; Schnier, J B; Zographos, S E; Skamnaki, V T; Tsitsanou, K E; Johnson, L N

    2000-11-01

    Flavopiridol (L86-8275) ((-)-cis-5, 7-dihydroxy-2-(2-chlorophenyl)-8-[4-(3-hydroxy-1-methyl)-piperidinyl] -4H-benzopyran-4-one), a potential antitumor drug, currently in phase II trials, has been shown to be an inhibitor of muscle glycogen phosphorylase (GP) and to cause glycogen accumulation in A549 non-small cell lung carcinoma cells (Kaiser, A., Nishi, K., Gorin, F.A., Walsh, D.A., Bradbury, E. M., and Schnier, J. B., unpublished data). Kinetic experiments reported here show that flavopiridol inhibits GPb with an IC(50) = 15.5 microm. The inhibition is synergistic with glucose resulting in a reduction of IC(50) for flavopiridol to 2.3 microm and mimics the inhibition of caffeine. In order to elucidate the structural basis of inhibition, we determined the structures of GPb complexed with flavopiridol, GPb complexed with caffeine, and GPa complexed with both glucose and flavopiridol at 1.76-, 2.30-, and 2.23-A resolution, and refined to crystallographic R values of 0.216 (R(free) = 0.247), 0.189 (R(free) = 0.219), and 0.195 (R(free) = 0.252), respectively. The structures provide a rational for flavopiridol potency and synergism with glucose inhibitory action. Flavopiridol binds at the allosteric inhibitor site, situated at the entrance to the catalytic site, the site where caffeine binds. Flavopiridol intercalates between the two aromatic rings of Phe(285) and Tyr(613). Both flavopiridol and glucose promote the less active T-state through localization of the closed position of the 280s loop which blocks access to the catalytic site, thereby explaining their synergistic inhibition. The mode of interactions of flavopiridol with GP is different from that of des-chloro-flavopiridol with CDK2, illustrating how different functional parts of the inhibitor can be used to provide specific and potent binding to two different enzymes. PMID:10924512

  7. Glycogen in honeybee queens, workers and drones (Apis mellifera carnica Pollm.).

    Science.gov (United States)

    Crailsheim, K; Panzenböck, U

    1997-02-21

    Honey bees (Apis mellifera carnica Pollm.) have low glycogen reserves in summer. Upon emergence drones have significantly larger amounts per unit weight when emerging, than workers; perhaps as adaption to the risk of not being fed as intensely as young workers. Maximum content was 0.23mg for workers (28d), and 0.59mg for drones (after emergence). Workers have relatively constant glycogen contents during their life, and very young drones have more glycogen than older ones. Young queens are similar to workers. In workers and queens in summer the greatest amounts of glycogen are found in the thorax. When the bees start flying (6th-8th day of life), drones have the highest amounts in the head (probably to supply their eyes), and upon maturity, drones have the least glycogen in the abdomen.Workers in winter show different glycogen values depending on whether they are active bees from the core area (0.23mg) or inactive ones from the outer surface of the winter cluster (0.37mg). They use glycogen from the thorax and the abdomen for their ongoing energy need.

  8. [3H] glycogen hydrolysis in brain slices: responses to meurotransmitters and modulation of noradrenaline receptors

    International Nuclear Information System (INIS)

    Different agents have been investigated for their effects on [3H] glycogen synthesized in mouse cortical slices. Of these noradrenaline, serotonin and histamine induced clear concentration-dependent glycogenesis. [3H] glycogen hydrolysis induced by noradrenaline appears to be mediated by beta-adrenergic receptors because it is completely prevented by timolol, while phentolamine is ineffective. It seems to involve cyclic AMP because it is potentiated in the presence of isobutylmethylxanthine; in addition dibutyryl cyclic AMP (but not dibutyryl cyclic GMP) promotes glycogenolysis. Lower concentrations of noradrenaline were necessary for [3H] glycogen hydrolysis (ECsub(50) 0.5μM) than for stimulation of cyclic AMP accumulation (ECsub(50) = 8μM). After subchronic reserpine treatment the concentration-response curve to noradrenaline was significantly shifted to the left (ECsub(50) = 0.09 +- 0.02 μM as compared with 0.49 +- 0.08μM in saline-pretreated mice) without modifications of either the basal [3H] glycogen level, maximal glycogenolytic effect, or the dibutyryl cAMP-induced glycogenolytic response. In addition to noradrenaline, clear concentration-dependent [3H] glycogen hydrolysis was observed in the presence of histamine or serotonin. In contrast to the partial [3H] glycogen hydrolysis elicited by these biogenic amines, depolarization of the slices by 50 mM K+ provoked a nearly total [3H] glycogen hydrolysis. (author)

  9. ORM Promotes Skeletal Muscle Glycogen Accumulation via CCR5-Activated AMPK Pathway in Mice

    Science.gov (United States)

    Qin, Zhen; Wan, Jing-Jing; Sun, Yang; Wang, Peng-Yuan; Su, Ding-Feng; Lei, Hong; Liu, Xia

    2016-01-01

    We found previously that acute phase protein orosomucoid reacts to fatigue and activates C-C chemokine receptor type 5 to increase muscle glycogen storage and enhance muscle endurance (Lei et al., 2016). To explore the underlying molecular mechanisms, we investigated the role of AMP-activated protein kinase, a critical fuel sensor in skeletal muscle, in C-C chemokine receptor type 5-mediated orosomucoid action. It was found orosomucoid increased skeletal muscle AMP-activated protein kinase activation in a time- and dose- dependent manner, which was largely prevented by pharmacological blocking or knockout of C-C chemokine receptor type 5. Administration of orosomucoid also significantly increased the de-phosphorylation and activity of muscle glycogen synthase, the rate-limiting enzyme for glycogen synthesis. The effect was largely absent in mice deficient in C-C chemokine receptor type 5−/− or AMP-activated protein kinase α2−/−, the predominant isoform in skeletal muscle. Moreover, deletion of AMP-activated protein kinase α2 abolished the effect of orosomucoid on fatigue and muscle glycogen. These findings indicate that orosomucoid may promote glycogen storage and enhance muscle function through C-C chemokine receptor type 5-mdiated activation of AMP-activated protein kinase, which in turn activates glycogen synthase and increases muscle glycogen. PMID:27679573

  10. Duration-dependent hepatoprotective effects of propolis extract against carbon tetrachloride-induced acute liver damage in rats.

    Science.gov (United States)

    Bhadauria, Monika; Nirala, Satendra Kumar; Shukla, Sangeeta

    2007-01-01

    Propolis is a natural product produced by bees that was discovered through the study of traditional cures and knowledge of indigenous people throughout the world. It is rich in vitamins A, B, C, and E, and in amino acids, copper, iron, manganese, and zinc. The investigators studied the duration-dependent hepatoprotective effects of propolis extract (200 mg/kg, orally) against carbon tetrachloride (CCl 4; 1.5 mL/kg, intraperitoneally)-induced liver damage in rats. Administration of CCl 4 caused a sharp elevation in the activity of serum transaminases and serum alkaline phosphatase. A significant depletion in hepatically reduced glutathione was observed with significantly enhanced hepatic lipid peroxidation. After CCl 4 administration, glycogen contents and activities of alkaline phosphatase, adenosine triphosphatase, and succinic dehydrogenase were significantly decreased, whereas total protein contents and activity of acid phosphatase were increased in the liver and kidney. Propolis extract reversed alterations in all parameters when administered within 6, 12, and 24 h of toxicant exposure. Propolis therapy produced duration-dependent protection, with maximal protection achieved at 24 h after CCl 4 exposure. It is believed that propolis in its natural form has general pharmacologic value and marked hepatoprotective potential because of its composition of minerals, flavonoids, and phenolic compounds. PMID:18029340

  11. [Liver damage caused by drugs].

    Science.gov (United States)

    Strohmeyer, G; Weik, C

    1999-05-01

    The liver has a central role in the metabolism of many drugs, since this organ is the main site of biotransformation of endo- and xenobiotics. Water-soluble drugs have a small volume of distribution and can be eliminated unchanged in the urine. By contrast, lipid-soluble drugs have a larger volume of distribution and require conversion to water-soluble metabolites for their elimination in urine or bile. The liver with its specific receptors, transporters and enzymes is responsible for the uptake, transformation and excretion of the lipophilic drugs. While most of the drugs are transformed into stable metabolites, other drugs form reactive, potentially toxic, metabolites producing liver cell damage. Liver injury caused by drugs may mimic almost any kind of liver disease. Clinical findings are gastrointestinal symptoms with nausea, vomiting and abdominal pain, cholestatic liver injury with jaundice and pruritus of severe inflammatory and cirrhotic liver damage with signs of liver failure, encephalopathy and cerebral edema. The morphological changes vary from hepatitis, cholestasis, fatty liver, granulomatous hepatitis, peri-/portal inflammation, to fibrosis with cirrhotic alterations and vascular lesions and tumors. The most commonly used drugs causing severe liver injury are discussed in detail. These are anabolics, oral contraceptives, antituberculous and antifungal agents, nonsteroidal anti-inflammatory drugs, ring substituted amphetamins ("designer drugs"), antiarrhythmics and antibiotics.

  12. Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Takashige, E-mail: tkawakami@ph.bunri-u.ac.jp; Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2014-03-01

    The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport.

  13. Hepatic encephalopathy as a complication of liver disease

    Institute of Scientific and Technical Information of China (English)

    Stephan vom Dahl; Gerald Kircheis; Dieter Haussinger

    2001-01-01

    @@INTRODUCTION Hepatic encephalopathy ( HE) is a frequent complication of chronic liver disease .It is defined as a characteristic functional and reversible alteration of the mental state ,due to impaired liver function and / or increased portosystemic shunting .

  14. Glucose balance and muscle glycogen during TPN in the early post-operative phase

    DEFF Research Database (Denmark)

    Henneberg, S; Stjernström, H; Essén-Gustavsson, B;

    1985-01-01

    In order to study how muscle glycogen is influenced by different nutritional regimens in the early post-operative period we took muscle biopsies from 20 patients preoperatively and on the fourth post-operative day after abdominal aortic surgery. Ten patients received 93% of non-protein energy...... glycogen stores at pre-operative levels with a glucose-insulin regimen. With the fat regimen there was a 31% decrease in muscle glycogen and two patients had a negative glucose balance despite the fact that 150 g of glucose were given. Average glucose balance throughout the study correlated positively...

  15. Seasonal changes in hepatocytic lipid droplets, glycogen deposits, and rough endoplasmic reticulum along the natural breeding cycle of female ohrid trout (Salmo letnica Kar.)-A semiquantitative ultrastructural study.

    Science.gov (United States)

    Jordanova, Maja; Rebok, Katerina; Malhão, Fernanda; Rocha, Maria J; Rocha, Eduardo

    2016-08-01

    This study on wild female Ohrid trout was primarily designed to provide a general overview of the breeding cycle influence upon selected aspects of hepatocytes. According with a semiquantitatively evaluation, some of these cell's structural compartments change during the breeding cycle. Structural modifications were disclosed in the relative occurrence of lipid, glycogen, and RER content during breeding cycle. The relative amount of lipid deposits in the hepatocytes was much greater in previtellogenesis, and decreased postspawning. So, while the seasonal changes in RER were positively related with the ovary maturation status, those of the lipid droplets followed an opposite trend. The hepatocytic glycogen occurred rarely, mainly in late-vitellogenesis and spawning, suggesting that in this species such kind of energy storage is comparatively unimportant. Lipid accumulation and later usage is, probably, the relevant biochemical pathway for Ohrid trout in the wild. While glycogen and RER contents were positively correlated with the gonadosomatic index, lipids were negatively correlated. Additionally, glycogen inclusions were positively correlated with the plasma estradiol levels. When comparing seasonal patterns from wild Ohrid trout with those from well-studied rainbow and brown trout (specimens studied were from aquaculture), there are contradicting results as to lipid and glycogen reserves, and also as to RER loads. The differences among the mentioned trout can result from intrinsic interspecies differences or may be associated with natural feeding conditions versus feeding with commercially prepared diets, or other factors. This study offers new data useful as standard to access liver pathology in wild and aquacultured Ohrid trout. Microsc. Res. Tech. 79:700-706, 2016. © 2016 Wiley Periodicals, Inc. PMID:27223583

  16. Glycogen synthase kinase-3 facilitates con a-induced IFN-γ-- mediated immune hepatic injury.

    Science.gov (United States)

    Tsai, Cheng-Chieh; Huang, Wei-Ching; Chen, Chia-Ling; Hsieh, Chia-Yuan; Lin, Yee-Shin; Chen, Shun-Hua; Yang, Kao-Chi; Lin, Chiou-Feng

    2011-10-01

    Immune hepatic injury induced by Con A results primarily from IFN-γ-mediated inflammation, followed by hepatic cell death. Glycogen synthase kinase (GSK)-3, which acts proapoptotically and is proinflammatory, is also important for facilitating IFN-γ signaling. We hypothesized a pathogenic role for GSK-3 in Con A hepatic injury. Con A stimulation caused GSK-3 activation in the livers of C57BL/6 mice. Inhibiting GSK-3 reduced Con A hepatic injury, including hepatic necrosis and apoptosis, inflammation, infiltration of T cells and granulocytes, and deregulated expression of adhesion molecule CD54. Con A induced hepatic injury in an IFN-γ receptor 1-dependent manner. Con A/IFN-γ induced activation and expression of STAT1 in a GSK-3-dependent manner. GSK-3 facilitated IFN-γ-induced inducible NO synthase, but had limited effects on CD95 upregulation and CD95-mediated hepatocyte apoptosis in vitro. Notably, inhibiting GSK-3 decreased Con A-induced IFN-γ production in both wild-type and IFN-γ receptor 1-deficient C57BL/6 mice. In Con A-activated NKT cells, GSK-3 was also activated and was required for nuclear translocation of T-box transcription factor Tbx21, a transcription factor of IFN-γ, but it was not required for CD95 ligand expression or activation-induced cell death. These results demonstrate the dual and indispensable role of GSK-3 in Con A hepatic injury by facilitating IFN-γ-induced hepatopathy.

  17. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

    OpenAIRE

    Stefano Gitto; Erica Villa

    2016-01-01

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent signifi...

  18. Adiponectin levels correlate with the severity of hypertriglyceridaemia in glycogen storage disease Ia

    NARCIS (Netherlands)

    Bandsma, R. H. J.; Smit, G. P. A.; Reijngoud, D. -J.; Kuipers, F.

    2009-01-01

    Glycogen storage disease type Ia (GSD Ia) is characterized by severe hypercholesterolaemia and hypertriglyceridaemia. Little is known about the aetiology of the hyperlipidaemia in GSD Ia. Adipokines play an important regulatory role in lipid metabolism. We investigated whether adipokine concentratio

  19. Lipids in hepatic glycogen storage diseases : pathophysiology, monitoring of dietary management and future directions

    NARCIS (Netherlands)

    Derks, Terry G. J.; van Rijn, Margreet

    2015-01-01

    Hepatic glycogen storage diseases (GSD) underscore the intimate relationship between carbohydrate and lipid metabolism. The hyperlipidemias in hepatic GSD reflect perturbed intracellular metabolism, providing biomarkers in blood to monitor dietary management. In different types of GSD, hyperlipidemi

  20. Identification and Structural Basis of Binding to Host Lung Glycogen by Streptococcal Virulence Factors

    Energy Technology Data Exchange (ETDEWEB)

    Lammerts van Bueren,A.; Higgins, M.; Wang, D.; Burke, R.; Boraston, A.

