WorldWideScience

Sample records for hepatic glycogen repletion

  1. 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

  2. Free fatty acids increase hepatic glycogen content in obese males

    NARCIS (Netherlands)

    Allick, G.; Sprangers, F.; Weverling, G. J.; Ackermans, M. T.; Meijer, A. J.; Romijn, J. A.; Endert, E.; Bisschop, P. H.; Sauerwein, H. P.

    2004-01-01

    Obesity is associated with increased hepatic glycogen content. In vivo and in vitro data suggest that plasma free fatty acids (FFA) may cause this increase. In this study we investigated the effect of physiological plasma FFA levels on hepatic glycogen metabolism by studying intrahepatic glucose

  3. Pre-Exercise High-Fat Diet for 3 Days Affects Post-Exercise Skeletal Muscle Glycogen Repletion

    National Research Council Canada - National Science Library

    TAKAHASHI, Yumiko; MATSUNAGA, Yutaka; TAMURA, Yuki; TERADA, Shin; HATTA, Hideo

    2017-01-01

    ...) solution immediately after and at 60 min after exercise. A negative main effect of pre-exercise HFD intake was observed for skeletal muscle glycogen concentration from the pre-exercise phase to 120 min of post-exercise recovery (p<0.01...

  4. 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....

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

    NARCIS (Netherlands)

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

    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,

  6. 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.

  7. Activation of Basal Gluconeogenesis by Coactivator p300 Maintains Hepatic Glycogen Storage

    Science.gov (United States)

    Cao, Jia; Meng, Shumei; Ma, Anlin; Radovick, Sally; Wondisford, Fredric E.

    2013-01-01

    Because hepatic glycogenolysis maintains euglycemia during early fasting, proper hepatic glycogen synthesis in the fed/postprandial states is critical. It has been known for decades that gluconeogenesis is essential for hepatic glycogen synthesis; however, the molecular mechanism remains unknown. In this report, we show that depletion of hepatic p300 reduces glycogen synthesis, decreases hepatic glycogen storage, and leads to relative hypoglycemia. We previously reported that insulin suppressed gluconeogenesis by phosphorylating cAMP response element binding protein-binding protein (CBP) at S436 and disassembling the cAMP response element-binding protein-CBP complex. However, p300, which is closely related to CBP, lacks the corresponding S436 phosphorylation site found on CBP. In a phosphorylation-competent p300G422S knock-in mouse model, we found that mutant mice exhibited reduced hepatic glycogen content and produced significantly less glycogen in a tracer incorporation assay in the postprandial state. Our study demonstrates the important and unique role of p300 in glycogen synthesis through maintaining basal gluconeogenesis. PMID:23770612

  8. Rhodiola crenulata extract regulates hepatic glycogen and lipid metabolism via activation of the AMPK pathway.

    Science.gov (United States)

    Lin, Kuen-Tze; Hsu, Shih-Wei; Lai, Feng-Yi; Chang, Tsu-Chung; Shi, Li-Shian; Lee, Shih-Yu

    2016-05-17

    Metabolic syndrome may lead to many complications, such as nonalcoholic fatty liver disease (NAFLD). A natural and effective therapeutic agent for patients with NAFLD is urgently needed. In a previous study, we showed that Rhodiola crenulata root extract (RCE) regulated hepatic gluconeogenesis through activation of AMPK signaling. However, the manner in which RCE regulates hepatic lipid and glycogen metabolism remains unclear. The current study was conducted to investigate the effects of RCE on hepatic glycogen and lipid metabolism, as well as the mechanisms underlying such effects. Human hepatoma HepG2 cells were treated with RCE for 6 h under high glucose conditions, after which glycogen synthesis, lipogenesis, and relative gene expression were examined. In addition, lipogenesis-related genes were investigated in vivo. RCE significantly increased glycogen synthesis and inhibited lipogenesis, while regulating genes related to these processes, including glycogen synthase kinase 3β (GSK3β), glycogen synthase (GS), fatty acid synthase (FAS), CCAAT/enhancer-binding protein (C/EBP), and sterol regulatory element-binding protein 1c (SREBP-1c). However, the effects caused by RCE were neutralized by compound C, an AMPK antagonist. Further studies showed that expression levels of lipogenic genes decreased at the protein and mRNA levels in the rat liver. Our results demonstrate that RCE regulates hepatic glycogen and lipid metabolism through the AMPK signaling pathway. These results suggest that RCE is a potential intervention for patients with NAFLD.

  9. A novel mechanism for regulating hepatic glycogen synthesis involving serotonin and cyclin-dependent kinase-5.

    Science.gov (United States)

    Tudhope, Susan J; Wang, Chung-Chi; Petrie, John L; Potts, Lloyd; Malcomson, Fiona; Kieswich, Julius; Yaqoob, Muhammad M; Arden, Catherine; Hampson, Laura J; Agius, Loranne

    2012-01-01

    Hepatic autonomic nerves regulate postprandial hepatic glucose uptake, but the signaling pathways remain unknown. We tested the hypothesis that serotonin (5-hydroxytryptamine [5-HT]) exerts stimulatory and inhibitory effects on hepatic glucose disposal. Ligands of diverse 5-HT receptors were used to identify signaling pathway(s) regulating glucose metabolism in hepatocytes. 5-HT had stimulatory and inhibitory effects on glycogen synthesis in hepatocytes mediated by 5-HT1/2A and 5-HT2B receptors, respectively. Agonists of 5-HT1/2A receptors lowered blood glucose and increased hepatic glycogen after oral glucose loading and also stimulated glycogen synthesis in freshly isolated hepatocytes with greater efficacy than 5-HT. This effect was blocked by olanzapine, an antagonist of 5-HT1/2A receptors. It was mediated by activation of phosphorylase phosphatase, inactivation of glycogen phosphorylase, and activation of glycogen synthase. Unlike insulin action, it was not associated with stimulation of glycolysis and was counteracted by cyclin-dependent kinase (cdk) inhibitors. A role for cdk5 was supported by adaptive changes in the coactivator protein p35 and by elevated glycogen synthesis during overexpression of p35/cdk5. These results support a novel mechanism for serotonin stimulation of hepatic glycogenesis involving cdk5. The opposing effects of serotonin, mediated by distinct 5-HT receptors, could explain why drugs targeting serotonin function can cause either diabetes or hypoglycemia in humans.

  10. 13C MRS Studies of the Control of Hepatic Glycogen Metabolism at High Magnetic Fields

    Directory of Open Access Journals (Sweden)

    Corin O. Miller

    2017-06-01

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

  11. Hormonal control of hepatic glycogen metabolism in food-deprived, continuously swimming coho salmon Oncorhynchus kisutch

    Science.gov (United States)

    Vijayan, M.M.; Maule, A.G.; Schreck, C.B.; Moon, T.W.

    1993-01-01

    The plasma cortisol concentration and liver cytosolic glucocorticoid receptor activities of continuously swimming, food-deprived coho salmon (Oncorhynchus kisutch) did not differ from those of resting, fed fish. Plasma glucose concentration was significantly higher in the exercising, starved fish, but there were no significant differences in either hepatic glycogen concentration or hepatic activities of glycogen phosphorylase, glycogen synthase, pyruvate kinase, or lactate dehydrogenase between the two groups. Total glucose production by hepatocytes did not differ significantly between the two groups; glycogen breakdown accounted for all the glucose produced in the resting, fed fish whereas it explained only 59% of the glucose production in the exercised animals. Epinephrine and glucagon stimulation of glucose production by hepatocytes was decreased in the exercised fish without significantly affecting hepatocyte glycogen breakdown in either group. Insulin prevented glycogen breakdown and enhanced glycogen deposition in exercised fish. The results indicate that food-deprived, continuously swimming coho salmon conserve glycogen by decreasing the responsiveness of hepatocytes to catabolic hormones and by increasing the responsiveness to insulin (anabolic hormone).

  12. 13C Mrs Studies of the Control of Hepatic Glycogen Metabolism at High Magnetic Fields

    Science.gov (United States)

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

    2017-06-01

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

  13. Prevalent role of the insulin receptor isoform A in the regulation of hepatic glycogen metabolism in hepatocytes and in mice.

    Science.gov (United States)

    Diaz-Castroverde, Sabela; Baos, Selene; Luque, María; Di Scala, Marianna; González-Aseguinolaza, Gloria; Gómez-Hernández, Almudena; Beneit, Nuria; Escribano, Oscar; Benito, Manuel

    2016-12-01

    In the postprandial state, the liver regulates glucose homeostasis by glucose uptake and conversion to glycogen and lipids. Glucose and insulin signalling finely regulate glycogen synthesis through several mechanisms. Glucose uptake in hepatocytes is favoured by the insulin receptor isoform A (IRA), rather than isoform B (IRB). Thus, we hypothesised that, in hepatocytes, IRA would increase glycogen synthesis by promoting glucose uptake and glycogen storage. We addressed the role of insulin receptor isoforms on glycogen metabolism in vitro in immortalised neonatal hepatocytes. In vivo, IRA or IRB were specifically expressed in the liver using adeno-associated virus vectors in inducible liver insulin receptor knockout (iLIRKO) mice, a model of type 2 diabetes. The role of IR isoforms in glycogen synthesis and storage in iLIRKO was subsequently investigated. In immortalised hepatocytes, IRA, but not IRB expression induced an increase in insulin signalling that was associated with elevated glycogen synthesis, glycogen synthase activity and glycogen storage. Similarly, elevated IRA, but not IRB expression in the livers of iLIRKO mice induced an increase in glycogen content. We provide new insight into the role of IRA in the regulation of glycogen metabolism in cultured hepatocytes and in the livers of a mouse model of type 2 diabetes. Our data strongly suggest that IRA is more efficient than IRB at promoting glycogen synthesis and storage. Therefore, we suggest that IRA expression in the liver could provide an interesting therapeutic approach for the regulation of hepatic glucose content and glycogen storage.

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

    OpenAIRE

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

    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 analyz...

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

    Science.gov (United States)

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

    2017-06-23

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

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

    Directory of Open Access Journals (Sweden)

    Jefferson Pacheco Amaral Fortes

    2017-12-01

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

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

    Science.gov (United States)

    Derks, Terry G J; van Rijn, Margreet

    2015-05-01

    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, hyperlipidemias are of a different origin. Hypertriglyceridemia is most prominent in GSD type Ia and associated with long-term outcome morbidity, like pancreatitis and hepatic adenomas. In the ketotic subtypes of GSD, hypertriglyceridemia reflects the age-dependent fasting intolerance, secondary lipolysis and increased mitochondrial fatty acid oxidation. The role of high protein diets is established for ketotic types of GSD, but non-traditional dietary interventions (like medium-chain triglycerides and the ketogenic diet) in hepatic GSD are still controversial and necessitate further studies. Patients with these rare inherited disorders of carbohydrate metabolism meet several criteria of the metabolic syndrome, therefore close monitoring for cardiovascular diseases in ageing GSD patients may be justified.

  18. Downregulation of SIRT1 signaling underlies hepatic autophagy impairment in glycogen storage disease type Ia.

    Directory of Open Access Journals (Sweden)

    Jun-Ho Cho

    2017-05-01

    Full Text Available A deficiency in glucose-6-phosphatase-α (G6Pase-α in glycogen storage disease type Ia (GSD-Ia leads to impaired glucose homeostasis and metabolic manifestations including hepatomegaly caused by increased glycogen and neutral fat accumulation. A recent report showed that G6Pase-α deficiency causes impairment in autophagy, a recycling process important for cellular metabolism. However, the molecular mechanism underlying defective autophagy is unclear. Here we show that in mice, liver-specific knockout of G6Pase-α (L-G6pc-/- leads to downregulation of sirtuin 1 (SIRT1 signaling that activates autophagy via deacetylation of autophagy-related (ATG proteins and forkhead box O (FoxO family of transcriptional factors which transactivate autophagy genes. Consistently, defective autophagy in G6Pase-α-deficient liver is characterized by attenuated expressions of autophagy components, increased acetylation of ATG5 and ATG7, decreased conjugation of ATG5 and ATG12, and reduced autophagic flux. We further show that hepatic G6Pase-α deficiency results in activation of carbohydrate response element-binding protein, a lipogenic transcription factor, increased expression of peroxisome proliferator-activated receptor-γ (PPAR-γ, a lipid regulator, and suppressed expression of PPAR-α, a master regulator of fatty acid β-oxidation, all contributing to hepatic steatosis and downregulation of SIRT1 expression. An adenovirus vector-mediated increase in hepatic SIRT1 expression corrects autophagy defects but does not rectify metabolic abnormalities associated with G6Pase-α deficiency. Importantly, a recombinant adeno-associated virus (rAAV vector-mediated restoration of hepatic G6Pase-α expression corrects metabolic abnormalities, restores SIRT1-FoxO signaling, and normalizes defective autophagy. Taken together, these data show that hepatic G6Pase-α deficiency-mediated down-regulation of SIRT1 signaling underlies defective hepatic autophagy in GSD-Ia.

  19. Hepatic Glucose Production Increases in Response to Metformin Treatment in the Glycogen-depleted State

    DEFF Research Database (Denmark)

    Christensen, Mette Marie Hougaard; Højlund, Kurt; Hother-Nielsen, Ole

    Metformin is believed to reduce glucose levels primarily by inhibiting hepatic glucose production, but at the same time do not cause hypoglycemia. Recent data indicate that metformin antagonizes the major glucose counterregulatory hormone, glucagon suggesting that other mechanisms protect against...... hypoglycemia. Here, we examined the effect of metformin on whole-body glucose metabolism after a glycogen-depleting 40 h fast and the role of reduced-function alleles in OCT1. In a randomized cross-over trial, 34 healthy volunteers with known OCT1 genotypes (12 with two wild-type alleles, 13 with one and 9...... with two reduced-function alleles) were fasted for 42 h twice. In one of the periods, before the fasting, the volunteers were titrated to steady-state with 1 g metformin twice daily for seven days. Parameters of whole-body glucose metabolism were assessed using [3-3^H] glucose, indirect calorimetry...

  20. Resistance imparted by vitamin C, vitamin E and vitamin B12 to the acute hepatic glycogen change in rats caused by noise.

    Science.gov (United States)

    Zhu, Bei-Wei; Piao, Mei-Lan; Zhang, Yu; Han, Song; An, Qing-Da; Murata, Yoshiyuki; Tada, Mikiro

    2006-04-01

    The effects of vitamin C, vitamin E and vitamin B12 on the noise-induced acute change in hepatic glycogen content in rats were investigated. The exposure of rats to 95 dB and 110 dB of noise acutely reduced their hepatic glycogens. Vitamin C (ascorbic acid) and vitamin E (alpha-tocopherol) attenuated the noise-induced acute reduction in the hepatic glycogen contents. This result suggests that antioxidants could reduce the change via reactive oxygen species. Vitamin B12 (cobalamin) delayed the noise-induced change, a finding that suggests that vitamin B12 could postpone the acute change via compensating for vitamin B12 deficiency.

  1. Cod liver oil ameliorates sodium nitrite-induced insulin resistance and degradation of rat hepatic glycogen through inhibition of cAMP/PKA pathway.

    Science.gov (United States)

    Al-Gayyar, Mohammed M H; Alyoussef, Abdullah; Hamdan, Ahmed M; Abbas, Ahmed; Darweish, Mohamed M; El-Hawwary, Amany A

    2015-01-01

    Sodium nitrite is used to inhibit the growth of microorganisms and is responsible for the desirable red color of meat; however, it can be toxic in high quantities for humans and other animals. Moreover, glycogen, a branched polysaccharide, efficiently stores and releases glucose monosaccharides to be accessible for metabolic and synthetic requirements of the cell. Therefore, we examined the impact of dietary sodium nitrite and cod liver oil on liver glycogen. Thirty-two Sprague-Dawley rats were treated daily with sodium nitrite (80 mg/kg) in the presence/absence of cod liver oil (5 ml/kg). Liver sections were stained with Periodic acid-Schiff. Hepatic homogenates were used for measurements of glycogen, cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), glycogen synthase, glycogen synthase kinase, pyruvate carboxylase, fructose 1,6-diphosphatase, glucose 6-phosphatase, phosphodiesterase and glycogen phosphorylase. Glucose, pyruvate tolerances and HOMA insulin resistance were also determined. Sodium nitrite significantly increased plasma glucose and insulin resistance. Moreover, sodium nitrite significantly reduced hepatic glycogen content as well as activities of glycogen synthase, glycogen synthase kinase-3, and phosphodiesterase. Sodium nitrite elevated hepatic cAMP, PKA, pyruvate carboxylase, fructose 1,6-diphosphatase, glucose 6-phosphatase and phosphorylase. Cod liver oil significantly blocked all of these except pyruvate carboxylase, fructose 1,6-diphosphatase and glucose 6-phosphatase. Sodium nitrite inhibited liver glycogenesis and enhanced liver glycogenolysis and gluconeogenesis, which is accompanied by hyperglycemia and insulin resistance through the activation of cAMP/PKA and the inhibition of phosphodiesterase. Cod liver oil blocked the sodium nitrite effects on glycogenesis and glycogenolysis without affecting gluconeogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Dietary Methionine Restriction Alleviates Hyperglycemia in Pigs with Intrauterine Growth Restriction by Enhancing Hepatic Protein Kinase B Signaling and Glycogen Synthesis.

    Science.gov (United States)

    Ying, Zhixiong; Zhang, Hao; Su, Weipeng; Zhou, Le; Wang, Fei; Li, Yue; Zhang, Lili; Wang, Tian

    2017-10-01

    Background: Individuals with intrauterine growth restriction (IUGR) are prone to developing type 2 diabetes mellitus (T2DM). Dietary methionine restriction (MR) improves insulin sensitivity and glucose homeostasis in individuals with normal birth weight (NBW).Objective: This study investigated the effects of MR on plasma glucose concentration and hepatic and muscle glucose metabolism in pigs with IUGR.Methods: Thirty female NBW and 60 same-sex spontaneous IUGR piglets (Landrace × Yorkshire) were selected. After weaning (day 21), the piglets were fed diets with adequate methionine (NBW-CON and IUGR-CON) or 30% less methionine (IUGR-MR) (n = 6). At day 180, 1 pig with a body weight near the mean of each replication was selected for biochemical analysis.Results: The IUGR-CON group showed 41.6%, 68.6%, and 67.1% higher plasma glucose concentration, hepatic phosphoenolpyruvate carboxykinase activity, and glucose-6-phosphatase activity, respectively, than the NBW-CON group (P glycogen content and glycogen synthase activity were 36.9% and 38.8% lower, respectively, in the IUGR-CON than the NBW-CON group (P glycogen content and glycogen synthase activity of the IUGR-MR pigs were 62.9% and 50.8% higher than those of the IUGR-CON pigs (P glycogen synthesis, implying a potential nutritional strategy to prevent type 2 diabetes mellitus in IUGR offspring. © 2017 American Society for Nutrition.

  3. Glycogen storage disease type Ia mice with less than 2% of normal hepatic glucose-6-phosphatase-α activity restored are at risk of developing hepatic tumors.

    Science.gov (United States)

    Kim, Goo-Young; Lee, Young Mok; Kwon, Joon Hyun; Cho, Jun-Ho; Pan, Chi-Jiunn; Starost, Matthew F; Mansfield, Brian C; Chou, Janice Y

    2017-03-01

    Glycogen storage disease type Ia (GSD-Ia), characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA) and carcinoma (HCC), is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC). We have previously shown that G6pc-/- mice receiving gene transfer mediated by rAAV-G6PC, a recombinant adeno-associated virus (rAAV) vector expressing G6Pase-α, and expressing 3-63% of normal hepatic G6Pase-α activity maintain glucose homeostasis and do not develop HCA/HCC. However, the threshold of hepatic G6Pase-α activity required to prevent tumor formation remained unknown. In this study, we constructed rAAV-co-G6PC, a rAAV vector expressing a codon-optimized (co) G6Pase-α and showed that rAAV-co-G6PC was more efficacious than rAAV-G6PC in directing hepatic G6Pase-α expression. Over an 88-week study, we showed that both rAAV-G6PC- and rAAV-co-G6PC-treated G6pc-/- mice expressing 3-33% of normal hepatic G6Pase-α activity (AAV mice) maintained glucose homeostasis, lacked HCA/HCC, and were protected against age-related obesity and insulin resistance. Of the eleven rAAV-G6PC/rAAV-co-G6PC-treated G6pc-/- mice harboring 0.9-2.4% of normal hepatic G6Pase-α activity (AAV-low mice), 3 expressing 0.9-1.3% of normal hepatic G6Pase-α activity developed HCA/HCC, while 8 did not (AAV-low-NT). Finally, we showed that the AAV-low-NT mice exhibited a phenotype indistinguishable from that of AAV mice expressing ≥3% of normal hepatic G6Pase-α activity. The results establish the threshold of hepatic G6Pase-α activity required to prevent HCA/HCC and show that GSD-Ia mice harboring <2% of normal hepatic G6Pase-α activity are at risk of tumor development. Published by Elsevier Inc.

  4. Nutritional Status and Body Composition in Patients With Hepatic Glycogen Storage Diseases Treated With Uncooked Cornstarch—A Controlled Study

    Directory of Open Access Journals (Sweden)

    Bruna B. dos Santos MSc

    2017-09-01

    Full Text Available Hepatic glycogen storage diseases (GSDs are genetic diseases associated with fasting hypoglycemia. Periodic intake of uncooked cornstarch is one of the treatment strategies available for those disorders. For reasons that are still not clear, patients with hepatic GSDs may be overweight. Aims: To assess nutritional status and body composition in patients with hepatic GSDs receiving uncooked cornstarch. Methods: The sample included 25 patients with hepatic GSD (type Ia = 14; Ib = 6; III = 3; IXα = 1; IXβ = 1, with a median age of 11.0 years (interquartile range [IQR] = 9.0-17.5, matched by age and gender with 25 healthy controls (median age = 12.0 years, IQR = 10.0-17.5. Clinical, biochemical, and treatment-related variables were obtained from medical records. Nutritional status and body composition were prospectively evaluated by bioelectrical impedance. Results: Patients and controls did not differ with regard to age and gender. Height was significantly reduced in patients (median = 1.43 m, IQR = 1.25-1.54 in comparison to controls (median = 1.54 m, IQR = 1.42-1.61; P = .04. Body mass index for age z -score and fat mass percentage were higher in patients (median = 1.84, IQR = 0.55-3.06; and 27.5%, IQR = 22.6-32.0, respectively than in controls (median = 0.86, IQR = −0.55 to 1.82; P = .04 and 21.1%, IQR = 13.0-28.3; P = .01, respectively. When patients were stratified by type, those with GSD Ia had significantly higher adiposity (median fat mass = 28.7%, IQR = 25.3-32.9 than those with GSD III and GSD IXα/β (median fat mass = 20.9%, IQR = 14.9-22.6; P = .02. Conclusions: Our findings suggest that patients with hepatic GSD on treatment with cornstarch, especially those with GSD Ia, exhibit abnormalities in nutritional status and body composition, such as short stature and a trend toward overweight and obesity.

  5. Glycogen phosphorylase inhibitor N-(3,5-dimethyl-Benzoyl-N'-(β-D-glucopyranosylurea improves glucose tolerance under normoglycemic and diabetic conditions and rearranges hepatic metabolism.

    Directory of Open Access Journals (Sweden)

    Lilla Nagy

    Full Text Available Glycogen phosphorylase (GP catalyzes the breakdown of glycogen and largely contributes to hepatic glucose production making GP inhibition an attractive target to modulate glucose levels in diabetes. Hereby we present the metabolic effects of a novel, potent, glucose-based GP inhibitor (KB228 tested in vitro and in vivo under normoglycemic and diabetic conditions. KB228 administration enhanced glucose sensitivity in chow-fed and obese, diabetic mice that was a result of higher hepatic glucose uptake. Besides improved glucose sensitivity, we have observed further unexpected metabolic rearrangements. KB228 administration increased oxygen consumption that was probably due to the overexpression of uncoupling protein-2 (UCP2 that was observed in animal and cellular models. Furthermore, KB228 treatment induced mammalian target of rapamycin complex 2 (mTORC2 in mice. Our data demonstrate that glucose based GP inhibitors are capable of reducing glucose levels in mice under normo and hyperglycemic conditions. Moreover, these GP inhibitors induce accommodation in addition to GP inhibition--such as enhanced mitochondrial oxidation and mTORC2 signaling--to cope with the glucose influx and increased glycogen deposition in the cells, however the molecular mechanism of accommodation is unexplored.

  6. Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes.

    Science.gov (United States)

    Liu, Tong-Yan; Shi, Chang-Xiang; Gao, Run; Sun, Hai-Jian; Xiong, Xiao-Qing; Ding, Lei; Chen, Qi; Li, Yue-Hua; Wang, Jue-Jin; Kang, Yu-Ming; Zhu, Guo-Qing

    2015-11-01

    Increased glucose production and reduced hepatic glycogen storage contribute to metabolic abnormalities in diabetes. Irisin, a newly identified myokine, induces the browning of white adipose tissue, but its effects on gluconeogenesis and glycogenesis are unknown. In the present study, we investigated the effects and underlying mechanisms of irisin on gluconeogenesis and glycogenesis in hepatocytes with insulin resistance, and its therapeutic role in type 2 diabetic mice. Insulin resistance was induced by glucosamine (GlcN) or palmitate in human hepatocellular carcinoma (HepG2) cells and mouse primary hepatocytes. Type 2 diabetes was induced by streptozotocin/high-fat diet (STZ/HFD) in mice. In HepG2 cells, irisin ameliorated the GlcN-induced increases in glucose production, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression, and glycogen synthase (GS) phosphorylation; it prevented GlcN-induced decreases in glycogen content and the phosphoinositide 3-kinase (PI3K) p110α subunit level, and the phosphorylation of Akt/protein kinase B, forkhead box transcription factor O1 (FOXO1) and glycogen synthase kinase-3 (GSK3). These effects of irisin were abolished by the inhibition of PI3K or Akt. The effects of irisin were confirmed in mouse primary hepatocytes with GlcN-induced insulin resistance and in human HepG2 cells with palmitate-induced insulin resistance. In diabetic mice, persistent subcutaneous perfusion of irisin improved the insulin sensitivity, reduced fasting blood glucose, increased GSK3 and Akt phosphorylation, glycogen content and irisin level, and suppressed GS phosphorylation and PEPCK and G6Pase expression in the liver. Irisin improves glucose homoeostasis by reducing gluconeogenesis via PI3K/Akt/FOXO1-mediated PEPCK and G6Pase down-regulation and increasing glycogenesis via PI3K/Akt/GSK3-mediated GS activation. Irisin may be regarded as a novel therapeutic strategy for insulin resistance and type 2 diabetes. © 2015

  7. 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.

  8. Prior Exercise Training Prevent Hyperglycemia in STZ Mice by Increasing Hepatic Glycogen and Mitochondrial Function on Skeletal Muscle.

    Science.gov (United States)

    de Carvalho, Afonso Kopczynski; da Silva, Sabrina; Serafini, Edenir; de Souza, Daniela Roxo; Farias, Hemelin Resende; de Bem Silveira, Gustavo; Silveira, Paulo Cesar Lock; de Souza, Claudio Teodoro; Portela, Luis Valmor; Muller, Alexandre Pastoris

    2017-04-01

    Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. We investigated the effect of a prior 30 days voluntary exercise protocol on STZ-diabetic CF1 mice. Glycemia, and the liver and skeletal muscle glycogen, mitochondrial function, and redox status were analyzed up to 5 days after STZ injection. Animals were engaged in the following groups: Sedentary vehicle (Sed Veh), Sedentary STZ (Sed STZ), Exercise Vehicle (Ex Veh), and Exercise STZ (Ex STZ). Exercise prevented fasting hyperglycemia in the Ex STZ group. In the liver, there was decreased on glycogen level in Sed STZ group but not in EX STZ group. STZ groups showed decreased mitochondrial oxygen consumption compared to vehicle groups, whereas mitochondrial H2 O2 production was not different between groups. Addition of ADP to the medium did not decrease H2 O2 production in Sed STZ mice. Exercise increased GSH level. Sed STZ group increased nitrite levels compared to other groups. In quadriceps muscle, glycogen level was similar between groups. The Sed STZ group displayed decreased O2 consumption, and exercise prevented this reduction. The H2 O2 production was higher in Ex STZ when compared to other groups. Also, GSH level decreased whereas nitrite levels increased in the Sed STZ compared to other groups. The PGC1 α levels increased in Sed STZ, Ex Veh, and Ex STZ groups. In summary, prior exercise training prevents hyperglycemia in STZ-mice diabetic associated with increased liver glycogen storage, and oxygen consumption by the mitochondria of skeletal muscle implying in increased oxidative/biogenesis capacity, and improved redox status of both tissues. J. Cell. Biochem. 118: 678-685, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. 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...

  10. Repletion of branched chain amino acids reverses mTORC1 signaling but not improved metabolism during dietary protein dilution

    Directory of Open Access Journals (Sweden)

    Adriano Maida

    2017-08-01

    Conclusions: Repletion of BCAAs in dietary PD is sufficient to oppose changes in somatic mTORC1 signaling but does not reverse the hepatic ISR nor induce insulin resistance in type 2 diabetes during dietary PD.

  11. Genetics Home Reference: glycogen storage disease type IV

    Science.gov (United States)

    ... hepatic type of GSD IV often die of liver failure in early childhood. The non-progressive hepatic type ... and Advocacy Resources (7 links) American Heart Association: Pediatric Cardiomyopathies American Liver Foundation Association for Glycogen Storage Disease CLIMB: Children ...

  12. Biomarker for Glycogen Storage Diseases

    Science.gov (United States)

    2017-07-03

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

  13. 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

  14. Glycogen metabolism in humans ? ??

    OpenAIRE

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

    2016-01-01

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

  15. Postexercise repletion of muscle energy stores with fructose or glucose in mixed meals.

    Science.gov (United States)

    Rosset, Robin; Lecoultre, Virgile; Egli, Léonie; Cros, Jérémy; Dokumaci, Ayse Sila; Zwygart, Karin; Boesch, Chris; Kreis, Roland; Schneiter, Philippe; Tappy, Luc

    2017-03-01

    Background: Postexercise nutrition is paramount to the restoration of muscle energy stores by providing carbohydrate and fat as precursors of glycogen and intramyocellular lipid (IMCL) synthesis. Compared with glucose, fructose ingestion results in lower postprandial glucose and higher lactate and triglyceride concentrations. We hypothesized that these differences in substrate concentration would be associated with a different partition of energy stored as IMCLs or glycogen postexercise.Objective: The purpose of this study was to compare the effect of isocaloric liquid mixed meals containing fat, protein, and either fructose or glucose on the repletion of muscle energy stores over 24 h after a strenuous exercise session.Design: Eight male endurance athletes (mean ± SEM age: 29 ± 2 y; peak oxygen consumption: 66.8 ± 1.3 mL · kg-1 · min-1) were studied twice. On each occasion, muscle energy stores were first lowered by a combination of a 3-d controlled diet and prolonged exercise. After assessment of glycogen and IMCL concentrations in vastus muscles, subjects rested for 24 h and ingested mixed meals providing fat and protein together with 4.4 g/kg fructose (the fructose condition; FRU) or glucose (the glucose condition; GLU). Postprandial metabolism was assessed over 6 h, and glycogen and IMCL concentrations were measured again after 24 h. Finally, energy metabolism was evaluated during a subsequent exercise session.Results: FRU and GLU resulted in similar IMCL [+2.4 ± 0.4 compared with +2.0 ± 0.6 mmol · kg-1 wet weight · d-1; time × condition (mixed-model analysis): P = 0.45] and muscle glycogen (+10.9 ± 0.9 compared with +12.3 ± 1.9 mmol · kg-1 wet weight · d-1; time × condition: P = 0.45) repletion. Fructose consumption in FRU increased postprandial net carbohydrate oxidation and decreased net carbohydrate storage (estimating total, muscle, and liver glycogen synthesis) compared with GLU (+117 ± 9 compared with +135 ± 9 g/6 h, respectively; P

  16. Precursors to glycogen in ovine fetuses

    Energy Technology Data Exchange (ETDEWEB)

    Levitsky, L.L.; Paton, J.B.; Fisher, D.E. (Univ. of Chicago, IL (USA))

    1988-11-01

    Postprandial hepatic glycogenesis in the adult animal is now felt to proceed largely through gluconeogenic pathways rather than directly from glucose. The ovine fetus, like the mature sheep, lacks specific hepatic glucokinase. Therefore, the authors examined the role of lactate as a fetal glycogenic precursor in seven chronically catheterized 125-day sheep fetuses. Fetuses were infused with L-(U-{sup 14}C)lactate and D-(3-{sup 3}H)glucose, while maternal glucose was maintained at 50 mg/dl. Mean fetal hepatic glycogen specific activity ({mu}Ci/mg {times} 10{sup 3}) was 0.82 {plus minus} 0.08 for {sup 14}C and 2.6 {plus minus} 0.4 for {sup 3}H, whereas fetal renal glycogen specific activity was 0.46 {plus minus} 0.22 for {sup 14}C and 0.78 {plus minus} 0.16 for {sup 3}H. In contrast, ({sup 14}C)glucose specific activity was undetectable in blood and mean ({sup 3}H)glucose specific activity was 8.9 {plus minus} 1.3 {mu}Ci/mg {times} 10{sup 3}. The least detectable specific activity of ({sup 14}C)glucose did not differ significantly from the ({sup 14}C)glycogen enrichment in liver, whereas ({sup 3}H)glucose specific activity was significantly greater than ({sup 3}H)glycogen enrichment. The authors conclude that glycogenesis from glucose is partly through the indirect gluconeogenic route and that lactate may be a glycogenic precursor in the ovine fetus.

  17. Glycogen metabolism in cancer.

    Science.gov (United States)

    Zois, Christos E; Favaro, Elena; Harris, Adrian L

    2014-11-01

    Since its identification more than 150 years ago, there has been an extensive characterisation of glycogen metabolism and its regulatory pathways in the two main glycogen storage organs of the body, i.e. liver and muscle. In recent years, glycogen metabolism has also been demonstrated to be upregulated in many tumour types, suggesting it is an important aspect of cancer cell pathophysiology. Here, we provide an overview of glycogen metabolism and its regulation, with a focus on its role in metabolic reprogramming of cancer cells. The various methods to detect glycogen in tumours in vivo are also reviewed. Finally, we discuss the targeting of glycogen metabolism as a strategy for cancer treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.

    Science.gov (United States)

    Liu, Jun; Wang, Xue; Chen, Yu-Peng; Mao, Li-Fei; Shang, Jing; Sun, Hong-Bin; Zhang, Lu-Yong

    2014-04-01

    To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene maslinic acid (MA) exerts anti-diabetic effects. HepG2 cells were stimulated with various concentrations of MA. The effects of MA on glycogen phosphorylase a (GPa) activity and the cellular glycogen content were measured. Western blot analyses were performed with anti-insulin receptor β (IRβ), protein kinase B (also known as Akt), and glycogen synthase kinase-3β (GSK3β) antibodies. Activation status of the insulin pathway was investigated using phospho-IRβ, as well as phospho-Akt, and phospho-GSK3β antibodies. The specific PI3-kinase inhibitor wortmannin was added to the cells to analyze the Akt expression. Enzyme-linked immunosorbent assay (ELISA) was used to measure the effect of MA on IRβ auto-phosphorylation. Furthermore, the effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a high-fat diet (HFD). The results showed that MA exerts anti-diabetic effects by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells. Furthermore, MA was shown to induce the phosphorylation level of IRβ-subunit, Akt, and GSK3β. The MA-induced activation of Akt appeared to be specific, since it could be blocked by wortmannin. Finally, MA treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance, and increased the accumulated hepatic glycogen content. The results suggested that maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  19. [Effect of endotoxin pretreatment-induced glycogen synthase kinase-3 inhibition on glycogen metabolism in rat liver and the mechanism].

    Science.gov (United States)

    Chen, Xiaole; Gong, Jianping; Xu, Faliang

    2014-02-01

    To investigate the changes in the functional activity of glycogen synthase kinase-3 (GSK-3) in the hepatic tissue after endotoxin (lipopolysaccharide, LPS) tolerance and explore the effects of LPS-induced GSK-3 inhibition on glycogen metabolism in the liver. Male SD rats were randomly divided into normal control, endotoxin pretreatment and GSK-3 inhibitor (lithium chloride) groups with corresponding pretreatments prior to a large dose of LPS challenge (10 mg/kg) to induce liver injury. Glycogen deposition and content in the hepatic tissue was detected using periodic acid-Schiff (PAS) staining and a glycogen quantification kit, respectively. Western blotting was performed for semi-quantitative analysis of protein level and inhibitory phosphorylation of GSK-3, and a Coomassie brilliant blue G-250-based colorimetric assay was used to detect calpain activity in the liver. Glycogen content in the liver decreased significantly after LPS challenge in all the 3 groups (P0.05). Both LPS and lithium chloride pretreatments caused a significant increase of liver glycogen content (P0.05). Large-dose LPS challenge significantly increased the activity of calpain in the liver tissue (P0.05). Endotoxin pretreatment induces inhibitory phosphorylation of GSK-3β and partial cleavage of GSK-3α and promotes the deposition of liver glycogen but does not affect the activity of calpain, which may contribute to an increased glycogen reserve for energy supply in the event of large-dose LPS challenge.