    2007-01-01

    The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basis for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal {alpha}-glucan-metabolizing machinery as virulence factors.

  1. Physiological aspects of the subcellular localization of glycogen in skeletal muscle

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Ørtenblad, Niels

    2013-01-01

    with metabolic and scaffolding proteins. Although the subcellular localization of glycogen has been recognized for more than 40 years, the physiological role of the distinct localizations has received sparse attention. Recently, however, studies involving stereological, unbiased, quantitative methods have...

  2. Glycogen synthesis correlates with androgen-dependent growth arrest in prostate cancer

    Directory of Open Access Journals (Sweden)

    Gorin Frederic A

    2005-03-01

    Full Text Available Abstract Background Androgen withdrawal in normal prostate or androgen-dependent prostate cancer is associated with the downregulation of several glycolytic enzymes and with reduced glucose uptake. Although glycogen metabolism is known to regulate the intracellular glucose level its involvement in androgen response has not been studied. Methods We investigated the effects of androgen on glycogen phosphorylase (GP, glycogen synthase (GS and on glycogen accumulation in the androgen-receptor (AR reconstituted PC3 cell line containing either an empty vector (PC3-AR-V or vector with HPV-E7 (PC3-AR-E7 and the LNCaP cell line. Results Androgen addition in PC3 cells expressing the AR mimics androgen ablation in androgen-dependent prostate cells. Incubation of PC3-AR-V or PC3-AR-E7 cells with the androgen R1881 induced G1 cell cycle arrest within 24 hours and resulted in a gradual cell number reduction over 5 days thereafter, which was accompanied by a 2 to 5 fold increase in glycogen content. 24 hours after androgen-treatment the level of Glucose-6-P (G-6-P had increased threefold and after 48 hours the GS and GP activities increased twofold. Under this condition inhibition of glycogenolysis with the selective GP inhibitor CP-91149 enhanced the increase in glycogen content and further reduced the cell number. The androgen-dependent LNCaP cells that endogenously express AR responded to androgen withdrawal with growth arrest and increased glycogen content. CP-91149 further increased glycogen content and caused a reduction of cell number. Conclusion Increased glycogenesis is part of the androgen receptor-mediated cellular response and blockage of glycogenolysis by the GP inhibitor CP-91149 further increased glycogenesis. The combined use of a GP inhibitor with hormone therapy may increase the efficacy of hormone treatment by decreasing the survival of prostate cancer cells and thereby reducing the chance of cancer recurrence.

  3. Effect of pH on Cleavage of Glycogen by Vaginal Enzymes.

    Directory of Open Access Journals (Sweden)

    Greg T Spear

    Full Text Available Glycogen expressed by the lower genital tract epithelium is believed to support Lactobacillus growth in vivo, although most genital isolates of Lactobacillus are not able to use glycogen as an energy source in vitro. We recently reported that α-amylase is present in the genital fluid of women and that it breaks down glycogen into small carbohydrates that support growth of lactobacilli. Since the pH of the lower genital tract can be very low, we determined how low pH affects glycogen processing by α-amylase. α-amylase in saliva degraded glycogen similarly at pH 6 and 7, but activity was reduced by 52% at pH 4. The glycogen degrading activity in nine genital samples from seven women showed a similar profile with an average reduction of more than 50% at pH 4. However, two samples collected from one woman at different times had a strikingly different pH profile with increased glycogen degradation at pH 4, 5 and 6 compared to pH 7. This second pH profile did not correlate with levels of human α-acid glucosidase or human intestinal maltase glucoamylase. High-performance anion-exchange chromatography showed that mostly maltose was produced from glycogen by samples with the second pH profile in contrast to genital α-amylase that yielded maltose, maltotriose and maltotetraose. These studies show that at low pH, α-amylase activity is reduced to low but detectable levels, which we speculate helps maintain Lactobacillus growth at a limited but sustained rate. Additionally, some women have a genital enzyme distinct from α-amylase with higher activity at low pH. Further studies are needed to determine the identity and distribution of this second enzyme, and whether its presence influences the makeup of genital microbiota.

  4. Stimulation of glycogen synthesis and lipogenesis by glutamine in isolated rat hepatocytes.

    OpenAIRE

    Lavoinne, A; Baquet, A.; Hue, Louis

    1987-01-01

    Glutamine stimulated glycogen synthesis and lactate production in hepatocytes from overnight-fasted normal and diabetic rats. The effect, which was half-maximal with about 3 mM-glutamine, depended on glucose concentration and was maximal below 10 mM-glucose. beta-2-Aminobicyclo[2.2.1.]heptane-2-carboxylic acid, an analogue of leucine, stimulated glutaminase flux, but inhibited the stimulation of glycogen synthesis by glutamine. Various purine analogues and inhibitors of purine synthesis were ...

  5. Glycogen accumulation in alveolar type II cells in 3-methylindole--induced pulmonary edema in goats.

    OpenAIRE

    Atwal, O. S.; Bray, T. M.

    1981-01-01

    The present study shows that intravenous infusion of 3-methylindole (3MI) induced acute pulmonary edema in goats. Edematous changes were seen in the alveoli and the interalveolar interstitium. At 72 hours after treatment, an accumulation of glycogen that had a pathognomonic appearance of alpha particles was observed in the alveolar Type II cells. A rich accumulation of glycogen particles and defective lamellar bodies containing triglycerides were the significant morphologic changes in the alv...

  6. Exosomes in liver pathology.

    Science.gov (United States)

    Sato, Keisaku; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco

    2016-07-01

    Exosomes are small (∼100nm) membrane-bound extracellular vesicles released by various types of cells into biological fluids. They contain proteins, mRNAs and miRNAs as cargo. Different cell types can take up exosomes by endocytosis and the cargo contained within them can be transferred horizontally to these recipient cells. Exosomal proteins and miRNAs can be functional and regulate physiological cell events modifying the microenvironment in target cells, a key event of liver pathology. Exosome-mediated cell-cell communication can alter tumor growth, cell migration, antiviral infection and hepatocyte regeneration, indicating that exosomes have great potential for development as diagnostic or therapeutic tools. Analyses of circulating total or exosomal miRNAs have identified a large number of candidate miRNAs that are regulated in liver diseases, and the diagnostic testing using single or multiple miRNAs shows good sensitivity and specificity. Some candidate miRNAs have been identified to play an important role in various liver disorders. This review summarizes recent findings on the role of extracellular vesicles in liver diseases and their diagnostic and therapeutic potential, mainly focusing on exosomes but also includes microvesicles in liver pathology. PMID:26988731

  7. Contribution of glycogen in supporting axon conduction in the peripheral and central nervous systems: the role of lactate

    Directory of Open Access Journals (Sweden)

    Angus M Brown

    2014-11-01

    Full Text Available The role of glycogen in the central nervous system is intimately linked with the glycolytic pathway. Glycogen is synthesized from glucose, the primary substrate for glycolysis, and degraded to glucose-6-phosphate. The metabolic cost of shunting glucose via glycogen exceeds that of simple phosphorylation of glucose to glucose-6-phosphate by hexokinase; thus, there must be a metabolic advantage in utilizing this shunt pathway. The dogmatic view of glycogen as a storage depot persists, based on initial descriptions of glycogen supporting neural function in the face of aglycemia. The variable latency to conduction failure, dependent upon tissue glycogen levels, provided convincing evidence of the role played by glycogen in supporting neural function. Glycogen is located predominantly in astrocytes in the central nervous system, thus for glycogen to benefit neural elements, intercellular metabolic communication must exist in the form of astrocyte to neuron substrate transfer. Experimental evidence supports a model where glycogen is metabolized to lactate in astrocytes, with cellular expression of monocarboxylate transporters and enzymes appropriately located for lactate shuttling between astrocytes and neural elements, where lactate acts as a substrate for oxidative metabolism. Biosensor recordings have demonstrated a significant steady concentration of lactate present on the periphery of both central white matter and peripheral nerve under unstimulated baseline conditions, indicating continuous cellular efflux of lactate to the interstitium. The existence of this lactate pool argues we must reexamine the ‘on demand’ shuttling of lactate between cellular elements, and suggests continuous lactate efflux surplus to immediate neural requirements.

  8. Preconditioning ischemia time determines the degree of glycogen depletion and infarct size reduction in rat hearts.

    Science.gov (United States)

    Barbosa, V; Sievers, R E; Zaugg, C E; Wolfe, C L

    1996-02-01

    The cardioprotective effect of preconditioning is associated with glycogen depletion and attenuation of intracellular acidosis during subsequent prolonged ischemia. This study determined the effects of increasing preconditioning ischemia time on myocardial glycogen depletion and on infarct size reduction. In addition, this study determined whether infarct size reduction by preconditioning correlates with glycogen depletion before prolonged ischemia. Anesthetized rats underwent a single episode of preconditioning lasting 1.25, 2.5, 5, or 10 minutes or multiple episodes cumulating in 10 (2 x 5 min) or 20 minutes (4 x 5 or 2 x 10 min) of preconditioning ischemia time, each followed by 5 minutes of reperfusion. Then both preconditioned and control rats underwent 45 minutes of ischemia induced by left coronary artery (LCA) occlusion and 120 minutes of reperfusion. After prolonged ischemia, infarct size was determined by dual staining with triphenyltetrazolium chloride and phthalocyanine blue dye. Glycogen levels were determined by an enzymatic assay in selected rats from each group before prolonged ischemia. We found that increasing preconditioning ischemia time resulted in glycogen depletion and infarct size reduction that could both be described by exponential functions. Furthermore, infarct size reduction correlated with glycogen depletion before prolonged ischemia (r = 0.98; p ischemic injury in the preconditioned heart. PMID:8579012

  9. Glycogen accumulation in the pars recta of the proximal tubule in Fanconi syndrome.

    Science.gov (United States)

    Bendon, R W; Hug, G

    1986-01-01

    We reviewed the renal pathology in 10 cases of renal Fanconi syndrome. Five cases showed the Armanni-Ebstein lesion, i.e., clear glycogen-filled cells limited to the pars recta of the proximal tubules. The 5 cases included 2 siblings with a unique syndrome characterized by death in infancy, severe Fanconi syndrome, severe rickets, carnitine deficiency, and atrophy of the exocrine pancreas. Two other siblings had glycogen storage disease type XI. One of 4 cases of putative tyrosinemia had the lesion. The ultrastructure was studied in 2 cases. The Armanni-Ebstein lesion in these cases was morphologically indistinguishable from that seen in diabetic patients dying after prolonged hyperglycemia. Glycosuria is the only common factor in both diabetic hyperglycemia and the varied proximal tubular diseases studied. The mechanism of the glycogen accumulation in this short parts recta segment of the proximal renal tubule was further investigated by reviewing the renal histology in cases of glycogen storage disease types I, II, III, and VIII. None showed the Armanni-Ebstein lesion, but type I showed glycogen deposition throughout the proximal tubule. Thus, the Armanni-Ebstein lesion is not the result of an enzymatic deficiency for glycogen synthesis in the convoluted tubules. PMID:3588439

  10. Glycogen accumulation in the pars recta of the proximal tubule in Fanconi syndrome.

    Science.gov (United States)

    Bendon, R W; Hug, G

    1986-01-01

    We reviewed the renal pathology in 10 cases of renal Fanconi syndrome. Five cases showed the Armanni-Ebstein lesion, i.e., clear glycogen-filled cells limited to the pars recta of the proximal tubules. The 5 cases included 2 siblings with a unique syndrome characterized by death in infancy, severe Fanconi syndrome, severe rickets, carnitine deficiency, and atrophy of the exocrine pancreas. Two other siblings had glycogen storage disease type XI. One of 4 cases of putative tyrosinemia had the lesion. The ultrastructure was studied in 2 cases. The Armanni-Ebstein lesion in these cases was morphologically indistinguishable from that seen in diabetic patients dying after prolonged hyperglycemia. Glycosuria is the only common factor in both diabetic hyperglycemia and the varied proximal tubular diseases studied. The mechanism of the glycogen accumulation in this short parts recta segment of the proximal renal tubule was further investigated by reviewing the renal histology in cases of glycogen storage disease types I, II, III, and VIII. None showed the Armanni-Ebstein lesion, but type I showed glycogen deposition throughout the proximal tubule. Thus, the Armanni-Ebstein lesion is not the result of an enzymatic deficiency for glycogen synthesis in the convoluted tubules.

  11. The Saccharomyces cerevisiae YPR184w gene encodes the glycogen debranching enzyme.

    Science.gov (United States)

    Teste, M A; Enjalbert, B; Parrou, J L; François, J M

    2000-12-01

    The YPR184w gene encodes a 1536-amino acid protein that is 34-39% identical to the mammal, Drosophila melanogaster and Caenorhabditis elegans glycogen debranching enzyme. The N-terminal part of the protein possesses the four conserved sequences of the alpha-amylase superfamily, while the C-terminal part displays 50% similarity with the C-terminal of other eukaryotic glycogen debranching enzymes. Reliable measurement of alpha-1,4-glucanotransferase and alpha-1, 6-glucosidase activity of the yeast debranching enzyme was determined in strains overexpressing YPR184w. The alpha-1, 4-glucanotransferase activity of a partially purified preparation of debranching enzyme preferentially transferred maltosyl units than maltotriosyl. Deletion of YPR184w prevents glycogen degradation, whereas overexpression had no effect on the rate of glycogen breakdown. In response to stress and growth conditions, the transcriptional control of YPR184w gene, renamed GDB1 (for Glycogen DeBranching gene), is strictly identical to that of other genes involved in glycogen metabolism.

  12. Creatine supplementation spares muscle glycogen during high intensity intermittent exercise in rats

    Directory of Open Access Journals (Sweden)

    Costa André

    2010-01-01

    Full Text Available Abstract Background The effects of creatine (CR supplementation on glycogen content are still debatable. Thus, due to the current lack of clarity, we investigated the effects of CR supplementation on muscle glycogen content after high intensity intermittent exercise in rats. Methods First, the animals were submitted to a high intensity intermittent maximal swimming exercise protocol to ensure that CR-supplementation was able to delay fatigue (experiment 1. Then, the CR-mediated glycogen sparing effect was examined using a high intensity intermittent sub-maximal exercise test (fixed number of bouts; six bouts of 30-second duration interspersed by two-minute rest interval (experiment 2. For both experiments, male Wistar rats were given either CR supplementation or placebo (Pl for 5 days. Results As expected, CR-supplemented animals were able to exercise for a significant higher number of bouts than Pl. Experiment 2 revealed a higher gastrocnemius glycogen content for the CR vs. the Pl group (33.59%. Additionally, CR animals presented lower blood lactate concentrations throughout the intermittent exercise bouts compared to Pl. No difference was found between groups in soleus glycogen content. Conclusion The major finding of this study is that CR supplementation was able to spare muscle glycogen during a high intensity intermittent exercise in rats.

  13. Glucose analogue inhibitors of glycogen phosphorylase: from crystallographic analysis to drug prediction using GRID force-field and GOLPE variable selection.

    Science.gov (United States)

    Watson, K A; Mitchell, E P; Johnson, L N; Cruciani, G; Son, J C; Bichard, C J; Fleet, G W; Oikonomakos, N G; Kontou, M; Zographos, S E

    1995-07-01

    Several inhibitors of the large regulatory enzyme glycogen phosphorylase (GP) have been studied in crystallographic and kinetic experiments. GP catalyses the first step in the phosphorylysis of glycogen to glucose-l-phosphate, which is utilized via glycolysis to provide energy to sustain muscle contraction and in the liver is converted to glucose. alpha-D-Glucose is a weak inhibitor of glycogen phosphorylase form b (GPb, K(i) = 1.7 mM) and acts as a physiological regulator of hepatic glycogen metabolism. Glucose binds to phosphorylase at the catalytic site and results in a conformational change that stabilizes the inactive T state of the enzyme, promoting the action of protein phosphatase 1 and stimulating glycogen synthase. It has been suggested that in the liver, glucose analogues with greater affinity for glycogen phosphorylase may result in a more effective regulatory agent. Several N-acetyl glucopyranosylamine derivatives have been synthesized and tested in a series of crystallographic and kinetic binding studies with GPb. The structural results of the bound enzyme-ligand complexes have been analysed together with the resulting affinities in an effort to understand and exploit the molecular interactions that might give rise to a better inhibitor. Comparison of the N-methylacetyl glucopyranosylamine (N-methylamide, K(i) = 0.032 mM) with the analogous beta-methylamide derivative (C-methylamide, K(i) = 0.16 mM) illustrate the importance of forming good hydrogen bonds and obtaining complementarity of van der Waals interactions. These studies also have shown that the binding modes can be unpredictable but may be rationalized with the benefit of structural data and that a buried and mixed polar/non-polar catalytic site poses problems for the systematic addition of functional groups. Together with previous studies of glucose analogue inhibitors of GPb, this work forms the basis of a training set suitable for three-dimensional quantitative structure

  14. [A new case of hepatic adenomatosis treated with orthotopic liver transplantation].

    Science.gov (United States)

    Yunta, P J; Moya, A; San-Juan, F; López-Andújar, R; De Juan, M; Orbis, F; Mir, J

    2001-09-01

    Hepatic adenomatosis is a rare disease with multiple hepatic adenomas (10 or more), not associated with an history of oral contraceptive use or anabolic steroids use or with glycogen storage disease. A new case is reported in a 23 year-old woman who consulted for an abdominal mass and who had more than 50 adenomas of the liver. The suspicion of malignant transformation by the elevation of the alpha-foetoprotein, and the diffuse affectation of the liver, with minimum free parenchyma, suggested to carry out an orthotopic liver transplantation. The definitive histological examination of the surgical specimen confirmed the existence of local areas of hepatocellular carcinoma.

  15. Gut microbiota and probiotics in chronic liver diseases.

    Science.gov (United States)

    Cesaro, Claudia; Tiso, Angelo; Del Prete, Anna; Cariello, Rita; Tuccillo, Concetta; Cotticelli, Gaetano; Del Vecchio Blanco, Camillo; Loguercio, Carmelina

    2011-06-01

    There is a strong relationship between liver and gut: the portal system receives blood from the gut, and intestinal blood content activates liver functions. The liver, in turn, affects intestinal functions through bile secretion into the intestinal lumen. Alterations of intestinal microbiota seem to play an important role in induction and promotion of liver damage progression, in addition to direct injury resulting from different causal agents. Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of complications of liver cirrhosis, such as infections, hepatic encephalopathy, spontaneous bacterial peritonitis, and renal failure. Probiotics have been suggested as a useful integrative treatment of different types of chronic liver damage, for their ability to augment intestinal barrier function and prevent bacterial translocation. This review summarizes the main literature findings about the relationships between gut microbiota and chronic liver disease, both in the pathogenesis and in the treatment by probiotics of the liver damage. PMID:21163715

  16. Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib : Results of the European Study on Glycogen Storage Disease Type I

    NARCIS (Netherlands)

    Visser, G; Rake, JP; Fernandes, J; Labrune, P; Leonard, JV; Moses, S; Ullrich, K; Smit, GPA

    2000-01-01

    Objective: To investigate the incidence, the severity, and the course of neutropenia, neutrophil dysfunction, and inflammatory bowel disease (IBD) in glycogen storage disease (GSD) type Ib. Method: As part of a collaborative European Study on GSD type I, a retrospective registry was established in 1

  17. Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1

    NARCIS (Netherlands)

    Visser, G.; Rake, J.P.; Labrune, P.; Leonard, J.V.; Moses, S.; Ullrich, K.; Wendel, U.; Groenier, K.H.; Smit, G.P.

    2002-01-01

    Patients with glycogen storage disease type 1b (GSD-1b) have neutropenia and neutrophil dysfunction that predispose to frequent infections and inflammatory bowel disease (IBD), for which granulocyte colony-stimulating factor (GCSF) is given. To investigate the use and the value of GCSF treatment in

  18. Glycogen synthase kinase-3 in the etiology and treatment of mood disorders

    Directory of Open Access Journals (Sweden)

    Richard Scott Jope

    2011-08-01

    Full Text Available The mood disorders major depressive disorder and bipolar disorder are prevalent, are inadequately treated, and little is known about their etiologies. A better understanding of the causes of mood disorders would benefit from improved animal models of mood disorders, which now rely on behavioral measurements. This review considers the limitations in relating measures of rodent behaviors to mood disorders, and the evidence from behavioral assessments indicating that glycogen synthase kinase-3 (GSK3 dysregulation promotes mood disorders and is a potential target for treating mood disorders. The classical mood stabilizer lithium was identified by studying animal behaviors and later was discovered to be an inhibitor of GSK3. Several mood-relevant behavioral effects of lithium in rodents have been identified, and most have now been shown to be due to its inhibition of GSK3. An extensive variety of pharmacological and molecular approaches for manipulating GSK3 are discussed, the results of which strongly support the proposal that inhibition of GSK3 reduces both depression-like and manic-like behaviors. Studies in human postmortem brain and peripheral cells also have identified correlations between alterations in GSK3 and mood disorders. Evidence is reviewed that depression may be associated with impaired inhibitory control of GSK3, and mania by hyper-stimulation of GSK3. Taken together, these studies provide substantial support for the hypothesis that inhibition of GSK3 activity is therapeutic for mood disorders. Future research should identify the causes of dysregulated GSK3 in mood disorders and the actions of GSK3 that contribute to these diseases.

  19. Decreased glycogen synthase kinase-3 levels and activity contribute to Huntington's disease.

    Science.gov (United States)

    Fernández-Nogales, Marta; Hernández, Félix; Miguez, Andrés; Alberch, Jordi; Ginés, Silvia; Pérez-Navarro, Esther; Lucas, José J

    2015-09-01

    Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by brain atrophy particularly in striatum leading to personality changes, chorea and dementia. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase in the crossroad of many signaling pathways that is highly pleiotropic as it phosphorylates more than hundred substrates including structural, metabolic, and signaling proteins. Increased GSK-3 activity is believed to contribute to the pathogenesis of neurodegenerative diseases like Alzheimer's disease and GSK-3 inhibitors have been postulated as therapeutic agents for neurodegeneration. Regarding HD, GSK-3 inhibitors have shown beneficial effects in cell and invertebrate animal models but no evident efficacy in mouse models. Intriguingly, those studies were performed without interrogating GSK-3 level and activity in HD brain. Here we aim to explore the level and also the enzymatic activity of GSK-3 in the striatum and other less affected brain regions of HD patients and of the R6/1 mouse model to then elucidate the possible contribution of its alteration to HD pathogenesis by genetic manipulation in mice. We report a dramatic decrease in GSK-3 levels and activity in striatum and cortex of HD patients with similar results in the mouse model. Correction of the GSK-3 deficit in HD mice, by combining with transgenic mice with conditional GSK-3 expression, resulted in amelioration of their brain atrophy and behavioral motor and learning deficits. Thus, our results demonstrate that decreased brain GSK-3 contributes to HD neurological phenotype and open new therapeutic opportunities based on increasing GSK-3 activity or attenuating the harmful consequences of its decrease. PMID:26082469

  20. Differential Liver Protein Expression during Schistosomiasis▿ †

    OpenAIRE

    Harvie, Marina; Jordan, Thomas William; La Flamme, Anne Camille

    2006-01-01

    The arrival of eggs in the liver during Schistosoma mansoni infection initiates a protective granulomatous response; however, as the infection progresses, this response results in chronic liver fibrosis. To better understand the impact of schistosomiasis on liver function, we used a proteomic approach to identify proteins whose expression was significantly altered in schistosome-infected mice 8 weeks postinfection. Identification of differentially expressed proteins by mass fingerprinting rev...

  1. 1-Deoxynojirimycin Alleviates Liver Injury and Improves Hepatic Glucose Metabolism in db/db Mice

    Directory of Open Access Journals (Sweden)

    Qingpu Liu

    2016-02-01

    Full Text Available The present study investigated the effect of 1-Deoxynojirimycin (DNJ on liver injury and hepatic glucose metabolism in db/db mice. Mice were divided into five groups: normal control, db/db control, DNJ-20 (DNJ 20 mg·kg−1·day−1, DNJ-40 (DNJ 40 mg·kg−1·day−1 and DNJ-80 (DNJ 80 mg·kg−1·day−1. All doses were treated intravenously by tail vein for four weeks. DNJ was observed to significantly reduce the levels of serum triglyceride (TG, total cholesterol (TC, low density lipoprotein cholesterol (LDL-C and liver TG, as well as activities of serum alanine aminotransferase (ALT, and aspartate transaminase (AST; DNJ also alleviated macrovesicular steatosis and decreased tumor necrosis factor α (TNF-α, interleukin-1 (IL-1, interleukin-6 (IL-6 levels in liver tissue. Furthermore, DNJ treatment significantly increased hepatic glycogen content, the activities of hexokinase (HK, pyruvate kinase (PK in liver tissue, and decreased the activities of glucose-6-phosphatase (G6Pase, glycogen phosphorylase (GP, and phosphoenolpyruvate carboxykinase (PEPCK. Moreover, DNJ increased the phosphorylation of phosphatidylinositol 3 kinase (PI3K on p85, protein kinase B (PKB on Ser473, glycogen synthase kinase 3β (GSK-3β on Ser9, and inhibited phosphorylation of glycogen synthase (GS on Ser645 in liver tissue of db/db mice. These results demonstrate that DNJ can increase hepatic insulin sensitivity via strengthening of the insulin-stimulated PKB/GSK-3β signal pathway and by modulating glucose metabolic enzymes in db/db mice. Moreover, DNJ also can improve lipid homeostasis and attenuate hepatic steatosis in db/db mice.

  2. Ethanolic Extract of Butea monosperma Leaves Elevate Blood Insulin Level in Type 2 Diabetic Rats, Stimulate Insulin Secretion in Isolated Rat Islets, and Enhance Hepatic Glycogen Formation

    Directory of Open Access Journals (Sweden)

    Mehdi Bin Samad

    2014-01-01

    Full Text Available We measured a vast range of parameters, in an attempt to further elucidate previously claimed antihyperglycemic activity of Butea monosperma. Our study clearly negates the possibility of antidiabetic activity by inhibited gastrointestinal enzyme action or by reduced glucose absorption. Reduction of fasting and postprandial glucose level was reconfirmed (P<0.05. Improved serum lipid profile via reduced low density lipoprotein (LDL, cholesterol, triglycerides (TG, and increased high density lipoprotein (HDL was also reestablished (P<0.05. Significant insulin secretagogue activity of B. monosperma was found in serum insulin assay of B. monosperma treated type 2 diabetic rats (P<0.01. This was further ascertained by our study on insulin secretion on isolated rat islets (P<0.05. Improved sensitivity of glucose was shown by the significant increase in hepatic glycogen deposition (P<0.05. Hence, we concluded that antihyperglycemic activity of B. monosperma was mediated by enhanced insulin secretion and enhanced glycogen formation in the liver.

  3. Quantitative comparison of pathways of hepatic glycogen repletion in fed and fasted humans

    International Nuclear Information System (INIS)

    The effect of fasting vs. refeeding on hepatic glycogen repletion by the direct pathway, i.e., glucose----glucose 6-phosphate (G-6-P)----glycogen, was determined. Acetaminophen was administered during an infusion of glucose labeled with [1-13C]- and [6-14C]glucose into four healthy volunteers after an overnight fast and into the same subjects 4 h after breakfast. 13C enrichments in C-1 and C-6 of glucose formed from urinary acetaminophen glucuronide compared with enrichments in C-1 and C-6 of plasma glucose provided an estimate of glycogen formation by the direct pathway. The specific activity of glucose from the glucuronide compared with the specific activity of the plasma glucose, along with the percentages of 14C in C-1 and C-6 of the glucose from the glucuronide, also provided an estimate of the amount of glycogen formed by the direct pathway. The estimates were similar. Those from [6-14C]glucose would have been higher than from [1-13C]glucose if the pentose cycle contribution to overall glucose utilization had been significant. After an overnight fast, during the last hour of infusion, 49 +/- 3% of the glycogen formed was formed via the direct pathway. After breakfast, at similar plasma glucose and insulin concentrations, the percentage increased to 69 +/- 7% (P less than 0.02). Thus the contributions of the pathways to hepatic glycogen formation depend on the dietary state of the individual. For a dietary regimen in which individuals consume multiple meals per day containing at least a moderate amount of carbohydrates most glycogen synthesis occurs by the direct pathway

  4. Glycogenotic hepatocellular carcinoma with glycogen-ground-glass hepatocytes: A heuristically highly relevant phenotype

    Institute of Scientific and Technical Information of China (English)

    Peter Bannasch

    2012-01-01

    Glycogenotic hepatocellular carcinoma (HCC) with glycogen-ground-glass hepatocytes has recently been described as an allegedly "novel variant" of HCC,but neither the historical background nor the heuristic relevance of this observation were put in perspective.In the present contribution,the most important findings in animal models and human beings related to the emergence and further evolution of excessively glycogen storing (glycogenotic) hepatocytes with and without ground glass features during neoplastic development have been summarized.Glycogenotic HCCs with glycogen-ground-glass hepatocytes represent highly differentiated neoplasms which contain subpopulations of cells phenotypically resembling those of certain types of preneoplastic hepatic foci and benign hepatocellular neoplasms.It is questionable whether the occurrence of glycogen-ground-glass hepatocytes in a glycogenotic HCC justifies its classification as a specific entity.The typical appearance of ground-glass hepatocytes is due to a hypertrophy of the smooth endoplasmic reticulum,which is usually associated with an excessive storage of glycogen and frequently also with an expression of the hepatitis B surface antigen.Sequential studies in animal models and observations in humans indicate that glycogen-ground-glass hepatocytes are a facultative,integral part of a characteristic cellular sequence commencing with focal hepatic glycogenosis potentially progressing to benign and malignant neoplasms.During this process highly differentiated glycogenotic cells including ground-glass hepatocytes are gradually transformed via various intermediate stages into poorly differentiated glycogen-poor,basophilic (ribosome-rich) cancer cells.Histochemical,microbiochemical,and molecular biochemical studies on focal hepatic glycogenosis and advanced preneoplastic and neoplastic lesions in tissue sections and laser-dissected specimens in rat and mouse models have provided compelling evidence for an early insulinomimetic

  5. Human α-amylase present in lower-genital-tract mucosal fluid processes glycogen to support vaginal colonization by Lactobacillus.