  20. Muscle ceramide content in man is higher in type I than type II fibers and not influenced by glycogen content

    DEFF Research Database (Denmark)

    Nordby, P; Prats, C; Kristensen, D

    2010-01-01

    Human muscle is studied during glycogen depletion and repletion to understand the influence of exercise and muscle glycogen on total ceramide content. In addition, fiber-type-specific ceramide storage is investigated. Ten healthy males (26.4 +/- 0.9 years, BMI 24.4 +/- 0.7 kg m(-2) and VO2max 57...... +/- 2 mL O2 min(-1) kg(-1)) participated in the study. On the first day, one leg was glycogen-depleted (DL) by exhaustive intermittent exercise followed by low carbohydrate diet. Next day, in the overnight fasted condition, muscle biopsies were excised from vastus lateralis before and after exhaustive...... exercise from both DL and control leg (CL). Muscle glycogen was analyzed biochemically and total muscle ceramide content by 2D quantitative lipidomic approach. Furthermore, fiber-type ceramide content was determined by fluorescence immunohistochemistry. Basal muscle glycogen was decreased (P

  1. Type I Glycogen Storage Disease

    Science.gov (United States)

    ... Liver Tumors Biliary Atresia Cirrhosis of the Liver Galactosemia Gilbert’s Syndrome Diseases of the Liver Glycogen Storage ... Liver Tumors Biliary Atresia Cirrhosis of the Liver Galactosemia Gilbert’s Syndrome Diseases of the Liver Glycogen Storage ...

  2. Relationship between Genetic Variation at PPP1R3B and Liver Glycogen and Triglyceride Levels

    DEFF Research Database (Denmark)

    Stender, Stefan; Smagris, Eriks; Lauridsen, Bo K

    2018-01-01

    Genetic variation at rs4240624 on chromosome 8 is associated with an attenuated signal on hepatic computerized tomography (CT), which has been attributed to changes in hepatic fat. The closest coding gene to rs4240624, PPP1R3B, encodes a protein that promotes hepatic glycogen synthesis. Here we...

  3. Lack of efficacy of ergocalciferol repletion

    Directory of Open Access Journals (Sweden)

    Thomas Wasser

    2012-04-01

    Full Text Available Introduction: Vitamin D has become an area of intensive scrutiny, both in medical and lay literature. However, there are limited data to suggest proper repletion regimens for those patients who have hypovitaminosis D. Consequently, various methods are used in clinical practice. The aim of this study was to assess the efficacy of various treatment strategies for hypovitaminosis D in an ambulatory internal medicine practice. Methods: A retrospective chart review between October 2005 and June 2010 of a suburban internal medicine practice was performed via query of the electronic medical record (Centricity, General Electric Healthcare, UK. Patients with a 25-hydroxyvitamin D concentration less than 32 mg/dl were identified and treated. Treatment success was defined as 25-hydroxyvitamin D concentrations greater than 32 mg/dl. Statistical analysis to assess changes in vitamin D level controlling for season, comorbidities, and demographics were used. Results: A total of 607 treatment episodes were identified, with 395 excluded due to lack of follow-up vitamin D level within 16 weeks, no treatment documented, topical treatment, doxercalciferol treatment, or non-compliance. Of the remaining patients, there were 212 treatment instances on 178 patients. Ergocalciferol 50,000 international units (IU was used most frequently (71.4% of the time.. A higher initial vitamin D level was positively associated with treatment success (adjusted odds ratio = 1.11, p=0.002. Increased doses of ergocalciferol increased the likelihood of treatment success (p=0.0011. Seasonal variation was related to posttreatment 25-hydroxyvitamin D concentration as was body mass index (BMI (p=0.003 and p=0.044. Conclusion: Pretreatment levels of 25-hydroxyvitamin D, BMI, season, and vitamin D dose are predictors of successful hypovitaminosis D treatment. Our data suggest that patients with initial 25-hydroxyvitamin D concentrations of <20 should be treated with a higher total dose of

  4. Hepatitis

    Science.gov (United States)

    ... yourself against hepatitis A is by vaccination. Other ways to protect yourself include avoiding rimming and other anal and oral contact. While condom use is essential in preventing the spread of HIV, hepatitis B and other STDs, it does not ...

  5. Disturbed lipid metabolism in glycogen storage disease type 1

    NARCIS (Netherlands)

    Bandsma, RHJ; Smit, GPA; Kuipers, F

    2002-01-01

    Glycogen storage disease type 1 (GSD1) is an inborn error of metabolism caused by deficiency of glucose-6-phosphatase, the enzyme catalysing the conversion of glucose-6-phosphate (G6P) to glucose. GSD1 is associated with severe hyperlipidaemia and hepatic steatosis. The underlying mechanisms

  6. Hepatic autoregulation

    DEFF Research Database (Denmark)

    Staehr, Peter; Hother-Nielsen, Ole; Beck-Nielsen, Henning

    2007-01-01

    The effect of increased glycogenolysis, simulated by galactose's conversion to glucose, on the contribution of gluconeogenesis (GNG) to hepatic glucose production (GP) was determined. The conversion of galactose to glucose is by the same pathway as glycogen's conversion to glucose, i.e., glucose 1...

  7. Metabolic crosstalk: molecular links between glycogen and lipid metabolism in obesity.

    Science.gov (United States)

    Lu, Binbin; Bridges, Dave; Yang, Yemen; Fisher, Kaleigh; Cheng, Alan; Chang, Louise; Meng, Zhuo-Xian; Lin, Jiandie D; Downes, Michael; Yu, Ruth T; Liddle, Christopher; Evans, Ronald M; Saltiel, Alan R

    2014-09-01

    Glycogen and lipids are major storage forms of energy that are tightly regulated by hormones and metabolic signals. We demonstrate that feeding mice a high-fat diet (HFD) increases hepatic glycogen due to increased expression of the glycogenic scaffolding protein PTG/R5. PTG promoter activity was increased and glycogen levels were augmented in mice and cells after activation of the mechanistic target of rapamycin complex 1 (mTORC1) and its downstream target SREBP1. Deletion of the PTG gene in mice prevented HFD-induced hepatic glycogen accumulation. Of note, PTG deletion also blocked hepatic steatosis in HFD-fed mice and reduced the expression of numerous lipogenic genes. Additionally, PTG deletion reduced fasting glucose and insulin levels in obese mice while improving insulin sensitivity, a result of reduced hepatic glucose output. This metabolic crosstalk was due to decreased mTORC1 and SREBP activity in PTG knockout mice or knockdown cells, suggesting a positive feedback loop in which once accumulated, glycogen stimulates the mTORC1/SREBP1 pathway to shift energy storage to lipogenesis. Together, these data reveal a previously unappreciated broad role for glycogen in the control of energy homeostasis. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  8. Muscle glycogen stores and fatigue

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Westerblad, Håkan; Nielsen, Joachim

    2013-01-01

    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......  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...... the sarcoplasmic reticulum (SR). We and others have provided experimental evidence in favour of a direct role of decreased glycogen, localized within the myofibrils, for the reduction in SR Ca2+ release during fatigue. This is consistent with compartmentalized energy turnover and distinctly localized glycogen...

  9. 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.

  10. Restoration of Muscle Glycogen and Functional Capacity: Role of Post-Exercise Carbohydrate and Protein Co-Ingestion

    Directory of Open Access Journals (Sweden)

    Abdullah F. Alghannam

    2018-02-01

    Full Text Available The importance of post-exercise recovery nutrition has been well described in recent years, leading to its incorporation as an integral part of training regimes in both athletes and active individuals. Muscle glycogen depletion during an initial prolonged exercise bout is a main factor in the onset of fatigue and so the replenishment of glycogen stores may be important for recovery of functional capacity. Nevertheless, nutritional considerations for optimal short-term (3–6 h recovery remain incompletely elucidated, particularly surrounding the precise amount of specific types of nutrients required. Current nutritional guidelines to maximise muscle glycogen availability within limited recovery are provided under the assumption that similar fatigue mechanisms (i.e., muscle glycogen depletion are involved during a repeated exercise bout. Indeed, recent data support the notion that muscle glycogen availability is a determinant of subsequent endurance capacity following limited recovery. Thus, carbohydrate ingestion can be utilised to influence the restoration of endurance capacity following exhaustive exercise. One strategy with the potential to accelerate muscle glycogen resynthesis and/or functional capacity beyond merely ingesting adequate carbohydrate is the co-ingestion of added protein. While numerous studies have been instigated, a consensus that is related to the influence of carbohydrate-protein ingestion in maximising muscle glycogen during short-term recovery and repeated exercise capacity has not been established. When considered collectively, carbohydrate intake during limited recovery appears to primarily determine muscle glycogen resynthesis and repeated exercise capacity. Thus, when the goal is to optimise repeated exercise capacity following short-term recovery, ingesting carbohydrate at an amount of ≥1.2 g kg body mass−1·h−1 can maximise muscle glycogen repletion. The addition of protein to carbohydrate during post

  11. 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.

  12. Differential pattern of glycogen accumulation after protein phosphatase 1 glycogen-targeting subunit PPP1R6 overexpression, compared to PPP1R3C and PPP1R3A, in skeletal muscle cells.

    Science.gov (United States)

    Montori-Grau, Marta; Guitart, Maria; García-Martínez, Cèlia; Orozco, Anna; Gómez-Foix, Anna Maria

    2011-11-04

    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/G(M). 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 G(M). 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 G(M) (28.3 nm) or those in control cells (29.2 nm). Both PPP1R6- and G(M)-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. PPP1R6 exerts a powerful glycogenic effect in cultured muscle cells, more than G(M) 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 G(M) scaffolding.

  13. Massive intestinal resection in rats fed up on glutamine: hepatic glycogen content valuation Ressecção intestinal extensa em ratos tratados com oferta oral de glutamina: avaliação do conteúdo hepático de glicogênio

    Directory of Open Access Journals (Sweden)

    Ariney Costa de Miranda

    2006-03-01

    Full Text Available BACKGROUND: Glutamine has been widely used in treatment of small bowel syndrome and its metabolic effects on the small intestine are well known, however, it has been little studied its effects on hepatic metabolism under this condition. AIM: To verify through experimental model, a glutamine based supplemental diet, administered via oral to rats submitted to massive intestinal resection, evaluating weight evolution and hepatic glycogen content. MATERIAL AND METHODS: Male rats, Wistar, were allocated into three groups to undergo enterectomy. Following diets were applied: with glutamine (G group, without glutamine (NG group, and standard diet from the laboratory (R group. All animals had massive small intestine resection including ileocecal valve removal. After 20 days, all animals were sacrificed. The liver was removed to histological analysis by light microscopy. Slides were stained by periodic acid of Schiff with diastasis. RESULTS: All animals lost weight from the beginning to the end of experiment. Comparing weight loss average expressed in percentage, there was no difference statistically significant on this variance. In analyzed groups, the hepatic glycogen content did not differ statistically, in the histological method evaluated. CONCLUSION: Glutamine feeding via oral did not influence weight loss reduction of animal submitted to massive intestinal resection and did not stimulate glycogen synthesis and storage into hepatocytes.RACIONAL: A glutamina tem sido utilizada amplamente no tratamento da síndrome do intestino curto e seus efeitos metabólicos são bem conhecidos no intestino delgado, porém pouco se tem relatado sobre seus efeitos no metabolismo hepático nessa condição. OBJETIVO: Verificar em modelo experimental, o efeito de dieta suplementada com glutamina administrada por via oral, em ratos submetidos a ressecção intestinal extensa, na evolução ponderal e no conteúdo de glicogênio hepático. MATERIAL E MÉTODOS: Ratos

  14. Imaging liver and brain glycogen metabolism at the nanometer scale.

    Science.gov (United States)

    Takado, Yuhei; Knott, Graham; Humbel, Bruno M; Escrig, Stéphane; Masoodi, Mojgan; Meibom, Anders; Comment, Arnaud

    2015-01-01

    In mammals, glycogen synthesis and degradation are dynamic processes regulating blood and cerebral glucose-levels within a well-defined physiological range. Despite the essential role of glycogen in hepatic and cerebral metabolism, its spatiotemporal distribution at the molecular and cellular level is unclear. By correlating electron microscopy and ultra-high resolution ion microprobe (NanoSIMS) imaging of tissue from fasted mice injected with (13)C-labeled glucose, we demonstrate that liver glycogenesis initiates in the hepatocyte perinuclear region before spreading toward the cell membrane. In the mouse brain, we observe that (13)C is inhomogeneously incorporated into astrocytic glycogen at a rate ~25 times slower than in the liver, in agreement with prior bulk studies. This experiment, using temporally resolved, nanometer-scale imaging of glycogen synthesis and degradation, provides greater insight into glucose metabolism in mammalian organs and shows how this technique can be used to explore biochemical pathways in healthy and diseased states. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Swelling of rat hepatocytes stimulates glycogen synthesis

    NARCIS (Netherlands)

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

    1990-01-01

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

  16. Pathway-Level Acceleration of Glycogen Catabolism by a Response Regulator in the Cyanobacterium Synechocystis Species PCC 68031[W

    Science.gov (United States)

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

    2014-01-01

    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. PMID:24521880

  17. 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.

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

    KAUST Repository

    Ruchti, E.

    2016-10-08

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

  19. 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

  20. Muscle Ultrasound in Patients with Glycogen Storage Disease Types I and III

    NARCIS (Netherlands)

    Verbeek, Renate J.; Sentner, Christiaan P.; Smit, G. Peter A.; Maurits, Natasha M.; Derks, Terry G. J.; van der Hoeven, Johannes H.; Sival, Deborah A.

    In glycogen storage diseases (GSDs), improved longevity has resulted in the need for neuromuscular surveillance. In 12 children and 14 adults with the "hepatic'' (GSD-I) and "myopathic'' (GSD-III) phenotypes, we cross-sectionally assessed muscle ultrasound density (MUD) and muscle force. Children

  1. Muscle glycogen synthesis before and after exercise.

    Science.gov (United States)

    Ivy, J L

    1991-01-01

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

  2. Multiple Glycogen-binding Sites in Eukaryotic Glycogen Synthase Are Required for High Catalytic Efficiency toward Glycogen

    Energy Technology Data Exchange (ETDEWEB)

    Baskaran, Sulochanadevi; Chikwana, Vimbai M.; Contreras, Christopher J.; Davis, Keri D.; Wilson, Wayne A.; DePaoli-Roach, Anna A.; Roach, Peter J.; Hurley, Thomas D. (Indiana-Med); (Des Moines U)

    2012-12-10

    Glycogen synthase is a rate-limiting enzyme in the biosynthesis of glycogen and has an essential role in glucose homeostasis. The three-dimensional structures of yeast glycogen synthase (Gsy2p) complexed with maltooctaose identified four conserved maltodextrin-binding sites distributed across the surface of the enzyme. Site-1 is positioned on the N-terminal domain, site-2 and site-3 are present on the C-terminal domain, and site-4 is located in an interdomain cleft adjacent to the active site. Mutation of these surface sites decreased glycogen binding and catalytic efficiency toward glycogen. Mutations within site-1 and site-2 reduced the V{sub max}/S{sub 0.5} for glycogen by 40- and 70-fold, respectively. Combined mutation of site-1 and site-2 decreased the V{sub max}/S{sub 0.5} for glycogen by >3000-fold. Consistent with the in vitro data, glycogen accumulation in glycogen synthase-deficient yeast cells ({Delta}gsy1-gsy2) transformed with the site-1, site-2, combined site-1/site-2, or site-4 mutant form of Gsy2p was decreased by up to 40-fold. In contrast to the glycogen results, the ability to utilize maltooctaose as an in vitro substrate was unaffected in the site-2 mutant, moderately affected in the site-1 mutant, and almost completely abolished in the site-4 mutant. These data show that the ability to utilize maltooctaose as a substrate can be independent of the ability to utilize glycogen. Our data support the hypothesis that site-1 and site-2 provide a 'toehold mechanism,' keeping glycogen synthase tightly associated with the glycogen particle, whereas site-4 is more closely associated with positioning of the nonreducing end during catalysis.

  3. Dietary Management of the Ketogenic Glycogen Storage Diseases

    Directory of Open Access Journals (Sweden)

    Kaustuv Bhattacharya MBBS, MRCPCH, FRACP, MD

    2016-08-01

    Full Text Available The glycogen storage diseases (GSDs comprise a group of rare inherited disorders of glycogen metabolism. The hepatic glycogenolytic forms of these disorders are typically associated with hypoglycemia and hepatomegaly. For GSD I, secondary metabolic disturbances include fasting hyperlactatemia, hyperuricemia, and hyperlipidemia. Glycogen storage disease III is caused by reduced activity of the debrancher enzyme, GSD VI by phosphorylase, and GSD IX by phosphorylase kinase. It has often been reported that the non-GSD I group of disorders have a benign course. However, myopathy, cardiomyopathy, and cirrhosis have been reported significant clinical morbidities associated with GSD III and IX in particular. There have been a range of reports indicating high-protein diets, high-fat diets, medium chain triglyceride (MCT, modified Atkins diet, and therapeutic ketones as rescuing severe phenotypes of GSD III in particular. The etiology of these severe phenotypes has not been defined. Cases presented in this report indicate potential harm from excessive simple sugar use in GSD IX C. Review of the literature indicates that most interventions have reduced the glycemic load and provide alternate substrates for energy in rescue situations. Prevention of complications is most likely to occur with a mixed balanced low glycemic index diet potentially with relative increases in protein.

  4. 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), respective...

  5. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice.

    Science.gov (United States)

    Gariani, Karim; Menzies, Keir J; Ryu, Dongryeol; Wegner, Casey J; Wang, Xu; Ropelle, Eduardo R; Moullan, Norman; Zhang, Hongbo; Perino, Alessia; Lemos, Vera; Kim, Bohkyung; Park, Young-Ki; Piersigilli, Alessandra; Pham, Tho X; Yang, Yue; Ku, Chai Siah; Koo, Sung I; Fomitchova, Anna; Cantó, Carlos; Schoonjans, Kristina; Sauve, Anthony A; Lee, Ji-Young; Auwerx, Johan

    2016-04-01

    With no approved pharmacological treatment, nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in Western countries and its worldwide prevalence continues to increase along with the growing obesity epidemic. Here, we show that a high-fat high-sucrose (HFHS) diet, eliciting chronic hepatosteatosis resembling human fatty liver, lowers hepatic nicotinamide adenine dinucleotide (NAD(+) ) levels driving reductions in hepatic mitochondrial content, function, and adenosine triphosphate (ATP) levels, in conjunction with robust increases in hepatic weight, lipid content, and peroxidation in C57BL/6J mice. To assess the effect of NAD(+) repletion on the development of steatosis in mice, nicotinamide riboside, a precursor of NAD(+) biosynthesis, was added to the HFHS diet, either as a preventive strategy or as a therapeutic intervention. We demonstrate that NR prevents and reverts NAFLD by inducing a sirtuin (SIRT)1- and SIRT3-dependent mitochondrial unfolded protein response, triggering an adaptive mitohormetic pathway to increase hepatic β-oxidation and mitochondrial complex content and activity. The cell-autonomous beneficial component of NR treatment was revealed in liver-specific Sirt1 knockout mice (Sirt1(hep-/-) ), whereas apolipoprotein E-deficient mice (Apoe(-/-) ) challenged with a high-fat high-cholesterol diet affirmed the use of NR in other independent models of NAFLD. Our data warrant the future evaluation of NAD(+) boosting strategies to manage the development or progression of NAFLD. © 2015 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

  6. The menstrual cycle and exercise: performance, muscle glycogen, and substrate responses.

    Science.gov (United States)

    Nicklas, B J; Hackney, A C; Sharp, R L

    1989-08-01

    Six eumenorrheic females (age = 26.3 +/- 2.4 yrs; X +/- SE) exercised until exhaustion (EE; 70% VO2max) at the midluteal (LP, 7-8 days after ovulation) and midfollicular (FP, days 7-8) phases of their menstrual cycles. Phases were confirmed by estradiol and progesterone concentrations. Each EE test was preceded by a depletion exercise bout (DE; 90 min, 60% VO2max and 4 x 1 min, 100% VO2max) and 3 days of rest/diet control. Muscle biopsies 1% (vastus lateralis) were taken post-DE, pre-EE, and post-EE and then analyzed for glycogen content. There was a strong tendency (P less than 0.07) for EE duration to be greater during LP (139.2 +/- 14.9 min) than FP (126 +/- 17.5 min). Glycogen repletion (pre-EE minus post-DE) following DE was greater (P = 0.05) during the LP than FP (88.2 +/- 4.7 vs 72.8 +/- 5.7 mumol/g w. w. muscle). However, EE glycogen utilization (pre-EE minus post-EE/EE time) did not differ between phases (LP = 0.41 +/- 0.08 mumol/g w. w. muscle/min vs FP = 0.33 +/- 0.11 mumol/g w. w. muscle/min; P = 0.17). The results suggest that exercise performance and muscle glycogen content are enhanced during the LP of the menstrual cycle. These findings imply athletic performance may be affected by the phases of the menstrual cycle.

  7. 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

  8. Determination of the glycogen content in cyanobacteria

    DEFF Research Database (Denmark)

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

    2017-01-01

    of non-coding RNA. At the same time, efforts are being made to redirect carbon from glycogen to desirable products in genetically engineered cyanobacteria to enhance product yields. Several methods are used to determine the glycogen contents in cyanobacteria, with variable accuracies and technical...... complexities. Here, we provide a detailed protocol for the reliable determination of the glycogen content in cyanobacteria that can be performed in a standard life science laboratory. The protocol entails the selective precipitation of glycogen from the cell lysate and the enzymatic depolymerization...... of glycogen to generate glucose monomers, which are detected by a glucose oxidase-peroxidase (GOD-POD) enzyme coupled assay. The method has been applied to Synechocystis sp. PCC 6803 and Synechococcus sp. PCC 7002, two model cyanobacterial species that are widely used in metabolic engineering. Moreover...

  9. Exercise in muscle glycogen storage diseases

    DEFF Research Database (Denmark)

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

    2015-01-01

    Glycogen storage diseases (GSD) are inborn errors of glycogen or glucose metabolism. In the GSDs that affect muscle, the consequence of a block in skeletal muscle glycogen breakdown or glucose use, is an impairment of muscular performance and exercise intolerance, owing to 1) an increase...... in glycogen storage that disrupts contractile function and/or 2) a reduced substrate turnover below the block, which inhibits skeletal muscle ATP production. Immobility is associated with metabolic alterations in muscle leading to an increased dependence on glycogen use and a reduced capacity for fatty acid...... oxidation. Such changes may be detrimental for persons with GSD from a metabolic perspective. However, exercise may alter skeletal muscle substrate metabolism in ways that are beneficial for patients with GSD, such as improving exercise tolerance and increasing fatty acid oxidation. In addition, a regular...

  10. Glycogen-gold nanohybrid escalates the potency of silymarin.

    Science.gov (United States)

    Kandimalla, Raghuram; Dash, Suvakanta; Bhowal, Ashim Chandra; Kalita, Sanjeeb; Talukdar, Narayan Chandra; Kundu, Sarathi; Kotoky, Jibon

    2017-01-01

    In this study, a glycogen-gold nanohybrid was fabricated to enhance the potency of a promising hepatoprotective agent silymarin (Sly) by improving its solubility and gut permeation. By utilizing a facile green chemistry approach, biogenic gold nanoparticles were synthesized from Annona reticulata leaf phytoconstituents in combination with Sly (SGNPs). Further, the SGNPs were aggregated in glycogen biopolymer to yield the therapeutic nanohybrids (GSGNPs). Transmission electron microscopy, UV-Vis spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis confirmed the successful formation and conjugation of both SGNPs and GSGNPs. The fabricated nanohybrids showed significant protection against CCl 4 -induced hepatic injury in Wistar rats and maintained natural antioxidant (superoxide dismutase and catalase) levels. Animals treated with GSGNPs (10 mg/kg) and SGNPs (20 mg/kg) retained usual hepatic functions with routine levels of hepatobiliary enzymes (aspartate transferase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase) and inflammatory markers (interleukin-1β and tumor necrosis factor-α) with minimal lipid peroxidation, whereas those treated with 100 mg/kg of Sly showed the similar effect. These results were also supported by histopathology of the livers where pronounced hepatoprotection with normal hepatic physiology and negligible inflammatory infiltrate were observed. Significant higher plasma C max supported the enhanced bioavailability of Sly upon GSGNPs treatment compared to SGNPs and free Sly. Graphite furnace atomic absorption spectrophotometry analysis also substantiated the efficient delivery of GSGNPs over SGNPs. The fabricated therapeutic nanohybrids were also found to be biocompatible toward human erythrocytes and L929 mouse fibroblast cells. Overall, due to increased solubility, bioavailability and profuse gut absorption; GSGNPs demonstrated tenfold enhanced potency compared to free Sly.

  11. Glycogen Synthase Kinase-3β

    DEFF Research Database (Denmark)

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

    2016-01-01

    Evidence indicates a role for glycogen synthase kinase-3β (GSK-3β) in the pathophysiology of mood disorders and in cognitive disturbances; however, the natural variation in GSK-3β activity over time is unknown. We aimed to investigate GSK-3β activity over time and its possible correlation...... with emotional lability, subjective mood fluctuations and cognitive function in healthy individuals. Thirty-seven healthy subjects were evaluated with neuropsychological tests and blood samples at baseline and 12-week follow-up. Total GSK-3β and serine-9-phosphorylated GSK-3β in peripheral blood mononuclear...... analysis revealed lower activity of GSK-3β in spring and summer compared with the fall season. No correlation was observed between GSK-3β activity and emotional lability, subjective mood fluctuations or cognitive function. The results suggest that intra- and interindividual variation in GSK-3β activity...

  12. 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.

  13. Targeting glycogen metabolism in bladder cancer.

    Science.gov (United States)

    Ritterson Lew, Carolyn; Guin, Sunny; Theodorescu, Dan

    2015-07-01

    Metabolism has been a heavily investigated topic in cancer research for the past decade. Although the role of aerobic glycolysis (the Warburg effect) in cancer has been extensively studied, abnormalities in other metabolic pathways are only just being understood in cancer. One such pathway is glycogen metabolism; its involvement in cancer development, particularly in urothelial malignancies, and possible ways of exploiting aberrations in this process for treatment are currently being studied. New research shows that the glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL) is a novel tumour suppressor in bladder cancer. Loss of AGL leads to rapid proliferation of bladder cancer cells. Another enzyme involved in glycogen debranching, glycogen phosphorylase, has been shown to be a tumour promoter in cancer, including in prostate cancer. Studies demonstrate that bladder cancer cells in which AGL expression is lost are more metabolically active than cells with intact AGL expression, and these cells are more sensitive to inhibition of both glycolysis and glycine synthesis--two targetable pathways. As a tumour promoter and enzyme, glycogen phosphorylase can be directly targeted, and preclinical inhibitor studies are promising. However, few of these glycogen phosphorylase inhibitors have been tested for cancer treatment in the clinical setting. Several possible limitations to the targeting of AGL and glycogen phosphorylase might also exist.

  14. Glycogen metabolism in the rat retina.

    Science.gov (United States)

    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío

    2004-02-01

    It has been reported that glycogen levels in retina vary with retinal vascularization. However, the electrical activity of isolated retina depends on glucose supply, suggesting that it does not contain energetic reserves. We determined glycogen levels and pyruvate and lactate production under various conditions in isolated retina. Ex vivo retinas from light- and dark-adapted rats showed values of 44 +/- 0.3 and 19.5 +/- 0.4 nmol glucosyl residues/mg protein, respectively. The glycogen content of retinas from light-adapted animals was reduced by 50% when they were transferred to darkness. Glycogen levels were low in retinas incubated in glucose-free media and increased in the presence of glucose. The highest glycogen values were found in media containing 20 mm of glucose. A rapid increase in lactate production was observed in the presence of glucose. Surprisingly, glycogen levels were the lowest and lactate production was also very low in the presence of 30 mm glucose. Our results suggest that glycogen can be used as an immediate accessible energy reserve in retina. We speculate on the possibility that gluconeogenesis may play a protective role by removal of lactic acid.

  15. Rapid turnover of glycogen in memory formation.

    Science.gov (United States)

    Gibbs, Marie E; Hutchinson, Dana S

    2012-11-01

    The influence of noradrenaline acting at α(2)-AR and β(2)-ARs on the turnover of glycogen after learning has been investigated. The role of glycogen turnover in memory formation was examined using weakly-reinforced, single trial bead discrimination training in day-old domestic chickens. This study follows our previous work that focused on the need for glycogen breakdown (glycogenolysis) during learning. Inhibition of glycogenolysis by 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) prevented the consolidation of strongly-reinforced learning and inhibited memory. The action of DAB could be prevented by stimulating glycogenolysis with the selective β(2)-AR agonist, zinterol. Stimulation of α(2)-ARs has been shown to lead to an increase in the turnover and synthesis of glycogen. In the present study, we examined the effect of inhibition of α(2)-AR stimulated glycogen turnover (measured as(14)C-glucose incorporation into glycogen) on the ability of zinterol to promote the consolidation of weakly reinforced memory. In astrocytes, the selective α(2)-AR agonist clonidine stimulated (14)C-glucose incorporation into glycogen in chick astrocytes and this was inhibited by the selective α(2)-AR antagonist, ARC239. The critical importance of the timing of ARC239 injection relative to training and intracerebral administration of zinterol was examined. It is concluded that our data provides evidence for a readily accessible labile pool of glycogen in brain astrocytes. If glycogen synthesis is inhibited, the can be depleted within 10 min, thus preventing zinterol from promoting consolidation.

  16. Selective photoregulation of the activity of glycogen synthase and glycogen phosphorylase, two key enzymes in glycogen metabolism.

    Science.gov (United States)

    Díaz-Lobo, Mireia; Garcia-Amorós, Jaume; Fita, Ignacio; Velasco, Dolores; Guinovart, Joan J; Ferrer, Joan C

    2015-07-14

    Glycogen is a polymer of α-1,4- and α-1,6-linked glucose units that provides a readily available source of energy in living organisms. Glycogen synthase (GS) and glycogen phosphorylase (GP) are the two enzymes that control, respectively, the synthesis and degradation of this polysaccharide and constitute adequate pharmacological targets to modulate cellular glycogen levels, by means of inhibition of their catalytic activity. Here we report on the synthesis and biological evaluation of a selective inhibitor that consists of an azobenzene moiety glycosidically linked to the anomeric carbon of a glucose molecule. In the ground state, the more stable (E)-isomer of the azobenzene glucoside had a slight inhibitory effect on rat muscle GP (RMGP, IC50 = 4.9 mM) and Escherichia coli GS (EcGS, IC50 = 1.6 mM). After irradiation and subsequent conversion to the (Z)-form, the inhibitory potency of the azobenzene glucoside did not significantly change for RMGP (IC50 = 2.4 mM), while its effect on EcGS increased 50-fold (IC50 = 32 μM). Sucrose synthase 4 from potatoes, a glycosyltransferase that does not operate on glycogen, was only slightly inhibited by the (E)-isomer (IC50 = 0.73 mM). These findings could be rationalized on the basis of kinetic and computer-aided docking analysis, which indicated that both isomers of the azobenzene glucoside mimic the EcGS acceptor substrate and exert their inhibitory effect by binding to the glycogen subsite in the active center of the enzyme. The ability to selectively photoregulate the catalytic activity of key enzymes of glycogen metabolism may represent a new approach for the treatment of glycogen metabolism disorders.

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

    OpenAIRE

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

    2007-01-01

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

  18. Oligosaccharide Binding in Escherichia coli Glycogen Synthase

    Energy Technology Data Exchange (ETDEWEB)

    Sheng, Fang; Yep, Alejandra; Feng, Lei; Preiss, Jack; Geiger, James H.; (MSU)

    2010-11-17

    Glycogen/starch synthase elongates glucan chains and is the key enzyme in the synthesis of glycogen in bacteria and starch in plants. Cocrystallization of Escherichia coli wild-type glycogen synthase (GS) with substrate ADPGlc and the glucan acceptor mimic HEPPSO produced a closed form of GS and suggests that domain-domain closure accompanies glycogen synthesis. Cocrystallization of the inactive GS mutant E377A with substrate ADPGlc and oligosaccharide results in the first oligosaccharide-bound glycogen synthase structure. Four bound oligosaccharides are observed, one in the interdomain cleft (G6a) and three on the N-terminal domain surface (G6b, G6c, and G6d). Extending from the center of the enzyme to the interdomain cleft opening, G6a mostly interacts with the highly conserved N-terminal domain residues lining the cleft of GS. The surface-bound oligosaccharides G6c and G6d have less interaction with enzyme and exhibit a more curled, helixlike structural arrangement. The observation that oligosaccharides bind only to the N-terminal domain of GS suggests that glycogen in vivo probably binds to only one side of the enzyme to ensure unencumbered interdomain movement, which is required for efficient, continuous glucan-chain synthesis.

  19. Glycogen Shunt Activity and Glycolytic Supercompensation in Astrocytes May Be Distinctly Mediated via the Muscle Form of Glycogen Phosphorylase

    DEFF Research Database (Denmark)

    Jakobsen, Emil; Bak, Lasse K; Walls, Anne B

    2017-01-01

    not expressing the muscle isoform of glycogen phosphorylase. Based on these results and previously published data we couple the muscle isoform of glycogen phosphorylase to glycolytic supercompensation and glycogen shunt activity, giving insights to the underlying mechanistic of these phenomena.......Glycogen is the main storage form of glucose in the brain. In contrast with previous beliefs, brain glycogen has recently been shown to play important roles in several brain functions. A fraction of metabolized glucose molecules are being shunted through glycogen before reentering the glycolytic...... pathway, a phenomenon known as the glycogen shunt. The significance of glycogen in astrocyte energetics is underlined by high activity of the glycogen shunt and the finding that inhibition of glycogen degradation, under some conditions leads to a disproportional increase in glycolytic activity, so...

  20. Metabolic demands and replenishment of muscle glycogen after a rugby league match simulation protocol.

    Science.gov (United States)

    Bradley, Warren J; Hannon, Marcus P; Benford, Victoria; Morehen, James C; Twist, Craig; Shepherd, Sam; Cocks, Matthew; Impey, Samuel G; Cooper, Robert G; Morton, James P; Close, Graeme L

    2017-09-01

    The metabolic requirements of a rugby league match simulation protocol and the timing of carbohydrate provision on glycogen re-synthesis in damaged muscle were examined. Fifteen (mean±SD: age 20.9±2.9 year, body-mass 87.3±14.1kg, height 177.4±6.0cm) rugby league (RL) players consumed a 6gkgday-1 CHO diet for 7-days, completed a time to exhaustion test (TTE) and a glycogen depletion protocol on day-3, a RL simulated-match protocol (RLMSP) on day-5 and a TTE on day-7. Players were prescribed an immediate or delayed (2-h-post) re-feed post-simulation. Muscle biopsies and blood samples were obtained post-depletion, before and after simulated match-play, and 48-h after match-play with PlayerLoad and heart-rate collected throughout the simulation. Data were analysed using effects sizes±90% CI and magnitude-based inferences. PlayerLoad (8.0±0.7 AUmin-1) and %HRpeak (83±4.9%) during the simulation were similar to values reported for RL match-play. Muscle glycogen very likely increased from immediately after to 48-h post-simulation (272±97 cf. 416±162mmolkg-1d.w.; ES±90%CI) after immediate re-feed, but changes were unclear (283±68 cf. 361±144mmolkg-1d.w.; ES±90%CI) after delayed re-feed. CK almost certainly increased by 77.9±25.4% (0.75±0.19) post-simulation for all players. The RLMSP presents a replication of the internal loads associated with professional RL match-play, although difficulties in replicating the collision reduced the metabolic demands and glycogen utilisation. Further, it is possible to replete muscle glycogen in damaged muscle employing an immediate re-feed strategy. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

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

  2. 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

    INTRODUCTION: In skeletal muscle, glucose is stored as glycogen, which is a major source of energy during most forms of muscle activity. It is now well recognized that muscle glycogen stores are closely related to performance and endurance capacity. Thus, successful competition or training depend...

  3. 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

    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......, 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......, preexercise muscle glycogen concentrations were 364 +/- 23 and 568 +/- 35 mumol.g-1 d.w. in the N and CHR condition, respectively (P glycogen concentration in the M. quadriceps decreased to the same extent in both groups. Accordingly, the exercise-induced increases in muscle...

  4. The human serum metabolome of vitamin B-12 deficiency and repletion, and associations with neurological function

    Science.gov (United States)

    We characterize the human serum metabolome in sub-clinical vitamin B-12 (B-12) deficiency and repletion. A pre-post treatment study provided one injection of 10 mg B-12 to 27 community-dwelling elderly Chileans with B-12 deficiency evaluated with serum B-12, plasma homocysteine, methylmalonic acid a...

  5. Microarray analysis of pancreatic gene expression during biotin repletion in biotin-deficient rats.

    Science.gov (United States)

    Dakshinamurti, Krishnamurti; Bagchi, Rushita A; Abrenica, Bernard; Czubryt, Michael P

    2015-12-01

    Biotin is a B vitamin involved in multiple metabolic pathways. In humans, biotin deficiency is relatively rare but can cause dermatitis, alopecia, and perosis. Low biotin levels occur in individuals with type-2 diabetes, and supplementation with biotin plus chromium may improve blood sugar control. The acute effect on pancreatic gene expression of biotin repletion following chronic deficiency is unclear, therefore we induced biotin deficiency in adult male rats by feeding them a 20% raw egg white diet for 6 weeks. Animals were then randomized into 2 groups: one group received a single biotin supplement and returned to normal chow lacking egg white, while the second group remained on the depletion diet. After 1 week, pancreata were removed from biotin-deficient (BD) and biotin-repleted (BR) animals and RNA was isolated for microarray analysis. Biotin depletion altered gene expression in a manner indicative of inflammation, fibrosis, and defective pancreatic function. Conversely, biotin repletion activated numerous repair and anti-inflammatory pathways, reduced fibrotic gene expression, and induced multiple genes involved in pancreatic endocrine and exocrine function. A subset of the results was confirmed by quantitative real-time PCR analysis, as well as by treatment of pancreatic AR42J cells with biotin. The results indicate that biotin repletion, even after lengthy deficiency, results in the rapid induction of repair processes in the pancreas.

  6. Regulation of glucose and glycogen metabolism during and after exercise

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Richter, Erik

    2012-01-01

    Utilization of carbohydrate in the form of intramuscular glycogen stores and glucose delivered from plasma becomes an increasingly important energy substrate to the working muscle with increasing exercise intensity. This review gives an update on the molecular signals by which glucose transport...... is increased in the contracting muscle followed by a discussion of glycogen mobilization and synthesis by the action of glycogen phosphorylase and glycogen synthase, respectively. Finally, this review deals with the signalling relaying the well-described increased sensitivity of glucose transport to insulin...... in the post-exercise period which can result in an overshoot of intramuscular glycogen resynthesis post exercise (glycogen supercompensation)....

  7. Effect of acetic acid feeding on the circadian changes in glycogen and metabolites of glucose and lipid in liver and skeletal muscle of rats.

    Science.gov (United States)

    Fushimi, Takashi; Sato, Yuzo

    2005-11-01

    The aim of the present study is to investigate the effect of acetic acid feeding on the circadian changes in glycogen concentration in liver and skeletal muscle. Rats were provided meal once daily (09.00-13.00 hours) for 10 d. On the 11th day, they were either killed immediately or given 9 g diet containing either 0 (control) or 0.7 g/kg-diet acetic acid beginning at 09.00 hours for 4 h, as in the previous regimen. Rats in the fed group were killed at 4, 8 or 24 h after the start of feeding. At 4 h after the start of feeding, the acetic acid group had significantly greater liver and gastrocnemius muscle glycogen concentrations (Pacetic acid group than in the control group (Pacetic acid group had a significantly lower serum lactate concentration and lower ratio of insulin to glucagon than the control group at the same point (Pacetic acid may enhance glycogen repletion but not induce supercompensation, a large increase in the glycogen level that is beneficial in improving performance, in liver and skeletal muscle by transitory inhibition of glycolysis. Further, we indicate the possibility of a transient enhancement of fatty acid oxidation in liver by acetic acid feeding.

  8. 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

  9. Glycogen metabolism in aerobic mixed cultures

    DEFF Research Database (Denmark)

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

    2001-01-01

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

  10. Genetics Home Reference: glycogen storage disease type I

    Science.gov (United States)

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

  11. Muscle glycogen remodeling and glycogen phosphate metabolism following exhaustive exercise of wild type and laforin knockout mice.

    Science.gov (United States)

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

    2015-09-11

    Glycogen, the repository of glucose in many cell types, contains small amounts of covalent phosphate, of uncertain function and poorly understood metabolism. Loss-of-function mutations in the laforin gene cause the fatal neurodegenerative disorder, Lafora disease, characterized by increased glycogen phosphorylation and the formation of abnormal deposits of glycogen-like material called Lafora bodies. It is generally accepted that the phosphate is removed by the laforin phosphatase. To study the dynamics of skeletal muscle glycogen phosphorylation in vivo under physiological conditions, mice were subjected to glycogen-depleting exercise and then monitored while they resynthesized glycogen. Depletion of glycogen by exercise was associated with a substantial reduction in total glycogen phosphate and the newly resynthesized glycogen was less branched and less phosphorylated. Branching returned to normal on a time frame of days, whereas phosphorylation remained suppressed over a longer period of time. We observed no change in markers of autophagy. Exercise of 3-month-old laforin knock-out mice caused a similar depletion of glycogen but no loss of glycogen phosphate. Furthermore, remodeling of glycogen to restore the basal branching pattern was delayed in the knock-out animals. From these results, we infer that 1) laforin is responsible for glycogen dephosphorylation during exercise and acts during the cytosolic degradation of glycogen, 2) excess glycogen phosphorylation in the absence of laforin delays the normal remodeling of the branching structure, and 3) the accumulation of glycogen phosphate is a relatively slow process involving multiple cycles of glycogen synthesis-degradation, consistent with the slow onset of the symptoms of Lafora disease. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

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

    2015-01-01

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

  13. 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

  14. Cell swelling and glycogen metabolism in hepatocytes from fasted rats

    NARCIS (Netherlands)

    Gustafson, L. A.; Jumelle-Laclau, M. N.; van Woerkom, G. M.; van Kuilenburg, A. B.; Meijer, A. J.

    1997-01-01

    Cell swelling is known to increase net glycogen production from glucose in hepatocytes from fasted rats by activating glycogen synthase. Since both active glycogen synthase and phosphorylase are present in hepatocytes, suppression of flux through phosphorylase may also contribute to the net increase

  15. Effect of diabetes on glycogen metabolism in rat retina.

    Science.gov (United States)

    Sánchez-Chávez, Gustavo; Hernández-Berrones, Jethro; Luna-Ulloa, Luis Bernardo; Coffe, Víctor; Salceda, Rocío

    2008-07-01

    Glucose is the main fuel for energy metabolism in retina. The regulatory mechanisms that maintain glucose homeostasis in retina could include hormonal action. Retinopathy is one of the chemical manifestations of long-standing diabetes mellitus. In order to better understand the effect of hyperglycemia in retina, we studied glycogen content as well as glycogen synthase and phosphorylase activities in both normal and streptozotocin-induced diabetic rat retina and compared them with other tissues. Glycogen levels in normal rat retina are low (46 +/- 4.0 nmol glucosyl residues/mg protein). However, high specific activity of glycogen synthase was found in retina, indicating a substantial capacity for glycogen synthesis. In diabetic rats, glycogen synthase activity increased between 50% and 100% in retina, brain cortex and liver of diabetic rats, but only retina exhibited an increase in glycogen content. Although, total and phosphorylated glycogen synthase levels were similar in normal and diabetic retina, activation of glycogen synthase by glucose-6-P was remarkable increased. Glycogen phosphorylase activity decreased 50% in the liver of diabetic animals; it was not modified in the other tissues examined. We conclude that the increase in glycogen levels in diabetic retina was due to alterations in glycogen synthase regulation.

  16. Molecular Structure of Human-Liver Glycogen.

    Directory of Open Access Journals (Sweden)

    Bin Deng

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

  17. Repletion of Zinc and Iron Deficiencies Improves Cognition of Premenopausal Women.

    Science.gov (United States)

    1997-10-01

    Work This 3 year project tests the hypothesis: "Repletion of mild zinc and iron deficiencies will improve neuropsychological ( neuromotor and...zinc turnover rate were highly related to lean body mass. These findings are original with us and represent an advance in basic knowledge. The double...different models based on Ramakrishnan’s matrix transformation [21]. His basic idea was derived from Berman’s model [21]. As was proven in the Appendix

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

    Science.gov (United States)

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

    2012-02-01

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

  19. Glycogen and other soluble glucans from chytridiomycete and oomycete species.

    Science.gov (United States)

    Coulter, D B; Aronson, J M

    1977-12-15

    Dry weight, protein, lipid, and glycogen were determined at various times during cultivation of the Chytridiomycetes, Rhizophydium sphaerotheca and Monoblepharella elongata. M. elongata had relatively stable levels of glycogen, but, in R. sphaerotheca, glycogen levels showed significant changes, particularly in older cultures in which a depletion of glycogen was accompanied by a marked thickening of the cell walls. Glycogen was a significant cellular constituent in both chytridiomycete species. In R. sphaerotheca and M. elongata, respectively, glycogen accounted for as much as 6% and 8.1% of the dry weight. In purified glycogens of both species, only alpha-1,4- and alpha-1,6-linked glucosyl residues were detected and the absorbance spectra of I2-complexes were similar to those of other well characterized glycogens. Purified Rhizophydium glycogen had a beta-amylolysis limit of 43%, and a CL of approximately 12. For the Monoblepharella polysaccharide, the respective values were 45% and 11. In extracts of the Oomycetes, Pythium debaryanum, Mindeniella spinospora, and Apodachlya sp., only beta-1,3- and beta-1,6-linked glucosyl residues were detected. These glucans were not iodophilic nor were they sensitive to alpha-amylase and beta-amylase. The properties of the oomycete polysaccharides suggested that they were similar to the mycolaminarans of Phytophthora spp. Although both investigated chytridiomycete species produced glycogen with typical properties, glycogen was apparently absent in the investigated Oomycetes.

  20. Increased de novo lipogenesis and delayed conversion of large VLDL into intermediate density lipoprotein particles contribute to Hyperlipidemia in glycogen storage disease type 1a

    NARCIS (Netherlands)

    Bandsma, Robert H. J.; Prinsen, Berthil H.; Van Der Velden, Monique De Sain; Rake, Jan-Peter; Boer, Theo; Smit, G. Peter A.; Reijngoud, Dirk-Jan; Kuipers, Folkert

    Glycogen storage disease type 1a (GSD-1a) is a metabolic disorder characterized by fasting-induced hypoglycemia, hepatic steatosis, and hyperlipidemia. The mechanisms underlying the lipid abnormalities are largely unknown. To investigate these mechanisms seven GSD-1a patients and four healthy

  1. Muscle glycogen and cell function - Location, location, location

    DEFF Research Database (Denmark)

    Ørtenblad, N; Nielsen, Joachim

    2015-01-01

    that the subcellular localization of glycogen has to be considered to fully understand the role of glycogen metabolism and signaling in skeletal muscle function. Here, we propose that the effect of low muscle glycogen on excitation-contraction coupling may serve as a built-in mechanism, which links the energetic state......The importance of glycogen, as a fuel during exercise, is a fundamental concept in exercise physiology. The use of electron microscopy has revealed that glycogen is not evenly distributed in skeletal muscle fibers, but rather localized in distinct pools. In this review, we present the available...... evidence regarding the subcellular localization of glycogen in skeletal muscle and discuss this from the perspective of skeletal muscle fiber function. The distribution of glycogen in the defined pools within the skeletal muscle varies depending on exercise intensity, fiber phenotype, training status...

  2. Functional significance of brain glycogen in sustaining glutamatergic neurotransmission

    DEFF Research Database (Denmark)

    Sickmann, Helle M; Walls, Anne B; Schousboe, Arne

    2009-01-01

    unclear. The significance of glycogen in fueling glutamate uptake into astrocytes was specifically addressed in cultured astrocytes. Moreover, the objective was to elucidate whether glycogen derived energy is important for maintaining glutamatergic neurotransmission, induced by repetitive exposure to NMDA...... in co-cultures of cerebellar neurons and astrocytes. In the astrocytes it was shown that uptake of the glutamate analogue D-[3H]aspartate was impaired when glycogen degradation was inhibited irrespective of the presence of glucose, signifying that energy derived from glycogen degradation is important...... for the astrocytic compartment. By inhibiting glycogen degradation in co-cultures it was evident that glycogen provides energy to sustain glutamatergic neurotransmission, i.e. release and uptake of glutamate. The relocation of glycogen derived lactate to the neuronal compartment was investigated by employing d...

  3. Low birth weight and zygosity status is associated with defective muscle glycogen and glycogen synthase regulation in elderly twins

    DEFF Research Database (Denmark)

    Poulsen, Pernille; Wojtaszewski, Jørgen; Richter, Erik

    2007-01-01

    OBJECTIVE: An adverse intrauterine environment indicated by both low birth weight and monozygosity is associated with an age- or time-dependent reduction in glucose disposal and nonoxidative glucose metabolism in twins, suggesting impaired regulation of muscle glycogen synthesis. RESEARCH DESIGN...... fractional GS activity amidst higher glycogen and GS protein levels compared with dizygotic twins. In addition, we demonstrated strong nongenetic associations between birth weight and defect muscle glycogen metabolism in elderly--but not in younger--twins. Thus, for every 100 g increase in birth weight...... feedback inhibition of glycogen metabolism by glycogen per se may contribute to the insulin resistance in elderly monozygotic compared with dizygotic twins...

  4. Epinephrine-stimulated glycogen breakdown activates glycogen synthase and increases insulin-stimulated glucose uptake in epitrochlearis muscles

    DEFF Research Database (Denmark)

    Kolnes, Anders J; Birk, Jesper Bratz; Eilertsen, Einar

    2015-01-01

    Adrenaline increases glycogen synthase (GS) phosphorylation and decreases GS activity but also stimulates glycogen breakdown and low glycogen content normally activates GS. To test the hypothesis that glycogen content directly regulates GS phosphorylation, glycogen breakdown was stimulated...... in condition with decreased GS activation. Saline or adrenaline (0.02mg/100g rat) was injected subcutaneously in Wistar rats (~130 g) with low (24 h fasted), normal (normal diet) and high glycogen content (fasted-refed) and epitrochlearis muscles were removed after 3 h and incubated ex vivo eliminating...... adrenaline action. Adrenaline injection reduced glycogen content in epitrochlearis muscles with high (120.7±17.8 vs 204.6±14.5 mmol•kg(-1); pglycogen (89.5±7.6 vs 152.6±8.1 mmol•kg(-1); pglycogen (90.0±5.0 vs 102.8±7.8 mmol•kg(-1); p=0...

  5. Glycogen resynthesis in the absence of food ingestion during recovery from moderate or high intensity physical activity: novel insights from rat and human studies.

    Science.gov (United States)

    Fournier, P A; Bräu, L; Ferreira, L D M C-B; Fairchild, T; Raja, G; James, A; Palmer, T N

    2002-11-01

    The finding that during recovery from high intensity exercise, rats have the capacity to replenish their muscle glycogen stores even in the absence of food intake has provided us with an experimental model of choice to explore further this process. Our objective here is to share those questions arising from research carried out by others and ourselves on rats and humans that are likely to be of interest to comparative biochemists/physiologists. On the basis of our findings and those of others, it is proposed that across vertebrate species: (1). the capacity of muscles to replenish their glycogen stores from endogenous carbon sources is dependent on the type of physical activity and animal species; (2). lactate and amino acids are the major endogenous carbon sources mobilized for the resynthesis of muscle glycogen during recovery from exercise, their relative contributions depending on the duration of recovery and type of exercise; (3). the relative contributions of lactate glyconeogenesis and hepatic/renal gluconeogenesis to muscle glycogen synthesis is species- and muscle fiber-dependent; and (4). glycogen synthase and phosphorylase play an important role in the control of the rate of glycogen synthesis post-exercise, with the role of glucose transport being species-dependent.

  6. 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.

  7. 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...... biopsies were obtained from pathologic hippocampus (n=19) and from apparently 'normal' cortical grey and white matter. We determined the in vivo brain glycogen level and the activity of glycogen phosphorylase and synthase. Regional differences in glycogen concentration were examined similarly in healthy...... pigs (n=5). In the patients, the glycogen concentration in 'normal' grey and white matter was 5 to 6 mmol/L, but much higher in the hippocampus, 13.1+/-4.3 mmol/L (mean+/-s.d.; Pglycogen phosphorylase and synthase displayed the same pattern. In normal hippocampus from pigs...

  8. Qualitative and Quantitative Analyses of Glycogen in Human Milk.

    Science.gov (United States)

    Matsui-Yatsuhashi, Hiroko; Furuyashiki, Takashi; Takata, Hiroki; Ishida, Miyuki; Takumi, Hiroko; Kakutani, Ryo; Kamasaka, Hiroshi; Nagao, Saeko; Hirose, Junko; Kuriki, Takashi

    2017-02-22

    Identification as well as a detailed analysis of glycogen in human milk has not been shown yet. The present study confirmed that glycogen is contained in human milk by qualitative and quantitative analyses. High-performance anion exchange chromatography (HPAEC) and high-performance size exclusion chromatography with a multiangle laser light scattering detector (HPSEC-MALLS) were used for qualitative analysis of glycogen in human milk. Quantitative analysis was carried out by using samples obtained from the individual milks. The result revealed that the concentration of human milk glycogen varied depending on the mother's condition-such as the period postpartum and inflammation. The amounts of glycogen in human milk collected at 0 and 1-2 months postpartum were higher than in milk collected at 3-14 months postpartum. In the milk from mothers with severe mastitis, the concentration of glycogen was about 40 times higher than that in normal milk.

  9. Glycogen distribution in adult and geriatric mice brains

    KAUST Repository

    Alrabeh, Rana

    2017-05-01

    Astrocytes, the most abundant glial cell type in the brain, undergo a number of roles in brain physiology; among them, the energetic support of neurons is the best characterized. Contained within astrocytes is the brain’s obligate energy store, glycogen. Through glycogenolysis, glycogen, a storage form of glucose, is converted to pyruvate that is further reduced to lactate and transferred to neurons as an energy source via MCTs. Glycogen is a multi-branched polysaccharide synthesized from the glucose uptaken in astrocytes. It has been shown that glycogen accumulates with age and contributes to the physiological ageing process in the brain. In this study, we compared glycogen distribution between young adults and geriatric mice to understand the energy consumption of synaptic terminals during ageing using computational tools. We segmented and densely reconstructed neuropil and glycogen granules within six (three 4 month old old and three 24 month old) volumes of Layer 1 somatosensory cortex mice brains from FIB-SEM stacks, using a combination of semi-automated and manual tools, ilastik and TrakEM2. Finally, the 3D visualization software, Blender, was used to analyze the dataset using the DBSCAN and KDTree Nearest neighbor algorithms to study the distribution of glycogen granules compared to synapses, using a plugin that was developed for this purpose. The Nearest Neighbors and clustering results of 6 datasets show that glycogen clusters around excitatory synapses more than inhibitory synapses and that, in general, glycogen is found around axonal boutons more than dendritic spines. There was no significant accumulation of glycogen with ageing within our admittedly small dataset. However, there was a homogenization of glycogen distribution with age and that is consistent with published literature. We conclude that glycogen distribution in the brain is not a random process but follows a function distribution.

  10. Fructose and galactose enhance postexercise human liver glycogen synthesis.

    OpenAIRE

    Décombaz Jacques; Jentjens Roy; Ith Michael; Scheurer Eva; Buehler Tania; Jeukendrup Asker; Boesch Chris

    2011-01-01

    PURPOSE Both liver and muscle glycogen stores play a fundamental role in exercise and fatigue but the effect of different CHO sources on liver glycogen synthesis in humans is unclear. The aim was to compare the effect of maltodextrin (MD) drinks containing galactose fructose or glucose on postexercise liver glycogen synthesis. METHODS In this double blind triple crossover randomized clinical trial 10 well trained male cyclists performed three experimental exercise sessions separated by at ...

  11. Glycogen metabolism and the homeostatic regulation of sleep

    OpenAIRE

    Petit, Jean-Marie; Burlet-Godinot, Sophie; Pierre J Magistretti; Allaman, Igor

    2014-01-01

    In 1995 Benington and Heller formulated an energy hypothesis of sleep centered on a key role of glycogen. It was postulated that a major function of sleep is to replenish glycogen stores in the brain that have been depleted during wakefulness which 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 ques...

  12. Drug induced exocytosis of glycogen in Pompe disease.

    Science.gov (United States)

    Turner, Christopher T; Fuller, Maria; Hopwood, John J; Meikle, Peter J; Brooks, Doug A

    2016-10-28

    Pompe disease is caused by a deficiency in the lysosomal enzyme α-glucosidase, and this leads to glycogen accumulation in the autolysosomes of patient cells. Glycogen storage material is exocytosed at a basal rate in cultured Pompe cells, with one study showing up to 80% is released under specific culture conditions. Critically, exocytosis induction may reduce glycogen storage in Pompe patients, providing the basis for a therapeutic strategy whereby stored glycogen is redirected to an extracellular location and subsequently degraded by circulating amylases. The focus of the current study was to identify compounds capable of inducing rapid glycogen exocytosis in cultured Pompe cells. Here, calcimycin, lysophosphatidylcholine and α-l-iduronidase each significantly increased glycogen exocytosis compared to vehicle-treated controls. The most effective compound, calcimycin, induced exocytosis through a Ca 2+ -dependent mechanism, although was unable to release a pool of vesicular glycogen larger than the calcimycin-induced exocytic pore. There was reduced glycogen release from Pompe compared to unaffected cells, primarily due to increased granule size in Pompe cells. Drug induced exocytosis therefore shows promise as a therapeutic approach for Pompe patients but strategies are required to enhance the release of large molecular weight glycogen granules. Copyright © 2016. Published by Elsevier Inc.

  13. Estimating Coastal Lagoon Tidal Flooding and Repletion with Multidate ASTER Thermal Imagery

    Directory of Open Access Journals (Sweden)

    Thomas R. Allen

    2012-10-01

    Full Text Available Coastal lagoons mix inflowing freshwater and tidal marine waters in complex spatial patterns. This project sought to detect and measure temperature and spatial variability of flood tides for a constricted coastal lagoon using multitemporal remote sensing. Advanced Spaceborne Thermal Emission Radiometer (ASTER thermal infrared data provided estimates of surface temperature for delineation of repletion zones in portions of Chincoteague Bay, Virginia. ASTER high spatial resolution sea-surface temperature imagery in conjunction with in situ observations and tidal predictions helped determine the optimal seasonal data for analyses. The selected time series ASTER satellite data sets were analyzed at different tidal phases and seasons in 2004–2006. Skin surface temperatures of ocean and estuarine waters were differentiated by flood tidal penetration and ebb flows. Spatially variable tidal flood penetration was evaluated using discrete seed-pixel area analysis and time series Principal Components Analysis. Results from these techniques provide spatial extent and variability dynamics of tidal repletion, flushing, and mixing, important factors in eutrophication assessment, water quality and resource monitoring, and application of hydrodynamic modeling for coastal estuary science and management.

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

    Science.gov (United States)

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

    2016-10-01

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

  15. Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis

    NARCIS (Netherlands)

    Serlie, Mireille J. M.; de Haan, Jacco H.; Tack, Cees J.; Verberne, Hein J.; Ackermans, Mariette T.; Heerschap, Arend; Sauerwein, Hans P.

    2005-01-01

    The introduction of C-13 magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus

  16. Muscular glycogen storage diseases without increased glycogen content on histoplathological examination

    NARCIS (Netherlands)

    Hoeksma, M.; den Dunnen, W. F. A.; Niezen-Koning, K. E.; van Diggelen, O. P.; van Spronsen, F. J.

    Histopathological findings of muscle biopsies from five patients with two different muscular glycogen storage diseases (mGSD) were presented. From these investigations it emerged that the yield of histopathology in mGSD is low. In only one of five patients histopathological findings gave a clue

  17. Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis.

    NARCIS (Netherlands)

    Serlie, M.J.; Haan, J.H.A. de; Tack, C.J.J.; Verberne, H.J.; Ackermans, M.T.; Heerschap, A.; Sauerwein, H.P.

    2005-01-01

    The introduction of 13C magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus

  18. Apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ.

    Directory of Open Access Journals (Sweden)

    Jiaojiao Chu

    Full Text Available Apelin, a novel adipokine, is the specific endogenous ligand of G protein-coupled receptor APJ. Consistent with its putative role as an adipokine, apelin has been linked to states of insulin resistance. However, the function of apelin in hepatic insulin resistance, a vital part of insulin resistance, and its underlying mechanisms still remains unclear. Here we define the impacts of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes. Our studies indicate that apelin reversed TNF-α-induced reduction of glycogen synthesis in HepG2 cells, mouse primary hepatocytes and liver tissues of C57BL/6J mice by improving JNK-IRS1-AKT-GSK pathway. Moreover, Western blot revealed that APJ, but not apelin, expressed in the hepatocytes and liver tissues of mice. We found that F13A, a competitive antagonist for G protein-coupled receptor APJ, suppressed the effects of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes, suggesting APJ is involved in the function of apelin. In conclusion, we show novel evidence suggesting that apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ. Apelin appears as a beneficial adipokine with anti-insulin resistance properties, and thus as a promising therapeutic target in metabolic disorders.

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

    Science.gov (United States)

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

    2017-02-01

    Glycogen is important not only for the energy supplementary of oysters, but also for human consumption. High glycogen content can improve the stress survival of oyster. A key enzyme in glycogenesis is glycogen synthase that is encoded by glycogen synthase gene GYS. In this study, the relationship between single nucleotide polymorphisms (SNPs) in coding regions of Crassostrea gigas GYS (Cg-GYS) and individual glycogen content was investigated with 321 individuals from five full-sib families. Single-strand conformation polymorphism (SSCP) procedure was combined with sequencing to confirm individual SNP genotypes of Cg-GYS. Least-square analysis of variance was performed to assess the relationship of variation in glycogen content of C. gigas with single SNP genotype and SNP haplotype. As a consequence, six SNPs were found in coding regions to be significantly associated with glycogen content ( P haplotypes due to linkage disequilibrium. Furthermore, the most effective haplotype H2 (GAGGAT) had extremely significant relationship with high glycogen content ( P < 0.0001). These findings revealed the potential influence of Cg-GYS polymorphism on the glycogen content and provided molecular biological information for the selective breeding of good quality traits of C. gigas.

  20. Contributions of Glycogen to Astrocytic Energetics during Brain Activation

    Science.gov (United States)

    Dienel, Gerald A.; Cruz, Nancy F.

    2014-01-01

    Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 mol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K+ level, oxidative stress management, and memory consolidation; it is a multi-functional compound. PMID:24515302

  1. FIH-1/c-Kit Signaling: A Novel Contributor to Corneal Epithelial Glycogen Metabolism

    OpenAIRE

    Peng, Han; Katsnelson, Julia; Yang, Wending; Brown, Melissa A.; Lavker, Robert M.

    2013-01-01

    Maintenance of limbal/corneal epithelial glycogen is essential for homeostasis as glycogen is a primary energy source. We demonstrate that FIH-1, a novel hydroxylase, alters c-kit signaling, which results in a negative regulation of glycogen metabolism.

  2. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M

    1987-01-01

    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....

  3. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M

    1987-01-01

    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 tumo...... was classified as a mucin-containing variant of glycogen-rich, clear cell carcinoma of the breast....

  4. Hepatocellular carcinoma in glycogen storage disease type IV

    OpenAIRE

    de Moor, R A; Schweizer, J.; Van Hoek, B.; Wasser, M.; Vink, R.; Maaswinkel-Mooy, P.

    2000-01-01

    A 13 year old patient with juvenile type IV glycogen storage disease died of the complications of hepatocellular carcinoma. To our knowledge this is the first reported case of hepatocellular carcinoma in association with type IV glycogen storage disease.



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

    DEFF Research Database (Denmark)

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

    1984-01-01

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

  6. Repletion of TNFα or leptin in calorically restricted mice suppresses post-restriction hyperphagia

    Directory of Open Access Journals (Sweden)

    Catherine Hambly

    2012-01-01

    The causes of post-restriction hyperphagia (PRH represent a target for drug-based therapies to prevent obesity. However, the factors causing PRH are poorly understood. We show that, in mice, the extent of PRH was independent of the time under restriction, but depended on its severity, suggesting that PRH was driven by signals from altered body composition. Signals related to fat mass were important drivers. Circulating levels of leptin and TNFα were significantly depleted following caloric restriction (CR. We experimentally repleted their levels to match those of controls, and found that in both treatment groups the level of PRH was significantly blunted. These data establish a role for TNFα and leptin in the non-pathological regulation of energy homeostasis. Signals from adipose tissue, including but not limited to leptin and TNFα, regulate PRH and might be targets for therapies that support people engaged in CR to reduce obesity.

  7. Repletion of TNFα or leptin in calorically restricted mice suppresses post-restriction hyperphagia

    Science.gov (United States)

    Hambly, Catherine; Duncan, Jacqueline S.; Archer, Zoë A.; Moar, Kim M.; Mercer, Julian G.; Speakman, John R.

    2012-01-01

    SUMMARY The causes of post-restriction hyperphagia (PRH) represent a target for drug-based therapies to prevent obesity. However, the factors causing PRH are poorly understood. We show that, in mice, the extent of PRH was independent of the time under restriction, but depended on its severity, suggesting that PRH was driven by signals from altered body composition. Signals related to fat mass were important drivers. Circulating levels of leptin and TNFα were significantly depleted following caloric restriction (CR). We experimentally repleted their levels to match those of controls, and found that in both treatment groups the level of PRH was significantly blunted. These data establish a role for TNFα and leptin in the non-pathological regulation of energy homeostasis. Signals from adipose tissue, including but not limited to leptin and TNFα, regulate PRH and might be targets for therapies that support people engaged in CR to reduce obesity. PMID:21954068

  8. Hepatitis E

    Science.gov (United States)

    ... sheets Fact files Questions & answers Features Multimedia Contacts Hepatitis E Fact sheet Updated July 2017 Key facts ... in 2005 . Report Global hepatitis report, 2017 World Hepatitis Day Know hepatitis - Act now Event notice Key ...

  9. Viral Hepatitis

    Science.gov (United States)

    ... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

  10. Hepatitis A

    Science.gov (United States)

    ... or care for someone who has hepatitis A People who travel to developing countries are more likely to get hepatitis A. What are the complications of hepatitis A? People typically recover from hepatitis A without complications. In ...

  11. Comparison of Nitrogen Depletion and Repletion on Lipid Production in Yeast and Fungal Species

    Directory of Open Access Journals (Sweden)

    Shihui Yang

    2016-08-01

    Full Text Available Although it is well known that low nitrogen stimulates lipid accumulation, especially for algae and some oleaginous yeast, few studies have been conducted in fungal species, especially on the impact of different nitrogen deficiency strategies. In this study, we use two promising consolidated bioprocessing (CBP candidates to examine the impact of two nitrogen deficiency strategies on lipid production, which are the extensively investigated oleaginous yeast Yarrowia lipolytica, and the commercial cellulase producer Trichoderma reesei. We first utilized bioinformatics approaches to reconstruct the fatty acid metabolic pathway and demonstrated the presence of a triacylglycerol (TAG biosynthesis pathway in Trichoderma reesei. We then examined the lipid production of Trichoderma reesei and Y. lipomyces in different media using two nitrogen deficiency strategies of nitrogen natural repletion and nitrogen depletion through centrifugation. Our results demonstrated that nitrogen depletion was better than nitrogen repletion with about 30% lipid increase for Trichoderma reesei and Y. lipomyces, and could be an option to improve lipid production in both oleaginous yeast and filamentous fungal species. The resulting distinctive lipid composition profiles indicated that the impacts of nitrogen depletion on yeast were different from those for fungal species. Under three types of C/N ratio conditions, C16 and C18 fatty acids were the predominant forms of lipids for both Trichoderma reesei and Y. lipolytica. While the overall fatty acid methyl ester (FAME profiles of Trichoderma reesei were similar, the overall FAME profiles of Y. lipolytica observed a shift. The fatty acid metabolic pathway reconstructed in this work supports previous reports of lipid production in T. reesei, and provides a pathway for future omics studies and metabolic engineering efforts. Further investigation to identify the genetic targets responsible for the effect of nitrogen depletion on

  12. Functional coupling of renal K+ and Na+ handling causes high blood pressure in Na+ replete mice.

    Science.gov (United States)

    Vitzthum, Helga; Seniuk, Anika; Schulte, Laura Helene; Müller, Maxie Luise; Hetz, Hannah; Ehmke, Heimo

    2014-03-01

    A network of kinases, including WNKs, SPAK and Sgk1, is critical for the independent regulation of K+ and Na+ transport in the distal nephron. Angiotensin II is thought to act as a key hormone in orchestrating these kinases to switch from K+ secretion during hyperkalaemia to Na+ reabsorption during intravascular volume depletion, thus keeping disturbances in electrolyte and blood pressure homeostasis at a minimum. It remains unclear, however, how K+ and Na+ transport are regulated during a high Na+ intake, which is associated with suppressed angiotensin II levels and a high distal tubular Na+ load. We therefore investigated the integrated blood pressure, renal, hormonal and gene and protein expression responses to large changes of K+ intake in Na+ replete mice. Both low and high K+ intake increased blood pressure and caused Na+ retention. Low K+ intake was accompanied by an upregulation of the sodium-chloride cotransporter (NCC) and its activating kinase SPAK, and inhibition of NCC normalized blood pressure. Renal responses were unaffected by angiotensin AT1 receptor antagonism, indicating that low K+ intake activates the distal nephron by an angiotensin-independent mode of action. High K+ intake was associated with elevated plasma aldosterone concentrations and an upregulation of the epithelial sodium channel (ENaC) and its activating kinase Sgk1. Surprisingly, high K+ intake increased blood pressure even during ENaC or mineralocorticoid receptor antagonism, suggesting the contribution of aldosterone-independent mechanisms. These findings show that in a Na+ replete state, changes in K+ intake induce specific molecular and functional adaptations in the distal nephron that cause a functional coupling of renal K+ and Na+ handling, resulting in Na+ retention and high blood pressure when K+ intake is either restricted or excessively increased.

  13. Glycogen synthase from the parabasalian parasite Trichomonas vaginalis: An unusual member of the starch/glycogen synthase family.

    Science.gov (United States)

    Wilson, Wayne A; Pradhan, Prajakta; Madhan, Nayasha; Gist, Galen C; Brittingham, Andrew

    2017-07-01

    Trichomonas vaginalis, a parasitic protist, is the causative agent of the common sexually-transmitted infection trichomoniasis. The organism has long been known to synthesize substantial glycogen as a storage polysaccharide, presumably mobilizing this compound during periods of carbohydrate limitation, such as might be encountered during transmission between hosts. However, little is known regarding the enzymes of glycogen metabolism in T. vaginalis. We had previously described the identification and characterization of two forms of glycogen phosphorylase in the organism. Here, we measure UDP-glucose-dependent glycogen synthase activity in cell-free extracts of T. vaginalis. We then demonstrate that the TVAG_258220 open reading frame encodes a glycosyltransferase that is presumably responsible for this synthetic activity. We show that expression of TVAG_258220 in a yeast strain lacking endogenous glycogen synthase activity is sufficient to restore glycogen accumulation. Furthermore, when TVAG_258220 is expressed in bacteria, the resulting recombinant protein has glycogen synthase activity in vitro, transferring glucose from either UDP-glucose or ADP-glucose to glycogen and using both substrates with similar affinity. This protein is also able to transfer glucose from UDP-glucose or ADP-glucose to maltose and longer oligomers of glucose but not to glucose itself. However, with these substrates, there is no evidence of processivity and sugar transfer is limited to between one and three glucose residues. Taken together with our earlier work on glycogen phosphorylase, we are now well positioned to define both how T. vaginalis synthesizes and utilizes glycogen, and how these processes are regulated. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  14. Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice.

    Science.gov (United States)

    Kiang, Anne; Hartman, Zachary C; Liao, Shaoxi; Xu, Fang; Serra, Delila; Palmer, Donna J; Ng, Philip; Amalfitano, Andrea

    2006-01-01

    Glycogen storage disease type II (GSD-II) patients manifest symptoms of muscular dystrophy secondary to abnormal glycogen storage in cardiac and skeletal muscles. For GSD-II, we hypothesized that a fully deleted adenovirus (FDAd) vector expressing hGAA via nonviral regulatory elements (PEPCK promoter/ApoE enhancer) would facilitate long-term efficacy and decrease propensity to generate anti-hGAA antibody responses against hepatically secreted hGAA. Intravenous delivery of FDAdhGAA into GAA-tolerant or nontolerant GAA-KO mice resulted in long-term hepatic secretion of hGAA. Specifically, nontolerant mice achieved complete reversal of cardiac glycogen storage and near-complete skeletal glycogen correction for at least 180 days and tolerant mice for minimally 300 days coupled with the preservation of muscle strength. Anti-hGAA antibody levels in both mouse strains were significantly less relative to those previously generated by CMV-driven hGAA expression in nontolerant GAA-KO mice. However, plasma GAA levels decreased in nontolerant GAA-KO mice despite long-term intrahepatic GAA expression from the persistent vector. This intriguing result is discussed in light of other examples of "tolerance" induction by gene-transfer-based approaches.

  15. 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.

  16. Glycogen metabolism and the homeostatic regulation of sleep.

    Science.gov (United States)

    Petit, Jean-Marie; Burlet-Godinot, Sophie; Magistretti, Pierre J; Allaman, Igor

    2015-02-01

    In 1995 Benington and Heller formulated an energy hypothesis of sleep centered on a key role of glycogen. It was postulated that a major function of sleep is to replenish glycogen stores in the brain that have been depleted during wakefulness which 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.