    Science.gov (United States)

    Spear, Gregory T; French, Audrey L; Gilbert, Douglas; Zariffard, M Reza; Mirmonsef, Paria; Sullivan, Thomas H; Spear, William W; Landay, Alan; Micci, Sandra; Lee, Byung-Hoo; Hamaker, Bruce R

    2014-10-01

    Lactobacillus colonization of the lower female genital tract provides protection from the acquisition of sexually transmitted diseases, including human immunodeficiency virus, and from adverse pregnancy outcomes. While glycogen in vaginal epithelium is thought to support Lactobacillus colonization in vivo, many Lactobacillus isolates cannot utilize glycogen in vitro. This study investigated how glycogen could be utilized by vaginal lactobacilli in the genital tract. Several Lactobacillus isolates were confirmed to not grow in glycogen, but did grow in glycogen-breakdown products, including maltose, maltotriose, maltopentaose, maltodextrins, and glycogen treated with salivary α-amylase. A temperature-dependent glycogen-degrading activity was detected in genital fluids that correlated with levels of α-amylase. Treatment of glycogen with genital fluids resulted in production of maltose, maltotriose, and maltotetraose, the major products of α-amylase digestion. These studies show that human α-amylase is present in the female lower genital tract and elucidates how epithelial glycogen can support Lactobacillus colonization in the genital tract.

  6. Liver spots

    Science.gov (United States)

    Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... your skin by using skin bleaching lotions or creams. Most bleaching lotions use hydroquinone. This medicine is ...

  7. Liver Facts

    Science.gov (United States)

    ... idiopapathic) Liver tumors Biliary atresia Was this information helpful? E-mail us with feedback or questions. Reference ... or other discrepancies. Share this: Was this information helpful? Related topics Find transplant centers specializing in certain ...

  8. Liver function

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008308 Study on transplantation of induced bone marrow mesenchymal stem cells via a series of the treatment of chronic liver injury. SUN Yan(孙艳), et al. Dept Gastroenterol, 1st Hosp, Jilin Univ, Changchun 130021. Chin J Dig 2008;28(3):171-174.Objective To investigate the efficacy of transplantation of induced bone marrow mesenchymal stem cells(MSCs)via a series of treatment of chronic liver injury.Methods MSCs were isolated and expanded by density

  9. Migratory preparation associated alterations in pectoralis muscle biochemistry and proteome in Palearctic-Indian emberizid migratory finch, red-headed bunting, Emberiza bruniceps.

    Science.gov (United States)

    Banerjee, Somanshu; Chaturvedi, Chandra Mohini

    2016-03-01

    Avian migration is an exceptionally high-energy-demanding process, which is met by the accumulation and utilization of fuel stores as well as the alterations in muscle physiology prior to their flight. Pre-migratory fattening coupled with changes in flight muscle metabolic enzymes and proteome is required to provide the necessary fuel and muscle performance required for migration. We studied how the serum metabolites (urea, uric acid, and creatinine), pectoralis muscle metabolites (glycogen, glucose, and cholesterol), muscle metabolic enzymes (CPT, HOAD, CS, MDH, CCO, CK, LDH, PFK, MLPL, and PK), liver lipogenic enzyme (FAS), and pectoralis muscle proteins get altered in pre-migratory and non-migratory buntings. Significantly increased pectoralis muscle fatty acid oxidation (CPT and HOAD activity), aerobic/anaerobic capacity (CS, CCO, and MDH activity), glycolytic capacity (PFK and PK activity), lipolysis (muscle LPL), and burst power (CK activity) were observed prior to the spring migration in pre-migratory buntings, whereas significantly increased pectoralis muscle anaerobic capacity (LDH activity) was observed in non-migratory buntings. Significant increase in the liver FAS showed profound lipogenesis prior to the spring migration. In this study, we have also investigated whether muscle has differential protein content during the pre-migratory and non-migratory phases of the annual migratory cycle. Twenty-nine proteins are identified and well characterized varying in expression significantly during the pre-migratory and non-migratory phases. These findings indicate that significant pre-migratory fattening and alterations in flight (pectoralis) muscle biochemistry and proteome in between the non- and pre-migratory phases may play a significant role in pre-migratory flight muscle preparation in these long-route migrants. PMID:26656601

  10. Glycogen phosphorylase is involved in stress endurance and biofilm formation in Azospirillum brasilense Sp7.

    Science.gov (United States)

    Lerner, Anat; Castro-Sowinski, Susana; Lerner, Hadas; Okon, Yaacov; Burdman, Saul

    2009-11-01

    Here we report the identification of a glycogen phosphorylase (glgP) gene in the plant growth-promoting rhizobacterium Azospirillum brasilense, Sp7, and the characterization of a glgP marker exchange mutant of this strain. The glgP mutant showed a twofold reduction of glycogen phosphorylase activity and an increased glycogen accumulation as compared with wild-type Sp7, indicating that the identified gene indeed encodes a protein with glycogen phosphorylase activity. Interestingly, the glgP mutant had higher survival rates than the wild type after exposure to starvation, desiccation and osmotic pressure. The mutant was shown to be compromised in its biofilm formation ability. Analysis of the exopolysaccharide sugar composition of the glgP mutant revealed a decrease in the amount of glucose, accompanied by increases in rhamnose, fucose and ribose, as compared with the Sp7 exopolysaccharide. To the best of our knowledge, this is the first study that demonstrates GlgP activity in A. brasilense, and shows that glycogen accumulation may play an important role in the stress endurance of this bacterium.

  11. [Studies on the initiation of glycogen metabolism in Escherichia coli (author's transl)].

    Science.gov (United States)

    Barengo, R; Krisman, C R

    1976-01-01

    Glycogen biosynthesis was studied in Escherichia coli. An enzyme complex composed of UDP-glucose; protein glucosyltransferase, ADP-glucose: protein glucosyltransferase and ADP-glucose: alpha-1,4 glucan alpha-4-glucosyltransferase was found. Further results revealed that while glycogen concentration remained unchanged, the specific activity of the glucosyltransferase complex increased during the growth phase of the culture. The detergents Lubrol and Brij provoked a decrease of 80% and 20% in the glucose transfer to protein from ADP-glucose and UDP-glucose, respectively. These detergents did not inhibit the glucose incorporation into glycogen by ADP-glucose: alpha-1,4-glucosyltransferase. We postulated that the biosynthesis of glycogen in Escherichia coli could be initiated by two different enzymes which catalyze the transfer of glucose from UDP-glucose or ADP-glucose to an acceptor protien. In a second step, the glucan protein formed is used as primer by the ADP-glucose: alpha-1,4 glucan alpha-1-glucosyltransferase for glycogen formation.

  12. Platelet-derived growth factor (PDGF) stimulates glycogen synthase activity in 3T3 cells

    International Nuclear Information System (INIS)

    Hormonal regulation of glycogen synthase, an enzyme that can be phosphorylated on multiple sites, is often associated with changes in its phosphorylation state. Enzyme activation is conventionally monitored by determining the synthase activity ratio [(activity in the absence of glucose 6-P)/(activity in the presence of glucose 6-P)]. Insulin causes an activation of glycogen synthase with a concomitant decrease in its phosphate content. In a previous report, the authors showed that epidermal growth factor (EGF) increases the glycogen synthase activity ratio in Swiss 3T3 cells. The time and dose-dependency of this response was similar to that of insulin. Their recent results indicate that PDGF also stimulates glycogen synthase activity. Enzyme activation was maximal after 30 min. of incubation with PDGF; the time course observed was very similar to that with insulin and EGF. At 1 ng/ml (0.03nM), PDGF caused a maximal stimulation of 4-fold in synthase activity ratio. Half-maximal stimulation was observed at 0.2 ng/ml (6 pM). The time course of changes in enzyme activity ratio closely followed that of 125I-PDGF binding. The authors data suggest that PDGF, as well as EFG and insulin, may be important in regulating glycogen synthesis through phosphorylation/dephosphorylation mechanisms

  13. REGULATION OF MUSCLE GLYCOGEN REPLETION, MUSCLE PROTEIN SYNTHESIS AND REPAIR FOLLOWING EXERCISE

    Directory of Open Access Journals (Sweden)

    John L. Ivy

    2004-09-01

    Full Text Available Recovery from prolonged strenuous exercise requires that depleted fuel stores be replenished, that damaged tissue be repaired and that training adaptations be initiated. Critical to these processes are the type, amount and timing of nutrient intake. Muscle glycogen is an essential fuel for intense exercise, whether the exercise is of an aerobic or anaerobic nature. Glycogen synthesis is a relatively slow process, and therefore the restoration of muscle glycogen requires special considerations when there is limited time between training sessions or competition. To maximize the rate of muscle glycogen synthesis it is important to consume a carbohydrate supplement immediately post exercise, to continue to supplement at frequent intervals and to consume approximately 1.2 g carbohydrate·kg-1 body wt·h-1. Maximizing glycogen synthesis with less frequent supplementation and less carbohydrate can be achieved with the addition of protein to the carbohydrate supplement. This will also promote protein synthesis and reduce protein degradation, thus having the added benefit of stimulating muscle tissue repair and adaptation. Moreover, recent research suggests that consuming a carbohydrate/protein supplement post exercise will have a more positive influence on subsequent exercise performance than a carbohydrate supplement.

  14. Homeostasis and the glycogen shunt explains aerobic ethanol production in yeast

    Science.gov (United States)

    Shulman, Robert G.; Rothman, Douglas L.

    2015-01-01

    Aerobic glycolysis in yeast and cancer cells produces pyruvate beyond oxidative needs, a paradox noted by Warburg almost a century ago. To address this question, we reanalyzed extensive measurements from 13C magnetic resonance spectroscopy of yeast glycolysis and the coupled pathways of futile cycling and glycogen and trehalose synthesis (which we refer to as the glycogen shunt). When yeast are given a large glucose load under aerobic conditions, the fluxes of these pathways adapt to maintain homeostasis of glycolytic intermediates and ATP. The glycogen shunt uses glycolytic ATP to store glycolytic intermediates as glycogen and trehalose, generating pyruvate and ethanol as byproducts. This conclusion is supported by studies of yeast with a partial block in the glycogen shunt due to the cif mutation, which found that when challenged with glucose, the yeast cells accumulate glycolytic intermediates and ATP, which ultimately leads to cell death. The control of the relative fluxes, which is critical to maintain homeostasis, is most likely exerted by the enzymes pyruvate kinase and fructose bisphosphatase. The kinetic properties of yeast PK and mammalian PKM2, the isoform found in cancer, are similar, suggesting that the same mechanism may exist in cancer cells, which, under these conditions, could explain their excess lactate generation. The general principle that homeostasis of metabolite and ATP concentrations is a critical requirement for metabolic function suggests that enzymes and pathways that perform this critical role could be effective drug targets in cancer and other diseases. PMID:26283370

  15. Liver Biopsy in Liver Transplant Recipients

    OpenAIRE

    Van Ha, Thuong G.

    2004-01-01

    Liver biopsy has been used in the assessment of the nature and course of liver diseases and to monitor treatments. In nontransplanted patients, liver biopsies have been well described. Less has been written on the biopsies of transplanted livers. In the liver transplant population, liver biopsy remains the “gold standard” for the diagnosis of rejection. The transplanted liver has additional considerations that can make biopsy less routine and more challenging.

  16. Folate, alcohol, and liver disease.

    Science.gov (United States)

    Medici, Valentina; Halsted, Charles H

    2013-04-01

    Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of ALD with particular focus on ethanol-induced alterations in methionine metabolism, which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of ALD based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

  17. Ameliorating effect of Semecarpus anacardium Linn. nut milk extract on altered glucose metabolism in high fat diet STZ induced type 2 diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Kaladevi Siddhi Vinayagam; Shanthi Palanivelu; Sachdanandam Panchanadham

    2012-01-01

    Objective: To explore the protective effect of the drug Semecarpus anacardium (S. anacardium) on altered glucose metabolism in diabetic rats. Methods: Type 2 diabetes mellitus was induced by feeding rats with high fat diet followed by single intraperitoneal injection of streptozotocin (STZ) (35 mg/kg b.w.). Seven days after STZ induction, diabetic rats received nut milk extract ofS. anacardium Linn. nut milk extract orally at a dosage of 200 mg/kg daily for 4 weeks. The effect of nut milk extract of S. anacardium on blood glucose, plasma insulin, glucose metabolising enzymes and GSK were studied. Results: Treatment with SA extract showed a significant reduction in blood glucose levels and increase in plasma insulin levels and also increase in HOMA - β and decrease in HOMA -IR. The drug significantly increased the activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase activity and increased the glycogen content in liver of diabetic rats while reducing the activities of gluconeogenic enzymes. The drug also effectively ameliorated the alterations in GSK-3 mRNA expression. Conclusions: Overall, the present study demonstrates the possible mechanism of glucose regulation of S. anacardium suggestive of its therapeutic potential for the management of diabetes mellitus.

  18. Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type 1a

    Energy Technology Data Exchange (ETDEWEB)

    Chou, J.Y.; Lei, K.J.; Shelly, L.L. [National Institutes of Health, Bethesda, MD (United States)

    1994-09-01

    Glycogen storage disease (GSD) type la (von Gierke disease) is caused by the deficiency of glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. The disease presents with clinical manifestations of severe hypoglycemia, hepatomegaly, growth retardation, lactic acidemia, hyperlipidemia, and hyperuricemia. We have succeeded in isolating a murine G6Pase cDNA from a normal mouse liver cDNA library by differentially screening method. We then isolated the human G6Pase cDNA and gene. To date, we have characterized the G6Pase genes of twelve GSD type la patients and uncovered a total of six different mutations. The mutations are comprised of R83C (an Arg at codon 83 to a Cys), Q347X (a Gly at codon 347 to a stop codon), 459insTA (a two basepair insertion at nucleotide 459 yielding a truncated G6Pase of 129 residues), R295C (an Arg at codon 295 to a Cys), G222R (a Gly at codon 222 to an Arg) and {delta}F327 (a codon deletion for Phe-327 at nucleotides 1058 to 1060). The relative incidences of these mutations are 37.5% (R83C), 33.3% (Q347X), 16.6% (459insTA), 4.2% (G222R), 4.2% (R295C) and 4.2% ({delta}F327). Site-directed mutagenesis and transient expression assays demonstrated that the R83C, Q347X, R295C, and {delta}F327 mutations abolished whereas the G222R mutation greatly reduced G6Pase activity. We further characterized the structure-function requirements of amino acids 83, 222, and 295 in G6Pase catalysis. The identification of mutations in GSD type la patients has unequivocally established the molecular basis of the type la disorder. Knowledge of the mutations may be applied to prenatal diagnosis and opens the way for developing and evaluating new therapeutic approaches.