  17. Regulation of glycogen metabolism in yeast and bacteria

    Science.gov (United States)

    Wilson, Wayne A.; Roach, Peter J.; Montero, Manuel; Baroja-Fernández, Edurne; Muñoz, Francisco José; Eydallin, Gustavo; Viale, Alejandro M.; Pozueta-Romero, Javier

    2010-01-01

    Microorganisms have the capacity to utilize a variety of nutrients and adapt to continuously changing environmental conditions. Many microorganisms, including yeast and bacteria, accumulate carbon and energy reserves to cope with starvation conditions temporarily present in the environment. Glycogen biosynthesis is a main strategy for such metabolic storage and a variety of sensing and signaling mechanisms have evolved in evolutionarily distant species to guarantee the production of this homopolysaccharide. At the most fundamental level, the processes of glycogen synthesis and degradation in yeast and bacteria share certain broad similarities. However, the regulation of these processes is sometimes quite distinct, indicating that they have evolved separately to respond optimally to the habitat conditions of each species. This review aims to highlight the mechanisms, both at the transcriptional and post-transcriptional levels, which regulate glycogen metabolism in yeast and bacteria, focusing on selected areas where the greatest increase in knowledge has occurred during the last few years. In the yeast system, we focus particularly on the various signaling pathways that control the activity of the enzymes of glycogen storage. We also discuss our recent understanding of the important role played by the vacuole in glycogen metabolism. In the case of bacterial glycogen, especial emphasis is given to aspects related with genetic regulation of glycogen metabolism and its connection with other biological processes. PMID:20412306

  18. Histochemical detection of glycogen using Griffonia simplicifolia agglutinin II.

    Science.gov (United States)

    Hennigar, R A; Schulte, B A; Spicer, S S

    1986-01-01

    The utility of a lectin from Griffonia simplicifolia (GSA II) for demonstrating glycogen in situ was tested on fixed paraffin-embedded sections of a variety of tissues from rodents and man. The histochemical specificity of GSA II conjugated to horseradish peroxidase (GSA II-HRP) for glycogen was documented by the lability of such staining on adjacent sections treated with either malt diastase or alpha-amylase. In some tissue sites, the lectin-HRP conjugate imparted cytoplasmic staining that was diastase- and amylase-labile but resisted digestion with N-acetylglucosaminidase. Reactivity in the latter sites was attributed to glycogen and occurred in cell types having well-documented glycogen content, including liver hepatocytes, skeletal muscle fibres and polymorphonuclear leukocytes. In other tissue loci, GSA II binding was confined to cell surfaces or intracellular compartments, was not affected by prior diastase or amylase digestion, but was abolished with N-acetylglucosaminidase. Staining in these sites was attributed not to glycogen, but instead to glycoconjugate having sugar chains terminated with N-acetylglucosamine. These findings document the affinity of GSA II for glycogen in situ but do not conflict with the biochemically demonstrated affinity of GSA II for terminal N-acetylglucosamine. The results reported here show that the GSA II-HRP method may be useful for detecting physiological or pathological changes in the glycogen content of cells.

  19. Study of Cholesterol Repletion Effect on Nanomechanical Properties of Human Umbilical Vein Endothelial Cell Via Rapid Broadband Atomic Force Microscopy.

    Science.gov (United States)

    Yan, Bo; Ren, Juan; Liu, Yue; Huang, Huarong; Zheng, Xi; Zou, Qingze

    2017-03-01

    Abnormalities of blood cholesterol concentration are associated with increased risks for vascular disease, especially heart attacks and strokes. As one of the main lipid components of plasma membrane in all mammalian cells, cholesterol has a major impact on the mechanical properties of the membrane of endothelial cells. Although the effect of cholesterol depletion on cell mechanical properties has been studied, no results yet have been reported on quantitative investigation of cholesterol repletion effect. In this study, the cholesterol repletion effect on the nanomechanical properties of human umbilical vein endothelial cell (EA.hy926) was studied using a control-based atomic force microscope (AFM) nanomechanical measurement protocol. The viscoelasticity of EA.hy926 cells were measured over a large frequency range (0.1-100 Hz) using both constant-rate excitation force with different loading rates and a broadband excitation force. The viscoelasticity oscillation of the cell membranes under the cholesterol effect was also monitored in real-time. The experiment results showed that under the effect of cholesterol repletion, both the Young's modulus and the complex modulus of EA.hy926 cell were increased over 30%, respectively, and moreover, the amplitudes of both the elasticity oscillation and the viscosity oscillation at a period of around 200 s were increased over 70%, respectively. Therefore, this work is among the first to investigate the mechanical properties, particularly, the broadband viscoelasticity variations of EA.hy926 cells under cholesterol repletion treatment. The results revealed that cholesterol repletion may reinforce the coupling of F-actin to plasma membrane by increasing actin stability, and the cholesterol might have modified the submembrane cytoskeletal organization of EA.hy926 cell by causing the involvement of the motor protein nonmuscle myosin II.

  20. Consequences of dietary calcium and phosphorus depletion and repletion feeding sequences on growth performance and body composition of growing pigs.

    Science.gov (United States)

    Gonzalo, E; Létourneau-Montminy, M P; Narcy, A; Bernier, J F; Pomar, C

    2017-10-25

    The effect of a calcium (Ca) and phosphorus (P) depletion and repletion strategy was studied in four consecutive feeding phases of 28 days each. In all, 60 castrated male pigs (14±1.6 kg initial BW) received 60% (low (L) diet; depletion) or 100% (control (C) diet; repletion) of their Ca and digestible P requirements according to six feeding sequences (CCCC, CCCL, CLCC, CCLC, LCLC and LLLL; subsequent letters indicate the diet received in phases 1, 2, 3 and 4, respectively). Pigs bone mineral content in whole-body (BMCb) and lumbar vertebrae L2 to L4 (BMCv) was measured in every feeding phase by dual-energy X-ray absorptiometry. Growth performance was slightly (dietary treatments did not affect overall growth. Compared with control pigs, depletion reduced BMCb (34%, 38%, 33% and 22%) and BMCv (46%, 54%, 38% and 26%) in phases 1 to 4, respectively. Depletion increased however digestible P retention efficiency from the second to the fourth phases allowing LLLL pigs to present no differences in BMCb and BMCv gain compared with CCCC pigs in phase 4. Growth performance in repleted compared with control pigs was lower in phase 2, was no different in phase 3 and was lower in CLCC pigs in phase 4. Repletion increased body P and Ca retention efficiency when compared with control pigs (respectively, 8% and 10% for LC v. CC, PDietary Ca was, however, oversupply in L compared with C diets (3.1 v. 2.5 Ca:digestible P ratio, respectively) suggesting that P has probably driven the regulations. Phosphorus and Ca depletion and repletion increases dietary P utilization efficiency and can help to reduce dietary P supply, but the underlying mechanisms need elucidation before its practical application.

  1. Molecular basis of impaired glycogen metabolism during ischemic stroke and hypoxia.

    Science.gov (United States)

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

    2014-01-01

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

  2. Lauric acid production in a glycogen-less Synechococcus sp. PCC 7002 mutant

    Directory of Open Access Journals (Sweden)

    Victoria H. Work

    2015-04-01

    Full Text Available The cyanobacterium Synechococcus sp. PCC 7002 was genetically engineered to synthesize biofuel compatible medium-chain fatty acids during photoautotrophic growth. Expression of a heterologous lauroyl-acyl carrier protein (C12:0-ACP thioesterase with concurrent deletion of the endogenous putative acyl-ACP synthetase led to secretion of transesterifiable C12:0 fatty acid in CO2-supplemented batch cultures. When grown at steady state over a range of light intensities in an LED turbidostat photobioreactor, the C12-secreting mutant exhibited a modest reduction in growth rate and increased O2 evolution relative to the wildtype. Inhibition of i glycogen synthesis by deletion of the glgC-encoded ADP-glucose pyrophosphorylase (AGPase, and ii protein synthesis by nitrogen deprivation were investigated as potential mechanisms for metabolite redistribution to increase fatty acid synthesis. Deletion of AGPase led to a ten-fold decrease in reducing carbohydrates and secretion of organic acids during nitrogen deprivation consistent with an energy spilling phenotype. When the carbohydrate-deficient background (∆glgC was modified for C12 secretion, no increase in C12 was achieved during nutrient replete growth, and no C12 was recovered from any strain upon nitrogen deprivation under the conditions used. At steady state, the growth rate of the ∆glgC strain saturated at a lower light intensity than the wildtype, but O2 evolution was not compromised and became increasingly decoupled from growth rate with rising irradiance. Photophysiological properties of the ∆glgC strain suggest energy dissipation from photosystem II and reconfiguration of electron flow at the level of the plastoquinone pool.

  3. Regulation of glucose and glycogen metabolism during and after exercise

    National Research Council Canada - National Science Library

    Jensen, Thomas E; Richter, Erik A

    2012-01-01

    Abstract  Utilization of carbohydrate in the form of intramuscular glycogen stores and glucose delivered from plasma becomes an increasingly important energy substrate to the working muscle with increasing exercise intensity...

  4. Genetics Home Reference: glycogen storage disease type VII

    Science.gov (United States)

    ... GSD) Disease InfoSearch: Phosphofructokinase Deficiency Johns Hopkins Medicine: Glycogen Storage Disease Merck Manual Consumer Version: Disorders of Carbohydrate Metabolism Muscular Dystrophy Association: Facts About Metabolic Diseases of ...

  5. Genetics Home Reference: glycogen storage disease type III

    Science.gov (United States)

    ... to use for fuel. Most AGL gene mutations lead to the production of a nonfunctional glycogen debranching enzyme. These mutations ... GSD types IIIc and IIId are thought to lead to the production of an enzyme with reduced function. All AGL ...

  6. Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas

    2011-01-01

    The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... and insulin signalling transduction remain elusive. We believe that one of the reasons is that the role of intracellular compartmentalization as a regulator of metabolic pathways and signalling transduction has been rather ignored. This paper briefly reviews the literature to discuss the role of intracellular...... compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss...

  7. Inadequate Brain Glycogen or Sleep Increases Spreading Depression Susceptibility

    KAUST Repository

    Kilic, Kivilcim

    2017-12-16

    Glycogen in astrocyte endfeet contributes to maintenance of low extracellular glutamate and K+ concentrations around synapses. Sleep deprivation (SD), a common migraine trigger induces transcriptional changes in astrocytes reducing glycogen breakdown. We hypothesize that when glycogen utilization cannot match synaptic energy demand, extracellular K+ can rise to levels that activate neuronal pannexin-1 channels and downstream inflammatory pathway, which might be one of the mechanisms initiating migraine headaches.We suppressed glycogen breakdown by inhibiting glycogen phosphorylation with 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) and by SD.DAB caused neuronal pannexin-1 large-pore opening and activation of the downstream inflammatory pathway as shown by procaspase-1 cleavage and HMGB1 release from neurons. Six-hour SD induced pannexin-1 mRNA. DAB and SD also lowered the cortical spreading depression (CSD) induction threshold, which was reversed by glucose or lactate supplement, suggesting that glycogen-derived energy substrates are needed to prevent CSD generation. Supporting this, knocking-down neuronal lactate transporter, MCT2 with an anti-sense oligonucleotide or inhibiting glucose transport from vessels to astrocytes with intracerebroventricularly given phloretin reduced the CSD threshold. In vivo recordings with a K+ -sensitive/selective fluoroprobe, APG-4 disclosed that DAB treatment or SD caused significant rise in extracellular K+ during whisker-stimulation, illustrating the critical role of glycogen in extracellular K+ clearance.Synaptic metabolic stress caused by insufficient glycogen-derived energy substrate supply can activate neuronal pannexin-1 channels as well as lowering the CSD threshold. Therefore, conditions that limit energy supply to synapse (e.g. SD) may predispose to migraine attacks as suggested by genetic studies associating glucose or lactate transporter deficiency with migraine. This article is protected by copyright. All rights reserved.

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

    OpenAIRE

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

    2012-01-01

    Glycogen is a branched polymer of glucose that acts as a store of energy in times of nutritional sufficiency for utilization in times of need. Its metabolism has been the subject of extensive investigation and much is known about its regulation by hormones such as insulin, glucagon and adrenaline (epinephrine). There has been debate over the relative importance of allosteric compared with covalent control of the key biosynthetic enzyme, glycogen synthase, as well as the relative importance of...

  9. Quantifying the Contribution of the Liver to Glucose Homeostasis: A Detailed Kinetic Model of Human Hepatic Glucose Metabolism

    Science.gov (United States)

    König, Matthias; Bulik, Sascha; Holzhütter, Hermann-Georg

    2012-01-01

    Despite the crucial role of the liver in glucose homeostasis, a detailed mathematical model of human hepatic glucose metabolism is lacking so far. Here we present a detailed kinetic model of glycolysis, gluconeogenesis and glycogen metabolism in human hepatocytes integrated with the hormonal control of these pathways by insulin, glucagon and epinephrine. Model simulations are in good agreement with experimental data on (i) the quantitative contributions of glycolysis, gluconeogenesis, and glycogen metabolism to hepatic glucose production and hepatic glucose utilization under varying physiological states. (ii) the time courses of postprandial glycogen storage as well as glycogen depletion in overnight fasting and short term fasting (iii) the switch from net hepatic glucose production under hypoglycemia to net hepatic glucose utilization under hyperglycemia essential for glucose homeostasis (iv) hormone perturbations of hepatic glucose metabolism. Response analysis reveals an extra high capacity of the liver to counteract changes of plasma glucose level below 5 mM (hypoglycemia) and above 7.5 mM (hyperglycemia). Our model may serve as an important module of a whole-body model of human glucose metabolism and as a valuable tool for understanding the role of the liver in glucose homeostasis under normal conditions and in diseases like diabetes or glycogen storage diseases. PMID:22761565

  10. Glycogen synthase kinase-3: cryoprotection and glycogen metabolism in the freeze-tolerant wood frog.

    Science.gov (United States)

    Dieni, Christopher A; Bouffard, Melanie C; Storey, Kenneth B

    2012-02-01

    The terrestrial anuran Rana sylvatica tolerates extended periods of whole-body freezing during the winter. Freezing survival is facilitated by extensive glycogen hydrolysis and distribution of high concentrations of the cryoprotectant glucose into blood and all tissues. As glycogenesis is both an energy-expensive process and counter-productive to maintaining sustained high cryoprotectant levels, we proposed that glycogen synthase kinase-3 (GSK-3) would be activated when wood frogs froze and would phosphorylate its downstream substrates to inactivate glycogen synthesis. Western blot analysis determined that the amount of phosphorylated (inactive) GSK-3 decreased in all five tissues tested in 24 h frozen frogs compared with unfrozen controls. Total GSK-3 protein levels did not change, with the exception of heart GSK-3, indicating that post-translational modification was the primary regulatory mechanism for this kinase. Kinetic properties of skeletal muscle GSK-3 from control and frozen frogs displayed differential responses to a temperature change (22 versus 4°C) and high glucose. For example, when assayed at 4°C, the K(m) for the GSK-3 substrate peptide was ∼44% lower for frozen frogs than the corresponding value in control frogs, indicating greater GSK-3 affinity for its substrates in the frozen state. This indicates that at temperatures similar to the environment encountered by frogs, GSK-3 in frozen frogs will phosphorylate its downstream targets more readily than in unfrozen controls. GSK-3 from skeletal muscle of control frogs was also allosterically regulated. AMP and phosphoenolpyruvate activated GSK-3 whereas inhibitors included glucose, glucose 6-phosphate, pyruvate, ATP, glutamate, glutamine, glycerol, NH(4)Cl, NaCl and KCl. The combination of phosphorylation and allosteric control argues for a regulatory role of GSK-3 in inactivating glycogenesis to preserve high glucose cryoprotectant levels throughout each freezing bout.

  11. Structure and solution properties of enzymatically synthesized glycogen.

    Science.gov (United States)

    Kajiura, Hideki; Takata, Hiroki; Kuriki, Takashi; Kitamura, Shinichi

    2010-04-19

    Recently, a new enzymatic process for glycogen production was developed. In this process, short-chain amylose is used as a substrate for branching enzymes (BE, EC 2.4.1.18). The molecular weight of the enzymatically synthesized glycogen (ESG) depends on the size and concentration of the substrate. Structural and physicochemical properties of ESG were compared to those of natural source glycogen (NSG). The average chain length, interior chain length, and exterior chain length of ESG were 8.2-11.6, 2.0-3.3, and 4.2-7.6, respectively. These values were within the range of variation of NSG. The appearances of both ESG and NSG in solution were opalescent (milky white and slightly bluish). Furthermore, transmission electron microscopy and atomic force microscopy showed that ESG molecules formed spherical particles, and that there were no differences between ESG and NSG. Viscometric analyses also showed the spherical nature of both glycogens. When ESG and NSG were treated with pullulanase, a glucan-hydrolyzing enzyme known to degrade glycogen only on its surface portion, both glycogens were similarly degraded. These analyses revealed that ESG shares similar molecular shapes and surface properties with NSG. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  12. Intravenous Iron Repletion Does Not Significantly Decrease Platelet Counts in CKD Patients with Iron Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Neville R. Dossabhoy

    2013-01-01

    Full Text Available Purpose. We sought to investigate the effect of IV iron repletion on platelet (PLT counts in CKD patients with iron deficiency anemia (IDA. Methods. We conducted a retrospective chart review, including all patients with CKD and IDA who were treated with iron dextran total dose infusion (TDI between 2002 and 2007. Patient demographics were noted, and laboratory values for creatinine, hemoglobin (Hgb, iron stores and PLT were recorded pre- and post-dose. Results. 153 patients received a total of 251 doses of TDI (mean ± SD = 971 ± 175 mg; age years and Creatinine  mg/dL. All CKD stages were represented (stage 4 commonest. Hgb and Fe stores improved post-TDI (. There was a very mild decrease in PLT (pre-TDI 255 versus post-TDI 244, . The mild reduction in PLT after TDI remained non-significant ( when data was stratified by molecular weight (MW of iron dextran used (low versus high, as well as by dose administered (<1000 versus ≥1000 mg. Linear regression analysis between pre-dose PLT and Tsat and Fe showed R2 of 0.01 and 0.04, respectively. Conclusion. Correction of iron deficiency did not significantly lower PLT in CKD patients, regardless of MW or dose used. Correlation of PLT to severity of iron deficiency was very weak.

  13. In vitro immune functions in thiamine-replete and -depleted lake trout (Salvelinus namaycush)

    Science.gov (United States)

    Ottinger, Christopher A.; Honeyfield, Dale C.; Densmore, Christine L.; Iwanowicz, Luke R.

    2014-01-01

    In this study we examined the impacts of in vivo thiamine deficiency on lake trout leukocyte function measured in vitro. When compared outside the context of individual-specific thiamine concentrations no significant differences were observed in leukocyte bactericidal activity or in concanavalin A (Con A), and phytohemagglutinin-P (PHA-P) stimulated leukocyte proliferation. Placing immune functions into context with the ratio of in vivo liver thiamine monophosphate (TMP – biologically inactive form) to thiamine pyrophosphate (TPP – biologically active form) proved to be the best indicator of thiamine depletion impacts as determined using regression modeling. These observed relationships indicated differential effects on the immune measures with bactericidal activity exhibiting an inverse relationship with TMP to TPP ratios, Con A stimulated mitogenesis exhibiting a positive relationship with TMP to TPP ratios and PHA-P stimulated mitogenesis exhibiting no significant relationships. In addition, these relationships showed considerable complexity which included the consistent observation of a thiamine-replete subgroup with characteristics similar to those seen in the leukocytes from thiamine-depleted fish. When considered together, our observations indicate that lake trout leukocytes experience cell-type specific impacts as well as an altered physiologic environment when confronted with a thiamine-limited state.

  14. 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

  15. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia.

    Science.gov (United States)

    Saez, Isabel; Duran, Jordi; Sinadinos, Christopher; Beltran, Antoni; Yanes, Oscar; Tevy, María F; Martínez-Pons, Carlos; Milán, Marco; Guinovart, Joan J

    2014-06-01

    Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that-against general belief-neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress.

  17. Glucose uptake and transport in contracting, perfused rat muscle with different pre-contraction glycogen concentrations

    DEFF Research Database (Denmark)

    Hespel, P; Richter, Erik

    1990-01-01

    1. Glucose uptake and transport, muscle glycogen, free glucose and glucose-6-phosphate concentrations were studied in perfused resting and contracting rat skeletal muscle with different pre-contraction glycogen concentrations. Rats were pre-conditioned by a combination of swimming exercise and diet......, resulting in either low (glycogen-depleted rats), normal (control rats) or high (supercompensated rats) muscle glycogen concentrations at the time their hindlimbs were perfused. 2. Compared with control rats, pre-contraction muscle glycogen concentration was approximately 40% lower in glycogen-depleted rats......, whereas it was 40% higher in supercompensated rats. Muscle glycogen break-down correlated positively (r = 0.76; P less than 0.001) with pre-contraction muscle glycogen concentration. 3. Glucose uptake during contractions was approximately 50% higher in glycogen-depleted hindquarters than in control...

  18. Estradiol stimulates glycogen synthesis whereas progesterone promotes glycogen catabolism in the uterus of the American mink (Neovison vison).

    Science.gov (United States)

    Bowman, Kole; Rose, Jack

    2017-01-01

    Glycogen synthesis by mink uterine glandular and luminal epithelia (GE and LE) is stimulated by estradiol (E 2 ) during estrus. Subsequently, the glycogen deposits are mobilized to near completion to meet the energy requirements of pre-embryonic development and implantation by as yet undetermined mechanisms. We hypothesized that progesterone (P 4 ) was responsible for catabolism of uterine glycogen reserves as one of its actions to ensure reproductive success. Mink were treated with E 2 , P 4 or vehicle (controls) for 3 days and uteri collected 24 h (E 2 , P 4 and vehicle) and 96 h (E 2 ) later. To evaluate E 2 priming, mink were treated with E 2 for 3 days, then P 4 for an additional 3 days (E 2 →P 4 ) and uteri collected 24 h later. Percent glycogen content of uterine epithelia was greater at E 2 + 96 h (GE = 5.71 ± 0.55; LE = 11.54 ± 2.32) than E 2 +24 h (GE = 3.63 ± 0.71; LE = 2.82 ± 1.03), and both were higher than controls (GE = 0.27 ± 0.15; LE = 0.54 ± 0.30; P < 0.05). Treatment as E 2 →P 4 reduced glycogen content (GE = 0.61 ± 0.16; LE = 0.51 ± 0.13), to levels not different from controls, while concomitantly increasing catabolic enzyme (glycogen phosphorylase m and glucose-6-phosphatase) gene expression and amount of phospho-glycogen synthase protein (inactive) in uterine homogenates. Interestingly, E 2 →P 4 increased glycogen synthase 1 messenger RNA (mRNA) and hexokinase 1mRNA and protein. Our findings suggest to us that while E 2 promotes glycogen accumulation by the mink uterus during estrus and pregnancy, it is P 4 that induces uterine glycogen catabolism, releasing the glucose that is essential to support pre-embryonic survival and implantation. © 2016 Japanese Society of Animal Science.

  19. The transcriptional landscape of Campylobacter jejuni under iron replete and iron limited growth conditions.

    Directory of Open Access Journals (Sweden)

    James Butcher

    Full Text Available The genome-wide Campylobacter jejuni transcriptional response under iron replete and iron limited conditions was characterized using RNA-seq. We have identified 111 novel C. jejuni 5'UTRs and mapped 377 co-transcribed genes into 230 transcriptional operons. In contrast to previous microarray results, the C. jejuni iron stimulon is less extensive than previously believed and consists of 77 iron activated genes and 50 iron repressed genes. As anticipated, the iron repressed genes are primarily those involved in iron acquisition or oxidative stress defense. Interestingly, these experiments have revealed that iron is an important modulator of flagellar biogenesis with almost all the components of the flagella found to be iron activated. Given that motility is a well-known C. jejuni colonization factor, this suggests that there is an important regulatory coupling of flagellar biogenesis and iron level in C. jejuni. In addition we have identified several consensus mutations in the C. jejuni NCTC11168 strain that are widespread in the Campylobacter research community and which may explain conflicting phenotypic reports for this strain. Comparative analysis of iron responsive genes with the known Fur regulon indicates that many iron responsive genes are not Fur responsive; suggesting that additional iron regulatory factors remain to be characterized in C. jejuni. Further analysis of the RNA-seq data identified multiple novel transcripts including 19 potential ncRNAs. The expression of selected ncRNAs was confirmed and quantified with qRT-PCR. The qRT-PCR results indicate that several of these novel transcripts are either Fur and/or iron responsive. The fact that several of these ncRNAs are iron responsive or Fur regulated suggests that they may perform regulatory roles in iron homeostasis.

  20. [Insulin edema in hepatic glycogenosis].

    Science.gov (United States)

    Mahévas, T; Gobert, D; Gatfossé, M; Mekinian, A; Fain, O

    2017-03-01

    Hepatic glycogenosis is a rare syndrome, which includes poorly controlled diabetes mellitus, hepatomegaly, delayed puberty, and growth delay. Insulin edema is sometimes associated. An 18-year-old woman presented with diffuse edema, hepatomegaly, amenorrhea, uncontrolled diabetes, and elevated transaminases and cholestasis. Hepatic ultrasonography and abdominal computed tomographic scan confirmed the hepatomegaly. The liver biopsy showed a massive glycogenosis and the diagnosis of hepatic glycogenosis was confirmed. Too large doses of insulin were responsible of diffuse edema. Diabetes equilibration and diminution of insulin intakes allow correction of this disorder. Excess of insulin can lead to excessive hepatic glycogen storage by activation of glycogenosis enzymes. Biological manifestations consist on elevated liver enzymes and hyperlactatemia. There is a link between administration of high dose of insulin and edema. Hepatic glycogenosis should be suspected when diabetes is uncontrolled and be considered as a differential diagnosis of steatosis. It may be associated and revealed by insulin edema directly related to excessive insulin intakes. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  1. 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

  2. Menorrhagia in patients with type I glycogen storage disease.

    Science.gov (United States)

    Austin, Stephanie L; El-Gharbawy, Areeg H; Kasturi, Vellore G; James, Andra; Kishnani, Priya S

    2013-12-01

    To evaluate menorrhagia in a cohort of women with glycogen storage disease type I because it appears to be an under-recognized problem in females of reproductive age. A retrospective chart review was performed on 13 menstruating patients with glycogen storage disease type I (age 23-48 years) for a diagnosis of menorrhagia. Nine (69%) (confidence interval 0.39-0.91) women had development of menorrhagia. Median hemoglobin values in these patients were generally low (range 9.5-12.85 g/dL) but not different from those of the nonmenorrhagia group (hemoglobin range 9.55-11.0 g/dL) with glycogen storage disease type I. Four patients with menorrhagia required hospitalization or emergency department visits for treatment of menorrhagia. Two of the four patients hospitalized required blood transfusion, with an additional patient requiring a transfusion during pregnancy. Eight patients (89%) either were recommended to have or required medical or surgical treatment of their menorrhagia. Glycogen storage disease type I is associated with menorrhagia. The evaluation should include assessment of coagulation functions and referral to a gynecologist, hematologist, or both, because bleeding diathesis and polycystic ovary syndrome are common in patients with glycogen storage disease type I.

  3. Adenosine diphosphate sugar pyrophosphatase prevents glycogen biosynthesis in Escherichia coli

    Science.gov (United States)

    Moreno-Bruna, Beatriz; Baroja-Fernández, Edurne; Muñoz, Francisco José; Bastarrica-Berasategui, Ainara; Zandueta-Criado, Aitor; Rodríguez-López, Milagros; Lasa, Iñigo; Akazawa, Takashi; Pozueta-Romero, Javier

    2001-01-01

    An adenosine diphosphate sugar pyrophosphatase (ASPPase, EC 3.6.1.21) has been characterized by using Escherichia coli. This enzyme, whose activities in the cell are inversely correlated with the intracellular glycogen content and the glucose concentration in the culture medium, hydrolyzes ADP-glucose, the precursor molecule of glycogen biosynthesis. ASPPase was purified to apparent homogeneity (over 3,000-fold), and sequence analyses revealed that it is a member of the ubiquitously distributed group of nucleotide pyrophosphatases designated as “nudix” hydrolases. Insertional mutagenesis experiments leading to the inactivation of the ASPPase encoding gene, aspP, produced cells with marginally low enzymatic activities and higher glycogen content than wild-type bacteria. aspP was cloned into an expression vector and introduced into E. coli. Transformed cells were shown to contain a dramatically reduced amount of glycogen, as compared with the untransformed bacteria. No pleiotropic changes in the bacterial growth occurred in both the aspP-overexpressing and aspP-deficient strains. The overall results pinpoint the reaction catalyzed by ASPPase as a potential step of regulating glycogen biosynthesis in E. coli. PMID:11416161

  4. Hepatitis B

    Science.gov (United States)

    ... are 2 vaccines for hepatitis B on the market. There is 1 combination vaccine on the market for hepatitis A and B together. Vaccination Schedule ... hepatitis B vaccine with no risk to their babies. Resources Products and Publications Hepatitis B Fact Sheets ...

  5. 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......Insulin resistance in skeletal muscle is a major hallmark of type 2 diabetes and an early detectable abnormality in the development of this disease. The cellular mechanisms of insulin resistance include impaired insulin-mediated muscle glycogen synthesis and increased intramyocellular lipid content......, whereas impaired insulin activation of muscle glycogen synthase represents a consistent, molecular defect found in both type 2 diabetic and high-risk individuals. Despite several studies of the insulin signaling pathway believed to mediate dephosphorylation and hence activation of glycogen synthase...

  6. A functional glycogen biosynthesis pathway in Lactobacillus acidophilus: expression and analysis of the glg operon

    Science.gov (United States)

    Goh, Yong Jun; Klaenhammer, Todd R

    2013-01-01

    Glycogen metabolism contributes to energy storage and various physiological functions in some prokaryotes, including colonization persistence. A role for glycogen metabolism is proposed on the survival and fitness of Lactobacillus acidophilus, a probiotic microbe, in the human gastrointestinal environment. L. acidophilus NCFM possesses a glycogen metabolism (glg) operon consisting of glgBCDAP-amy-pgm genes. Expression of the glg operon and glycogen accumulation were carbon source- and growth phase-dependent, and were repressed by glucose. The highest intracellular glycogen content was observed in early log-phase cells grown on trehalose, which was followed by a drastic decrease of glycogen content prior to entering stationary phase. In raffinose-grown cells, however, glycogen accumulation gradually declined following early log phase and was maintained at stable levels throughout stationary phase. Raffinose also induced an overall higher temporal glg expression throughout growth compared with trehalose. Isogenic ΔglgA (glycogen synthase) and ΔglgB (glycogen-branching enzyme) mutants are glycogen-deficient and exhibited growth defects on raffinose. The latter observation suggests a reciprocal relationship between glycogen synthesis and raffinose metabolism. Deletion of glgB or glgP (glycogen phosphorylase) resulted in defective growth and increased bile sensitivity. The data indicate that glycogen metabolism is involved in growth maintenance, bile tolerance and complex carbohydrate utilization in L. acidophilus. PMID:23879596

  7. Human skeletal muscle glycogen utilization in exhaustive exercise

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Holmberg, Hans-Christer; Schrøder, Henrik Daa

    2011-01-01

    that utilization of glycogen with different subcellular localizations during exhaustive arm and leg exercise differs and examined the influence of fibre type and carbohydrate availability on its subsequent resynthesis. When 10 elite endurance athletes (22 ± 1 years, VO2 max = 68 ± 5 ml kg-1 min-1, mean ± SD......) performed one hour of exhaustive arm and leg exercise, transmission electron microscopy revealed more pronounced depletion of intramyofibrillar than of intermyofibrillar and subsarcolemmal glycogen. This phenomenon was the same for type I and II fibres, although at rest prior to exercise, the former...

  8. 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

  9. Acute inhibition of glucose-6-phosphate translocator activity leads to increased de novo lipogenesis and development of hepatic steatosis without affecting VLDL production in rats

    NARCIS (Netherlands)

    Bandsma, RHJ; Wiegman, CH; Herling, AW; Burger, HJ; Meijer, AJ; Romijn, JA; Reijngoud, DJ; Kuipers, F

    2001-01-01

    Glucose-6-phosphatase (G6Pase) is a key enzyme in hepatic glucose metabolism. Altered G6Pase activity in glycogen storage disease and diabetic states is associated with disturbances in lipid metabolism. We studied the effects of acute inhibition of G6Pase activity on hepatic lipid metabolism in

  10. A functional glycogen biosynthesis pathway in Lactobacillus acidophilus: expression and analysis of the glg operon

    OpenAIRE

    Goh, Yong Jun; Klaenhammer, Todd R.

    2013-01-01

    Glycogen metabolism contributes to energy storage and various physiological functions in some prokaryotes, including colonization persistence. A role for glycogen metabolism is proposed on the survival and fitness of Lactobacillus acidophilus, a probiotic microbe, in the human gastrointestinal environment. L.?acidophilus?NCFM possesses a glycogen metabolism (glg) operon consisting of glgBCDAP - amy - pgm genes. Expression of the glg operon and glycogen accumulation were carbon source- and gro...

  11. Introduction to workshop on iron screening and supplementation in iron-replete pregnant women and young children.

    Science.gov (United States)

    Taylor, Christine L; Brannon, Patsy M

    2017-12-01

    The NIH Office of Dietary Supplements convened a public workshop on iron screening and supplementation in iron-replete pregnant women and young children in 2016 in Bethesda, Maryland. The starting point for the workshop was the recent reports from the US Preventive Services Task Force concluding that there was insufficient evidence to evaluate the benefits and harms associated with iron screening and routine supplementation among asymptomatic pregnant women and young children (6-24 mo old) in the United States. The goal of the workshop was to explore and refine understanding about the existing knowledge gaps and research needs associated with these preventive services for these groups. Given the focus on the United States, planning for the workshop took into account the higher iron status in the United States compared with developing countries and, in turn, included a focus on iron-replete individuals consistent with the U-shaped risk curve for nutrient-health relations. Topic areas included adaptations in iron homeostasis associated with pregnancy and young childhood, the impact of inflammation, measurement of iron status, current estimates of iron status for pregnant women and young children in the United States and in Europe, and emerging evidence suggesting adverse effects associated with iron supplementation of iron-replete individuals. A crosscutting dialogue conducted at the close of the workshop formed the basis for a workshop summary that specified evidence gaps and research needs in a range of areas centered on the relation of these adaptations of iron homeostasis with the response to and risk from iron supplementation as well as the need for indicators informative of the full continuum of iron status and based on health outcomes, not just erythropoiesis. © 2017 American Society for Nutrition.

  12. Insights into glycogen metabolism in Lactobacillus acidophilus: impact on carbohydrate metabolism, stress tolerance and gut retention.

    Science.gov (United States)

    Goh, Yong Jun; Klaenhammer, Todd R

    2014-11-20

    In prokaryotic species equipped with glycogen metabolism machinery, the co-regulation of glycogen biosynthesis and degradation has been associated with the synthesis of energy storage compounds and various crucial physiological functions, including global cellular processes such as carbon and nitrogen metabolism, energy sensing and production, stress response and cell-cell communication. In addition, the glycogen metabolic pathway was proposed to serve as a carbon capacitor that regulates downstream carbon fluxes, and in some microorganisms the ability to synthesize intracellular glycogen has been implicated in host persistence. Among lactobacilli, complete glycogen metabolic pathway genes are present only in select species predominantly associated with mammalian hosts or natural environments. This observation highlights the potential involvement of glycogen biosynthesis in probiotic activities and persistence of intestinal lactobacilli in the human gastrointestinal tract. In this review, we summarize recent findings on (i) the presence and potential ecological distribution of glycogen metabolic pathways among lactobacilli, (ii) influence of carbon substrates and growth phases on glycogen metabolic gene expression and glycogen accumulation in L. acidophilus, and (iii) the involvement of glycogen metabolism on growth, sugar utilization and bile tolerance. Our present in vivo studies established the significance of glycogen biosynthesis on the competitive retention of L. acidophilus in the mouse intestinal tract, demonstrating for the first time that the ability to synthesize intracellular glycogen contributes to gut fitness and retention among probiotic microorganisms.

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

    NARCIS (Netherlands)

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

    Adult Schistosoma mansoni worms rapidly degrade their endogenous glycogen stores immediately after isolation from the host. In NCTC 109 or in a diphasic culture medium the glycogen levels slowly recovered again after the initial decrease. The rapid degradation of glycogen could be prevented, even in

  14. Acoustic Accessibility Investigation for Ultrasound Mediated Treatment of Glycogen Storage Disease Type la Patients

    NARCIS (Netherlands)

    Wang, S.; Raju, B.I.; Leyvi, E.; Weinstein, D.A.; Seip, R.

    2011-01-01

    GSD1a, the most prevalent type among the glycogen storage disease families, is caused by an inherited glycogen-6-phosphatase gene defectresulting in an impaired glycogen to glucose conversion pathway. Strict dietary management continues to be the only treatment for GSD1apatients. Recently, the

  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. Purification and characterization of glycogen phosphorylase b from ...

    African Journals Online (AJOL)

    The kinetic and physicochemical properties of glycogen phosphorylase b from the breast muscle of the fruit bat, Eidolon helvum Kerr were investigated in order to obtain some information about the possible physiological role of the enzyme in meeting the energy requirements of the bat muscle either at the initiation of or ...

  17. Effects of Petrol Exposure on Glucose, Liver and Muscle glycogen ...

    African Journals Online (AJOL)

    olayemitoyin

    However, there is dearth of information on the effect of petrol on carbohydrate metabolism in amphibians. Ezike and Ufodike (2008) reported that sublethal concentration of water soluble fraction. (WSF) of petrol increased plasma glucose level and decreased liver glycogen of catfish while blood glucose and cortisol levels ...

  18. Effects of Petrol Exposure on Glucose, Liver and Muscle glycogen ...

    African Journals Online (AJOL)

    This study investigated the effects of exposure to petrol on blood glucose, liver and muscle glycogen levels in the common African toad Bufo regularis. A total of 126 adult toads of either sex weighing between 70-100g were used for this study. The experiment was divided into three phases. The phase 1 experiment the acute ...

  19. Mountain bike racing - the influence of prior glycogen-inducing ...

    African Journals Online (AJOL)

    Objective. To investigate the effect of pre-exercise glutamine supplementation and the influence of a prior acute bout of glycogen-reducing exercise on the general stress and immune response to acute high-intensity cycling. Design. Randomised, double-blind, cross-over supplementation study. Setting and intervention.

  20. Is glycogen storage disease 1a associated with atherosclerosis?

    NARCIS (Netherlands)

    Ubels, FL; Rake, JP; Slaets, JPJ; Smit, Gerrit; Smit, Andries

    2002-01-01

    Deficiency of microsomal glucose-6-phosphatase in liver and kidney leads to glycogen storage disease type 1a (GSD 1a). Notwithstanding intensive dietary therapy, moderate to severe dyslipidaemia and microalbuminuria, both known atherosclerotic risk factors, remain present. Although more patients

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

    Science.gov (United States)

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

    2014-01-01

    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%, (Pglycogen synthesis is initiated by glycogenin, the expression of which was increased by 50% in mdx mice (PGlycogen synthase activity was 12% higher (Pglycogen branching enzyme activity was 70% lower (Pglycogen breakdown, glycogen phosphorylase, had 62% lower activity (Pglycogen debranching enzyme expression was 50% higher (Pglycogen (Pglycogen metabolism in mdx mice identified reduced glycogenin protein expression (46% less; Pglycogen but reduced amounts of liver glycogen.

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

    African Journals Online (AJOL)

    Administrator

    2011-09-05

    Sep 5, 2011 ... Accepted 15 June, 2011. This study was conducted between December 2006 and November 2007 on Capoeta umbla fish species ... Gonad weight)/Fish length³]*100 formula for the determination of the condition factor ... Statistical analysis. In each sex, the significance of differences between liver glycogen.

  3. Genetics Home Reference: glycogen storage disease type 0

    Science.gov (United States)

    ... journal.pmed.0050025. Citation on PubMed or Free article on PubMed Central Kollberg G, Tulinius M, Gilljam T, Ostman-Smith I, Forsander G, Jotorp P, Oldfors A, Holme E. Cardiomyopathy and exercise intolerance in muscle glycogen storage disease ...

  4. Molecular analysis of glycogen storage disease type Ia in Iranian ...

    Indian Academy of Sciences (India)

    Glycogen storage diseases (GSDs) are caused by abnormalities in enzymes that are involved in the regulation of gluconeogenesis and glycogenolysis. GSD I, an autosomal recessive metabolic disorder, is the most common GSD and has four subtypes. Here, we examined GSD Ia caused by the defective ...

  5. Glycogenic hepatopathy in young adults: a case series

    Directory of Open Access Journals (Sweden)

    Marco Silva

    Full Text Available Glycogenic hepatopathy is a rare and underecognized complication in long-standing poorly controlled type 1 diabetes mellitus patients. This is a distinct entity from other causes of hepatomegaly and elevated liver enzymes in diabetics, such as nonalcoholic fatty liver disease. Glycogenic hepatopathy is characterized by the combination of poorly controlled diabetes, acute liver injury with marked elevation in serum aminotransferases, and the characteristic histological features on liver biopsy. It is important to distinguish this entity as it has the potential for resolution following improved glycemic control. In this report, we describe four cases of adult patients presenting elevated serum transaminases and hepatomegaly with a history of poorly controlled type I diabetes mellitus. One of the patients had also elevated amylase and lipase in the serum, without clinical or imagiologic evidence of acute pancreatitis. Liver biopsy was performed in all patients and revealed glycogenic hepatopathy. Clinician's awareness of glycogenic hepatopathy should prevent diagnostic delay or misdiagnosis and will provide better insight and management for this condition.

  6. Molecular analysis of glycogen storage disease type Ia in Iranian ...

    Indian Academy of Sciences (India)

    SHEKARI KHANIANI MAHMOUD1,2

    Abstract. Glycogen storage diseases (GSDs) are caused by abnormalities in enzymes that are involved in the regulation of gluconeo- genesis and glycogenolysis. GSD I, an autosomal recessive metabolic disorder, is the most common GSD and has four sub- types. Here, we examined GSD Ia caused by the defective ...

  7. 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

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

    Directory of Open Access Journals (Sweden)

    Laura Nocito

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

  9. Fine structural properties of natural and synthetic glycogens.

    Science.gov (United States)

    Takata, Hiroki; Kajiura, Hideki; Furuyashiki, Takashi; Kakutani, Ryo; Kuriki, Takashi

    2009-03-31

    Glycogen, highly branched (1-->4)(1-->6)-linked alpha-d-glucan, can be extracted from natural sources such as animal tissues or shellfish (natural source glycogen, NSG). Glycogen can also be synthesized in vitro from glucose-1-phosphate using the cooperative action of alpha-glucan phosphorylase (GP, EC 2.4.1.1) and branching enzyme (BE, EC 2.4.1.18), or from short-chain amylose by the cooperative action of BE and amylomaltase (AM, EC 2.4.1.25). It has been shown that enzymatically synthesized glycogen (ESG) has structural and physicochemical properties similar to those of NSG. In this study, the fine structures of ESG and NSG were analyzed using isoamylase and alpha-amylase. Isoamylase completely hydrolyzed the alpha-1,6 linkages of ESG and NSG. The unit-chain distribution (distribution of degrees of polymerization (DP) of alpha-1,4 linked chains) of ESG was slightly narrower than that of NSG. alpha-Amylase treatment revealed that initial profiles of hydrolyses of ESG and NSG were almost the same: both glycogens were digested slowly, compared with starch. The final products from NSG by alpha-amylase hydrolysis were glucose, maltose, maltotriose, branched oligosaccharides with DP4, and highly branched macrodextrin molecules with molecular weights of up to 10,000. When ESG was digested with excess amounts of alpha-amylase, much larger macrodextrins (molecular weight>10(6)) were detected. In contrast, oligosaccharides with DP 4-7 could not be detected from ESG. These results suggest that the alpha-1,6 linkages in ESG molecules are more regularly distributed than those in NSG molecules.

  10. Nrf2-Mediated Regulation of Skeletal Muscle Glycogen Metabolism.

    Science.gov (United States)

    Uruno, Akira; Yagishita, Yoko; Katsuoka, Fumiki; Kitajima, Yasuo; Nunomiya, Aki; Nagatomi, Ryoichi; Pi, Jingbo; Biswal, Shyam S; Yamamoto, Masayuki

    2016-06-01

    Nrf2 (NF-E2-related factor 2) contributes to the maintenance of glucose homeostasis in vivo Nrf2 suppresses blood glucose levels by protecting pancreatic β cells from oxidative stress and improving peripheral tissue glucose utilization. To elucidate the molecular mechanisms by which Nrf2 contributes to the maintenance of glucose homeostasis, we generated skeletal muscle (SkM)-specific Keap1 knockout (Keap1MuKO) mice that express abundant Nrf2 in their SkM and then examined Nrf2 target gene expression in that tissue. In Keap1MuKO mice, blood glucose levels were significantly downregulated and the levels of the glycogen branching enzyme (Gbe1) and muscle-type PhKα subunit (Phka1) mRNAs, along with those of the glycogen branching enzyme (GBE) and the phosphorylase b kinase α subunit (PhKα) protein, were significantly upregulated in mouse SkM. Consistent with this result, chemical Nrf2 inducers promoted Gbe1 and Phka1 mRNA expression in both mouse SkM and C2C12 myotubes. Chromatin immunoprecipitation analysis demonstrated that Nrf2 binds the Gbe1 and Phka1 upstream promoter regions. In Keap1MuKO mice, muscle glycogen content was strongly reduced and forced GBE expression in C2C12 myotubes promoted glucose uptake. Therefore, our results demonstrate that Nrf2 induction in SkM increases GBE and PhKα expression and reduces muscle glycogen content, resulting in improved glucose tolerance. Our results also indicate that Nrf2 differentially regulates glycogen metabolism in SkM and the liver. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  11. Impact of caffeine and protein on postexercise muscle glycogen synthesis.

    Science.gov (United States)

    Beelen, Milou; Kranenburg, Janneau van; Senden, Joan M; Kuipers, Harm; Loon, Luc J C van

    2012-04-01

    Both protein and caffeine coingestion with CHO have been suggested to represent effective dietary strategies to further accelerate postexercise muscle glycogen synthesis in athletes. This study aimed to assess the effect of protein or caffeine coingestion on postexercise muscle glycogen synthesis rates when optimal amounts of CHO are ingested. Fourteen male cyclists were studied on three different test days. Each test day started with a glycogen-depleting exercise session. This was followed by a 6-h recovery period, during which subjects received 1.2 g·kg⁻¹·h⁻¹ CHO, the same amount of CHO with 0.3 g·kg⁻¹·h⁻¹ of a protein plus leucine mixture (CHO + PRO), or 1.7 mg·kg⁻¹·h⁻¹ caffeine (CHO + CAF). All drinks were enriched with [U-¹³C₆]-labeled glucose to assess potential differences in the appearance rate of ingested glucose from the gut. Muscle biopsies were collected immediately after cessation of exercise and after 6 h of postexercise recovery. The plasma insulin response was higher in CHO + PRO compared with CHO and CHO + CAF (P synthesis rates averaged 31 ± 4, 34 ± 4, and 31 ± 4 mmol·kg⁻¹ dry weight·h⁻¹ in CHO, CHO + PRO, and CHO + CAF, respectively (P = NS). In accordance, histochemical analyses did not show any differences between net changes in Type I and Type II muscle fiber glycogen content between experiments. Coingestion of protein or caffeine does not further accelerate postexercise muscle glycogen synthesis when ample amounts of CHO (1.2 g·kg⁻¹·h⁻¹) are ingested.

  12. Hepatitis A

    Science.gov (United States)

    ... an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... washed in untreated water Putting into your mouth a finger or object that came into contact with ...

  13. Hepatitis C

    Science.gov (United States)

    ... Weight loss Confusion, drowsiness and slurred speech (hepatic encephalopathy) Spider-like blood vessels on your skin (spider angiomas) Every chronic hepatitis C infection starts with an acute phase. ...

  14. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Hepatic Encephalopathy Treatment Options Treatment Basics Treatment Medications Importance of Adhering to Your Treatment Plan Long-Term ... disease is. It’s important for you and your family to become familiar with the signs of Hepatic ...

  15. Hepatitis C

    Science.gov (United States)

    ... especially important for people who are showing signs liver fibrosis or scarring. Medicines used to treat hepatitis C ... Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology . ...

  16. Hepatitis C

    Science.gov (United States)

    ... Doctors treat hepatitis C with antiviral medicines that attack the virus and can cure the disease in most cases. ... Doctors treat hepatitis C with antiviral medicines that attack the virus. You may need to take medicines for 12 ...

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

    Directory of Open Access Journals (Sweden)

    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. Consensus guidelines for management of glycogen storage disease type 1b - European Study on Glycogen Storage Disease Type 1

    NARCIS (Netherlands)

    Visser, G; Rake, JP; Labrune, P; Leonard, JV; Moses, S; Ullrich, K; Wendel, U; Smit, GPA

    2002-01-01

    Life expectancy in glycogen storage disease type 1 (GSD-1) has improved considerably. Its relative rarity implies that no metabolic centre has experience of large series of patients and therefore experience with long-term management and follow-up at each centre is limited. There is wide variation in

  19. Guidelines for management of glycogen storage disease type I - European study on glycogen storage disease type I (ESGSD I)

    NARCIS (Netherlands)

    Rake, JP; Visser, G; Labrune, P; Leonard, JV; Ullrich, K; Smit, GPA

    2002-01-01

    Life-expectancy in glycogen storage disease type I (GSD I) has improved considerably. Its relative rarity implies that no metabolic centre has experience of large series of patients and experience with long-term management and follow-up at each centre is limited. There is wide variation in methods

  20. Hepatitis C: Treatment

    Science.gov (United States)

    ... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

  1. Alcohol and Hepatitis

    Science.gov (United States)

    ... Home » Living with Hepatitis » Daily Living: Alcohol Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... heavy drinking, most heavy drinkers have developed cirrhosis. Hepatitis C and cirrhosis In general, someone with hepatitis ...

  2. [Lupus hepatitis].

    Science.gov (United States)

    Ben Hadj, Yahia Chiraz; Chaabouni, Lilia; Montacer, Kchir Mohamed; Abid, Feriel; Zouari, Rafik

    2002-07-01

    We report the case of 42 year-old man who presents an acute polyarthritis associated with systemic manifestation and immunologic disorders related to systemic lupus erythematosus. Hepatic tests show cholostase and cytolysis. Hepatic involvement is linked with systemic lupus erythematosus after exclusion of hepatotoxic drugs, viral hepatitis and absence of anti mitochondrial and anti muscle antibodies. Lupus hepatitis seems to be correlated with autoantibodies to ribosomal P protein. Its treatment remains to be defined.

  3. Strong association of relatively low and extremely excessive iodine intakes with thyroid cancer in an iodine-replete area.

    Science.gov (United States)

    Kim, Hye Jeong; Kim, Na Kyung; Park, Hyeong Kyu; Byun, Dong Won; Suh, Kyoil; Yoo, Myung Hi; Min, Yong-Ki; Kim, Sun Wook; Chung, Jae Hoon

    2017-04-01

    The relationship between iodine intake and development of thyroid diseases shows a U-shaped curve with an increase of risk in both deficient and excessive iodine intakes. Our aim was to investigate the relationship between iodine intake and thyroid cancer in patients with thyroid nodules in an iodine-replete area. Retrospective analysis of 1170 patients with thyroid nodules was performed. Urinary iodine concentration (UIC) was measured by inductively-coupled plasma mass spectrometry. Predictive factors for thyroid cancer were evaluated using multivariate logistic regression models. The median UIC in all patients with thyroid nodules was 360 μg/L (range from 4 to 9631 μg/L). More than half of the patients (650/1170, 56 %) belonged to the category of excessive iodine intake (UIC ≥ 300 μg/L) according to WHO iodine recommendations. Patients with thyroid cancer were more likely to be distributed in UIC cancer. The multivariate-adjusted OR (95 % CI) in the relatively low (UIC cancer were 1.519 (1.099-2.098) and 1.874 (1.094-3.208), respectively, compared to the other iodine intake group (300-2499 μg/L). Male gender and UIC were independent predictors of thyroid cancer in patients with thyroid nodules. This study suggests that relatively low and extremely excessive iodine intakes are associated with thyroid cancer in an iodine-replete area.

  4. Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review.

    Science.gov (United States)

    Pacis, Michelle M; Fortin, Chelsea N; Zarek, Shvetha M; Mumford, Sunni L; Segars, James H

    2015-03-01

    To review the current literature regarding the role of vitamin D status in pregnancy outcomes in women undergoing assisted reproductive technology (ART) and to assess cost-effectiveness of routine vitamin D deficiency screening and repletion prior to initiation of ART. A systematic literature review was conducted using PubMed. Relevant study outcomes were compared among the selected studies. A cost-benefit analysis was performed using a decision tree mathematical model with sensitivity analyses from the perspective of direct societal cost. Published data were used to estimate probabilities and costs in 2014 US dollars. Thirty-four articles were retrieved, of which eight met inclusion criteria. One study demonstrated a negative relationship between vitamin D status and ART outcomes, while two studies showed no association. The remaining five studies concluded that ART outcomes improved after vitamin D repletion. The majority of reviewed studies reported a decrement in ART outcomes in patients with vitamin D deficiency. Cost-benefit analyses suggested that screening and supplementing vitamin D prior to ART might be cost effective, but further evidence is needed. Given the absence of Level I evidence regarding vitamin D status and ART outcomes, full endorsement of routine vitamin D screening and supplementation prior to ART is premature.

  5. Partly ordered synthesis and degradation of glycogen in cultured rat myotubes

    DEFF Research Database (Denmark)

    Elsner, Peter; Quistorff, Bjørn; Hansen, Gert H

    2001-01-01

    in skeletal muscle as a readily available energy store and with the known structure of the glycogen molecule. It is emphasized that the observed nonlinear relation between the change in glycogen concentration and release of label during glycogen degradation may have important practical consequences...... (the last-in-first-out principle), or is it a random process? 2) Are all glycogen molecules in skeletal muscle synthesized and degraded in phase (simultaneous order) or out of phase (sequential order)? Basal glycogen stores were minimized by fasting and were subsequently replenished in two intervals...

  6. 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...... with an impairment of muscle ability to release Ca(2+), which is an important signal in the muscle activation. Thus, depletion of glycogen during prolonged, exhausting exercise may contribute to muscle fatigue by causing decreased Ca(2+) release inside the muscle. These data provide indications of a signal...

  7. Hepatitis C

    Science.gov (United States)

    ... an inflammation of the liver. One type, hepatitis C, is caused by the hepatitis C virus (HCV). It usually spreads through contact with ... childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. If ...

  8. Direct pathway for hepatic glycogenesis predominates in meal-fed rats

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-05-01

    The pathway for hepatic glycogen synthesis in the postprandial state was studied in meal-fed rats chronically cannulated in the portal vein. The rate of glycogen synthesis in livers of rats meal-fed for seven days was found to be about 1 umol/g/min. Plasma glucose concentration in the portal vein was generally below 8 mM before meal-feeding and could reach up to 12 mM at the end of the meal-feeding. Studies on the hepatic-portal (H-P) difference of plasma glucose showed that liver released glucose in the fasted state and could either extract or release glucose after feeding, depending on plasma glucose concentration in the portal vein. The cross-over concentration for the transition was found to be 8 mM. The relative importance of the direct vs indirect pathway for the replenishment of hepatic glycogen was determined by injecting (3-/sup 3/H,U-/sup 14/C)-glucose into the portal vein at the end of meal-feeding. Six minutes after the injection, the ratio of /sup 3/H//sup 14/C in glycogen-glucose was found to be 83-92% of the ratio in liver free glucose. The H-P differences of glucose, lactate, pyruvate, and alanine during feeding were determined. It was found that the H-P difference of (glc) was about 9 times greater than the combined total of ..delta.. (lac), ..delta.. (pyr), and ..delta.. (ala) as early as 10 minutes after the onset of feeding. It is concluded that the direct pathway for the replenishment of hepatic glycogen is predominant and can account for more than 80% of the total glycogen synthesized in vivo in the postprandial state, in contrast to the result of < 30% reported previously by Newgard et al in acute traumatized rats.

  9. The influence of social status on hepatic glucose metabolism in rainbow trout Oncorhynchus mykiss.

    Science.gov (United States)

    Gilmour, Kathleen M; Kirkpatrick, Sheryn; Massarsky, Andrey; Pearce, Brenda; Saliba, Sarah; Stephany, Céleste-Élise; Moon, Thomas W

    2012-01-01

    The effects of chronic social stress on hepatic glycogen metabolism were examined in rainbow trout Oncorhynchus mykiss by comparing hepatocyte glucose production, liver glycogen phosphorylase (GP) activity, and liver β-adrenergic receptors in dominant, subordinate, control, fasted, and cortisol-treated fish. Hepatocyte glucose production in subordinate fish was approximately half that of dominant fish, reflecting hepatocyte glycogen stores in subordinate trout that were just 16% of those in dominant fish. Fasting and/or chronic elevation of cortisol likely contributed to these differences based on similarities among subordinate, fasted, and cortisol-treated fish. However, calculation of the "glycogen gap"--the difference between glycogen stores used and glucose produced--suggested an enhanced gluconeogenic potential in subordinate fish that was not present in fasted or cortisol-treated trout. Subordinate, fasted, and cortisol-treated trout also exhibited similar GP activities (both total activity and that of the active or a form), and these activities were in all cases significantly lower than those in control trout, perhaps reflecting an attempt to protect liver glycogen stores or a modified capacity to activate GP. Dominant trout exhibited the lowest GP activities (20%-24% of the values in control trout). Low GP activities, presumably in conjunction with incoming energy from feeding, allowed dominant fish to achieve the highest liver glycogen concentrations (double the value in control trout). Liver membrane β-adrenoceptor numbers (assessed as the number of (3)H-CGP binding sites) were significantly lower in subordinate than in dominant trout, although this difference did not translate into attenuated adrenergic responsiveness in hepatocyte glucose production in vitro. Transcriptional regulation, likely as a result of fasting, was indicated by significantly lower β(2)-adrenoceptor relative mRNA levels in subordinate and fasted trout. Collectively, the data

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

    Science.gov (United States)

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

    2017-08-01

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

  11. Glycogen catabolism, but not its biosynthesis, affects virulence of Fusarium oxysporum on the plant host.

    Science.gov (United States)

    Corral-Ramos, Cristina; Roncero, M Isabel G

    2015-04-01

    The role of glycogen metabolism was investigated in the fungal pathogen Fusarium oxysporum. Targeted inactivation was performed of genes responsible for glycogen biosynthesis: gnn1 encoding glycogenin, gls1 encoding glycogen synthase, and gbe1 encoding glycogen branching enzyme. Moreover genes involved in glycogen catabolism were deleted: gph1 encoding glycogen phosphorylase and gdb1 encoding glycogen de-branching enzyme. Glycogen reserves increased steadily during growth of the wild type strain in axenic cultures, to reach up to 1500μg glucose equivalents mg(-1) protein after 14 days. Glycogen accumulation was abolished in mutants lacking biosynthesis genes, whereas it increased by 20-40% or 80%, respectively, in the single and double mutants affected in catabolic genes. Transcript levels of glycogen metabolism genes during tomato plant infection peaked at four days post inoculation, similar to the results observed during axenic culture. Significant differences were observed between gdb mutants and the wild type strain for vegetative hyphal fusion ability. The single mutants defective in glycogen metabolism showed similar levels of virulence in the invertebrate animal model Galleria mellonella. Interestingly, the deletion of gdb1 reduced virulence on the plant host up to 40% compared to the wild type in single and in double mutant backgrounds, whereas the other mutants showed the virulence at the wild-type level. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Glycogen metabolism in the glucose-sensing and supply-driven β-cell.

    Science.gov (United States)

    Andersson, Lotta E; Nicholas, Lisa M; Filipsson, Karin; Sun, Jiangming; Medina, Anya; Al-Majdoub, Mahmoud; Fex, Malin; Mulder, Hindrik; Spégel, Peter

    2016-12-01

    Glycogen metabolism in β-cells may affect downstream metabolic pathways controlling insulin release. We examined glycogen metabolism in human islets and in the rodent-derived INS-1 832/13 β-cells and found them to express the same isoforms of key enzymes required for glycogen metabolism. Our findings indicate that glycogenesis is insulin-independent but influenced by extracellular glucose concentrations. Levels of glycogen synthase decrease with increasing glucose concentrations, paralleling accumulation of glycogen. We did not find cAMP-elicited glycogenolysis and insulin secretion to be causally related. In conclusion, our results reveal regulated glycogen metabolism in human islets and insulin-secreting cells. Whether glycogen metabolism affects insulin secretion under physiological conditions remains to be determined. © 2016 Federation of European Biochemical Societies.

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

    Science.gov (United States)

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

    2015-02-01

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

  14. Insoluble glycogen, a metabolizable internal adsorbent, decreases the lethality of endotoxin shock in rats

    Directory of Open Access Journals (Sweden)

    S. Sipka

    1997-01-01

    Full Text Available Insoluble glycogen is an enzymatically modified form of naturally occurring soluble glycogen with a great adsorbing capacity. It can be metabolized by phagocytes to glucose. In this study we used insoluble glycogen intravenously in the experimental endotoxin shock of rats. Wistar male rats were sensitized to endotoxin by Pb acetate. The survival of rats were compared in groups of animals endotoxin shock treated and non-treated with insoluble glycogen. Furthermore, we have determined in vitro the binding capacity of insoluble glycogen for endotoxin, tumour necrosis factor alpha, interleukin-1 and secretable phospholipase A2. Use of 10 mg/kg dose of insoluble glycogen could completely prevent the lethality of shock induced by LD50 quantity of endotoxin in rats. All animals treated survived. Insoluble glycogen is a form of ‘metabolizable internal adsorbents’. It can potentially be used for treatment of septic shock.

  15. Glycogen pathways in disease: new developments in a classical field of medical genetics.

    Science.gov (United States)

    Kilimann, Manfred W; Oldfors, Anders

    2015-05-01

    Glycogen is the storage form of glucose in animal cells. Its degradation can rapidly provide fuel for energy production (particularly important in muscle), or replenish blood glucose during fasting by the liver. Genetic defects of glycogen metabolism give rise to glycogen storage diseases (GSDs), manifesting histologically in abnormal quantity or quality of glycogen in the cells. GSDs can be caused by defects of proteins participating in the synthesis or degradation of glycogen itself, in the glycolytic degradation of glucose phosphates in muscle and erythrocytes, in the release of glucose from liver and kidney into the bloodstream, in the clearance of glycogen from lysosomes (all, "primary GSDs"), or in the control of these pathways ("secondary GSDs"). Most genes responsible for classical, primary GSDs have probably been identified, and future progress in understanding the biochemical and genetic defects underlying unsolved disorders presenting with glycogen storage abnormalities will perhaps be predominantly in the field of secondary GSDs.

  16. Hypoksisk hepatitis

    DEFF Research Database (Denmark)

    Amadid, Hanan; Schiødt, Frank Vinholt

    2014-01-01

    Hypoxic hepatitis (HH), also known as ischaemic hepatitis or shock liver, is an acute liver injury caused by hepatic hypoxia. Cardiac failure, respiratory failure and septic shock are the main underlying conditions. In each of these conditions, several haemodynamic mechanisms lead to hepatic...... hypoxia. A shock state is observed in only 50% of cases. Thus, shock liver and ischaemic hepatitis are misnomers. HH can be a diagnostic pitfall but the diagnosis can be established when three criteria are met. Prognosis is poor and prompt identification and treatment of the underlying conditions...

  17. Exercise Training-Induced Adaptations Associated with Increases in Skeletal Muscle Glycogen Content

    Science.gov (United States)

    Manabe, Yasuko; Gollisch, Katja S.C.; Holton, Laura; Kim, Young–Bum; Brandauer, Josef; Fujii, Nobuharu L.; Hirshman, Michael F.; Goodyear, Laurie J.

    2012-01-01

    Chronic exercise training results in numerous skeletal muscle adaptations, including increases in insulin sensitivity and glycogen content. To understand the mechanism for increased muscle glycogen, we studied the effects of exercise training on glycogen regulatory proteins in rat skeletal muscle. Female Sprague Dawley rats performed voluntary wheel running for 1, 4, or 7 weeks. After 7 weeks of training, insulin-stimulated glucose uptake was increased in epitrochlearis muscle. Compared to sedentary control rats, muscle glycogen did not change after 1 week of training, but increased significantly after 4 and 7 weeks. The increases in muscle glycogen were accompanied by elevated glycogen synthase activity and protein expression. To assess the regulation of glycogen synthase, we examined its major activator, protein phosphatase 1 (PP1), and its major deactivator, glycogen synthase kinase 3 (GSK3). Consistent with glycogen synthase activity, PP1 activity was unchanged after 1 week of training but significantly increased after 4 and 7 weeks of training. Protein expression of RGL(GM), another regulatory PP1 subunit, significantly decreased after 4 and 7 weeks of training. Unlike PP1, GSK3 phosphorylation did not follow the pattern of glycogen synthase activity. The ~40% decrease in GSK-3α phosphorylation after 1 week of exercise training persisted until 7 weeks and may function as a negative feedback to elevated glycogen. Our findings suggest that exercise training-induced increases in muscle glycogen content could be regulated by multiple mechanisms including enhanced insulin sensitivity, glycogen synthase expression, allosteric activation of glycogen synthase and PP1activity. PMID:23206309

  18. Engineering limonene and bisabolene production in wild type and a glycogen-deficient mutant of Synechococcus sp. PCC 7002

    Energy Technology Data Exchange (ETDEWEB)

    Davies, Fiona K.; Work, Victoria H.; Beliaev, Alex S.; Posewitz, Matthew C.

    2014-06-19

    The plant terpenoids limonene (C10H16) and α-bisabolene (C15H24) are hydrocarbon precursors to a range of industrially-relevant chemicals. High-titer microbial synthesis of limonene and α- bisabolene could pave the way for advances in in vivo engineering of tailor-made hydrocarbons, and production at commercial scale. We have engineered the fast-growing unicellular euryhaline cyanobacterium Synechococcus sp. PCC 7002 to produce yields of 4 mg L-1 limonene and 0.6 mg L-1 α-bisabolene through heterologous expression of the Mentha spicata L-limonene synthase or the Abies grandis (E)-α-bisabolene synthase genes, respectively. Titers were significantly higher when a dodecane overlay was applied during culturing, suggesting either that dodecane traps large quantities of volatile limonene and α-bisabolene that would otherwise be lost to evaporation, and/or that continuous product removal in dodecane alleviates product feedback inhibition to promote higher rates of synthesis. We also investigate limonene and bisabolene production in the ΔglgC genetic background, where carbon partitioning is redirected at the expense of glycogen biosynthesis. The Synechococcus sp. PCC 7002 ΔglgC mutant excreted a suite of overflow metabolites (α-ketoisocaproate, pyruvate, α-ketoglutarate, succinate and acetate) during nitrogen deprivation, and also at the onset of stationary growth in nutrient-replete media. None of the excreted metabolites, however, appeared to be effectively utilized for terpenoid metabolism. Interestingly, we observed a 1.6 to 2.5-fold increase in the extracellular concentration of most excreted organic acids when the ΔglgC mutant was conferred with the ability to produce limonene. Overall, Synechococcus sp. PCC 7002 provides a highly promising platform for terpenoid biosynthetic and metabolic engineering efforts.

  19. Skeletal muscle insulin resistance promotes increased hepatic de novo lipogenesis, hyperlipidemia, and hepatic steatosis in the elderly.

    Science.gov (United States)

    Flannery, Clare; Dufour, Sylvie; Rabøl, Rasmus; Shulman, Gerald I; Petersen, Kitt Falk

    2012-11-01

    Aging is closely associated with muscle insulin resistance, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. We examined the hypothesis that muscle insulin resistance in healthy aging promotes increased hepatic de novo lipogenesis (DNL) and hyperlipidemia by altering the distribution pattern of postprandial energy storage. Healthy, normal weight, sedentary elderly subjects pair-matched to young subjects were given two high-carbohydrate meals followed by ¹³C/¹H magnetic resonance spectroscopy measurements of postprandial changes in muscle and liver glycogen and lipid content, and assessment of DNL using ²H₂O. Net muscle glycogen synthesis was reduced by 45% (P < 0.007) in the elderly subjects compared with the young, reflecting severe muscle insulin resistance. Net liver glycogen synthesis was similar between groups (elderly, 143 ± 23 mmol/L vs. young, 138 ± 13 mmol/L; P = NS). Hepatic DNL was more than twofold higher in the elderly than in the young subjects (elderly, 14.5 ± 1.4% vs. young, 6.9 ± 0.7%; P = 0.00015) and was associated with approximately threefold higher postprandial hepatic triglyceride (TG) content (P < 0.005) and increased fasting plasma TGs (elderly, 1.19 ± 0.18 mmol/L vs. young, 0.74 ± 0.11 mmol/L; P = 0.02). These results strongly support the hypothesis that muscle insulin resistance in aging promotes hyperlipidemia and NAFLD by altering the pattern of postprandial carbohydrate storage away from muscle glycogen and into hepatic DNL.

  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 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. Dumping syndrome, a cause of acquired glycogenic hepatopathy.

    Science.gov (United States)

    Resnick, Jeffrey M; Zador, Ivan; Fish, Daryl L

    2011-01-01

    A 2-year-old boy, having undergone fundoplication for gastroesophageal reflux disease and fed by gastrostomy, presented with recurrent emesis, syncope with hypoglycemia, and persistently elevated serum liver transaminase levels. Liver biopsy revealed hepatocellular glycogenosis by light and electron microscopy. Further evaluation showed no evidence of diabetes mellitus, glycogen storage disease, or corticosteroid use. Since the hyperglycemic-hyperinsulinemic state of dumping syndrome would provide a mechanism for hepatocellular glycogenosis, the biopsy findings prompted consideration of dumping syndrome. Metabolic evaluation confirmed the diagnosis of dumping syndrome, and appropriate dietary management led to sustained resolution of symptomatology and hypertransaminasemia. Dumping syndrome is proposed to be a cause of hepatocellular glycogenosis, the latter representing a form of acquired glycogenic hepatopathy.

  2. Transition from glycogen to starch metabolism in Archaeplastida.

    Science.gov (United States)

    Cenci, Ugo; Nitschke, Felix; Steup, Martin; Minassian, Berge A; Colleoni, Christophe; Ball, Steven G

    2014-01-01

    In this opinion article we propose a scenario detailing how two crucial components have evolved simultaneously to ensure the transition of glycogen to starch in the cytosol of the Archaeplastida last common ancestor: (i) the recruitment of an enzyme from intracellular Chlamydiae pathogens to facilitate crystallization of α-glucan chains; and (ii) the evolution of novel types of polysaccharide (de)phosphorylating enzymes from preexisting glycogen (de)phosphorylation host pathways to allow the turnover of such crystals. We speculate that the transition to starch benefitted Archaeplastida in three ways: more carbon could be packed into osmotically inert material; the host could resume control of carbon assimilation from the chlamydial pathogen that triggered plastid endosymbiosis; and cyanobacterial photosynthate export could be integrated in the emerging Archaeplastida. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Impaired glycogen breakdown and synthesis in phosphoglucomutase 1 deficiency

    DEFF Research Database (Denmark)

    Preisler, Nicolai; Cohen, Jonathan; Vissing, Christoffer Rasmus

    2017-01-01

    , and the patient had exaggerated oxidation of fat to fuel exercise. Exercise heart rate and perceived exertion were lower after IV glucose and oral sucrose. Muscle glycogen level was low normal. CONCLUSIONS: The second wind phenomenon has been considered to be pathognomonic for McArdle disease, but we demonstrate...... that it can also be present in PGM1 deficiency. We show that severe loss of PGM1 activity causes blocked muscle glycogenolysis that mimics McArdle disease, but may also limit glycogen synthesis, which broadens the phenotypic spectrum of this disorder......., assessed physiological responses to forearm and cycle-ergometer exercise combined with stable-isotope techniques and indirect calorimetry, and evaluated the effect of IV glucose infusion and oral sucrose ingestion on the exercise response. RESULTS: Phosphoglucomutase type 1 (PGM1) activity in muscle...

  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

    Glycosylation of proteins and lipids involves over 200 known glycosyltransferases, and deleterious defects in many of the genes encoding these enzymes cause disorders collectively classified as Congenital Disorders of Glycosylation (CDGs). Most known CDGs are caused by defects in glycogenes...... 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. Muscle glycogen storage after different amounts of carbohydrate ingestion.

    Science.gov (United States)

    Ivy, J L; Lee, M C; Brozinick, J T; Reed, M J

    1988-11-01

    The purpose of this study was to determine whether the rate of muscle glycogen storage could be enhanced during the initial 4-h period postexercise by substantially increasing the amount of the carbohydrate consumed. Eight subjects cycled for 2 h on three separate occasions to deplete their muscle glycogen stores. Immediately and 2 h after exercise they consumed either 0 (P), 1.5 (L), or 3.0 g glucose/kg body wt (H) from a 50% glucose polymer solution. Blood samples were drawn from an antecubital vein before exercise, during exercise, and throughout recovery. Muscle biopsies were taken from the vastus lateralis immediately, 2 h, and 4 h after exercise. Blood glucose and insulin declined significantly during exercise in each of the three treatments. They remained below the preexercise concentrations during recovery in the P treatment but increased significantly above the preexercise concentrations during the L and H treatments. By the end of the 4 h-recovery period, blood glucose and insulin were still significantly above the preexercise concentrations in both treatments. Muscle glycogen storage was significantly increased above the basal rate (P, 0.5 mumol.g wet wt-1.h-1) after ingestion of either glucose polymer supplement. The rates of muscle glycogen storage, however, were not different between the L and H treatments during the first 2 h (L, 5.2 +/- 0.9 vs. H, 5.8 +/- 0.7 mumol.g wet wt-1.h-1) or the second 2 h of recovery (L, 4.0 +/- 0.9 vs. H, 4.5 +/- 0.6 mumol.g wet wt-1. h-1).(ABSTRACT TRUNCATED AT 250 WORDS)

  6. AMPK and autophagy in glucose/glycogen metabolism.

    Science.gov (United States)

    Ha, Joohun; Guan, Kun-Liang; Kim, Joungmok

    2015-12-01

    Glucose/glycogen metabolism is a primary metabolic pathway acting on a variety of cellular needs, such as proliferation, growth, and survival against stresses. The multiple regulatory mechanisms underlying a specific metabolic fate have been documented and explained the molecular basis of various pathophysiological conditions, including metabolic disorders and cancers. AMP-activated protein kinase (AMPK) has been appreciated for many years as a central metabolic regulator to inhibit energy-consuming pathways as well as to activate the compensating energy-producing programs. In fact, glucose starvation is a potent physiological AMPK activating condition, in which AMPK triggers various subsequent metabolic events depending on cells or tissues. Of note, the recent studies show bidirectional interplay between AMPK and glycogen. A growing number of studies have proposed additional level of metabolic regulation by a lysosome-dependent catabolic program, autophagy. Autophagy is a critical degradative pathway not only for maintenance of cellular homeostasis to remove potentially dangerous constituents, such as protein aggregates and dysfunctional subcellular organelles, but also for adaptive responses to metabolic stress, such as nutrient starvation. Importantly, many lines of evidence indicate that autophagy is closely connected with nutrient signaling modules, including AMPK, to fine-tune the metabolic pathways in response to many different cellular cues. In this review, we introduce the studies demonstrating the role of AMPK and autophagy in glucose/glycogen metabolism. Also, we describe the recent advances on their contributions to the metabolic disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Pathological characteristics of glycogen storage disease III in skeletal muscle.