  19. Body metal concentrations and glycogen reserves in earthworms (Dendrobaena octaedra) from contaminated and uncontaminated forest soil.

    Science.gov (United States)

    Holmstrup, Martin; Sørensen, Jesper G; Overgaard, Johannes; Bayley, Mark; Bindesbøl, Anne-Mette; Slotsbo, Stine; Fisker, Karina V; Maraldo, Kristine; Waagner, Dorthe; Labouriau, Rodrigo; Asmund, Gert

    2011-01-01

    Stress originating from toxicants such as heavy metals can induce compensatory changes in the energy metabolism of organisms due to increased energy expenses associated with detoxification and excretion processes. These energy expenses may be reflected in the available energy reserves such as glycogen. In a field study the earthworm, Dendrobaena octaedra, was collected from polluted areas, and from unpolluted reference areas. If present in the environment, cadmium, lead and copper accumulated to high concentrations in D. octaedra. In contrast, other toxic metals such as aluminium, nickel and zinc appeared to be regulated and kept at low internal concentrations compared to soil concentrations. Lead, cadmium and copper accumulation did not correlate with glycogen reserves of individual worms. In contrast, aluminium, nickel and zinc were negatively correlated with glycogen reserves. These results suggest that coping with different metals in earthworms is associated with differential energy demands depending on the associated detoxification strategy. PMID:20870326

  20. Glucose balance and muscle glycogen during TPN in the early post-operative phase

    DEFF Research Database (Denmark)

    Henneberg, S; Stjernström, H; Essén-Gustavsson, B;

    1985-01-01

    as glucose, 7% as fat (Intralipid) and insulin was given to keep the blood glucose below 10 mmol/l. The remaining patients had 80% of non-protein energy as fat (Intralipid). Amino acids constituting 12 g of nitrogen daily were given to both groups. Daily measurements of gas exchange (oxygen uptake, CO2......-production) were performed and from these data glucose balance was calculated as the difference between glucose intake and glucose expenditure. Muscle biopsies were analysed for glycogen, adenosine triphosphate, glucose-6-phosphate, lactate and citrate. We found that it was possible to maintain muscle...... glycogen stores at pre-operative levels with a glucose-insulin regimen. With the fat regimen there was a 31% decrease in muscle glycogen and two patients had a negative glucose balance despite the fact that 150 g of glucose were given. Average glucose balance throughout the study correlated positively...

  1. Body metal concentrations and glycogen reserves in earthworms (Dendrobaena octaedra) from contaminated and uncontaminated forest soil

    DEFF Research Database (Denmark)

    Holmstrup, Martin; Sørensen, Jesper Givskov; Overgaard, Johannes;

    2011-01-01

    and zinc appeared to be regulated and kept at low internal concentrations compared to soil concentrations. Lead, cadmium and copper accumulation did not correlate with glycogen reserves of individual worms. In contrast, aluminium, nickel and zinc were negatively correlated with glycogen reserves...... such as glycogen. In a field study the earthworm, Dendrobaena octaedra, was collected from polluted areas, and from unpolluted reference areas. If present in the environment, cadmium, lead and copper accumulated to high concentrations in D. octaedra. In contrast, other toxic metals such as aluminium, nickel....... These results suggest that coping with different metals in earthworms is associated with differential energy demands depending on the associated detoxification strategy. Detoxification and accumulation of cadmium and lead by earthworms carries little energetic expenses whereas strict internal regulation...

  2. A Genome-wide Screen for Neurospora crassa Transcription Factors Regulating Glycogen Metabolism*

    Science.gov (United States)

    Gonçalves, Rodrigo Duarte; Cupertino, Fernanda Barbosa; Freitas, Fernanda Zanolli; Luchessi, Augusto Ducati; Bertolini, Maria Célia

    2011-01-01

    Transcription factors play a key role in transcription regulation as they recognize and directly bind to defined sites in promoter regions of target genes, and thus modulate differential expression. The overall process is extremely dynamic, as they have to move through the nucleus and transiently bind to chromatin in order to regulate gene transcription. To identify transcription factors that affect glycogen accumulation in Neurospora crassa, we performed a systematic screen of a deletion strains set generated by the Neurospora Knockout Project and available at the Fungal Genetics Stock Center. In a wild-type strain of N. crassa, glycogen content reaches a maximal level at the end of the exponential growth phase, but upon heat stress the glycogen content rapidly drops. The gene encoding glycogen synthase (gsn) is transcriptionally down-regulated when the mycelium is exposed to the same stress condition. We identified 17 deleted strains having glycogen accumulation profiles different from that of the wild-type strain under both normal growth and heat stress conditions. Most of the transcription factors identified were annotated as hypothetical protein, however some of them, such as the PacC, XlnR, and NIT2 proteins, were biochemically well-characterized either in N. crassa or in other fungi. The identification of some of the transcription factors was coincident with the presence of DNA-binding motifs specific for the transcription factors in the gsn 5′-flanking region, and some of these DNA-binding motifs were demonstrated to be functional by Electrophoretic Mobility Shift Assay (EMSA) experiments. Strains knocked-out in these transcription factors presented impairment in the regulation of gsn expression, suggesting that the transcription factors regulate glycogen accumulation by directly regulating gsn gene expression. Five selected mutant strains showed defects in cell cycle progression, and two transcription factors were light-regulated. The results indicate

  3. Postexercise Glycogen Recovery and Exercise Performance is Not Significantly Different Between Fast Food and Sport Supplements.

    Science.gov (United States)

    Cramer, Michael J; Dumke, Charles L; Hailes, Walter S; Cuddy, John S; Ruby, Brent C

    2015-10-01

    A variety of dietary choices are marketed to enhance glycogen recovery after physical activity. Past research informs recommendations regarding the timing, dose, and nutrient compositions to facilitate glycogen recovery. This study examined the effects of isoenergetic sport supplements (SS) vs. fast food (FF) on glycogen recovery and exercise performance. Eleven males completed two experimental trials in a randomized, counterbalanced order. Each trial included a 90-min glycogen depletion ride followed by a 4-hr recovery period. Absolute amounts of macronutrients (1.54 ± 0.27 g·kg-1 carbohydrate, 0.24 ± 0.04 g·kg fat-1, and 0.18 ±0.03g·kg protein-1) as either SS or FF were provided at 0 and 2 hr. Muscle biopsies were collected from the vastus lateralis at 0 and 4 hr post exercise. Blood samples were analyzed at 0, 30, 60, 120, 150, 180, and 240 min post exercise for insulin and glucose, with blood lipids analyzed at 0 and 240 min. A 20k time-trial (TT) was completed following the final muscle biopsy. There were no differences in the blood glucose and insulin responses. Similarly, rates of glycogen recovery were not different across the diets (6.9 ± 1.7 and 7.9 ± 2.4 mmol·kg wet weight- 1·hr-1 for SS and FF, respectively). There was also no difference across the diets for TT performance (34.1 ± 1.8 and 34.3 ± 1.7 min for SS and FF, respectively. These data indicate that short-term food options to initiate glycogen resynthesis can include dietary options not typically marketed as sports nutrition products such as fast food menu items. PMID:25811308

  4. Postexercise Glycogen Recovery and Exercise Performance is Not Significantly Different Between Fast Food and Sport Supplements.

    Science.gov (United States)

    Cramer, Michael J; Dumke, Charles L; Hailes, Walter S; Cuddy, John S; Ruby, Brent C

    2015-10-01

    A variety of dietary choices are marketed to enhance glycogen recovery after physical activity. Past research informs recommendations regarding the timing, dose, and nutrient compositions to facilitate glycogen recovery. This study examined the effects of isoenergetic sport supplements (SS) vs. fast food (FF) on glycogen recovery and exercise performance. Eleven males completed two experimental trials in a randomized, counterbalanced order. Each trial included a 90-min glycogen depletion ride followed by a 4-hr recovery period. Absolute amounts of macronutrients (1.54 ± 0.27 g·kg-1 carbohydrate, 0.24 ± 0.04 g·kg fat-1, and 0.18 ±0.03g·kg protein-1) as either SS or FF were provided at 0 and 2 hr. Muscle biopsies were collected from the vastus lateralis at 0 and 4 hr post exercise. Blood samples were analyzed at 0, 30, 60, 120, 150, 180, and 240 min post exercise for insulin and glucose, with blood lipids analyzed at 0 and 240 min. A 20k time-trial (TT) was completed following the final muscle biopsy. There were no differences in the blood glucose and insulin responses. Similarly, rates of glycogen recovery were not different across the diets (6.9 ± 1.7 and 7.9 ± 2.4 mmol·kg wet weight- 1·hr-1 for SS and FF, respectively). There was also no difference across the diets for TT performance (34.1 ± 1.8 and 34.3 ± 1.7 min for SS and FF, respectively. These data indicate that short-term food options to initiate glycogen resynthesis can include dietary options not typically marketed as sports nutrition products such as fast food menu items.

  5. Hypertension and liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens H; Møller, Søren

    2004-01-01

    to increased arterial blood pressure. Subjects with established arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin......Arterial hypertension is a common disorder with a frequency of 10% to 15% in subjects in the 40- to 60-year age group. Yet most reports find the prevalence of arterial hypertension in patients with chronic liver disease (cirrhosis) much lower. In this review, we consider the alterations in systemic...

  6. REGULATION OF MEMORY – FROM THE ADRENAL MEDULLA TO LIVER TO ASTROCYTES TO NEURONS1

    OpenAIRE

    Gold, Paul E.

    2014-01-01

    Epinephrine, released into blood from the adrenal medulla in response to arousing experiences, is a potent enhancer of learning and memory processing. This review examines mechanisms by which epinephrine exerts its effects on these cognitive functions. Because epinephrine is largely blocked from moving from blood to brain, it is likely that the hormone's effects on memory are mediated by peripheral actions. A classic effect of epinephrine is to act at the liver to break down glycogen stores, ...

  7. Effect of Oyster mushroom in Paracetamol Induced Toxicity of Liver in Wistar albino Rats

    OpenAIRE

    Afroza Khanam Sumy; Nasim Jahan; Nayma Sultana; Abdul Mannan Sikder

    2014-01-01

    Backgroud: Liver is an important metabolic organ. It has wide range of functions including detoxification, storage of glycogen, vitamins A, D and B12, production of several coagulation factors, growth factors such as insulin-like growth factor-1 (IGF-1), angiotensinogen, and biochemicals necessary for digestion (bile). Its damage occurs due to its multidimensional functions, various xenobiotics and oxidative stress leading to distortion of all of its functions. Oyster mushroom which is excell...

  8. Nonalcoholic fatty liver disease.

    Science.gov (United States)

    Brunt, Elizabeth M; Wong, Vincent W-S; Nobili, Valerio; Day, Christopher P; Sookoian, Silvia; Maher, Jacquelyn J; Bugianesi, Elisabetta; Sirlin, Claude B; Neuschwander-Tetri, Brent A; Rinella, Mary E

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by excess accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)); in up to 40% of individuals, there are additional findings of portal and lobular inflammation and hepatocyte injury (which characterize nonalcoholic steatohepatitis (NASH)). A subset of patients will develop progressive fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma and cardiovascular complications are life-threatening co-morbidities of both NAFL and NASH. NAFLD is closely associated with insulin resistance; obesity and metabolic syndrome are common underlying factors. As a consequence, the prevalence of NAFLD is estimated to be 10-40% in adults worldwide, and it is the most common liver disease in children and adolescents in developed countries. Mechanistic insights into fat accumulation, subsequent hepatocyte injury, the role of the immune system and fibrosis as well as the role of the gut microbiota are unfolding. Furthermore, genetic and epigenetic factors might explain the considerable interindividual variation in disease phenotype, severity and progression. To date, no effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery. However, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation. Diagnosis of NAFLD can be established by imaging, but detection of the lesions of NASH still depend on the gold-standard but invasive liver biopsy. Several non-invasive strategies are being evaluated to replace or complement biopsies, especially for follow-up monitoring. PMID:27188459

  9. Augmenter of liver regeneration

    Directory of Open Access Journals (Sweden)

    Gandhi Chandrashekhar R

    2012-07-01

    Full Text Available Abstract ‘Augmenter of liver regeneration’ (ALR (also known as hepatic stimulatory substance or hepatopoietin was originally found to promote growth of hepatocytes in the regenerating or injured liver. ALR is expressed ubiquitously in all organs, and exclusively in hepatocytes in the liver. ALR, a survival factor for hepatocytes, exhibits significant homology with ERV1 (essential for respiration and viability protein that is essential for the survival of the yeast, Saccharomyces cerevisiae. ALR comprises 198 to 205 amino acids (approximately 22 kDa, but is post-translationally modified to three high molecular weight species (approximately 38 to 42 kDa found in hepatocytes. ALR is present in mitochondria, cytosol, endoplasmic reticulum, and nucleus. Mitochondrial ALR may be involved in oxidative phosphorylation, but also functions as sulfhydryl oxidase and cytochrome c reductase, and causes Fe/S maturation of proteins. ALR, secreted by hepatocytes, stimulates synthesis of TNF-α, IL-6, and nitric oxide in Kupffer cells via a G-protein coupled receptor. While the 22 kDa rat recombinant ALR does not stimulate DNA synthesis in hepatocytes, the short form (15 kDa of human recombinant ALR was reported to be equipotent as or even stronger than TGF-α or HGF as a mitogen for hepatocytes. Altered serum ALR levels in certain pathological conditions suggest that it may be a diagnostic marker for liver injury/disease. Although ALR appears to have multiple functions, the knowledge of its role in various organs, including the liver, is extremely inadequate, and it is not known whether different ALR species have distinct functions. Future research should provide better understanding of the expression and functions of this enigmatic molecule.

  10. Rapid height growth after liver transplantation in adulthood.

    Science.gov (United States)

    Szili, Balázs; Görög, Dénes; Gerlei, Zsuzsanna; Győri, Gabriella; Lakatos, Péter; Takács, István

    2016-08-01

    Glycogen storage disease Ib is a rare, inherited metabolic disorder caused by glucose-6-phosphatase translocase deficiency. Its main symptoms are hypoglycemia, hyperlipidemia, neutropenia, hepatomegaly, liver adenomas and short stature. The exact mechanism of short stature in this disease is unclear, the most feasible possibility is that it is caused by impairment of growth-hormone and insulin-like growth factor I axis. Here we report the case of a patient who showed typical symptoms of glycogen storage disease Ib since his infancy, his height being under 1 percentile since then. Later-developed hypothyroidism and hypogonadism have also contributed to his short stature. Hypothyroidism was treated but sexual steroid substitution was not started because of an increased risk of hepatic adenomas. Because he developed hepatic adenoma at the age of 23, he had to undergo orthotopic liver transplantation. At the time of the transplantation his height was 128cm. The transplantation was followed by rapid height growth; our patient's height reached 160.3cm 62months after transplantation. We observed that while his IGF-I level increased, his GH level remained unchanged. During the post-transplantation period we ensured adequate calcium and vitamin D supplementation, leaving hormonal substitution unchanged. According to our knowledge, this is the first report of a rapid height growth as big as 32cm, of an individual over the age of 20, not related to endocrine treatment but liver transplantation. PMID:27041087

  11. Partial recovery of erythrocyte glycogen in diabetic rats treated with phenobarbital

    Directory of Open Access Journals (Sweden)

    da-Silva C.A.

    1997-01-01

    Full Text Available Erythrocytes may play a role in glucose homeostasis during the postprandial period. Erythrocytes from diabetic patients are defective in glucose transport and metabolism, functions that may affect glycogen storage. Phenobarbital, a hepatic enzyme inducer, has been used in the treatment of patients with non-insulin-dependent diabetes mellitus (NIDDM, increasing the insulin-mediated glucose disposal. We studied the effects of phenobarbital treatment in vivo on glycemia and erythrocyte glycogen content in control and alloxan-diabetic rats during the postprandial period. In control rats (blood glucose, 73 to 111 mg/dl in femoral and suprahepatic veins the erythrocyte glycogen content was 45.4 ± 1.1 and 39.1 ± 0.8 µg/g Hb (mean ± SEM, N = 4-6 in the femoral artery and vein, respectively, and 37.9 ± 1.1 in the portal vein and 47.5 ± 0.9 in the suprahepatic vein. Diabetic rats (blood glucose, 300-350 mg/dl presented low (P<0.05 erythrocyte glycogen content, i.e., 9.6 ± 0.1 and 7.1 ± 0.7 µg/g Hb in the femoral artery and vein, respectively, and 10.0 ± 0.7 and 10.7 ± 0.5 in the portal and suprahepatic veins, respectively. After 10 days of treatment, phenobarbital (0.5 mg/ml in the drinking water did not change blood glucose or erythrocyte glycogen content in control rats. In diabetic rats, however, it lowered (P<0.05 blood glucose in the femoral artery (from 305 ± 18 to 204 ± 45 mg/dl and femoral vein (from 300 ± 11 to 174 ± 48 mg/dl and suprahepatic vein (from 350 ± 10 to 174 ± 42 mg/dl, but the reduction was not sufficient for complete recovery. Phenobarbital also stimulated the glycogen synthesis, leading to a partial recovery of glycogen stores in erythrocytes. In treated rats, erythrocyte glycogen content increased to 20.7 ± 3.8 µg/g Hb in the femoral artery and 30.9 ± 0.9 µg/g Hb in the suprahepatic vein (P<0.05. These data indicate that phenobarbital activated some of the insulin-stimulated glucose metabolism steps which were

  12. A whole-body model for glycogen regulation reveals a critical role for substrate cycling in maintaining blood glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Ke Xu

    2011-12-01

    Full Text Available Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into "whole-body" contextual models that mimic in vivo conditions.

  13. Role of glycogen-lowering exercise in the change of fat oxidation in response to a high-fat diet.

    NARCIS (Netherlands)

    Schrauwen, P.; van Marken Lichtenbelt, W.D.; Saris, W.H.M.; Westerterp, K.R.

    1997-01-01

    Department of Human Biology, Maastricht University, The Netherlands. One of the candidate factors for determining the increase of fat oxidation after a switch from a reduced-fat diet to a high-fat diet is the size of the glycogen storage. Therefore, we studied the effect of low glycogen stores on fa

  14. Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter

    DEFF Research Database (Denmark)

    Brown, Angus M; Sickmann, Helle M; Fosgerau, Keld;

    2005-01-01

    We tested the hypothesis that inhibiting glycogen degradation accelerates compound action potential (CAP) failure in mouse optic nerve (MON) during aglycemia or high-intensity stimulation. Axon function was assessed as the evoked CAP, and glycogen content was measured biochemically. Isofagomine...

  15. The unique branching patterns of Deinococcus glycogen branching enzymes are determined by their N-terminal domains.

    NARCIS (Netherlands)

    Palomo, M.; Kralj, S.; van der Maarel, M. J. E. C.; Dijkhuizen, L.

    2009-01-01

    Glycogen branching enzymes (GBE) or 1,4-alpha-glucan branching enzymes (EC 2.4.1.18) introduce alpha-1,6 branching points in alpha-glucans, e.g., glycogen. To identify structural features in GBEs that determine their branching pattern specificity, the Deinococcus geothermalis and Deinococcus radiodu

  16. Influence of pre-exercise muscle glycogen content on exercise-induced transcriptional regulation of metabolic genes

    DEFF Research Database (Denmark)

    Pilegaard, Henriette; Keller, Charlotte; Steensberg, Adam;

    2002-01-01

    to lower muscle glycogen content in one leg and then, the following day, completed 2.5 h low intensity two-legged cycling exercise. Nuclei and mRNA were isolated from biopsies obtained from the vastus lateralis muscle of the control and reduced glycogen (pre-exercise glycogen = 609 +/- 47 and 337 +/- 33...... in response to exercise, raising the possibility that signalling mechanisms sensitive to glycogen content and/or FFA availability may be linked to the transcriptional control of exercise-responsive genes.......Transcription of metabolic genes is transiently induced during recovery from exercise in skeletal muscle of humans. To determine whether pre-exercise muscle glycogen content influences the magnitude and/or duration of this adaptive response, six male subjects performed one-legged cycling exercise...

  17. HIF-1α is necessary to support gluconeogenesis during liver regeneration

    International Nuclear Information System (INIS)

    Coordinated recovery of hepatic glucose metabolism is prerequisite for normal liver regeneration. To examine roles of hypoxia inducible factor-1α (HIF-1α) for hepatic glucose homeostasis during the reparative process, we inactivated the gene in hepatocytes in vivo. Following partial hepatectomy (PH), recovery of residual liver weight was initially retarded in the mutant mice by down-regulation of hepatocyte proliferation, but occurred comparably between the mutant and control mice at 72 h after PH. At this time point, the mutant mice showed lowered blood glucose levels with enhanced accumulation of glycogen in the liver. The mutant mice exhibited impairment of hepatic gluconeogenesis as assessed by alanine tolerance test. This appeared to result from reduced expression of PGK-1 and PEPCK since 3-PG, PEP and malate were accumulated to greater extents in the regenerated liver. In conclusion, these findings provide evidence for roles of HIF-1α in the regulation of gluconeogenesis under liver regeneration.

  18. The role of zinc in liver cirrhosis.

    Science.gov (United States)

    Grüngreiff, Kurt; Reinhold, Dirk; Wedemeyer, Heiner

    2016-01-01

    Zinc is an essential trace element playing fundamental roles in cellular metabolism. It acts mostly by binding a wide range of proteins, thus affecting a broad spectrum of biological processes, which include cell division, growth and differentiation. Zinc is critical to a large number of structural proteins, enzymatic processes, and transcription factors. Zinc deficiency can result in a spectrum of clinical manifestations, such as poor of appetite, loss of body hair, altered taste and smell, testicular atrophy, cerebral and immune dysfunction, and diminished drug elimination capacity. These are common symptoms in patients with chronic liver diseases, especially liver cirrhosis. The liver is the main organ responsible for the zinc metabolism which can be affected by liver diseases. On the other hand, zinc deficiency may alter hepatocyte functions and also immune responses in inflammatory liver diseases. Liver cirrhosis represents the most advanced stage of chronic liver diseases and is the common outcome of chronic liver injury. It is associated with energy malnutrition, with numerous metabolic disorders, such as hypoalbuminemia, with imbalance between branched-chain amino acids and aromatic amino acids, and with reduced zinc serum concentrations. All these processes can influence the clinical outcome of patients, such ascites, hepatic encephalopathy and hepatocellular carcinoma. In the present review, we summarize the emerging evidence on the pitoval role of zinc in the pathogenesis of liver cirrhosis. PMID:26626635

  19. Carbon tetrachloride-induced liver injury in the rabbit.

    OpenAIRE

    Bernacchi, A. S.; de Castro, C. R.; de Ferreyra, E. C.; Villarruel, M. C.; Fernández, G.; de Fenos, O. M.; Castro, J.A.

    1983-01-01

    CCl4 administration to rabbits leads to early destruction of liver microsomal cytochrome P-450, to depression of glucose 6 phosphatase, to ultrastructurally revealable alterations and to an intense necrosis and fat accumulation in liver. Despite the known resistance of rabbit liver microsomes to lipid peroxidation, CCl4 administration to rabbits promoted lipid peroxidation of their liver microsomal lipids as revealable by the diene hyperconjugation technique, at periods of time from 1 to 12 h...

  20. Learning to program the liver.

    Science.gov (United States)

    Klaassen, Curtis D

    2014-01-01

    Half a century ago, people were learning to program computers. Similarly, we have been trying to learn how to program the liver to protect us from chemicals. We have given various chemicals that activate transcription factors such as the nuclear receptors: These ligand-activated nuclear receptors enter the nucleus of liver cells (hepatocytes) and bind to their specific motifs in DNA to increase the transcription of various genes that protect against chemical-induced injury. Several examples from our laboratory are given to demonstrate this detoxification process: (a) a steroid chemical that increases the expression of a hepatic transporter to enhance the elimination of other chemicals and thus decrease their toxicity, (b) a metal that decreases its own toxicity by increasing the production of a protein to which it binds, and (c) an herbal chemical that activates a transcription factor that serves as a sensor of oxidative stress and electrophiles to protect against cytotoxicity by increasing the expression of numerous antioxidant proteins. In addition, at the present time, we are investigating which bile acids that are synthesized in the liver and altered by bacteria in the intestine may be used to alter the programming of the liver, as well as how the liver reprograms itself after birth in the transition from a hematopoietic organ to one that decreases the toxicity of chemicals.

  1. Differential pattern of glycogen accumulation after protein phosphatase 1 glycogen-targeting subunit PPP1R6 overexpression, compared to PPP1R3C and PPP1R3A, in skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Montori-Grau Marta

    2011-11-01

    Full Text Available Abstract Background PPP1R6 is a protein phosphatase 1 glycogen-targeting subunit (PP1-GTS abundant in skeletal muscle with an undefined metabolic control role. Here PPP1R6 effects on myotube glycogen metabolism, particle size and subcellular distribution are examined and compared with PPP1R3C/PTG and PPP1R3A/GM. Results PPP1R6 overexpression activates glycogen synthase (GS, reduces its phosphorylation at Ser-641/0 and increases the extracted and cytochemically-stained glycogen content, less than PTG but more than GM. PPP1R6 does not change glycogen phosphorylase activity. All tested PP1-GTS-cells have more glycogen particles than controls as found by electron microscopy of myotube sections. Glycogen particle size is distributed for all cell-types in a continuous range, but PPP1R6 forms smaller particles (mean diameter 14.4 nm than PTG (36.9 nm and GM (28.3 nm or those in control cells (29.2 nm. Both PPP1R6- and GM-derived glycogen particles are in cytosol associated with cellular structures; PTG-derived glycogen is found in membrane- and organelle-devoid cytosolic glycogen-rich areas; and glycogen particles are dispersed in the cytosol in control cells. A tagged PPP1R6 protein at the C-terminus with EGFP shows a diffuse cytosol pattern in glucose-replete and -depleted cells and a punctuate pattern surrounding the nucleus in glucose-depleted cells, which colocates with RFP tagged with the Golgi targeting domain of β-1,4-galactosyltransferase, according to a computational prediction for PPP1R6 Golgi location. Conclusions PPP1R6 exerts a powerful glycogenic effect in cultured muscle cells, more than GM and less than PTG. PPP1R6 protein translocates from a Golgi to cytosolic location in response to glucose. The molecular size and subcellular location of myotube glycogen particles is determined by the PPP1R6, PTG and GM scaffolding.

  2. Chromosomal mapping and mutational analysis of the coding region of the glycogen synthase kinase-3alpha and beta isoforms in patients with NIDDM

    DEFF Research Database (Denmark)

    Hansen, L; Arden, K C; Rasmussen, S B;

    1997-01-01

    Activation of glycogen synthesis in skeletal muscle in response to insulin results from the combined inactivation of glycogen synthase kinase-3 (GSK-3) and activation of the protein phosphatase-1, changing the ratio between the inactive phosphorylated state of the glycogen synthase to the active ...

  3. Liver transplantation

    OpenAIRE

    Rodríguez-Perálvarez, M; De La Mata, M; Burroughs, A K

    2014-01-01

    Purpose of review: Long-term survival of liver transplant recipients is threatened by increased rates of de-novo malignancy and recurrence of hepatocellular carcinoma (HCC), both events tightly related to immunosuppression. Recent findings: There is accumulating evidence linking increased exposure to immunosuppressants and carcinogenesis, particularly concerning calcineurin inhibitors (CNIs), azathioprine and antilymphocyte agents. A recent study including 219 HCC transplanted patients sh...

  4. Liver disease - resources

    Science.gov (United States)

    Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services -- www.classkids.org Hepatitis ...

  5. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. ...

  6. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008075 Effect of Jiangzhi granules on expression of leptin receptor mRNA, P-JAK2 and P-STAT3 in rats with non-alcoholic fatty liver disease. MA Zansong(马赞颂), et al. Dept Gastroenterol, Instit Spleen and Stomach Dis, Longhua Hosp. Shanghai TCM Univ, Shanghai 200032.World Chin J Digestol 2007;15(32):3360-3366. Objective To study the effect of Jiangzhi granules on non-alcoholic fatty liver disease in rats, and on the expression of

  7. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008447 Identification of gene expression patterns in a rat model of nonalcoholic fatty liver disease. ZHANG Xuequn(张雪群), et al. Dept Gastroenterol, 1st Hosp, Med Coll, Zhejiang Univ, Hangzhou 310003. Chin J Dig 2008;28(5):323-327. Objective To compare and analyze gene expression patterns in a rat model of nonalcoholic fatty liver disease (NAFLD). Methods Twelve male Sprague-Dawley rats were randomly given either general diet (control group) or a high-fat diet (model group) for 4 weeks.

  8. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008310 Expression of αVβ3 integrin and platelet-endothelial cell adhesion molecule-1 in progressive liver fibrosis: experiment with rats. SONG Zhengji(宋正已), et al. Dept Gastroenterol, Zhongshan Hosp, Fudan Univ, Shanghai 200032. Natl Med J China 2008;88(16):1121-1125.Objective To investigate the expression ofαVβ3 integrin and platelet endothelial cell adhesion molecule-1(CD31)in progressive liver fibrosis of rats.Methods Sixty-four SD rats were randomly divided into 4 equal groups:TAA group,undergoing peritoneal injection of

  9. A review on laboratory liver function tests

    Directory of Open Access Journals (Sweden)

    Shruthi Kulkarni

    2009-11-01

    Full Text Available Laboratory liver tests are broadly defined as tests useful in the evaluation and treatment of patients with hepatic dysfunction. The liver carries out metabolism of carbohydrate, protein and fats. Some of the enzymes and the end products of the metabolic pathway which are very sensitive for the abnormality occurred may be considered as biochemical marker of liver dysfunction. Some of the biochemical markers such as serum bilirubin, alanine amino transferase, aspartate amino transferase, ratio of aminotransferases, alkaline phosphatase, gamma glutamyl transferase, 5´ nucleotidase, ceruloplasmin, alpha-fetoprotein are considered in this article. An isolated or conjugated alteration of biochemical markers of liver damage in patients can challenge the clinicians during the diagnosis of disease related to liver directly or with some other organs. The term “liver chemistry tests” is a frequently used but poorly defined phrase that encompasses the numerous serum chemistries that can be assayed to assess hepatic function and/or injury.