    Science.gov (United States)

    Gershen, Leah D; Prayson, Brigid E; Prayson, Richard A

    2015-10-01

    We report a 25-year-old man with glycogenosis III who presented with a progressive 2 year history of fatigue, hand stiffness and cramping. The glycogenoses are a group of rare metabolic disorders which develop as a result of deficiencies in various enzymes involved in the metabolism of glycogen. Some, but not all, glycogenoses, may result in skeletal muscle pathology. Among those that result in vacuolar myopathic changes, glycogen storage disease III or debrancher enzyme deficiency, an autosomal recessive condition, is less commonly encountered than acid maltase (Type II) and myophosphorylase (Type V) deficiencies. Many patients with debrancher enzyme deficiency also have liver involvement. The neurological examination of our patient showed mild proximal limb weakness and decreased reflexes. He had elevated creatine kinase and aldolase levels. He also demonstrated some elevations in his liver function tests, suggesting possible liver involvement. A skeletal muscle biopsy demonstrated vacuolar myopathic changes (acid phosphatase negative) accompanied by focal endomysial fibrosis and chronic inflammation. An ultrastructural examination showed that his vacuoles were filled with glycogen material. An enzyme assay of skeletal muscle tissue showed a significant decrease in debrancher enzyme activity (11% of normal). We review the typical clinical presentation of patients with glycogenosis III and discuss the differential diagnoses of glycogenosis III versus the other glycogenoses resulting in vacuolar myopathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-07-15

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

  9. Early NK Cell Reconstitution Predicts Overall Survival in T-Cell Replete Allogeneic Hematopoietic Stem Cell Transplantation

    DEFF Research Database (Denmark)

    Minculescu, Lia; Marquart, Hanne Vibeke; Friis, Lone Smidstrups

    2016-01-01

    Early immune reconstitution plays a critical role in clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are the first lymphocytes to recover after transplantation and are considered powerful effector cells in HSCT. We aimed to evaluate...... the clinical impact of early NK cell recovery in T-cell replete transplant recipients. Immune reconstitution was studied in 298 adult patients undergoing HSCT for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndrome (MDS) from 2005 to 2013. In multivariate analysis NK...... cell numbers day 30 (NK30) >150cells/µL were independently associated with superior overall survival (hazard ratio 0.79, 95% confidence interval 0.66-0.95, p=0.01). Cumulative incidence analyses showed that patients with NK30 >150cells/µL had significantly less transplant related mortality (TRM), p=0...

  10. Endogenous glucose production increases in response to metformin treatment in the glycogen-depleted state in humans

    DEFF Research Database (Denmark)

    Christensen, Mette Marie H; Højlund, Kurt; Hother-Nielsen, Ole

    2015-01-01

    AIMS/HYPOTHESIS: Metformin is believed to reduce glucose levels primarily by inhibiting hepatic glucose production. Recent data indicate that metformin antagonises glucagon-dependent glucose output, suggesting that compensatory mechanisms protect against hypoglycaemia. Here, we examined the effect...... of metformin on glucose metabolism in humans after a glycogen-depleting fast and the role of reduced-function alleles in OCT1 (also known as SLC22A1). METHODS: In a randomised, crossover trial, healthy individuals with or without reduced-function alleles in OCT1 were fasted for 42 h twice, either...... with or without prior treatment with 1 g metformin twice daily. Participants were recruited from the Pharmacogenomics Biobank of the University of Southern Denmark. Treatment allocation was generated by the Good Clinical Practice Unit, Odense University Hospital, Denmark. Variables of whole-body glucose...

  11. Structured Dietary Management Dramatically Improves Marked Transaminitis, Metabolic and Clinical Profiles in Glycogen Storage Disease Type IXa

    Directory of Open Access Journals (Sweden)

    Indrajit S. Karande DCH, FRACP

    2016-12-01

    Full Text Available Glycogen storage disease type IXa (GSD IXa presents in childhood with hepatomegaly, poor growth, and ketotic hypoglycemia. Clinical course is usually mild, often not requiring treatment with attenuation of symptoms with increasing age. The phenotypic spectrum has recently expanded to include more severe involvement with hepatic fibrosis or cirrhosis warranting dietary therapy. We report a 2-year-old boy with a severe phenotype of GSD IXa presenting with a massive hepatomegaly, significant transaminitis, recurrent ketotic hypoglycemia, and short stature. Aggressive dietary management with regular feeds, frequent uncooked cornstarch doses, and protein supplementation resulted in clinical improvements including enhanced growth velocity, energy levels, overall well-being, and reduction in hepatomegaly with restitutions in biochemical parameters. We concur with a recent report which proposed that GSD IXa is not always a mild condition but instead part of an expanding phenotypic spectrum warranting intensive dietary management to optimize metabolic control and quality of life.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Arterial pressure variations as parameters of brain perfusion in response to central blood volume depletion and repletion

    Science.gov (United States)

    Bronzwaer, Anne-Sophie G. T.; Stok, Wim J.; Westerhof, Berend E.; van Lieshout, Johannes J.

    2014-01-01

    Rationale: A critical reduction in central blood volume (CBV) is often characterized by hemodynamic instability. Restoration of a volume deficit may be established by goal-directed fluid therapy guided by respiration-related variation in systolic- and pulse pressure (SPV and PPV). Stroke volume index (SVI) serves as a surrogate end-point of a fluid challenge but tissue perfusion itself has not been addressed. Objective: To delineate the relationship between arterial pressure variations, SVI and regional brain perfusion during CBV depletion and repletion in spontaneously breathing volunteers. Methods: This study quantified in 14 healthy subjects (11 male) the effects of CBV depletion [by 30 and 70 degrees passive head-up tilt (HUT)] and a fluid challenge (by tilt back) on CBV (thoracic admittance), mean middle cerebral artery (MCA) blood flow velocity (Vmean), SVI, cardiac index (CI), PPV, and SPV. Results: PPV (103 ± 89%, p pressure. The reduction in MCAVmean correlated to the fall in SVI (R2 = 0.52, p < 0.0001) and inversely to PPV and SPV [R2 = 0.46 (p < 0.0001) and R2 = 0.45 (p < 0.0001), respectively]. PPV and SPV predicted a ≥15% reduction in MCAVmean and SVI with comparable sensitivity (67/67% vs. 63/68%, respectively) and specificity (89/94 vs. 89/94%, respectively). A rapid fluid challenge by tilt-back restored all parameters to baseline values within 1 min. Conclusion: In spontaneously breathing subjects, a reduction in MCAVmean was related to an increase in PPV and SPV during graded CBV depletion and repletion. Specifically, PPV and SPV predicted changes in both SVI and MCAVmean with comparable sensitivity and specificity, however the predictive value is limited in spontaneously breathing subjects. PMID:24795652

  15. Metabolic changes and nutrient repletion in lambs provided with electrolyte solutions before and after feed and water deprivation.

    Science.gov (United States)

    Cole, N A

    1996-02-01

    Providing feeder calves and lambs with electrolyte solutions before and(or) after a transport period could potentially reduce tissue shrink and speed repletion of nutrients and weight that are lost during transport. This trial was conducted to determine metabolic changes and nutrient repletion in lambs provided with electrolyte solutions before and after feed and water deprivation. Solutions were 1) deionized water, 2) ES1 (g/10 L: NaCl, 2.0; K carbonate, 2.8; Mg sulfate.7H2O, 2.0; equal mixture of amino acids [Lys, Thr, Phe, His, Trp, Met, Leu, Ile, and Val], .45; and phosphoric acid to pH 7.0), 3) ES2 (twice the concentrations as in ES1), and ES3 (g/10 L: NaCl 2.0; K carbonate, 8.0; Mg sulfate.7H2O, 4.0; amino acid mixture from ES1, .45; and phosphoric acid to pH 7.0). Eight Suffolk x Hampshire crossbred lambs (average BW 35 +/- 2 kg) were used in an 8 x 8 Latin square design with treatments arranged in a 2 x 4 factorial. Main treatments consisted of two deprivation electrolyte solutions (deionized water or ES1) and four realimentation electrolyte solutions (deionized water, ES1, ES2, and ES3). Lambs were limit-fed (600 g/d, as-fed basis) before and after a 3-d feed and water deprivation phase. Lambs provided the ES1 solution during the pre-deprivation phase had greater (P electrolytes in the solution was doubled (i.e., ES2 solution), Na, K, and Mg retentions were increased (P electrolytes in the electrolyte solution may need to be increased to improve nutrient balance.

  16. Feature Hepatitis: Hepatitis Can Strike Anyone

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis Can Strike Anyone Past Issues / Spring 2009 Table ... from all walks of life are affected by hepatitis, especially hepatitis C, the most common form of ...

  17. Hepatitis A through E (Viral Hepatitis)

    Science.gov (United States)

    ... Hepatitis B Hepatitis C Hepatitis D Hepatitis E Liver Transplant Definition & Facts Transplant Process Transplant Surgery Living with a Liver Transplant Clinical Trials Nonalcoholic Fatty Liver Disease & NASH Definition & ...

  18. Travelers' Health: Hepatitis C

    Science.gov (United States)

    ... Chapter 3 - Hepatitis B Chapter 3 - Hepatitis E Hepatitis C Deborah Holtzman INFECTIOUS AGENT Hepatitis C virus ( ... mother to child. Map 3-05. Prevalence of hepatitis C virus infection 1 PDF Version (printable) 1 ...

  19. Travelers' Health: Hepatitis B

    Science.gov (United States)

    ... Chapter 3 - Hepatitis A Chapter 3 - Hepatitis C Hepatitis B Francisco Averhoff INFECTIOUS AGENT Hepatitis B virus ( ... progression of disease. Map 3-04. Prevalence of hepatitis B virus infection 1 PDF Version (printable) 1 ...

  20. Travelers' Health: Hepatitis A

    Science.gov (United States)

    ... 3 - Helminths, Soil-Transmitted Chapter 3 - Hepatitis B Hepatitis A Noele P. Nelson INFECTIOUS AGENT Hepatitis A ... hepatitis/HAV Table 3-02. Vaccines to prevent hepatitis A VACCINE TRADE NAME (MANUFACTURER) AGE (Y) DOSE ...

  1. Hepatitis C: Clinical Trials

    Science.gov (United States)

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  2. Hepatitis (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Hepatitis KidsHealth / For Parents / Hepatitis Print en español Hepatitis What Is Hepatitis? Hepatitis is an inflammation of the liver. The ...

  3. Glycogen storage in normal and wing-mutant strains of Drosophila melanogaster.

    Science.gov (United States)

    Barnes, W S

    1994-10-01

    Total body weight, total glycogen content and the percentage of body weight attributable to stored glycogen were measured in wild-type and two wing-mutant strains of 0-2-day-old (immature) and 5-7-day-old (mature) Drosophila melanogaster. Wild-type and wing mutant strains did not differ significantly in any of the measured parameters at 0-2 days of age. By 5-7 days of age, significant increases in glycogen content and glycogen percent had occurred in both wild-type and wing-mutant strains. Likewise, by 5-7 days of age, total body weight had increased significantly in the mature wild-type and vestigial strains but not in apterous flies. Mature wild-type flies displayed significantly greater total body glycogen content and glycogen percent when compared with the mature apterous and vestigial wing-mutant strains.

  4. Vitamin A Repletion in rats with concurrent vitamin A and iodine deficiency affects pituitary THS {beta} gene expression and reduces thyroid hyperstimulation and thyroid size

    NARCIS (Netherlands)

    Biebinger, R.; Arnold, M.; Langhans, W.; Hurrell, R.F.; Zimmermann, M.B.

    2007-01-01

    Concurrent vitamin A (VA) deficiency (VAD) and iodine deficiency (ID) are common in developing countries. VAD has effects on thyroid metabolism that may be dependent on iodine status. The aim of this study was to investigate the effect of VA supplementation (VAS) and/or dietary iodine repletion,

  5. Effect of the temperature, pH and irradiance on the photosynthetic activity by Scenedesmus obtusiusculus under nitrogen replete and deplete conditions.

    Science.gov (United States)

    Cabello, Juan; Toledo-Cervantes, Alma; Sánchez, León; Revah, Sergio; Morales, Marcia

    2015-04-01

    This paper evaluates the effect of the irradiance, pH and temperature on the photosynthetic activity (PA) of Scenedesmus obtusiusculus under N-replete and N-deplete conditions through oxygen measurements. The highest PA values were 160 mgO2 gb(-1) h(-1) at 620 μmol m(-2) s(-1), 35 °C and pH of 8 under N-replete conditions and 3.3 mgO2 gb(-1) h(-1) at 100 μmol m(-2) s(-1), 28.5 °C and pH of 5.5 for N-deplete conditions. Those operation conditions were tested in a flat-panel photobioreactor. The biomass productivity was 0.97 gb L(-1) d(-1) under N-replete conditions with a photosynthetic efficiency (PE) of 4.4% yielding 0.85 gb mol photon(-1). Similar biomass productivity was obtained under N-deplete condition; and the lipid productivity was 0.34 gL L(-1) d(-1) with a PE of 7.8% yielding 0.39 gL mol photon(-1). The apparent activation and deactivation energies were 16.1 and 30 kcal mol(-1), and 11.9 and 15.3 kcal mol(-1), for N-replete and N-deplete conditions, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Iron Depletion and Repletion with Ferrous Sulfate or Electrolytic Iron Modifies the Composition and Metabolic Activity of the Gut Microbiota in Rats

    NARCIS (Netherlands)

    Dostal, A.; Chassard, C.; Hilty, F.M.; Zimmermann, M.B.; Jaeggi, T.; Rossi, S.; Lacroix, C.

    2012-01-01

    Iron (Fe) deficiency anemia is a global health concern and Fe fortification and supplementation are common corrective strategies. Fe is essential not only for the human host but also for nearly all gut bacteria. We studied the impact of Fe deficiency and Fe repletion on the gut microbiota in rats.

  7. CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis.

    Science.gov (United States)

    Kim, Hyunbae; Zheng, Ze; Walker, Paul D; Kapatos, Gregory; Zhang, Kezhong

    2017-07-15

    Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. Copyright © 2017 American Society for Microbiology.

  8. Effects of Carbohydrates on Levels of Total Glycogen and Protein in Adult Female Pimpla turionellae L.

    OpenAIRE

    ÖZALP, Pınar; EMRE, İskender

    2014-01-01

    Effects of 22 carbohydrates belonging to various groups on the levels of total glycogen and protein in the adult female Pimpla turionellae L. were investigated. Sucrose was used as control in all experiments. Among the tested carbohydrates, xylose, ribose, rhamnose, mannose, maltose, cellobiose, melesitose, raffinose, glycogen, dulcitol and mannitol caused significant decreases on total glycogen level, but arabinose, fructose, galactose, glucose, sorbose, lactose, melibiose, trehalose, s...

  9. 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.

  10. Glycogen availability and skeletal muscle adaptations with endurance and resistance exercise

    OpenAIRE

    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 glycogen availability sheds new light on the role of the widely accepted energy source for adenosine triphosphate (ATP) resynthesis during endurance exercise. Indeed, several studies showed that endurance...

  11. Significance of glucagon for insulin secretion and hepatic glycogenolysis during exercise in rats

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H; Holst, J J

    1981-01-01

    The significance of glucagon and of the sympatho-adrenal system for insulin secretion and hepatic glycogen depletion during exercise was studied. Male rats were either adrenodemedullated and chemically sympathectomized with 6-hydroxydopamine (SX) or sham-treated (C). During light ether anesthesia...... attached (2% of body weight). Then cardiac blood was drawn for analysis of glucose, insulin and glucagon, and a sample of the liver was collected. In both CA and CN rats, the blood glucose concentration tended to increase (p less than 0.1) during exercise, whereas hepatic glycogen depletion and the plasma...... insulin concentration were lower in CA rats compared to CN rats. In SX rats, the blood glucose concentration did not increase during exercise, and in SXA but not in SXN rats, the hepatic glucogen depletion was lower than in CN rats. The plasma insulin concentration was consistently higher in SX rats than...

  12. A Rare Case of Persistent Lactic Acidosis in the ICU: Glycogenic Hepatopathy and Mauriac Syndrome

    Directory of Open Access Journals (Sweden)

    Kirsten S. Deemer

    2016-01-01

    Full Text Available Mauriac syndrome is a rare disorder that can present with the single feature of glycogenic hepatopathy in children and adults with poorly controlled diabetes mellitus. An often underrecognized finding of glycogenic hepatopathy is lactic acidosis and hyperlactatemia. Primary treatment of glycogenic hepatopathy is improved long-term blood glucose control. Resolution of symptoms and hepatomegaly will occur with improvement in hemoglobin A1C. We present here a case of a young adult female presenting to the intensive care unit with Mauriac syndrome. This case demonstrates exacerbation of lactic acidosis in a patient with glycogenic hepatopathy treated for diabetic ketoacidosis with high dose insulin and dextrose.

  13. A Rare Case of Persistent Lactic Acidosis in the ICU: Glycogenic Hepatopathy and Mauriac Syndrome.

    Science.gov (United States)

    Deemer, Kirsten S; Alvarez, George F

    2016-01-01

    Mauriac syndrome is a rare disorder that can present with the single feature of glycogenic hepatopathy in children and adults with poorly controlled diabetes mellitus. An often underrecognized finding of glycogenic hepatopathy is lactic acidosis and hyperlactatemia. Primary treatment of glycogenic hepatopathy is improved long-term blood glucose control. Resolution of symptoms and hepatomegaly will occur with improvement in hemoglobin A1C. We present here a case of a young adult female presenting to the intensive care unit with Mauriac syndrome. This case demonstrates exacerbation of lactic acidosis in a patient with glycogenic hepatopathy treated for diabetic ketoacidosis with high dose insulin and dextrose.

  14. Local depletion of glycogen with supra-maximal exercise in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Gejl, K D; Ørtenblad, N; Andersson, E

    2017-01-01

    four ∼4-minute supra-maximal sprint time trials (STT 1-4) with 45 min recovery. The sub-cellular glycogen volumes in m. triceps brachii were quantified from electron microscopy images before and after both STT 1 and STT 4. During STT 1, the depletion of intramyofibrillar glycogen was higher in type I...... fibres (-52% [-89:-15%]) than type 2 fibres (-15% [-52:22%]) (P = 0.02), while the depletion of intermyofibrillar glycogen (main effect: -19% [-33:0], P = 0.006) and subsarcolemmal glycogen (main effect: -35% [-66:0%], P = 0.03) was similar between fibre types. In contrast, only intermyofibrillar...

  15. Hepatitis amebiana

    OpenAIRE

    Cortés Mendoza, Eduardo

    2011-01-01

    Se ha considerado habitualmente la hepatitis amebiana como una inflamación del parénquima hepático causada por localización del parásito mismo en el hígado, distinguiéndose la forma supurada o absceso y el estado presupurativo o hepatitis aguda.

  16. Hepatic metabolism of anaesthetized growing pigs during acute portal infusion of volatile fatty acids and hydroxy-methyl butyrate

    DEFF Research Database (Denmark)

    Theil, Peter Kappel; Larsen, Uffe Krogh; Bjerre-Harpøth, Vibeke

    2016-01-01

    ABSTRACT: The objective of the experiment was to study hepatic metabolism during infusion of volatile fatty acids (VFA) differing in amounts and composition or infusion of HMB. Three fasted (20 h) pigs (mean BW ± SE; 58 kg ± 1) were fitted with indwelling catheters in the portal vein, hepatic vei...... from peripheral tissues were likely the two most important glycogenic precursors for gluconeogenesis in the liver during fasting....

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

    Directory of Open Access Journals (Sweden)

    Marin de Mas Igor

    2011-10-01

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

  18. [Renal involvement in glycogen storage disease type 1: Practical issues].

    Science.gov (United States)

    Ben Chehida, Amel; Bensmaïl, Takoua; Ben Rehouma, Faten; Ben Abdelaziz, Rim; Azzouz, Hatem; Boudabbous, Hela; Slim Abdelmoula, Mohamed; Abdelhak, Sonia; Kaabachi, Naziha; Ben Turkia, Hadhami; Tebib, Néji

    2015-07-01

    To investigate risk factors of renal complications in glycogen storage disease type I, in order to identify practical implications for renal preservation. A retrospective study of 38 patients with glycogen storage disease type I. The patients studied were 8.6 years old in average (1.5 to 22 years) and were followed during 7.4 ± 4.5 years. Hypercalciuria was detected in 23 patients and was related to acidosis (P=0.028), higher lactate levels (5.9 ± 3.5 versus 3.7 ± 1.7 mmol/L; P=0.013) and smaller height (-2.1 ± 1.5 SD versus -0.8 ± 1.5 SD; P=0.026). Urolithiasis was diagnosed in 7 cases. Glomerular disease (19/38) was more frequent in cases with severe hypertriglyceridemia (P=0.042) and occurred at an older age (P=0.007). Microalbuminuria occurred in 15/31 cases; ACE inhibitors were prescribed in only 8 cases. The frequency of renal complications did not differ according to the diet group (continuous enteral feeding or uncooked starch). Logistic regression concluded as risk factors: lactic acidosis for tubular disease and age>10 years for glomerular disease. Renal involvement is common in glycogen storage disease type I patients. Tubular abnormalities are precocious, related to lactic acidosis and may be detected by monitoring of urinary calcium. Glomerular hyperfiltration is the first stage of a progressive glomerular disease and is related to age. Practical implications for renal preservation are discussed based on our results and literature. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

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

    Science.gov (United States)

    de Mas, Igor Marin; Selivanov, Vitaly A; Marin, Silvia; Roca, Josep; Orešič, Matej; Agius, Loranne; Cascante, Marta

    2011-10-28

    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. 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. 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 phosphates in cytosol. In contrast, the observed distribution

  20. Muscle glycogen storage postexercise: effect of mode of carbohydrate administration.

    Science.gov (United States)

    Reed, M J; Brozinick, J T; Lee, M C; Ivy, J L

    1989-02-01

    The primary purpose of this study was to determine whether gastric emptying limits the rate of muscle glycogen storage during the initial 4 h after exercise when a carbohydrate supplement is provided. A secondary purpose was to determine whether liquid (L) and solid (S) carbohydrate (CHO) feedings result in different rates of muscle glycogen storage after exercise. Eight subjects cycled for 2 h on three separate occasions to deplete their muscle glycogen stores. After each exercise bout they received 3 g CHO/kg body wt in L (50% glucose polymer) or S (rice/banana cake) form or by intravenous infusion (I; 20% sterile glucose). The L and S supplements were divided into two equal doses and administered immediately after and 120 min after exercise, whereas the I supplement was administered continuously during the first 235 min of the 240-min recovery period. Blood samples were drawn from an antecubital vein before exercise, during exercise, and throughout recovery. Muscle biopsies were taken from the vastus lateralis immediately after and 120 and 240 min after exercise. Blood glucose and insulin declined during exercise and increased significantly above preexercise levels during recovery in all treatments. The increase in blood glucose during the I treatment, however, was three times greater than during the L or S treatments. The average insulin response of the L treatment (61.7 +/- 4.9 microU/ml) was significantly greater than that of the S treatment (47.5 +/- 4.2 microU/ml) but not that of the I (55.3 +/- 4.5 microU/ml) treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. FDG PET/CT in Type I Glycogen Storage Disease.

    Science.gov (United States)

    Manca, Chloé; Claudin, Marine; Belle, Arthur; Marie, Pierre Yves; Verger, Antoine

    2016-04-01

    Type I glycogen storage disease (GSD) is a rare autosomal recessive disorder caused by glucose-6-phosphatase deficiency. We report herein the particular pattern provided by FDG PET imaging in a 33-year-old patient with type Ib GSD. PET images yielded evidence of a pulmonary infectious focus as well as of: (1) a dramatically enlarged liver leading to a high global FDG uptake, (2) increased bone marrow activity, (3) splenomegalia leading to a high global spleen uptake, (4) a diffuse enhancement in muscle FDG uptake.

  2. 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.

  3. A highly prevalent equine glycogen storage disease is explained by constitutive activation of a mutant glycogen synthase

    DEFF Research Database (Denmark)

    Maile, C A; Hingst, Janne Rasmuss; Mahalingan, K K

    2017-01-01

    had significantly higher glycogen content than control horse muscle despite no difference in GS expression. GS activity was significantly higher in muscle from homozygous mutants than from heterozygote and control horses, in the absence and presence of the allosteric regulator, glucose 6 phosphate (G6......P). Muscle from homozygous mutant horses also had significantly increased GS phosphorylation at sites 2+2a and significantly higher AMPKα1 (an upstream kinase) expression than controls, likely reflecting a physiological attempt to reduce GS enzyme activity. Recombinant mutant GS was highly active...

  4. Glycogen-rich clear cell carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Hatzinikolaou ML

    2008-04-01

    Full Text Available Abstract Background Glycogen-rich carcinoma of the breast is a rare histological subtype of breast cancer, usually reported to have poor prognosis. Case presentation We present the case of a 59-year-old woman who underwent a mastectomy for a 3.5 cm clinically palpable left breast carcinoma, originally diagnosed as fibroadenoma on a screening mammogram four years before presentation. Diagnosis of clear cell carcinoma was based on certain histological characteristics of the tumour and immunohistochemical analysis (PAS staining, keratins AE1/AE3, EMA, cytokeratin 7, cytokeratin 20, melanosomes, vimentin, Chromogranin, Synaptophysin, S-100, SMA. No lymph node metastasis was found and as the tumour was ER positive and PgR negative, patient was treated only with an aromatase inhibitor upfront and remains free of disease 48 months now since operation. Conclusion Glycogen-rich clear cell carcinoma of the breast is a rare tumor, its clinical behavior reported to be rather aggressive so far, might varies depending on special characteristics such as low grade and strongly positive ER expression

  5. Metabolic fate of orally administered enzymatically synthesized glycogen in rats.

    Science.gov (United States)

    Furuyashiki, Takashi; Takata, Hiroki; Kojima, Iwao; Kuriki, Takashi; Fukuda, Itsuko; Ashida, Hitoshi

    2011-04-01

    We developed a new process for enzymatically synthesized glycogen (ESG), which is equivalent in physicochemical properties to natural-source glycogen (NSG) except its resistant property to degradation by α-amylase in vitro. In this study the metabolic fates of orally administered ESG in rats were investigated by a single oral administration test and a 2 week ingestion test. The glycemic index of ESG was 79. After the 2 week ingestion of ESG, the cecal content and production of short chain fatty acids were significantly increased, the pH value of cecal content was lowered, and the counts of Bifidobacterium and Lactobacillus in feces were significantly increased. Additionally, plasma levels of triacylglycerol and total cholesterol were significantly reduced by ESG. In contrast, NSG did not affect these parameters at all. The results collectively suggest that around 20% of orally administered ESG was transferred to the cecum in the form of polymer and assimilated into short chain fatty acids by microbiota and the polymer affected lipid metabolism.

  6. Altered glycogen metabolism causes hepatomegaly following an Atg7 deletion.

    Science.gov (United States)

    Kern, Lara; Spreckels, Johanne; Nist, Andrea; Stiewe, Thorsten; Skevaki, Chrysanthi; Greene, Brandon; Mernberger, Marco; Elsässer, Hans-Peter

    2016-12-01

    Autophagy is a lysosomal degradation process involved in the turnover of organelles or other cell constituents, in providing sources for energy production under starving conditions and in cell metabolism. A key protein in the macroautophagic machinery is the autophagy-related protein (Atg) 7. Constitutive deletion of Atg7 is lethal at birth. A conditional deletion of Atg7 in hepatocytes leads to hepatomegaly and in aged animals to liver tumors. With this study, we aim at analyzing the hepatomegaly development in more detail. The 3- to 4-fold enlargement of the liver takes place between days 25 and 35 after birth (P25-P35) and persists at least until P90. This is accompanied by a change in the expression of enzymes involved in the glycogen/glucose metabolism. While glycogen synthesis is inhibited, glucose is preferentially kept as glucose-6-phosphate inside the cells, inducing a swelling of the cells caused by hyperosmolarity. An increase of lipogenic enzymes suggests that glucose-6-phosphate is delivered to lipogenic pathways, which is supported by the occurrence of a steatosis around P30. The development of hepatomegaly is accompanied by a polyploidisation of hepatocytes, an enhanced expression of genes related to inflammatory processes and an infiltration of macrophages and granulocytes. Our data provide evidence that the attenuation of macroautophagy in hepatocytes leads to a glucose retention that causes cell swelling. The resulting hepatomegaly, which develops in a time interval of about 10 days, perturbs liver perfusion and induces an inflammatory reaction together with polyploidisation.

  7. 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.

  8. Changing shapes of glycogen-autophagy nexus in neurons: Perspective from a rare epilepsy

    Directory of Open Access Journals (Sweden)

    Pankaj Kumar Singh

    2015-02-01

    Full Text Available In brain, glycogen metabolism is predominantly restricted to astrocytes but it also indirectly supports neuronal functions. Increased accumulation of glycogen in neurons is mysteriously pathogenic triggering neurodegeneration as seen in ‘Lafora disease’ and in other transgenic animal models of neuronal glycogen accumulation. Lafora disease is a fatal neurodegenerative disorder with excessive glycogen inclusions in neurons. Autophagy, a pathway for bulk degradation of obsolete cellular constituents also degrades metabolites like lipid and glycogen. Recently, defects in this pathway emerged as a plausible reason for glycogen accumulation in neurons in Lafora disease, although some contradictions prevail. Albeit surprising, a reciprocal regulation of autophagy by glycogen in neurons has also just been proposed. Notably, increasing evidences of interaction between proteins of autophagy and glycogen metabolism from diverse model systems indicate a conserved, dynamic and regulatory cross-talk between these two pathways. Concerning these findings, we herein provide certain models for the molecular basis of this cross-talk and discuss its potential implication in the pathophysiology of Lafora disease.

  9. Glycogenic hepatopathy: a rare cause of elevated serum transaminases in diabetes mellitus.

    NARCIS (Netherlands)

    Brand, M. van den; Elving, L.D.; Drenth, J.P.H.; Krieken, J.H.J.M. van

    2009-01-01

    Glycogenic hepatopathy (GH) is a rare cause of serum transaminase elevations in type 1 diabetes mellitus (DM). We describe a 29-year-old woman with a history of poorly controlled type 1 DM who presented with hepatomegaly and severe transaminase flares. Liver histology confirmed GH, with glycogen

  10. 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....

  11. 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

    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 furt...

  12. 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. Paradoxically...

  13. Glycogen storage disease type III : diagnosis, genotype, management, clinical course and outcome

    NARCIS (Netherlands)

    Sentner, Christiaan P.; Hoogeveen, Irene J.; Weinstein, David A.; Santer, Rene; Murphy, Elaine; McKiernan, Patrick J.; Steuerwald, Ulrike; Beauchamp, Nicholas J.; Taybert, Joanna; Laforet, Pascal; Petit, Francois M.; Hubert, Aurelie; Labrune, Philippe; Smit, G. Peter A.; Derks, Terry G. J.

    Glycogen storage disease type III (GSDIII) is a rare disorder of glycogenolysis due to AGL gene mutations, causing glycogen debranching enzyme deficiency and storage of limited dextrin. Patients with GSDIIIa show involvement of liver and cardiac/skeletal muscle, whereas GSDIIIb patients display only

  14. Glycogen serves as an energy source that maintains astrocyte cell proliferation in the neonatal telencephalon.

    Science.gov (United States)

    Gotoh, Hitoshi; Nomura, Tadashi; Ono, Katsuhiko

    2017-06-01

    Large amounts of energy are required when cells undergo cell proliferation and differentiation for mammalian neuronal development. Early neonatal mice face transient starvation and use stored energy for survival or to support development. Glycogen is a branched polysaccharide that is formed by glucose, and serves as an astrocytic energy store for rapid energy requirements. Although it is present in radial glial cells and astrocytes, the role of glycogen during development remains unclear. In the present study, we demonstrated that glycogen accumulated in glutamate aspartate transporter (GLAST)+ astrocytes in the subventricular zone and rostral migratory stream. Glycogen levels markedly decreased after birth due to the increase of glycogen phosphorylase, an essential enzyme for glycogen metabolism. In primary cultures and in vivo, the inhibition of glycogen phosphorylase decreased the proliferation of astrocytic cells. The number of cells in the G1 phase increased in combination with the up-regulation of cyclin-dependent kinase inhibitors or down-regulation of the phosphorylation of retinoblastoma protein (pRB), a determinant for cell cycle progression. These results suggest that glycogen accumulates in astrocytes located in specific areas during the prenatal stage and is used as an energy source to maintain normal development in the early postnatal stage.

  15. 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...

  16. Acoustically Accessible Window Determination for Ultrasound Mediated Treatment of Glycogen Storage Disease Type Ia Patients

    NARCIS (Netherlands)

    Wang, S.; Raju, B.I.; Leyvi, E.; Weinstein, D.; Seip, R.

    2012-01-01

    Glycogen storage disease type Ia (GSDIa) is caused by an inherited single-gene defect resulting in an impaired glycogen to glucose conversion pathway. Targeted ultrasound mediated delivery (USMD) of plasmid DNA to liver in conjunction with microbubbles may provide a potential treatment for GSDIa

  17. Effects of cadmium exposure on glycogen phosphorylase activity in rat placenta as demonstrated by histochemical means

    NARCIS (Netherlands)

    Hazelhoff Roelfzema, W.; Hacker, H. J.; van Noorden, C. J.

    1989-01-01

    Glycogen phosphorylase (PHO) activity was demonstrated histochemically in unfixed cryostat sections of placentae from cadmium-treated and control rats with the use of the semipermeable membrane technique. Staining of the newly synthesized glycogen was performed by lugol. A high activity was present

  18. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ... travel through your body until they reach your brain, causing mental and physical symptoms of HE. Hepatic ...

  19. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... the Stages of Hepatic Encephalopathy? What Triggers or Can Cause HE to Get Worse? How is HE ... liver disease. When your liver is damaged it can no longer remove toxic substances from your blood. ...

  20. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Hepatic Encephalopathy so you can tell your doctor right away if you think you may have it. ... American Liver Foundation © 2018 American Liver Foundation. All rights reserved. Funding for the HE123 - Diagnosis, Treatment and ...

  1. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Get Worse? How is HE Diagnosed? Prior to Treatment Who treats HE? Preparing for your Medical Appointment Hepatic Encephalopathy Treatment Options Treatment Basics Treatment Medications Importance of Adhering ...

  2. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Hepatic Encephalopathy so you can tell your doctor right away if you think you may have it. ... American Liver Foundation © 2017 American Liver Foundation. All rights reserved. Funding for the HE123 - Diagnosis, Treatment and ...

  3. Viral Hepatitis

    Science.gov (United States)

    ... Us FAQs Ask a Question Toll Free Numbers Homeless Veterans Chat VA » Health Care » Viral Hepatitis » Veterans and ... Vet Centers) War Related Illness & Injury Study Center Homeless Veterans Returning Service Members Rural Veterans Seniors & Aging Veterans ...

  4. Hepatitis B

    Science.gov (United States)

    ... chemotherapy medicines have worked or lived in a prison had a blood transfusion or organ transplant before ... can lower your chances of developing serious health problems. Your doctor may recommend screening for hepatitis B ...

  5. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... to Treatment Who treats HE? Preparing for your Medical Appointment Hepatic Encephalopathy Treatment Options Treatment Basics Treatment ... treatment. Being a fully-informed participant in your medical care is an important factor in staying as ...

  6. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Symptoms to look for Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is ... questions about HE, one step at a time. Home About Us Ways to Give Contact Us Privacy ...

  7. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Stages of Hepatic Encephalopathy? What Triggers or Can Cause HE to Get Worse? How is HE Diagnosed? ... portosystemic encephalopathy or PSE, is a condition that causes temporary worsening of brain function in people with ...

  8. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Reading Webinars Caregivers The Role of a Caregiver Signs and Symptoms to look for Caregiver Support Caregiver ... and your family to become familiar with the signs of Hepatic Encephalopathy so you can tell your ...

  9. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Are the Symptoms of HE? What Are the Stages of Hepatic Encephalopathy? What Triggers or Can Cause ... may not be aware you have it. The stages of HE span from mild to severe and ...