  10. The effects of glycogen synthase kinase-3beta in serotonin neurons.

    Directory of Open Access Journals (Sweden)

    Wenjun Zhou

    Full Text Available Glycogen synthase kinase-3 (GSK3 is a constitutively active protein kinase in brain. Increasing evidence has shown that GSK3 acts as a modulator in the serotonin neurotransmission system, including direct interaction with serotonin 1B (5-HT1B receptors in a highly selective manner and prominent modulating effect on 5-HT1B receptor activity. In this study, we utilized the serotonin neuron-selective GSK3β knockout (snGSK3β-KO mice to test if GSK3β in serotonin neurons selectively modulates 5-HT1B autoreceptor activity and function. The snGSK3β-KO mice were generated by crossbreeding GSK3β-floxed mice and ePet1-Cre mice. These mice had normal growth and physiological characteristics, similar numbers of tryptophan hydroxylase-2 (TpH2-expressing serotonin neurons, and the same brain serotonin content as in littermate wild type mice. However, the expression of GSK3β in snGSK3β-KO mice was diminished in TpH2-expressing serotonin neurons. Compared to littermate wild type mice, snGSK3β-KO mice had a reduced response to the 5-HT1B receptor agonist anpirtoline in the regulation of serotonergic neuron firing, cAMP production, and serotonin release, whereas these animals displayed a normal response to the 5-HT1A receptor agonist 8-OH-DPAT. The effect of anpirtoline on the horizontal, center, and vertical activities in the open field test was differentially affected by GSK3β depletion in serotonin neurons, wherein vertical activity, but not horizontal activity, was significantly altered in snGSK3β-KO mice. In addition, there was an enhanced anti-immobility response to anpirtoline in the tail suspension test in snGSK3β-KO mice. Therefore, results of this study demonstrated a serotonin neuron-targeting function of GSK3β by regulating 5-HT1B autoreceptors, which impacts serotonergic neuron firing, serotonin release, and serotonin-regulated behaviors.

  11. Advanced glycation end products and the absence of premature atherosclerosis in glycogen storage disease Ia

    NARCIS (Netherlands)

    den Hollander, N. C.; Mulder, Douwe J.; Graaff, R.; Thorpe, S. R.; Baynes, J. W.; Smit, Gerrit; Smit, Andries

    2007-01-01

    Introducton: Despite their unfavourable cardiovascular risk profile, patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis. We hypothesized that this paradox might be related to a decreased formation of advanced glycation end products (AGEs) resulting from

  12. Effects of commonly used cryoprotectants on glycogen phosphorylase activity and structure.

    Science.gov (United States)

    Tsitsanou, K E; Oikonomakos, N G; Zographos, S E; Skamnaki, V T; Gregoriou, M; Watson, K A; Johnson, L N; Fleet, G W

    1999-04-01

    The effects of a number of cryoprotectants on the kinetic and structural properties of glycogen phosphorylase b have been investigated. Kinetic studies showed that glycerol, one of the most commonly used cryoprotectants in X-ray crystallographic studies, is a competitive inhibitor with respect to substrate glucose-1-P with an apparent Ki value of 3.8% (v/v). Cryogenic experiments, with the enzyme, have shown that glycerol binds at the catalytic site and competes with glucose analogues that bind at the catalytic site, thus preventing the formation of complexes. This necessitated a change in the conditions for cryoprotection in crystallographic binding experiments with glycogen phosphorylase. It was found that 2-methyl-2,4-pentanediol (MPD), polyethylene glycols (PEGs) of various molecular weights, and dimethyl sulfoxide (DMSO) activated glycogen phosphorylase b to different extents, by stabilizing its most active conformation, while sucrose acted as a noncompetitive inhibitor and ethylene glycol as an uncompetitive inhibitor with respect to glucose-1-P. A parallel experimental investigation by X-ray crystallography showed that, at 100 K, both MPD and DMSO do not bind at the catalytic site, do not induce any significant conformational change on the enzyme molecule, and hence, are more suitable cryoprotectants than glycerol for binding studies with glycogen phosphorylase. PMID:10211820

  13. Impaired muscle glycogen resynthesis after a marathon is not caused by decreased muscle GLUT-4 content

    DEFF Research Database (Denmark)

    Asp, S; Rohde, T; Richter, Erik

    1997-01-01

    Our purpose was to investigate whether the slow rate of muscle glycogen resynthesis after a competitive marathon is associated with a decrease in the total muscle content of the muscle glucose transporter (GLUT-4). Seven well-trained marathon runners participated in the study, and muscle biopsies...

  14. A patient with common glycogen storage disease type Ib mutations without neutropenia or neutrophil dysfunction

    NARCIS (Netherlands)

    Martens, DHJ; Kuijpers, TW; Maianski, NA; Rake, JP; Smit, GPA; Visser, G

    2006-01-01

    We describe a 16-year old boy with glycogen storage disease type Ib, homozygous for the common 1211-1212delCT mutation, who never experienced neutropenia, and did not suffer from frequent infections or inflammatory bowel disease. In addition, neutrophil function tests showed no abnormalities.

  15. RENAL-FUNCTION AND KIDNEY SIZE IN GLYCOGEN-STORAGE-DISEASE TYPE-I

    NARCIS (Netherlands)

    REITSMABIERENS, WCC; SMIT, GPA; TROELSTRA, JA

    1992-01-01

    Renal failure has been reported recently as a late complication of glycogen storage disease type I (GSD I). We studied the renal function of 23 patients, mean age 10.9 years (range 2.2-21.6 years). The mean glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were 188 +/- 50 and 9

  16. 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

    ingestion. Methods: In previously untrained males performance and various muscular adaptations were evaluated before and after 8 weeks of supervised endurance training conducted either with (n = 8; CHO group) or without (n = 7; placebo) glucose supplementation. Results: The two groups achieved similar.......05), while resting muscle glycogen increased (P supplementation consumed during exercise training influences various muscular training adaptations, but improvements...

  17. Reduced glycogen availability is associated with an elevation in HSP72 in contracting human skeletal muscle

    DEFF Research Database (Denmark)

    Febbraio, Mark A; Steensberg, Adam; Walsh, Rory;

    2002-01-01

    glycogen content was 40 % lower in the depleted compared with the control leg and this difference was maintained throughout the experiment (P < 0.05; main treatment effect). Neither HSP72 gene nor protein expression was different pre-exercise. However, both HSP72 gene and protein increased (P < 0.05) post...

  18. Muscle glycogen resynthesis during recovery from cycle exercise: no effect of additional protein ingestion

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Shirreffs, S M; Calbet, J A

    2000-01-01

    In the present study, we have investigated the effect of carbohydrate and protein hydrolysate ingestion on muscle glycogen resynthesis during 4 h of recovery from intense cycle exercise. Five volunteers were studied during recovery while they ingested, immediately after exercise, a 600-ml bolus...

  19. Epigenetic regulation in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Pranoti Mandrekar

    2011-01-01

    Alcoholic liver disease (ALD) is characterized by steatosis or fat deposition in the liver and inflammation, which leads to cirrhosis and hepatocellular carcinoma. Induction of target genes without involving changes in DNA sequence seems to contribute greatly to liver injury. Chromatin modifications including alterations in histones and DNA, as well as post-transcriptional changes collectively referred to as epigenetic effects are altered by alcohol. Recent studies have pointed to a significant role for epigenetic mechanisms at the nucleosomal level influencing gene expression and disease outcome in ALD. Specifically, epigenetic alterations by alcohol include histone modifications such as changes in acetylation and phosphorylation, hypomethylation of DNA, and alterations in miRNAs. These modifications can be induced by alcohol-induced oxidative stress that results in altered recruitment of transcriptional machinery and abnormal gene expression. Delineating these mechanisms in initiation and progression of ALD is becoming a major area of interest. This review summarizes key epigenetic mechanisms that are dysregulated by alcohol in the liver. Alterations by alcohol in histone and DNA modifications, enzymes related to histone acetylation such as histone acetyltransferases, histone deacetylases and sirtuins, and methylation enzymes such as DNA methyltransferases are discussed. Chromatin modifications and miRNA alterations that result in immune cell dysfunction contributing to inflammatory cytokine production in ALD is reviewed. Finally, the role of alcohol-mediated oxidative stress in epigenetic regulation in ALD is described. A better understanding of these mechanisms is crucial for designing novel epigenetic based therapies to ameliorate ALD.

  20. Hepato-biliary profile of potential candidate liver progenitor cells from healthy rat liver

    Institute of Scientific and Technical Information of China (English)

    Céric Maerckx; Isabelle Scheers; Tatiana Tondreau; David Campard; Omar Nyabi; Mustapha Najimi; Etienne Sokal

    2012-01-01

    AIM:To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent advanced hepatogenic profile as that obtained in humans.METHODS:Rat fibroblastic-like liver derived cells (rFLDC) were obtained from collagenase-isolated liver cell suspensions and characterized and their phenotype profile determined using flow cytometry,immunocyto-chemistry,reverse transcription polymerase chain reaction and functional assays.RESULTS:rFLDC exhibit fibroblastoid morphology,express mesenchymal (CD73,CD90,vimentin,α-smooth muscle actin),hepatocyte (UGT1A1,CK8) and biliary (CK19) markers.Moreover,these cells are able to store glycogen,and have glucose 6 phosphatase activity,but not UGT1A1 activity.Under the hepatogenic differentiation protocol,rFLDC display an up-regulation of hepatocyte markers expression (albumin,tryptophan 2,3-dioxygenase,G6Pase) correlated to a down-regulation of the expression of the biliary marker CK19.CONCLUSION:Advanced hepatic features observed in human liver progenitor cells could not be demonstrated in rFLDC.However,we demonstrated the presence of an original rodent hepato-biliary cell type.

  1. Etiologies of chronic liver disease in children

    Directory of Open Access Journals (Sweden)

    Farahmand F

    2001-11-01

    Full Text Available Chronic Liver diseases in children is the result of many different diseases including: metabolic, genetic, infectious, toxic and idiopathic causes. This was a case series study on 133 infants and children with age range 6 month to 12 years old, who presented clinically with manifestation of chronic liver disease and were admitted to Children Hospital Medical Center from year 1999 to 2000. In this study, 32 (24.5 percent patients had autoimmune chronic hepatitis, 15 (11.3 percent Glycogen storage diseases, 12 (9 percent extrahepatic biliary atresia, 11 (8.2 percent willson disease, 10 (7.5 percent cryptogenic cirrhosis, 6 (4.5 percent chronic hepatitis C, 5 (3.8 percen chronic hepatitic B, 5 (3.8 percent galactosemia 3 (2.25 percent congenital hepatic fibrosis, 3 (3.8 percent histiocytosis X, 3 (2.25 percent sclerosing cholangitis, 2 (1.5 percent byler’s disease 2 (1.5 percent primary tuberculosis, 1 (0.75 percent choledocalcyst, 1 (0.75 percent Alagyle syndrome. According to our data, chronic liver disease should be considered in infants and children. In our study, the most common causes are found to be: metabolic and genetic diseases (37.5 percent, chronic autoimmune hepatitis (24 percent and biliary disorders (14 percent, that encompass 86 percent of the patients.

  2. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970345 An experimental and clinical study on α1-adrenergic receptor of liver plasma membranes in cir-rhosis with portal hypertension. ZHANG Youcheng(张有成), et al. Dept Surg, People’s Hosp, Beijing MedUniv, Beijing, 100044 Chin J Dig 1996; 16(6): 332-335.

  3. Cadmium induced changes in the liver of langurs (Presbytis entellus-entellus dufresne).

    Science.gov (United States)

    Dixit, V P

    1977-01-01

    1- Cadmium-induced hepatic disturbances in Langurs have been studied following a single low dose administration of the salt (Cd Cl2 4 mg/kg s.c.). 2-Serum transaminases, choelsterol and liver glycogen levels were elevated. Alkaline phosphatase levels were in normal range. The blood sugar was at a low level. 3- Degranulation, vacuolization and distortion of the liver cells and lobules were conspicuous. 4- In conclusion this study would indicate that increased serum enzyme activity and increased plasma choelsterol levels are a manifestation of tissue damage. It would seem plausible to translate these observations in terms of similar infarcts occurring in man. PMID:207645

  4. Inhibition of glycogen synthase kinase-3β attenuates glucocorticoid-induced suppression of myogenic differentiation in vitro.

    Directory of Open Access Journals (Sweden)

    Zhenyu Ma

    Full Text Available Glucocorticoids are the only therapy that has been demonstrated to alter the progress of Duchenne muscular dystrophy (DMD, the most common muscular dystrophy in children. However, glucocorticoids disturb skeletal muscle metabolism and hamper myogenesis and muscle regeneration. The mechanisms involved in the glucocorticoid-mediated suppression of myogenic differentiation are not fully understood. Glycogen synthase kinase-3β (GSK-3β is considered to play a central role as a negative regulator in myogenic differentiation. Here, we showed that glucocorticoid treatment during the first 48 h in differentiation medium decreased the level of phosphorylated Ser9-GSK-3β, an inactive form of GSK-3β, suggesting that glucocorticoids affect GSK-3β activity. We then investigated whether GSK-3β inhibition could regulate glucocorticoid-mediated suppression of myogenic differentiation in vitro. Two methods were employed to inhibit GSK-3β: pharmacological inhibition with LiCl and GSK-3β gene knockdown. We found that both methods resulted in enhanced myotube formation and increased levels of muscle regulatory factors and muscle-specific protein expression. Importantly, GSK-3β inhibition attenuated glucocorticoid-induced suppression of myogenic differentiation. Collectively, these data suggest the involvement of GSK-3β in the glucocorticoid-mediated impairment of myogenic differentiation. Therefore, the inhibition of GSK-3β may be a strategy for preventing glucocorticoid-induced muscle degeneration.

  5. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    International Nuclear Information System (INIS)

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  6. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    Energy Technology Data Exchange (ETDEWEB)

    Manceur, Aziza P. [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Tseng, Michael [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Holowacz, Tamara [Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Witterick, Ian [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Department of Otolaryngology, Head and Neck Surgery, University of Toronto, ON (Canada); Weksberg, Rosanna [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); McCurdy, Richard D. [The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); Warsh, Jerry J. [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Audet, Julie, E-mail: julie.audet@utoronto.ca [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada)

    2011-09-10

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  7. Insulin promotes glycogen storage and cell proliferation in primary human astrocytes.

    Directory of Open Access Journals (Sweden)

    Martin Heni

    Full Text Available INTRODUCTION: In the human brain, there are at least as many astrocytes as neurons. Astrocytes are known to modulate neuronal function in several ways. Thus, they may also contribute to cerebral insulin actions. Therefore, we examined whether primary human astrocytes are insulin-responsive and whether their metabolic functions are affected by the hormone. METHODS: Commercially available Normal Human Astrocytes were grown in the recommended medium. Major players in the insulin signaling pathway were detected by real-time RT-PCR and Western blotting. Phosphorylation events were detected by phospho-specific antibodies. Glucose uptake and glycogen synthesis were assessed using radio-labeled glucose. Glycogen content was assessed by histochemistry. Lactate levels were measured enzymatically. Cell proliferation was assessed by WST-1 assay. RESULTS: We detected expression of key proteins for insulin signaling, such as insulin receptor β-subunit, insulin receptor substrat-1, Akt/protein kinase B and glycogen synthase kinase 3, in human astrocytes. Akt was phosphorylated and PI-3 kinase activity increased following insulin stimulation in a dose-dependent manner. Neither increased glucose uptake nor lactate secretion after insulin stimulation could be evidenced in this cell type. However, we found increased insulin-dependent glucose incorporation into glycogen. Furthermore, cell numbers increased dose-dependently upon insulin treatment. DISCUSSION: This study demonstrated that human astrocytes are insulin-responsive at the molecular level. We identified glycogen synthesis and cell proliferation as biological responses of insulin signaling in these brain cells. Hence, this cell type may contribute to the effects of insulin in the human brain.

  8. High density lipoprotein (HDL promotes glucose uptake in adipocytes and glycogen synthesis in muscle cells.

    Directory of Open Access Journals (Sweden)

    Qichun Zhang

    Full Text Available BACKGROUND: High density lipoprotein (HDL was reported to decrease plasma glucose and promote insulin secretion in type 2 diabetes patients. This investigation was designed to determine the effects and mechanisms of HDL on glucose uptake in adipocytes and glycogen synthesis in muscle cells. METHODS AND RESULTS: Actions of HDL on glucose uptake and GLUT4 translocation were assessed with 1-[(3H]-2-deoxyglucose and plasma membrane lawn, respectively, in 3T3-L1 adipocytes. Glycogen analysis was performed with amyloglucosidase and glucose oxidase-peroxidase methods in normal and palmitate-treated L6 cells. Small interfering RNA was used to observe role of scavenger receptor type I (SR-BI in glucose uptake of HDL. Corresponding signaling molecules were detected by immunoblotting. HDL stimulated glucose uptake in a time- and concentration-dependent manner in 3T3-L1 adipocytes. GLUT4 translocation was significantly increased by HDL. Glycogen deposition got enhanced in L6 muscle cells paralleling with elevated glycogen synthase kinase3 (GSK3 phosphorylation. Meanwhile, increased phosphorylations of Akt-Ser473 and AMP activated protein kinase (AMPK α were detected in 3T3-L1 adipocytes. Glucose uptake and Akt-Ser473 activation but not AMPK-α were diminished in SR-BI knock-down 3T3-L1 cells. CONCLUSIONS: HDL stimulates glucose uptake in 3T3-L1 adipocytes through enhancing GLUT4 translocation by mechanisms involving PI3K/Akt via SR-BI and AMPK signaling pathways, and increases glycogen deposition in L6 muscle cells through promoting GSK3 phosphorylation.

  9. Effects of short and long term exercise on intracellular glycogen and fat in pigeon pectoralis.

    Science.gov (United States)

    Parker, G H; George, J C

    1975-01-01

    In an attempt to determine the functional role of the component broad white and narrow red fibre types during activity, the pectroalis muscle of the adult pigeon (Columba livia) was electrically stimulated in situ after anaesthetizing the birds with sodium pentobarbital. For examination of the effect of short term exercise, the pectoral muscle of one side was stimulated through the innervating brachial plexus, using an electronic stimulator for 1 hr, and a biopsy sample was taken from the stimulated muscle. The stimulation was resumed for 17 hr more with additional doses of anaesthesia, and a muscle sample was taken after the decapitation of the birds in the long term experiment. Muscle samples from non-stimulated pigeons under identical conditions served as control. Fixed and frozen sections were made from the samples and were stained with Periodic Acid-Schiff's reagent for the demonstration of glycogen, while additional frozen muscle sections were stained with Fettrot 7B according to Pearse, A.G.E. (1960) for the demonstration of neutral lipids in the specimen. Thus histochemical examinations were made to study effects of short and long term exercises on energy stores in skeletal muscles. Short-term stimulation resulted in a selective depletion of intracellular glycogen stores from white fibre populations whereas prolonged long term stimulation resulted in the resynthesis of glycogen within these fibres and a concomitant reduction in the intracellular fat and glycogen reserves in most red fibres. It is postulated that during flight the white fibres indulge only in brief bursts of intense phasic activity such as in quick take-off, rapid accelerations or sudden manoeuvres and utilize glycogen as fuel whereas the red fibres perform sustained activity as in cruising flight and metabolize chiefly fat.

  10. Cypermethrin-Induced Toxic Effect on Glycogen Metabolism in Estuarine Clam, Marcia Opima (Gmelin, 1791 of Ratnagiri Coast, Maharashtra

    Directory of Open Access Journals (Sweden)

    Medha Tendulkar

    2012-01-01

    Full Text Available Cypermethrin is a synthetic pyrethroid class of insecticide. Toxic effects of cypermethrin were studied by selecting Marcia opima as an animal model. Cypermethrins effect on the total glycogen content of mantle, gill, foot, hepatopancreas, male gonad and a female gonad of an estuarine clam, Marcia opima was examined. The clams were exposed to 1.58 ppm cypermethrin for acute and 1/th of that concentration for chronic treatment. It was found that there was a decrease in glycogen content in various tissues as compared to control. In LC0 and LC50 groups, glycogen was decreased in all tissues except in hepatopancreas compared to control. This decrease is greater in mantle, gill, and foot in LC50 group than the decrease in those tissues of LC0 group. In chronic exposure it was found that glycogen was decreased in mantle, foot, male gonad, and female gonad when compared to the control group except in gill and hepatopancreas. Decrease in glycogen content indicates greater utilization of glycogen for metabolic purposes and too combat with cypermethrin stress. The significant increase in glycogen content in gill and hepatopancreas may be a reaction to the increase in energy demand.

  11. Palmitate action to inhibit glycogen synthase and stimulate protein phosphatase 2A increases with risk factors for type 2 diabetes.

    Science.gov (United States)

    Mott, David M; Stone, Karen; Gessel, Mary C; Bunt, Joy C; Bogardus, Clifton

    2008-02-01

    Recent studies have suggested that abnormal regulation of protein phosphatase 2A (PP2A) is associated with Type 2 diabetes in rodent and human tissues. Results with cultured mouse myotubes support a mechanism for palmitate activation of PP2A, leading to activation of glycogen synthase kinase 3. Phosphorylation and inactivation of glycogen synthase by glycogen synthase kinase 3 could be the mechanism for long-chain fatty acid inhibition of insulin-mediated carbohydrate storage in insulin-resistant subjects. Here, we test the effects of palmitic acid on cultured muscle glycogen synthase and PP2A activities. Palmitate inhibition of glycogen synthase fractional activity is increased in subjects with high body mass index compared with subjects with lower body mass index (r = -0.43, P = 0.03). Palmitate action on PP2A varies from inhibition in subjects with decreased 2-h plasma glucose concentration to activation in subjects with increased 2-h plasma glucose concentration (r = 0.45, P < 0.03) during oral glucose tolerance tests. The results do not show an association between palmitate effects on PP2A and glycogen synthase fractional activity. We conclude that subjects at risk for Type 2 diabetes have intrinsic differences in palmitate regulation of at least two enzymes (PP2A and glycogen synthase), contributing to abnormal insulin regulation of glucose metabolism.

  12. Liver function

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930536 Applied anatomy for interhepatic porto-caval shunt.DU Xiangke(杠湘珂),et al.DeptRadiol,Beijing People’s Hosp,Beijing Med U-niv,Beijing,100044.Chin J Radiol 1993;27(3):148—151.The results of measurement of the anatormicalrelationship of hepatic and portal vein in 70 hu-man liver specimens were reported including theirdistance and overlapping areas.The resultsdemonstrated that,when the catheter enteredthe posterior segment of IVC in the liver andthen passed into the left,middle or right branch-es of hepatic vein for an average of 4—5cm,thesegmental branches of portal vein would be over-lapped.The authors suggested that the catheter

  13. Engineering liver

    OpenAIRE

    Griffith, Linda G.; Wells, Alan; Stolz, Donna Beer

    2013-01-01

    Interest in “engineering liver” arises from multiple communities: therapeutic replacement; mechanistic models of human processes; and drug safety and efficacy studies. An explosion of micro- and nano-fabrication, biomaterials, microfluidic, and other technologies potentially afford unprecedented opportunity to create microphysiological models of human liver, but engineering design principles for how to deploy these tools effectively towards specific applications, including how to define the e...

  14. Towards a new therapy protocol for liver metastases. Effect of boron compounds and BNCT on normal liver regeneration

    International Nuclear Information System (INIS)

    The Taormina project developed a new method for BNCT treatment of multifocal unresectable liver metastases based on whole liver autograft. The Roffo Institute liver surgeons propose a new technique based on partial liver autograft that would pose less risk to the patient but would require significant healthy liver regeneration following BNCT. The aim of the present study was to assess the effect of BPA, GB-10 (Na210B10H10) and (GB-10 + BPA) and of BNCT mediated by these boron compounds on normal liver regeneration in the Wistar rat. Normal liver regeneration, body weight, hemogram, liver and kidney function were assessed following partial hepatectomy post administration of BPA, GB-10 or (GB-10 + BPA) and post in vivo BNCT at the RA-6 Reactor. These end-points were evaluated 9 days following partial hepatectomy, the time at which complete liver regeneration occurs in untreated controls. The corresponding biodistribution studies were conducted to perform dosimetric calculations. BPA, GB-10 and (GB-10 + PBA) and in vivo BNCT mediated by these boron compounds in dose ranges compatible with therapy did not cause alterations in the outcome of normal liver regeneration, and did not induce alterations in body weight, hemogram, liver or kidney function. The experimental data available to date support the development of a new BNCT protocol for the treatment of liver metastases that requires the regeneration of normal liver past-BNCT. (author)

  15. 合并脓毒症的肝移植患者免疫状态的变化特点%Alterations of immune status in liver transplant patients with sepsis

    Institute of Scientific and Technical Information of China (English)

    李敏如; 汪根树; 汪国营; 张琪; 陈规划

    2012-01-01

    Objective To explore the alterations of immune status in liver transplant recipients with sepsis so as to provide rationales for the adjustments of immunosuppressive agents.Methods A total of 47 cases complicated with sepsis after abdominal operations from January 2009 to December 2010 were divided into 4 groups according to the type of operations and the stage of sepsis:A.sepsis after transplantation ( TS,n =11 ),B.severe sepsis after transplantation ( TSS,n =10),C.sepsis without transplantation ( NTS,n =15) and D.severe sepsis without transplantation (NTSS,n =11 ).Ten healthy volunteers were selected as the control group.Blood samples were collected from these patients to measure the immunological parameters associated with T lymphocyte.Results The APACH Ⅱ and SOFA score of TSS group and NTSS group were both higher than TS group and NTS group respectively (all P < 0.01 ). In addition,SOFA score in TSS group was significantly higher than that in NTSS group ( 17.0 + 4.5 vs 12.1 ± 2.8,P < 0.01 ).The percentages of T cell in 4 groups were all significantly lower than healthy volunteers ( all P < 0.01 ).The CD4/CD8 ratio was slightly lower in the TSS group than those in the control group and the other three groups ( P =0.095 ).As compared with the control group,the IFN-γ/IL-4 ratios were significant lower in the TSS and NTSS groups (0.039 +0.012,0.047 ± 0.018 vs 0.062 + 0.006) while the level of IL-10 was higher ( (32.6±7.5),(25.9 +4.3) vs (8.2 ± 1.4)ng/L,all P <0.05).And the difference was more significant in the TSS group.As compared with the healther,the percentage of CD4 + CD25 + Foxp3 + Treg was lower in NTS group (2.21% ± 0.96% vs 4.06% ± 0.52%,P < 0.01 ),and significantly higher in NTSS group (8.02% ± 3.57% vs 4.06% ±0.52%,P =0.003).No significant difference existed in the percentage of Treg between the TS and control groups (P =0.398).And it was significantly higher that in the TSS group (5.16% ±0.99% vs 4.06% ±0

  16. Studies of methanolic extract of Amaranthus paniculatus L. on Mice Liver against

    Energy Technology Data Exchange (ETDEWEB)

    Jain, M.; Sisodia, R.; Bhatia, A. I.

    2004-07-01

    India has a rich heritage of medicinal plants, many of which have been explored for the various bioactivities since ages, but the radioprotective potential of the plants have been hardly explored. Since Amaranthus, a common weed and very often caten as vegetable by rural population, has been used as emollient, astringent, diuretic, blood purifier, hemorrhagic diathesis and biliousness from time immemorial. Hence the present study aims to judge whether Amaranthus paniculatus (Linn) has the antiradiation efficacy against radiation induced histopathological and biochemical alterations in mice liver. Amaranthus paniculatus (Linn) belongs to family Amaranthaceae and commonly called as Amaranth, has good natural sources of carotenoids (beta carotene-1490 {mu}g/100 gm of edible portion), vitamin C and high level of critical lysine and methionine, protein content (22 gm/100 gm of edible portion). Swiss albino mice of 6-8 weeks weighing 22 {+-} 3 gm were selected from an inbred colony and divided into four groups. One group served as normal and two groups were administered with alcoholic extract at a dose of 600 mg/Kg-body weight/day dissolved in distilled water for fifteen days. Fourth group was given distilled water, orally and ad libitum. Then two groups, one with drug treated and another with distilled water treated, were exposed to 5 Gy of gamma radiation at the dose rate of 1.07 Gy/min with a source to surface distance (SSD) of 77.5 cm. The animals were autopsied at 1, 3, 7, 15 and 30 days post exposure. the optimum dose was calculated to be 600mg/kg b.wt/day after treating mice with AE for fifteen consecutive days prior to irradiation (9 Gy) to get maximum protection against radiation injury. By the survival assay, DRF 1.43 was calculated with different doses of gammas radiation (6, 9, 12 Gy). The radiation induced augmentation in MDA, protein, glycogen, alkaline and acid phosphatase content of liver is significantly ameliorated by the drug. The radiation induced

  17. Studies of methanolic extract of Amaranthus paniculatus L. on Mice Liver against

    International Nuclear Information System (INIS)

    India has a rich heritage of medicinal plants, many of which have been explored for the various bioactivities since ages, but the radioprotective potential of the plants have been hardly explored. Since Amaranthus, a common weed and very often caten as vegetable by rural population, has been used as emollient, astringent, diuretic, blood purifier, hemorrhagic diathesis and biliousness from time immemorial. Hence the present study aims to judge whether Amaranthus paniculatus (Linn) has the antiradiation efficacy against radiation induced histopathological and biochemical alterations in mice liver. Amaranthus paniculatus (Linn) belongs to family Amaranthaceae and commonly called as Amaranth, has good natural sources of carotenoids (beta carotene-1490 μg/100 gm of edible portion), vitamin C and high level of critical lysine and methionine, protein content (22 gm/100 gm of edible portion). Swiss albino mice of 6-8 weeks weighing 22 ± 3 gm were selected from an inbred colony and divided into four groups. One group served as normal and two groups were administered with alcoholic extract at a dose of 600 mg/Kg-body weight/day dissolved in distilled water for fifteen days. Fourth group was given distilled water, orally and ad libitum. Then two groups, one with drug treated and another with distilled water treated, were exposed to 5 Gy of gamma radiation at the dose rate of 1.07 Gy/min