  10. Autoimmune Hepatitis

    Science.gov (United States)

    ... person usually needs blood tests for an exact diagnosis because a person with autoimmune hepatitis can have the same symptoms as those of other liver diseases or metabolic disorders. Blood tests. A blood test involves drawing ...

  11. Hepatic hemangioma

    Science.gov (United States)

    ... MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Hepatic hemangioma URL of this page: //medlineplus.gov/ency/ ...

  12. Hepatic ischemia

    Science.gov (United States)

    ... MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Hepatic ischemia URL of this page: //medlineplus.gov/ency/ ...

  13. Hepatitis B

    Science.gov (United States)

    ... you need the vaccine The ABCs of Viral Hepatitis Centers for Disease Control and Prevention (CDC): Fact Sheet ... Suite 750 Bethesda, MD 20814 T: (301) 656-0003 | F: (301) 907-0878 Privacy Policy Disclaimer Link to ...

  14. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Cirrhosis of the Liver & Symptoms Why it’s Important to Treat HE Symptoms of Liver Failure Glossary of ... Hepatic Encephalopathy? What Triggers or Can Cause HE to Get Worse? How is HE Diagnosed? Prior to ...

  15. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... liver is damaged it can no longer remove toxic substances from your blood. These toxins build up ... disease is. It’s important for you and your family to become familiar with the signs of Hepatic ...

  16. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... ALF HE Materials Suggested Reading Webinars Caregivers The Role of a Caregiver Signs and Symptoms to look ... disease is. It’s important for you and your family to become familiar with the signs of Hepatic ...

  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...... that macro- and proglycogen degrade simultaneously during the first hour of stimulation. After 3 h, the muscle showed net synthesis, with an increase in the proglycogen fraction. The glycogen content peaked after 4 days of stimulation, macroglycogen being the predominant fraction at that time. Glycogen...... 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. 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.

  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. Hepatitis B Foundation

    Science.gov (United States)

    ... worldwide 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working ... of people living with hepatitis B. Learn About Hepatitis B in 11 Other Languages . Resource Video See ...

  1. Hepatitis A FAQs

    Science.gov (United States)

    ... Professional Resources Patient Education Resources Quick Links to Hepatitis … A | B | C | D | E Viral Hepatitis Home ... Grantees Policy and Programs Resource Center Viral Hepatitis Hepatitis A Questions and Answers for the Public Recommend ...

  2. Impaired glucose metabolism and exercise capacity with muscle-specific glycogen synthase 1 (gys1 deletion in adult mice

    Directory of Open Access Journals (Sweden)

    Chrysovalantou E. Xirouchaki

    2016-03-01

    In brief: This study demonstrates why the body prioritises muscle glycogen storage over liver glycogen storage despite the critical role of the liver in supplying glucose to the brain in the fasting state and shows that glycogen deficiency results in impaired glucose metabolism and reduced exercise capacity.

  3. Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis: Symptoms, Diagnosis, Treatment & Prevention Past Issues / Spring 2009 ... No appetite Fever Headaches Diagnosis To check for hepatitis viruses, your doctor will test your blood. You ...

  4. Enzymatically synthesized glycogen reduces lipid accumulation in diet-induced obese rats.

    Science.gov (United States)

    Furuyashiki, Takashi; Ogawa, Rui; Nakayama, Yoko; Honda, Kazuhisa; Kamisoyama, Hiroshi; Takata, Hiroki; Yasuda, Michiko; Kuriki, Takashi; Ashida, Hitoshi

    2013-09-01

    Based on a recent study indicating that enzymatically synthesized glycogen (ESG) possesses a dietary, fiber-like action, we hypothesized that ESG can reduce the risk of obesity. In this study, the antiobesity effects of ESG were investigated in a model of diet-induced obesity. Male Sprague-Dawley rats were divided into 4 groups and fed a normal or high-fat diet, with or without 20% ESG, for 4 weeks. Body weight, food intake, lipid deposition in the white adipose tissues and liver, fecal lipid excretion, and plasma lipid profiles were measured. At week 3, the body fat mass was measured using an x-ray computed tomography system, which showed that ESG significantly suppressed the high-fat diet-induced lipid accumulation. Similar results were observed in the weight of the adipose tissue after the experiment. Moreover, ESG significantly suppressed the lipid accumulation in the liver but increased fecal lipid excretion. The plasma concentrations of triacylglycerol and nonesterified fatty acid were lowered after a high-fat diet, whereas the total bile acid concentration was increased by ESG. However, the hepatic messenger RNA (mRNA) levels of enzymes related to lipid metabolism were not affected by ESG. Conversely, the mRNA levels of long-chain acyl-CoA dehydrogenase and medium-chain acyl-CoA dehydrogenase were up-regulated by ESG in the muscle. These results suggest that the combined effects of increased fecal lipid excretion, increased mRNA levels of enzymes that oxidize fatty acids in the muscle, and increased total bile acid concentration in the plasma mediate the inhibitory effect of ESG on lipid accumulation. © 2013.

  5. Noncompaction myocardium in association with type Ib glycogen storage disease.

    Science.gov (United States)

    Goeppert, Benjamin; Lindner, Martin; Vogel, Monika Nadja; Warth, Arne; Stenzinger, Albrecht; Renner, Marcus; Schnabel, Philipp; Schirmacher, Peter; Autschbach, Frank; Weichert, Wilko

    2012-10-15

    Noncompaction myocardium is a rare disorder assumed to occur as an arrest of the compaction process during the normal development of the heart. Left ventricular noncompaction has been reported to be associated with a variety of cardiac and extracardiac, especially neuromuscular abnormalities. Moreover, it has been suggested that metabolic alterations could be responsible for the noncompaction. However, no association of noncompaction myocardium with type Ib glycogen storage disease (GSD) has been reported so far. Type Ib GSD is due to a defect of a transmembrane protein which results, similar to type Ia GSD, in hypoglycemia, a markedly enlarged liver and, additionally, in neutropenia, recurrent infections, and inflammatory bowel disease. Until now, no muscular or cardiac involvement has been described in type Ib GSD patients. The present case represents the first report of a noncompaction myocardium in a child with type Ib GSD who died of sudden clinical deterioration at the age of four. Copyright © 2012 Elsevier GmbH. All rights reserved.

  6. Pulmonary Arterial Hypertension in Glycogen Storage Disease Type I

    Directory of Open Access Journals (Sweden)

    Rachel D. Torok MD

    2017-05-01

    Full Text Available Pulmonary arterial hypertension (PAH is a rare and highly fatal disease that has been reported in 8 patients with glycogen storage disease type I (GSDI. We describe an additional case of an acute presentation of PAH in a 14-year-old patient with GSDI, which was successfully treated with inhaled nitric oxide and sildenafil. We investigated the incidence of PAH in 28 patients with GSDI on routine echocardiography and found no evidence of PAH and no significant cardiac abnormalities. This study highlights that PAH is a rare disease overall, but our case report and those previously described suggest an increased incidence in patients with GSDI. Should cardiopulmonary symptoms develop, clinicians caring for patients with GSDI should have a high degree of suspicion for acute PAH and recognize that prompt intervention can lead to survival in this otherwise highly fatal disease.

  7. The glamour and gloom of glycogen synthase kinase-3.

    Science.gov (United States)

    Jope, Richard S; Johnson, Gail V W

    2004-02-01

    Glycogen synthase kinase-3 (GSK3) is now recognized as a key component of a surprisingly large number of cellular processes and diseases. Several mechanisms play a part in controlling the actions of GSK3, including phosphorylation, protein complex formation, and subcellular distribution. These are used to control and direct the far-reaching influences of GSK3 on cellular structure, growth, motility and apoptosis. Dysregulation of GSK3 is linked to several prevalent pathological conditions, such as diabetes and/or insulin resistance, and Alzheimer's disease. Therefore, much effort is currently directed towards understanding the functions and control of GSK3, and identifying methods capable of diminishing the deleterious impact of GSK3 in pathological conditions.

  8. Vitamin D Repletion Reduces the Progression of Premalignant Squamous Lesions in the NTCU Lung Squamous Cell Carcinoma Mouse Model

    Science.gov (United States)

    Mazzilli, Sarah A.; Hershberger, Pamela A.; Reid, Mary E.; Bogner, Paul N.; Atwood, Kristopher; Trump, Donald L.; Johnson, Candace S.

    2015-01-01

    The chemopreventive actions of vitamin D were examined in the N-nitroso-tris-chloroethylurea (NTCU) mouse model, a progressive model of lung squamous cell carcinoma (SCC). SWR/J mice were fed a deficient diet (D) containing no vitamin D3, a sufficient diet (S) containing 2000 IU/kg vitamin D3, or the same diets in combination with the active metabolite of vitamin D, calcitriol (C) (80 μg/kg, weekly). The percentage (%) of the mucosal surface of large airways occupied by dysplastic lesions was determined in mice after treatment with a total dose of 15 or 25 μmol NTCU (N). After treatment with 15 μmol NTCU, the % of the surface of large airways containing high-grade dysplastic (HGD) lesions were vitamin D-deficient +NTCU (DN), 22.7 % (p<0.05 compared to vitamin D-sufficient +NTCU (SN)); DN + C, 12.3%; SN, 8.7%; and SN + C, 6.6%. The extent of HGD increased with NTCU dose in the DN group. Proliferation, assessed by Ki-67 labeling, increased upon NTCU treatment. The highest Ki-67 labeling index was seen in the DN group. As compared to SN mice, DN mice exhibited a 3-fold increase (p <0.005) in circulating white blood cells (WBC), a 20% (p <0.05) increase in IL-6 levels, and a 4 -fold (p <0.005) increase in WBC in bronchial lavages. Thus, vitamin D repletion reduces the progression of premalignant lesions, proliferation, and inflammation, and may thereby suppress development of lung SCC. Further investigations of the chemopreventive effects of vitamin D in lung SCC are warranted. PMID:26276745

  9. The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults.

    Science.gov (United States)

    Brito, Alex; Grapov, Dmitry; Fahrmann, Johannes; Harvey, Danielle; Green, Ralph; Miller, Joshua W; Fedosov, Sergey N; Shahab-Ferdows, Setareh; Hampel, Daniela; Pedersen, Theresa L; Fiehn, Oliver; Newman, John W; Uauy, Ricardo; Allen, Lindsay H

    2017-08-09

    Background: The specific metabolomic perturbations that occur in vitamin B-12 deficiency, and their associations with neurological function, are not well characterized.Objective: We sought to characterize the human serum metabolome in subclinical vitamin B-12 deficiency and repletion.Methods: A before-and-after treatment study provided 1 injection of 10 mg vitamin B-12 (with 100 mg pyridoxine and 100 mg thiamin) to 27 community-dwelling elderly Chileans (∼74 y old) with vitamin B-12 deficiency, as evaluated with serum vitamin B-12, total plasma homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin. The combined indicator of vitamin B-12 status (cB-12) was computed. Targeted metabolites [166 acylcarnitines, amino acids, sugars, glycerophospholipids, and sphingolipids (liquid chromatography-tandem mass spectrometry)], and untargeted metabolites [247 chemical entities (gas chromatography time-of-flight mass spectrometry)] were measured at baseline and 4 mo after treatment. A peripheral nerve score was developed. Differences before and after treatment were examined. For targeted metabolomics, the data from 18 individuals with adequate vitamin B-12 status (selected from the same population) were added to the before-and-after treatment data set. Network visualizations and metabolic pathways are illustrated.Results: The injection increased serum vitamin B-12, holotranscobalamin, and cB-12 (P vitamin B-12 status and nerve function. Multiple connections were identified with primary metabolites (e.g., an inverse relation between vitamin B-12 markers and tryptophan, tyrosine, and pyruvic, succinic, and citric acids, and a direct correlation between the nerve score and arginine).Conclusions: The human serum metabolome in vitamin B-12 deficiency and the changes that occur after supplementation are characterized. Metabolomics revealed connections between vitamin B-12 status and serum metabolic markers of mitochondrial function, myelin integrity, oxidative

  10. Glycogen storage disease type III: modified Atkins diet improves myopathy.

    Science.gov (United States)

    Mayorandan, Sebene; Meyer, Uta; Hartmann, Hans; Das, Anibh Martin

    2014-11-28

    Frequent feeds with carbohydrate-rich meals or continuous enteral feeding has been the therapy of choice in glycogen storage disease (Glycogenosis) type III. Recent guidelines on diagnosis and management recommend frequent feedings with high complex carbohydrates or cornstarch avoiding fasting in children, while in adults a low-carb-high-protein-diet is recommended. While this regimen can prevent hypoglycaemia in children it does not improve skeletal and heart muscle function, which are compromised in patients with glycogenosis IIIa. Administration of carbohydrates may elicit reactive hyperinsulinism, resulting in suppression of lipolysis, ketogenesis, gluconeogenesis, and activation of glycogen synthesis. Thus, heart and skeletal muscle are depleted of energy substrates. Modified Atkins diet leads to increased blood levels of ketone bodies and fatty acids. We hypothesize that this health care intervention improves the energetic balance of muscles. We treated 2 boys with glycogenosis IIIa aged 9 and 11 years with a modified Atkins diet (10 g carbohydrate per day, protein and fatty acids ad libitum) over a period of 32 and 26 months, respectively. In both patients, creatine kinase levels in blood dropped in response to Atkins diet. When diet was withdrawn in one of the patients he complained of chest pain, reduced physical strength and creatine kinase levels rapidly increased. This was reversed when Atkins diet was reintroduced. One patient suffered from severe cardiomyopathy which significantly improved under diet. Patients with glycogenosis IIIa benefit from an improved energetic state of heart and skeletal muscle by introduction of Atkins diet both on a biochemical and clinical level. Apart from transient hypoglycaemia no serious adverse effects were observed.

  11. Liver Cancer and Hepatitis B

    Science.gov (United States)

    ... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  12. Hepatitis B & C and HIV

    Science.gov (United States)

    ... Find Services HIV SERVICES LOCATOR Locator Search Search Hepatitis B & C Topics Hepatitis B Hepatitis C Hepatitis ... Infections Sexually Transmitted Diseases Smoking Women's Health Issues Hepatitis B Virus and Hepatitis C Virus Infection People ...

  13. Hepatitis C: Sex and Sexuality

    Science.gov (United States)

    ... with Hepatitis » Sex and Sexuality: Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... hepatitis C virus through sex. Can you pass hepatitis C to a sex partner? Yes, but it ...

  14. Hepatitis C: Diet and Nutrition

    Science.gov (United States)

    ... with Hepatitis » Daily Living: Diet and Nutrition Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... have high cholesterol and have fatty liver. How hepatitis C affects diet If you have hepatitis, you ...

  15. 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.

  16. FLCN and AMPK Confer Resistance to Hyperosmotic Stress via Remodeling of Glycogen Stores.

    Directory of Open Access Journals (Sweden)

    Elite Possik

    2015-10-01

    Full Text Available Mechanisms of adaptation to environmental changes in osmolarity are fundamental for cellular and organismal survival. Here we identify a novel osmotic stress resistance pathway in Caenorhabditis elegans (C. elegans, which is dependent on the metabolic master regulator 5'-AMP-activated protein kinase (AMPK and its negative regulator Folliculin (FLCN. FLCN-1 is the nematode ortholog of the tumor suppressor FLCN, responsible for the Birt-Hogg-Dubé (BHD tumor syndrome. We show that flcn-1 mutants exhibit increased resistance to hyperosmotic stress via constitutive AMPK-dependent accumulation of glycogen reserves. Upon hyperosmotic stress exposure, glycogen stores are rapidly degraded, leading to a significant accumulation of the organic osmolyte glycerol through transcriptional upregulation of glycerol-3-phosphate dehydrogenase enzymes (gpdh-1 and gpdh-2. Importantly, the hyperosmotic stress resistance in flcn-1 mutant and wild-type animals is strongly suppressed by loss of AMPK, glycogen synthase, glycogen phosphorylase, or simultaneous loss of gpdh-1 and gpdh-2 enzymes. Our studies show for the first time that animals normally exhibit AMPK-dependent glycogen stores, which can be utilized for rapid adaptation to either energy stress or hyperosmotic stress. Importantly, we show that glycogen accumulates in kidneys from mice lacking FLCN and in renal tumors from a BHD patient. Our findings suggest a dual role for glycogen, acting as a reservoir for energy supply and osmolyte production, and both processes might be supporting tumorigenesis.

  17. Effects of cycle strategy and fibre composition on muscle glycogen depletion pattern and subsequent running economy.

    Science.gov (United States)

    Suriano, R; Edge, J; Bishop, D

    2010-05-01

    In this study, the effects of variable and constant-intensity cycling on muscle glycogen depletion patterns and subsequent running economy was examined. 60 minutes of cycling at a constant power (CON) or variable intensity (VAR) followed by a treadmill run to determine running economy was completed by nine male triathletes (Vo(2)max = 67.7 (4.9 ml) kg(-) min(-1)). During CON, there was greater glycogen depletion in the type I fibres compared with type II (0.08 (0.04) vs 0.02 (0.01) optical density (OD) units; peconomy, which was not significantly different between conditions (52.1 vs 52.8 ml kg(-1) min(-1)). There was a strong correlation between total muscle glycogen depletion and the change in running Vo(2) (r = 0.73, ptrials were combined. There was also a negative correlation between type I fibre percentage and glycogen depletion within type II fibres during CON (r = -0.85, peconomy, subsequent to 60 minutes of cycling, is not affected by the cycling strategy employed. While different glycogen depletion patterns in the type I and II fibres were observed between conditions, total glycogen depletion may be more important to subsequent running economy. The percentage of type I fibres was associated with the glycogen depletion pattern during constant load, but not variable-intensity exercise.

  18. Aqueous size-exclusion chromatographic method for the quantification of cyanobacterial native glycogen.

    Science.gov (United States)

    Izumi, Yoshihiro; Aikawa, Shimpei; Matsuda, Fumio; Hasunuma, Tomohisa; Kondo, Akihiko

    2013-07-01

    Cyanobacterial glycogen has gained interest as a valuable biomass feedstock for biofuel production. However, an ideal method for native glycogen quantification has not been developed. Here, we have proposed a simple methodology that enables the quantitative determination of cyanobacterial glycogen concentration with high repeatability using aqueous size-exclusion chromatography with a differential refractive index detector (SEC/RID). Our SEC/RID system also allows size distributions for native glycogen based on hydrodynamic volumes (Vh), which is proportional to the product of the molecular mass (M) and intrinsic viscosity [η], obtained by universal calibration using linear homopolymers of known M with Mark-Houwink-Sakurada parameters. The universal calibration curve achieved a broad linear range (Vh parameter [η]M=2×10(2)-8×10(8)mLg(-1)) with a high correlation coefficient (R(2)=0.9942), because the developed system is equipped with an OHpak SB-806M HQ aqueous column containing four types of polyhydroxy methacrylate-based particles with different particle and pore sizes. Based on the SEC/RID system, response of molecular size distribution of glycogen in microalgae to the cultivation condition was first observed. Our established SEC/RID method has several advantages over conventional techniques, including the simultaneous quantitative and size distribution analyses of glycogen, and represents a potentially useful tool to elucidate the relationship between structural properties and the roles of glycogen in metabolism. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Subcellular distribution of glycogen and decreased tetanic Ca2+ in fatigued single intact mouse muscle fibres

    Science.gov (United States)

    Nielsen, Joachim; Cheng, Arthur J; Ørtenblad, Niels; Westerblad, Håkan

    2014-01-01

    In skeletal muscle fibres, glycogen has been shown to be stored at different subcellular locations: (i) between the myofibrils (intermyofibrillar); (ii) within the myofibrils (intramyofibrillar); and (iii) subsarcolemmal. Of these, intramyofibrillar glycogen has been implied as a critical regulator of sarcoplasmic reticulum Ca2+ release. The aim of the present study was to test directly how the decrease in cytoplasmic free Ca2+ ([Ca2+]i) during repeated tetanic contractions relates to the subcellular glycogen distribution. Single fibres of mouse flexor digitorum brevis muscles were fatigued with 70 Hz, 350 ms tetani given at 2 s (high-intensity fatigue, HIF) or 10 s (low-intensity fatigue, LIF) intervals, while force and [Ca2+]i were measured. Stimulation continued until force decreased to 30% of its initial value. Fibres were then prepared for analyses of subcellular glycogen distribution by transmission electron microscopy. At fatigue, tetanic [Ca2+]i was reduced to 70 ± 4% and 54 ± 4% of the initial in HIF (P fibres, respectively. At fatigue, the mean inter- and intramyofibrillar glycogen content was 60–75% lower than in rested control fibres (P fibres showed a good correlation between the fatigue-induced decrease in tetanic [Ca2+]i and the reduction in intermyofibrillar (P = 0.051) and intramyofibrillar (P = 0.0008) glycogen. In conclusion, the fatigue-induced decrease in tetanic [Ca2+]i, and hence force, is accompanied by major reductions in inter- and intramyofibrillar glycogen. The stronger correlation between decreased tetanic [Ca2+]i and reduced intramyofibrillar glycogen implies that sarcoplasmic reticulum Ca2+ release critically depends on energy supply from the intramyofibrillar glycogen pool. PMID:24591577

  20. Effect of glycogen synthase overexpression on insulin-stimulated muscle glucose uptake and storage.

    Science.gov (United States)

    Fogt, Donovan L; Pan, Shujia; Lee, Sukho; Ding, Zhenping; Scrimgeour, Angus; Lawrence, John C; Ivy, John L

    2004-03-01

    Insulin-stimulated muscle glucose uptake is inversely associated with the muscle glycogen concentration. To investigate whether this association is a cause and effect relationship, we compared insulin-stimulated muscle glucose uptake in noncontracted and postcontracted muscle of GSL3-transgenic and wild-type mice. GSL3-transgenic mice overexpress a constitutively active form of glycogen synthase, which results in an abundant storage of muscle glycogen. Muscle contraction was elicited by in situ electrical stimulation of the sciatic nerve. Right gastrocnemii from GSL3-transgenic and wild-type mice were subjected to 30 min of electrical stimulation followed by hindlimb perfusion of both hindlimbs. Thirty minutes of contraction significantly reduced muscle glycogen concentration in wild-type (49%) and transgenic (27%) mice, although transgenic mice retained 168.8 +/- 20.5 micromol/g glycogen compared with 17.7 +/- 2.6 micromol/g glycogen for wild-type mice. Muscle of transgenic and wild-type mice demonstrated similar pre- (3.6 +/- 0.3 and 3.9 +/- 0.6 micromol.g(-1).h(-1) for transgenic and wild-type, respectively) and postcontraction (7.9 +/- 0.4 and 7.0 +/- 0.4 micromol.g(-1).h(-1) for transgenic and wild-type, respectively) insulin-stimulated glucose uptakes. However, the [14C]glucose incorporated into glycogen was greater in noncontracted (151%) and postcontracted (157%) transgenic muscle vs. muscle of corresponding wild-type mice. These results indicate that glycogen synthase activity is not rate limiting for insulin-stimulated glucose uptake in skeletal muscle and that the inverse relationship between muscle glycogen and insulin-stimulated glucose uptake is an association, not a cause and effect relationship.

  1. 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...

  2. [Nervous regulation of glycogen concentration and the lactate dehydrogenase isoenzyme spectrum in the diaphragm of rats].

    Science.gov (United States)

    Iakovlev, V F

    1981-01-01

    Content of glycogen, activity of lactate dehydrogenase (LDH) and its isoenzyme spectrum were studied in two cases of partial diaphragm denervation as well as in electro-stimulation of separate phrenic nerve branches. Dissimilar postdenervational alterations were observed in the content of glycogen and in the isozyme spectrum of LDH, which depended on the type of partial denervation. Stimulation of individual branches of the phrenic nerve showed that they separately affected the synthesis and consumption of glycogen. The data obtained suggest the nervous regulation of glycogensynthetic processes in muscle tissue.

  3. Non-invasive measurement of brain glycogen by NMR spectroscopy and its application to the study of brain metabolism

    Science.gov (United States)

    Tesfaye, Nolawit; Seaquist, Elizabeth R.; Öz, Gülin

    2011-01-01

    Glycogen is the reservoir for glucose in the brain. Beyond the general agreement that glycogen serves as an energy source in the central nervous system, its exact role in brain energy metabolism has yet to be elucidated. Experiments performed in cell and tissue culture and animals have shown that glycogen content is affected by several factors including glucose, insulin, neurotransmitters, and neuronal activation. The study of in vivo glycogen metabolism has been hindered by the inability to measure glycogen non-invasively, but in the past several years, the development of a non-invasive localized 13C nuclear magnetic resonance (NMR) spectroscopy method has enabled the study of glycogen metabolism in the conscious human. With this technique, 13C-glucose is administered intravenously and its incorporation into and wash-out from brain glycogen is tracked. One application of this method has been to the study of brain glycogen metabolism in humans during hypoglycemia: data have shown that mobilization of brain glycogen is augmented during hypoglycemia and, after a single episode of hypoglycemia, glycogen synthesis rate is increased, suggesting that glycogen stores rebound to levels greater than baseline. Such studies suggest glycogen may serve as a potential energy reservoir in hypoglycemia and may participate in the brain's adaptation to recurrent hypoglycemia and eventual development of hypoglycemia unawareness. Beyond this focused area of study, 13C NMR spectroscopy has a broad potential for application in the study of brain glycogen metabolism and carries the promise of a better understanding of the role of brain glycogen in diabetes and other conditions. PMID:21732401

  4. Sphinganine-1-phosphate attenuates both hepatic and renal injury induced by hepatic ischemia and reperfusion in mice.

    Science.gov (United States)

    Park, Sang Won; Kim, Mihwa; Chen, Sean W C; D'Agati, Vivette D; Lee, H Thomas

    2010-01-01

    Hepatic ischemia/reperfusion (I/R) injury is a major complication after liver transplantation, major hepatic resection, or prolonged portal vein occlusion. Furthermore, acute kidney injury is frequent after hepatic I/R and greatly increases postoperative complications. Sphinganine-1-phosphate is a sphingolipid with uncharacterized physiological effects. We serendipitously determined that plasma levels of sphinganine-1-phosphate fell significantly after liver I/R in mice. In this study, we hypothesized that repletion of plasma sphinganine-1-phosphate would protect against liver and kidney injuries after liver I/R. C57BL/6 mice were subjected to 60 min of partial hepatic I/R and treated with either vehicle or with sphinganine-1-phosphate (given immediately before and 2 h after reperfusion). Vehicle-treated mice subjected to liver I/R developed acute liver and kidney injuries with elevated plasma alanine aminotransferase and creatinine 5 and 24 h after liver I/R. However, liver and kidney injuries were significantly attenuated with sphinganine-1-phosphate treatment. Sphinganine-1-phosphate markedly inhibited liver and kidney necrosis and apoptosis 24 h after liver I/R. Moreover, sphinganine-1-phosphate attenuated neutrophil infiltration, reduced plasma IL-6 and TNF-alpha upregulation, and preserved liver and kidney vascular integrity while reducing liver and kidney F-actin degradation after liver I/R. Finally, sphinganine-1-phosphate-mediated hepatic and renal protection was blocked by VPC23019, an antagonist for sphingosine-1-phosphate type 1 receptor. Therefore, sphinganine-1-phosphate improves acute liver and kidney injuries after hepatic I/R via sphingosine-1-phosphate type 1 receptor-mediated inhibition of necrosis and apoptosis and by improving vascular integrity. Harnessing the mechanisms of cytoprotection with sphinganine-1-phosphate activation may lead to new therapies for perioperative hepatic I/R injury and subsequent remote organ injury.

  5. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... toxic substances from your blood. These toxins build up and can travel through your body until they reach your brain, causing mental and physical symptoms of HE. Hepatic Encephalopathy often starts slowly, and at first you may not be ...

  6. Alcoholic Hepatitis

    Science.gov (United States)

    ... stop drinking alcohol. People who continue to drink alcohol face a high risk of serious liver damage and death. Symptoms The ... amount of alcohol you consume. The amount of alcohol intake that puts a person at risk of alcoholic hepatitis isn't known. But most ...

  7. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Triggers or Can Cause HE to Get Worse? How is HE Diagnosed? Prior to Treatment Who treats HE? Preparing for your Medical ... mild to severe and symptoms vary depending on how bad your liver disease is. It’s important for you and your family to become familiar with the signs of Hepatic Encephalopathy ...

  8. Hepatitis C

    Science.gov (United States)

    ... liver diseases like hepatitis C. An occasional alcoholic drink may be okay, but check with your doctor first.What are the side ... family doctor to find out if this information applies to you and to get more information on ... Urticaria Check Your Symptoms Find out what else could be ...

  9. Chronic hepatitis

    African Journals Online (AJOL)

    Lemon SM, Brown CO, Brookes OS, et al. Specific IgM response to hepatitis A virus determined by solid-phase radioimmunoassay. Infect Immun 1980 ..... benefit from review by a specialist centre interested in liver disease. It is our experience that many patients referred to the Liver Clinic of the University of Cape Town for.

  10. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Caregiver Signs and Symptoms to look for Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is ... questions about HE, one step at a time. Home About Us Ways to ... Funding for the HE123 - Diagnosis, Treatment and Support program is provided by Salix Pharmaceuticals

  11. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When your liver is damaged it can no longer remove toxic substances from your blood. ... reach your brain, causing mental and physical symptoms of HE. Hepatic ...

  12. Vescalagin from Pink Wax Apple [Syzygium samarangense (Blume) Merrill and Perry] Alleviates Hepatic Insulin Resistance and Ameliorates Glycemic Metabolism Abnormality in Rats Fed a High-Fructose Diet.

    Science.gov (United States)

    Huang, Da-Wei; Chang, Wen-Chang; Wu, James Swi-Bea; Shih, Rui-Wen; Shen, Szu-Chuan

    2016-02-10

    This study investigates the ameliorative effect of vescalagin (VES) isolated from Pink wax apple fruit on hepatic insulin resistance and abnormal carbohydrate metabolism in high-fructose diet (HFD)-induced hyperglycemic rats. The results show that in HFD rats, VES significantly reduced the values of the area under the curve for glucose in an oral glucose tolerance test and the homeostasis model assessment of insulin resistance index. VES significantly enhanced the activity of hepatic antioxidant enzymes while reducing thiobarbituric acid-reactive substances in HFD rats. Western blot assay revealed that VES reduced hepatic protein expression involved in inflammation pathways while up-regulating expression of hepatic insulin signaling-related proteins. Moreover, VES up-regulated the expression of hepatic glycogen synthase and hepatic glycolysis-related proteins while down-regulating hepatic gluconeogenesis-related proteins in HFD rats. This study suggests some therapeutic potential of VES in preventing the progression of diabetes mellitus.

  13. Enzymatically synthesized glycogen inhibits colitis through decreasing oxidative stress.

    Science.gov (United States)

    Mitani, Takakazu; Yoshioka, Yasukiyo; Furuyashiki, Takashi; Yamashita, Yoko; Shirai, Yasuhito; Ashida, Hitoshi

    2017-05-01

    Inflammatory bowel diseases are a group of chronic inflammation conditions of the gastrointestinal tract. Disruption of the mucosal immune response causes accumulation of oxidative stress, resulting in the induction of inflammatory bowel disease. In this study, we investigated the effect of enzymatically synthesized glycogen (ESG), which is produced from starch, on dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in C57BL/6 mice. Oral administration of ESG suppressed DSS- and TNBS-induced shortening of large intestine in female mice and significant decreased DSS-induced oxidative stress and TNBS-induced pro-inflammatory cytokine expression in the large intestine. ESG increase in the expression levels of heme oxygenase-1 (HO-1) and NF-E2-related factor-2 (Nrf2), a transcription factor for HO-1 expressed in the large intestine. Furthermore, ESG-induced HO-1 and Nrf2 were expressed mainly in intestinal macrophages. ESG is considered to be metabolized to resistant glycogen (RG) during digestion with α-amylase in vivo. In mouse macrophage RAW264.7 cells, RG, but not ESG decreased 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced reactive oxygen species (ROS). Knockdown of Nrf2 inhibited RG-induced HO-1 expression and negated the decrease in AAPH-induced ROS brought about by RG. RG up-regulated the protein stability of Nrf2 to decrease the formation of Nrf2-Keap1 complexes. RG-induced phosphorylation of Nrf2 at Ser40 was suppressed by ERK1/2 and JNK inhibitors. Our data indicate that ESG, digested with α-amylase to RG, suppresses DSS- and TNBS-induced colitis by increasing the expression of HO-1 in the large intestine of mice. Furthermore, we demonstrate that RG induces HO-1 expression by promoting phosphorylation of Nrf2 at Ser40 through activation of the ERK1/2 and JNK cascade in macrophages. Copyright © 2017. Published by Elsevier Inc.

  14. 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

    , C., Cadefau, J. A., Cussó, R., Qvortrup, K., Nielsen, J. N., Wojtaszewki, J. F., Wojtaszewki, J. F., Hardie, D. G., Stewart, G., Hansen, B. F., and Ploug, T. (2005) J. Biol. Chem. 280, 23165-23172). In the present study we investigate the regulation of human muscle GS activity by glycogen, exercise......, and insulin. Using immunocytochemistry we investigate the existence and relevance of GS intracellular compartmentalization during exercise and during glycogen re-synthesis. The results show that GS intrinsic activity is strongly dependent on glycogen levels and that such regulation involves associated...... dephosphorylation at sites 2+2a, 3a, and 3a + 3b. Furthermore, we report the existence of several glycogen metabolism regulatory mechanisms based on GS intracellular compartmentalization. After exhausting exercise, epinephrine-induced protein kinase A activation leads to GS site 1b phosphorylation targeting...

  15. 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.

  16. Capsular glucan and intracellular glycogen of Mycobacterium tuberculosis: biosynthesis and impact on the persistence in mice

    DEFF Research Database (Denmark)

    Sambou, Tounkang; Dinadayala, Premkumar; Stadthagen, Gustavo

    2008-01-01

    Mycobacterium tuberculosis and other pathogenic mycobacterial species produce large amounts of a glycogen-like alpha-glucan that represents the major polysaccharide of their outermost capsular layer. To determine the role of the surface-exposed glucan in the physiology and virulence...... of these bacteria, orthologues of the glg genes involved in the biosynthesis of glycogen in Escherichia coli were identified in M. tuberculosis H37Rv and inactivated by allelic replacement. Biochemical analyses of the mutants and complemented strains indicated that the synthesis of glucan and glycogen involves...... the alpha-1,4-glucosyltransferases Rv3032 and GlgA (Rv1212c), the ADP-glucose pyrophosphorylase GlgC (Rv1213) and the branching enzyme GlgB (Rv1326c). Disruption of glgC reduced by half the glucan and glycogen contents of M. tuberculosis, whereas the inactivation of glgA and Rv3032 affected the production...

  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

    To test the hypothesis that a decrease in intramuscular glycogen availability may stimulate heat shock protein expression, seven men depleted one leg of muscle glycogen the day before performing 4-5 h of exhaustive, two-legged knee extensor exercise at 40 % of leg peak power output. Subjects...... then rested for a further 3 h. Muscle biopsies were obtained from the depleted and control leg before, immediately after and 3 h into recovery from exercise. These samples were analysed for muscle glycogen, and HSP72 gene and protein expression. In addition, catheters were placed in one femoral artery...... glycogen content was 40 % lower in the depleted compared with the control leg and this difference was maintained throughout the experiment (P

  18. Glucose uptake and transport in contracting, perfused rat muscle with different pre-contraction glycogen concentrations

    DEFF Research Database (Denmark)

    Hespel, P; Richter, Erik

    1990-01-01

    1. Glucose uptake and transport, muscle glycogen, free glucose and glucose-6-phosphate concentrations were studied in perfused resting and contracting rat skeletal muscle with different pre-contraction glycogen concentrations. Rats were pre-conditioned by a combination of swimming exercise and diet...... on the preceding day. 4. Muscle membrane glucose transport, as measured by the rate of accumulation of 14C-3-O-methylglucose in the contracting muscles, was 25% lower in supercompensated than in glycogen-depleted muscles at the onset as well as at the end of the 15 min contraction period. 5. Intracellular...... as with glucose-6-phosphate (r = -0.49; P less than 0.01) concentrations. 6. It is concluded that: (a) The rate of glucose uptake in contracting skeletal muscle is dependent on the pre-contraction muscle glycogen concentration. Regulating mechanisms include limitations of membrane glucose transport as well...

  19. Glycogen Phosphorylase and Glycogen Synthase: Gene Cloning and Expression Analysis Reveal Their Role in Trehalose Metabolism in the Brown Planthopper, Nilaparvata lugens Stål (Hemiptera: Delphacidae).

    Science.gov (United States)

    Zhang, Lu; Wang, Huijuan; Chen, Jianyi; Shen, Qida; Wang, Shigui; Xu, Hongxing; Tang, Bin

    2017-01-01

    RNA interference has been used to study insects' gene function and regulation. Glycogen synthase (GS) and glycogen phosphorylase (GP) are two key enzymes in carbohydrates' conversion in insects. Glycogen content and GP and GS gene expression in several tissues and developmental stages of the Brown planthopper Nilaparvata lugens Stål (Hemiptera: Delphacidae) were analyzed in the present study, using quantitative reverse-transcription polymerase chain reaction to determine their response to double-stranded trehalases (dsTREs), trehalose-6-phosphate synthases (dsTPSs), and validamycin injection. The highest expression of both genes was detected in the wing bud, followed by leg and head tissues, and different expression patterns were shown across the developmental stages analyzed. Glycogen content significantly decreased 48 and 72 h after dsTPSs injection and 48 h after dsTREs injection. GP expression increased 48 h after dsTREs and dsTPSs injection and significantly decreased 72 h after dsTPSs, dsTRE1-1, and dsTRE1-2 injection. GS expression significantly decreased 48 h after dsTPS2 and dsTRE2 injection and 72 h after dsTRE1-1 and dsTRE1-2 injection. GP and GS expression and glycogen content significantly decreased 48 h after validamycin injection. The GP activity significantly decreased 48 h after validamycin injection, while GS activities of dsTPS1 and dsTRE2 injection groups were significantly higher than that of double-stranded GFP (dsGFP) 48 h after injection, respectively. Thus, glycogen is synthesized, released, and degraded across several insect tissues according to the need to maintain stable trehalose levels. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America.

  20. Manipulation of Muscle Glycogen Concentrations Using High and Low Carbohydrate Diets and Exercise

    Science.gov (United States)

    1987-08-01

    one week prior to his participation. At this time, any food allergies or intolerances were ident ..ied as well as individual food likes and dislikes...high in carbohydrates in the form of simple sugars (i.e., sucrose, fructose, lactose ) and complex carbohydrates (i.e., starches, dietary fiber...supercompensation of muscle glycogen because the Carbohydrate Loading Phase did not immediately follow the Glycogen Depletion Phase and in fact preceded it for

  1. The Csr System RegulatesEscherichia coliFitness by Controlling Glycogen Accumulation and Energy Levels.

    Science.gov (United States)

    Morin, Manon; Ropers, Delphine; Cinquemani, Eugenio; Portais, Jean-Charles; Enjalbert, Brice; Cocaign-Bousquet, Muriel

    2017-10-31

    In the bacterium Escherichia coli , the posttranscriptional regulatory system Csr was postulated to influence the transition from glycolysis to gluconeogenesis. Here, we explored the role of the Csr system in the glucose-acetate transition as a model of the glycolysis-to-gluconeogenesis switch. Mutations in the Csr system influence the reorganization of gene expression after glucose exhaustion and disturb the timing of acetate reconsumption after glucose exhaustion. Analysis of metabolite concentrations during the transition revealed that the Csr system has a major effect on the energy levels of the cells after glucose exhaustion. This influence was demonstrated to result directly from the effect of the Csr system on glycogen accumulation. Mutation in glycogen metabolism was also demonstrated to hinder metabolic adaptation after glucose exhaustion because of insufficient energy. This work explains how the Csr system influences E. coli fitness during the glycolysis-gluconeogenesis switch and demonstrates the role of glycogen in maintenance of the energy charge during metabolic adaptation. IMPORTANCE Glycogen is a polysaccharide and the main storage form of glucose from bacteria such as Escherichia coli to yeasts and mammals. Although its function as a sugar reserve in mammals is well documented, the role of glycogen in bacteria is not as clear. By studying the role of posttranscriptional regulation during metabolic adaptation, for the first time, we demonstrate the role of sugar reserve played by glycogen in E. coli Indeed, glycogen not only makes it possible to maintain sufficient energy during metabolic transitions but is also the key component in the capacity of cells to resume growth. Since the essential posttranscriptional regulatory system Csr is a major regulator of glycogen accumulation, this work also sheds light on the central role of posttranscriptional regulation in metabolic adaptation. Copyright © 2017 Morin et al.

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

    Science.gov (United States)

    Spear, Greg T; McKenna, Mary; Landay, Alan L; Makinde, Hadijat; Hamaker, Bruce; French, Audrey L; Lee, Byung-Hoo

    2015-01-01

    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.

  3. 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.

  4. FIH-1/c-kit signaling: a novel contributor to corneal epithelial glycogen metabolism.

    Science.gov (United States)

    Peng, Han; Katsnelson, Julia; Yang, Wending; Brown, Melissa A; Lavker, Robert M

    2013-04-17

    Corneal epithelial cells have large stores of glycogen, which serve as their primary energy source. Recently, we demonstrated that factor-inhibiting hypoxia-inducible factor 1 (FIH-1) diminished glycogen stores in vitro and in vivo, working through the Akt/Glycogen Synthase Kinase (GSK)-3β pathway. In this study we investigated the relationship between FIH-1 and c-kit as it pertains to limbal and corneal epithelial glycogen stores. Limbal and corneal epithelia from wild-type FIH-1(-/-) and Kit(W/Wv) mice were stained with periodic acid Schiff (PAS) to detect glycogen. RNA samples prepared from laser-capture microdissected populations of limbal epithelium were subjected to real-time quantitative PCR to determine c-kit ligand expression. Submerged cultures of primary human corneal epithelial keratinocytes (HCEKs) transduced with FIH-1 were treated with c-kit ligand to establish further a FIH-1/c-kit interaction via Western analysis. Akt phosphorylation was assessed by Western blotting. The limbal epithelial cells of FIH-1 null mice had an increase in glycogen levels as well as increased c-kit ligand mRNA compared with wild-type controls. Consistent with a FIH-1/c-kit association, the diminished Akt signaling observed in FIH-1-overexpressing HCEKs could be restored by the addition of c-kit ligand. Interestingly, Akt signaling and glycogen content of the corneal epithelium were significantly decreased in c-kit mutant mice. c-Kit signaling has been shown to affect glucose metabolism via the Akt/GSK-3β pathway. An inverse relationship between FIH-1 and c-kit signaling pathways accounts, in part, for differences in glycogen content between corneal and limbal epithelial cells.

  5. 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.

  6. A STUDY ON ENDOMETRIAL MORPHOLOGY AND GLYCOGEN CONTENT IN INFERTILE WOMEN

    OpenAIRE

    Swayam Prava Pradhan; Anusuya Dash; Sulata Choudhury; Debi Prasad Mishra

    2017-01-01

    BACKGROUND Infertility is a common problem in day-to-day practice. Therefore, the common uterine pathology should be excluded while investigating infertility. Endometrial biopsy plays an important role in diagnosing infertility and assessing the glycogen content of endometrium, which is essential for implantation of fertilised ovum. The aim of the study is to find out endometrial pathologies and glycogen content of endometrium as causes of infertility. MATERIALS AND METHODS ...

  7. Hepatitis B (HBV)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Hepatitis B KidsHealth / For Teens / Hepatitis B What's in ... Prevented? Print en español Hepatitis B What Is Hepatitis B? Hepatitis B is an infection of the ...

  8. Nuclear receptors and epigenetic signaling: novel regulators of glycogen metabolism in skeletal muscle.

    Science.gov (United States)

    Wang, Shu-Ching Mary; Muscat, George E O

    2013-08-01

    Glycogen is an energy storage depot for the mammalian species. This review focuses on recent developments that have identified the role of nuclear hormone receptor (NR) signaling and epigenomic control in the regulation of important genes that modulate glycogen metabolism. Specifically, new studies have revealed that the NR4A subgroup (of the NR superfamily) are strikingly sensitive to beta-adrenergic stimulation in skeletal muscle, and transgenic studies in mice have revealed the expression of these NRs affects endurance and glycogen levels in muscle. Furthermore, other studies have demonstrated that one of the NR coregulator class of enzymes that mediate chromatin remodeling, the histone methyltransferases (for example, protein arginine methyltransferase 4) regulates the expression of several genes involved in glycogen metabolism and glycogen storage diseases in skeletal muscle. Importantly, NRs and histone methyltransferases, have the potential to be pharmacologically exploited and may provide novel targets in the quest to treat disorders of glycogen storage. © 2013 International Union of Biochemistry and Molecular Biology.

  9. Skeletal muscle cellularity and glycogen distribution in the hypermuscular Compact mice

    Directory of Open Access Journals (Sweden)

    T. Kocsis

    2014-07-01

    Full Text Available Normal 0 21 false false false HU X-NONE X-NONE MicrosoftInternetExplorer4 The TGF-beta member myostatin acts as a negative regulator of skeletal muscle mass. The Compact mice were selected for high protein content and hypermuscularity, and carry a naturally occurring 12-bp deletion in the propeptide region of the myostatin precursor. We aimed to investigate the cellular characteristics and the glycogen distribution of the Compact tibialis anterior (TA muscle by quantitative histochemistry and spectrophotometry. We have found that the deficiency in myostatin resulted in significantly increased weight of the investigated hindlimb muscles compared to wild type. Although the average glycogen content of the individual fibers kept unchanged, the total amount of glycogen in the Compact TA muscle increased two-fold, which can be explained by the presence of more fibers in Compact compared to wild type muscle. Moreover, the ratio of the most glycolytic IIB fibers significantly increased in the Compact TA muscle, of which glycogen content was the highest among the fast fibers. In summary, myostatin deficiency caused elevated amount of glycogen in the TA muscle but did not increase the glycogen content of the individual fibers despite the marked glycolytic shift observed in Compact mice.

  10. Safety evaluation of an enzymatically-synthesized glycogen (ESG).

    Science.gov (United States)

    Tafazoli, Shahrzad; Wong, Andrea W; Kajiura, Hideki; Kakutani, Ryo; Furuyashiki, Takashi; Takata, Hiroki; Kuriki, Takashi

    2010-01-01

    An enzymatically-synthesized glycogen (ESG), intended for use as a food ingredient, was investigated for potential toxicity. ESG is synthesized in vitro from short-chain amylose by the co-operative action of branching enzyme and amylomaltase. In an acute toxicity study, oral administration of ESG to Sprague-Dawley rats at a dose of 2000 mg/kg body weight did not result in any signs of toxicity. ESG did not exhibit mutagenic activity in an in vitro bacterial reverse mutation assay. In a subchronic toxicity study, increased cecal weights noted in the mid- (10%) and high-dose (30%) animals are common findings in rodents fed excess amounts of carbohydrates that increase osmotic value of the cecal contents, and thus were considered a physiological rather than toxicological response. The hematological and histopathological effects observed in the high-dose groups were of no toxicological concern as they were secondary to the physiological responses resulting from the high carbohydrate levels in the test diets. The no-observed-adverse-effect level for ESG in rats was therefore established to be 30% in the diet (equivalent to approximately 18 and 21 g/kg body weight/day for male and female rats, respectively). These results support the safety of ESG as a food ingredient for human consumption. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Preclinical Development of New Therapy for Glycogen Storage Diseases

    Science.gov (United States)

    Sun, Baodong; Brooks, Elizabeth D.; Koeberl, Dwight D.

    2015-01-01

    Glycogen storage disease (GSD) consists of more than 10 discrete conditions for which the biochemical and genetic bases have been determined, and new therapies have been under development for several of these conditions. Gene therapy research has generated proof-of-concept for GSD types I (von Gierke disease) and II (Pompe disease). Key features of these gene therapy strategies include the choice of vector and regulatory cassette, and recently adeno-associated virus (AAV) vectors containing tissue-specific promoters have achieved a high degree of efficacy. Efficacy of gene therapy for Pompe disease depend upon the induction of immune tolerance to the therapeutic enzyme. Efficacy of von Gierke disease is transient, waning gradually over the months following vector administration. Small molecule therapies have been evaluated with the goal of improving standard of care therapy or ameliorating the cellular abnormalities associated with specific GSDs. The receptor-mediated uptake of the therapeutic enzyme in Pompe disease was enhanced by administration of β2 agonists. Rapamycin reduced the liver fibrosis observed in GSD III. Further development of gene therapy could provide curative therapy for patients with GSD, if efficacy from preclinical research is observed in future clinical trials and these treatments become clinically available. PMID:26122079

  12. Interleukin-10 repletion suppresses pro-inflammatory cytokines and decreases liver pathology without altering viral replication in murine cytomegalovirus (MCMV)-infected IL-10 knockout mice.

    Science.gov (United States)

    Tang-Feldman, Yajarayma J; Lochhead, G Raymond; Lochhead, Stephanie R; Yu, Cindy; Pomeroy, Claire

    2011-03-01

    To determine the role of interleukin-10 (IL-10) in protecting against the deleterious pro-inflammatory cytokine response to murine cytomegalovirus (MCMV), we studied the impact of IL-10 repletion in MCMV-infected IL-10 knockout (KO) mice. IL-10 KO mice were infected with a sub-lethal dose of MCMV and treated daily with 5 μg of mouse recombinant IL-10 (mrIL-10). Cytokine transcription, viral load, cytokine expression and liver histopathology were assessed in IL-10 treated and untreated mice. mrIL-10 repletion suppressed the exaggerated pro-inflammatory cytokine response observed in IL-10 KO mice (vs. control) both systemically and at the organ level, without affecting viral load. Levels of IFN-γ and TNF-α mRNA in livers of treated mice were ~50-70-fold lower than in untreated mice at day 5 post-infection (p ≤ 0.05). In spleens and sera, levels of IFN-γ and IL-6 were significantly lower in treated mice than in untreated mice at day 5-7 post-infection (p ≤ 0.05). IL-10 blunting of cytokine responses was accompanied by attenuation of inflammation in livers of treated mice. Repletion of IL-10 modulates the exaggerated pro-inflammatory cytokine responses that characterize IL-10 KO mice and protects against liver damage without altering viral load. IL-10 may be useful to control dysregulated pro-inflammatory cytokines responses during CMV infection.

  13. Downregulation of pathways implicated in liver inflammation and tumorigenesis of glycogen storage disease type Ia mice receiving gene therapy.

    Science.gov (United States)

    Kim, Goo-Young; Kwon, Joon Hyun; Cho, Jun-Ho; Zhang, Lisa; Mansfield, Brian C; Chou, Janice Y

    2017-05-15

    Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated. AMPK/sirtuin-1 inhibit the activity of STAT3 (signal transducer and activator of transcription 3) and NFκB (nuclear factor κB), the pro-inflammatory and cancer-promoting transcription factors. Sirtuin-1 also inhibits cancer metastasis via increasing the expression of E-cadherin, a tumor suppressor, and decreasing the expression of mesenchymal markers. Consistently, in AAV-NT mice, hepatic levels of active STAT3 and NFκB-p65 were reduced as were expression of mesenchymal markers, STAT3 targets, NFκB targets and β-catenin targets, all of which were consistent with the promotion of tumorigenesis. AAV-NT mice also expressed increased levels of E-cadherin and fibroblast growth factor 21 (FGF21), targets of sirtuin-1, and β-klotho, which can acts as a tumor suppressor. Importantly, treating AAV-NT mice with a sirtuin-1 inhibitor markedly reversed many of the observed anti-inflammatory/anti-tumorigenic signaling pathways. In summary, activation of hepatic AMPK/sirtuin-1 and FGF21/β-klotho signaling pathways combined with down-regulation of STAT3/NFκB-mediated inflammatory and tumorigenic signaling pathways can explain the absence of hepatic tumors in AAV-NT mice. Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.

  14. AUTOIMMUNE HEPATITIS

    Directory of Open Access Journals (Sweden)

    Yusri Dianne Jurnalis

    2010-05-01

    Full Text Available AbstrakHepatitis autoimun merupakan penyakit inflamasi hati yang berat dengan penyebab pasti yang tidak diketahui yang mengakibatkan morbiditas dan mortalitas yang tinggi. Semua usia dan jenis kelamin dapat dikenai dengan insiden tertinggi pada anak perempuan usia prepubertas, meskipun dapat didiagnosis pada usia 6 bulan. Hepatitis autoimun dapat diklasifikasikan menjadi 2 bagian berdasarkan adanya antibodi spesifik: Smooth Muscle Antibody (SMA dengan anti-actin specificity dan/atau Anti Nuclear Antibody (ANA pada tipe 1 dan Liver-Kidney Microsome antibody (LKM1 dan/atau anti-liver cytosol pada tipe 2. Gambaran histologisnya berupa “interface hepatitis”, dengan infiltrasi sel mononuklear pada saluran portal, berbagai tingkat nekrosis, dan fibrosis yang progresf. Penyakit berjalan secara kronik tetapi keadaan yang berat biasanya menjadi sirosis dan gagal hati.Tipe onset yang paling sering sama dengan hepatitis virus akut dengan gagal hati akut pada beberapa pasien; sekitar sepertiga pasien dengan onset tersembunyi dengan kelemahan dan ikterik progresif ketika 10-15% asimptomatik dan mendadak ditemukan hepatomegali dan/atau peningkatan kadar aminotransferase serum. Adanya predominasi perempuan pada kedua tipe. Pasien LKM1 positif menunjukkan keadaan lebih akut, pada usia yang lebih muda, dan biasanya dengan defisiensi Immunoglobulin A (IgA, dengan durasi gejala sebelum diagnosis, tanda klinis, riwayat penyakit autoimun pada keluarga, adanya kaitan dengan gangguan autoimun, respon pengobatan dan prognosis jangka panjang sama pada kedua tipe.Kortikosteroid yang digunakan secara tunggal atau kombinasi azathioprine merupakan terapi pilihan yang dapat menimbulkan remisi pada lebih dari 90% kasus. Strategi terapi alternatif adalah cyclosporine. Penurunan imunosupresi dikaitkan dengan tingginya relap. Transplantasi hati dianjurkan pada penyakit hati dekom-pensata yang tidak respon dengan pengobatan medis lainnya.Kata kunci : hepatitis Autoimmune

  15. Hepatitis B virus (image)

    Science.gov (United States)

    Hepatitis B is also known as serum hepatitis and is spread through blood and sexual contact. It is ... population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Image courtesy of the Centers for ...

  16. Hepatic (Liver) Function Panel

    Science.gov (United States)

    ... for Educators Search English Español Blood Test: Hepatic (Liver) Function Panel KidsHealth / For Parents / Blood Test: Hepatic ( ... or kidneys ) is working. What Is a Hepatic (Liver) Function Panel? A liver function panel is a ...

  17. Hepatitis Risk Assessment

    Science.gov (United States)

    ... visit this page: About CDC.gov . Hepatitis Risk Assessment Recommend on Facebook Tweet Share Compartir Viral Hepatitis. ... at risk? Take this 5 minute Hepatitis Risk Assessment developed by the CDC and get a personalized ...

  18. Preventing hepatitis A

    Science.gov (United States)

    Hepatitis A is inflammation (irritation and swelling) of the liver caused by the hepatitis A virus. You can take several steps to ... reduce your risk of spreading or catching the hepatitis A virus: Always wash your hands thoroughly after ...

  19. Identification of differentially expressed genes in chickens differing in muscle glycogen content and meat quality

    Directory of Open Access Journals (Sweden)

    Marthey Sylvain

    2011-02-01

    Full Text Available Abstract Background The processing ability of poultry meat is highly related to its ultimate pH, the latter being mainly determined by the amount of glycogen in the muscle at death. The genetic determinism of glycogen and related meat quality traits has been established in the chicken but the molecular mechanisms involved in variations in these traits remain to be fully described. In this study, Chicken Genome Arrays (20 K were used to compare muscle gene expression profiles of chickens from Fat (F and Lean (L lines that exhibited high and low muscle glycogen content, respectively, and of individuals exhibiting extremely high (G+ or low (G- muscle glycogen content originating from the F2 cross between the Fat and Lean lines. Real-time RT-PCR was subsequently performed to validate the differential expression of genes either selected from the microarray analysis or whose function in regulating glycogen metabolism was well known. Results Among the genes found to be expressed in chicken P. major muscle, 197 and 254 transcripts appeared to be differentially expressed on microarrays for the F vs. L and the G+ vs. G- comparisons, respectively. Some involved particularly in lipid and carbohydrate metabolism were selected for further validation studies by real-time RT-PCR. We confirmed that, as in mammals, the down-regulation of CEBPB and RGS2 coincides with a decrease in peripheral adiposity in the chicken, but these genes are also suggested to affect muscle glycogen turnover through their role in the cAMP-dependent signalling pathway. Several other genes were suggested to have roles in the regulation of glycogen storage in chicken muscle. PDK4 may act as a glycogen sensor in muscle, UGDH may compete for glycogen synthesis by using UDP-glucose for glucoronidation, and PRKAB1, PRKAG2, and PHKD may impact on glycogen turnover in muscle, through AMP-activated signalling pathways. Conclusions This study is the first stage in the understanding of molecular

  20. Hepatitis in Children

    OpenAIRE

    Tsuji, Yoshiro; Doi, Hiroshi; Yoshida, Yasuharu; Tohya, Yoshikazu; Yanagi, Tadamichi

    1986-01-01

    115 patients (71 male and 44 female) with infectious hepatitis were hospitalized in Nagasaki University Hospital during 1974-1984. They were all the hospitalized patients in our pediatric department. The total patient was 8150 and that of hepatitis was 115, that is 1.4%. On the classification of hepatitis, infectious mononucleosis patients were the most. Next was HB hepatitis. HA hepatitis were less than we had expected. Generally in Japan, childrens HA hepatitis patients are less usual than ...

  1. Hepatitis A: Questions and Answers

    Science.gov (United States)

    Hepatitis A: Questions and Answers Information about the disease and vaccines What causes hepatitis A? Hepatitis A is an infectious liver disease caused by hepatitis A virus (HAV). How does hepatitis A virus ...

  2. H2 production pathways in nutrient-replete mixotrophic Chlamydomonas cultures under low light. Response to the commentary article "On the pathways feeding the H2 production process in nutrient-replete, hypoxic conditions," by Alberto Scoma and Szilvia Z. Tóth.

    Science.gov (United States)

    González-Ballester, David; Jurado-Oller, Jose Luis; Galván, Aurora; Fernández, Emilio; Dubini, Alexandra

    2017-01-01

    A recent Commentary article entitled "On the pathways feeding the H2 production process in nutrient-replete, hypoxic conditions" by Dr. Scoma and Dr. Tóth, Biotechnology for Biofuels (2017), opened a very interesting debate about the H2 production photosynthetic-linked pathways occurring in Chlamydomonas cultures grown in acetate-containing media and incubated under hypoxia/anoxia conditions. This Commentary article mainly focused on the results of our previous article "Low oxygen levels contribute to improve photohydrogen production in mixotrophic non-stressed Chlamydomonas cultures," by Jurado-Oller et al., Biotechnology for Biofuels (7, 2015; 8:149). Here, we review some previous knowledge about the H2 production pathways linked to photosynthesis in Chlamydomonas, especially focusing on the role of the PSII-dependent and -independent pathways in acetate-containing nutrient-replete cultures. The potential contributions of these pathways to H2 production under anoxia/hypoxia are discussed. Despite the fact that the PSII inhibitor DCMU is broadly used to discern between the two different photosynthetic pathways operating under H2 production conditions, its use may lead to distinctive conclusions depending on the growth conditions. The different potential sources of reductive power needed for the PSII-independent H2 production in mixotrophic nutrient-replete cultures are a matter of debate and conclusive evidences are still missing.

  3. 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

    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

  4. Distinct effects of subcellular glycogen localization on tetanic relaxation time and endurance in mechanically skinned rat skeletal muscle fibres

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Schrøder, H D; Rix, C G

    2009-01-01

    In vitro experiments indicate a non-metabolic role of muscle glycogen in contracting skeletal muscles. Since the sequence of events in excitation\\#8211;contraction (E\\#8211;C) coupling is known to be located close to glycogen granules, at specific sites on the fibre, we hypothesized...... that the distinct compartments of glycogen have specific effects on muscle fibre contractility and fatigability. Single skeletal muscle fibres (n = 19) from fed and fasted rats were mechanically skinned and divided into two segments. In one segment glycogen localization and volume fraction were estimated......, range 22-252 contractions). Initially the total myofibrillar glycogen volume percentage was 0.46 +/- 0.07%, with 72 +/- 3% in the intermyofibrillar space and 28 +/- 3% in the intramyofibrillar space. The intramyofibrillar glycogen content was positively correlated with the fatigue resistance capacity (r...

  5. 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

    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...... and UCP3 mRNA in response to exercise was also significantly higher in the low glycogen (11.4- and 3.5-fold, respectively) than in the control (5.0- and 1.7-fold, respectively) trial. These data indicate that low muscle glycogen content enhances the transcriptional activation of some metabolic genes...... 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...

  6. Hepatitis B Vaccine

    Science.gov (United States)

    ... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

  7. Hepatic energy metabolism in human diabetes mellitus, obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Koliaki, Chrysi; Roden, Michael

    2013-10-15

    Alterations of hepatic mitochondrial function have been observed in states of insulin resistance and non-alcoholic fatty liver disease (NAFLD). Patients with overt type 2 diabetes mellitus (T2DM) can exhibit reduction in hepatic adenosine triphosphate (ATP) synthesis and impaired repletion of their hepatic ATP stores upon ATP depletion by fructose. Obesity and NAFLD may also associate with impaired ATP recovery after ATP-depleting challenges and augmented oxidative stress in the liver. On the other hand, patients with obesity or NAFLD can present with upregulated hepatic anaplerotic and oxidative fluxes, including β-oxidation and tricarboxylic cycle activity. The present review focuses on the methods and data on hepatic energy metabolism in various states of human insulin resistance. We propose that the liver can adapt to increased lipid exposition by greater lipid storing and oxidative capacity, resulting in increased oxidative stress, which in turn could deteriorate hepatic mitochondrial function in chronic insulin resistance and NAFLD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. 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.

  9. Dietary carbohydrate, muscle glycogen content, and endurance performance in well-trained women.

    Science.gov (United States)

    Walker, J L; Heigenhauser, G J; Hultman, E; Spriet, L L

    2000-06-01

    This study examined the ability of well-trained eumenorrheic women to increase muscle glycogen content and endurance performance in response to a high-carbohydrate diet (HCD; approximately 78% carbohydrate) compared with a moderate-carbohydrate diet (MD; approximately 48% carbohydrate) when tested during the luteal phase of the menstrual cycle. Six women cycled to exhaustion at approximately 80% maximal oxygen uptake (VO(2 max)) after each of the randomly assigned diet and exercise-tapering regimens. A biopsy was taken from the vastus lateralis before and after exercise in each trial. Preexercise muscle glycogen content was high after the MD (625.2 +/- 50.1 mmol/kg dry muscle) and 13% greater after the HCD (709.0 +/- 44.8 mmol/kg dry muscle). Postexercise muscle glycogen was low after both trials (MD, 91.4 +/- 34.5; HCD, 80.3 +/- 19.5 mmol/kg dry muscle), and net glycogen utilization during exercise was greater after the HCD. The subjects also cycled longer at approximately 80% VO(2 max) after the HCD vs. MD (115:31 +/- 10:47 vs. 106:35 +/- 8:36 min:s, respectively). In conclusion, aerobically trained women increased muscle glycogen content in response to a high-dietary carbohydrate intake during the luteal phase of the menstrual cycle, but the magnitude was smaller than previously observed in men. The increase in muscle glycogen, and possibly liver glycogen, after the HCD was associated with increased cycling performance to volitional exhaustion at approximately 80% VO(2 max).

  10. Essential role of Toll-like receptor 2 in macrophage activation by glycogen.

    Science.gov (United States)

    Kakutani, Ryo; Adachi, Yoshiyuki; Takata, Hiroki; Kuriki, Takashi; Ohno, Naohito

    2012-01-01

    We prepared enzymatically synthesized glycogen (ESG) with the same characteristics as natural glycogen and investigated whether the macrophage-stimulating activity of glycogen was related to Toll-like receptors (TLRs), which are important receptors for innate immunity. ESG induced no nuclear factor-kappa B (NF-κB) activity in TLR4/MD-2/CD14-expressed human embryonic kidney 293 (HEK293) reporter cells, whereas this polysaccharide did activate peritoneal exude cells (PECs) derived from TLR4-deficient mice at the same level as those from wild-type (WT) mice. Similarly, ESG did not activate HEK293 cells expressing TLR3, 5, 7, 8 or 9, suggesting that these TLRs were irrelevant to the activity of ESG. In contrast, ESG enhanced the NF-κB activity of TLR2-expressed HEK293 reporter cells in a concentration-dependent manner. Furthermore, the cell-stimulating activity of ESG was remarkably lower for PECs from TLR2-deficient mice compared with those from WT mice. The activity of ESG completely disappeared after treatment with a glycogen-degrading enzyme, indicating that the activity derived from ESG itself and not from contamination with canonical TLR2 ligands such as bacterial lipopeptides. Moreover, it was clarified by ELISA that ESG was directly bound to TLR2. Taken together, these results demonstrated that TLR2 directly recognizes glycogen and that the recognition activates immunocytes such as macrophages to enhance the production of nitric oxide and inflammatory cytokines. In addition, it was suggested that TLR2 could be involved in the glycogen activity in vivo. We propose that glycogen act as an activator to potentiate the host defense through TLR2 on the macrophage.

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

    Science.gov (United States)

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

    2017-05-01

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

  12. Bladder epithelial oxygen tension--a new means of monitoring regional perfusion? Preliminary study in a model of exsanguination/fluid repletion.

    Science.gov (United States)

    Singer, M; Millar, C; Stidwill, R; Unwin, R

    1996-04-01

    To assess whether monitoring of bladder epithelial oxygen tension (BEOT) would provide an indication of regional (renal) organ perfusion in an exsanguination/fluid repletion animal model. Prospective non-randomized laboratory study. Research laboratory. Eight anaesthetised, spontaneously breathing Sprague-Dawley male rats weighing approximately 200 g were instrumented. They received 1-ml aliquots of fluid until no further haemodynamic improvement was seen, followed by removal of 1-ml aliquots of blood until renal blood flow fell by 50%. The animal was then resuscitated with repeated 1 to 2-ml aliquots of fluid until no further improvement was achieved and, finally, progressively exsanguinated to cardiovascular collapse. A continuous Clark-type oxygen electrode lying in contact with the inside wall of the bladder measured changes in BEOT during these exsanguination and fluid repletion manoeuvres. Changes in BEOT closely mirrored both systemic (blood pressure and aortic blood flow) and regional (renal blood flow) haemodynamic changes. A direct correlation existed between percentage change in BEOT and base deficit, and an indirect correlation was seen with arterial oxygen tension. Measurement of BEOT may be a useful and relatively non-invasive means of monitoring regional organ perfusion. Further studies are warranted.

  13. Impaired glycogen synthesis causes metabolic overflow reactions and affects stress responses in the cyanobacterium Synechocystis sp. PCC 6803.

    Science.gov (United States)

    Gründel, Marianne; Scheunemann, Ramon; Lockau, Wolfgang; Zilliges, Yvonne

    2012-12-01

    The biosynthesis of glycogen or starch is one of the main strategies developed by living organisms for the intracellular storage of carbon and energy. In phototrophic organisms, such polyglucans accumulate due to carbon fixation during photosynthesis and are used to provide maintenance energy for cell integrity, function and viability in dark periods. Moreover, it is assumed that glycogen enables cyanobacteria to cope with transient starvation conditions, as observed in most micro-organisms. Here, glycogen accumulates when an appropriate carbon source is available in sufficient amounts but growth is inhibited by lack of other nutrients. In this study, the role of glycogen in energy and carbon metabolism of phototrophic cyanobacteria was first analysed via a comparative physiological and metabolic characterization of knockout mutants defective in glycogen synthesis. We first proved the role of glycogen as a respiratory substrate in periods of darkness, the role of glycogen as a reserve to survive starvation periods such as nitrogen depletion and the role of glycogen synthesis as an ameliorator of carbon excess conditions in the model organism Synechocystis sp. PCC 6803. We provide striking new insights into the complex carbon and nitrogen metabolism of non-diazotrophic cyanobacteria: a phenotype of sensitivity to photomixotrophic conditions and of reduced glucose uptake, a non-bleaching phenotype based on an impaired acclimation response to nitrogen depletion and furthermore a phenotype of energy spilling. This study shows that the analysis of deficiencies in glycogen metabolism is a valuable tool for the identification of metabolic regulatory principles and signals.

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

    Science.gov (United States)

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

    2016-02-01

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

  15. Hepatic glucose metabolism in late pregnancy: normal versus high-fat and -fructose diet.

    Science.gov (United States)

    Coate, Katie C; Smith, Marta S; Shiota, Masakazu; Irimia, Jose M; Roach, Peter J; Farmer, Ben; Williams, Phillip E; Moore, Mary Courtney

    2013-03-01

    Net hepatic glucose uptake (NHGU) is an important contributor to postprandial glycemic control. We hypothesized that NHGU is reduced during normal pregnancy and in a pregnant diet-induced model of impaired glucose intolerance/gestational diabetes mellitus (IGT/GDM). Dogs (n = 7 per group) that were nonpregnant (N), normal pregnant (P), or pregnant with IGT/GDM (pregnant dogs fed a high-fat and -fructose diet [P-HFF]) underwent a hyperinsulinemic-hyperglycemic clamp with intraportal glucose infusion. Clamp period insulin, glucagon, and glucose concentrations and hepatic glucose loads did not differ among groups. The N dogs reached near-maximal NHGU rates within 30 min; mean ± SEM NHGU was 105 ± 9 µmol·100 g liver⁻¹·min⁻¹. The P and P-HFF dogs reached maximal NHGU in 90-120 min; their NHGU was blunted (68 ± 9 and 16 ± 17 µmol·100 g liver⁻¹·min⁻¹, respectively). Hepatic glycogen synthesis was reduced 20% in P versus N and 40% in P-HFF versus P dogs. This was associated with a reduction (>70%) in glycogen synthase activity in P-HFF versus P and increased glycogen phosphorylase (GP) activity in both P (1.7-fold greater than N) and P-HFF (1.8-fold greater than P) dogs. Thus, NHGU under conditions mimicking the postprandial state is delayed and suppressed in normal pregnancy, with concomitant reduction in glycogen storage. NHGU is further blunted in IGT/GDM. This likely contributes to postprandial hyperglycemia during pregnancy, with potential adverse outcomes for the fetus and mother.

  16. The molecular basis of glycogen breakdown and transport in Streptococcus pneumoniae.

    Science.gov (United States)

    Abbott, D Wade; Higgins, Melanie A; Hyrnuik, Susanne; Pluvinage, Benjamin; Lammerts van Bueren, Alicia; Boraston, Alisdair B

    2010-07-01

    The genome of Streptococcus pneumoniae strains, as typified by the TIGR4 strain, contain several genes encoding proteins putatively involved in alpha-glucan degradation, modification and synthesis. The extracellular components comprise an ATP binding cassette-transporter with its solute binding protein, MalX, and the hydrolytic enzyme SpuA. We show that of the commonly occurring exogenous alpha-glucans, S. pneumoniae TIGR4 is only able to grow on glycogen in a MalX- and SpuA-dependent manner. SpuA is able to degrade glycogen into a ladder of alpha-1,4-glucooligosaccharides while the high-affinity interaction (K(a) approximately 10(6) M(-1)) of MalX with maltooligosaccharides plays a key role in promoting the selective uptake of the glycogen degradation products that are produced by SpuA. The X-ray crystallographic analyses of apo- and complexed MalX illuminate the protein's specificity for the degradation products of glycogen and its striking ability to recognize the helical structure of the ligand. Overall, the results of this work provide new structural and functional insight into streptococcal alpha-glucan metabolism while supplying biochemical support for the hypothesis that the substrate of the S. pneumoniaealpha-glucan metabolizing machinery is glycogen, which in a human host is abundant in lung epithelial cells, a common target for invasive S. pneumoniae.

  17. Fed-batch cultivation of baker's yeast followed by nitrogen or carbon starvation: effects on fermentative capacity and content of trehalose and glycogen

    DEFF Research Database (Denmark)

    Jørgensen, Henning; Olsson, Lisbeth; Rønnow, B.

    2002-01-01

    , trehalose and glycogen. Nitrogen starvation triggered the accumulation of trehalose and glycogen. After 8 h of starvation, the content of trehalose and glycogen was increased 4-fold and 2-fold, respectively. Carbon starvation resulted in a partial conversion of glycogen into trehalose. The trehalose content...... increased from 45 to 64 mg (g dry-weight)(-1), whereas the glycogen content in the same period was reduced from 55 to 5 mg (g dry-weight)(-1). Glycogen was consumed faster than trehalose during storage of the starved yeast for 1 month. Nitrogen starvation resulted in a decrease in the protein content...

  18. Tissue-specific analysis of glycogen synthase kinase-3α (GSK-3α in glucose metabolism: effect of strain variation.

    Directory of Open Access Journals (Sweden)

    Satish Patel

    Full Text Available BACKGROUND: Over-activity and elevated expression of glycogen synthase kinase-3 (GSK-3 has been implicated in the etiology of insulin resistance and Type 2 diabetes. Administration of specific GSK-3 inhibitors to diabetic or obese rodent models improves glycaemic control and insulin sensitivity. However, due to the indiscriminatory nature of these inhibitors, the relative contribution of the two isoforms of GSK-3 (GSK-3α and GSK-3β is not known. Recently, we demonstrated that an out-bred strain of mice (ICR lacking expression of GSK-3α in all tissues displayed improved insulin sensitivity and enhanced hepatic glucose metabolism. We also found that muscle (but not liver inactivation of GSK-3β conferred insulin and glucose sensitization in an in-bred strain of mice (C57BL/6. METHODOLOGY/PRINCIPAL FINDINGS: Here, we have employed tissue-specific deletion of GSK-3α, to examine the relative contribution of two insulin-sensitive tissues, muscle and liver, towards the insulin sensitization phenotype originally observed in the global GSK-3α KO animals. We found that mice in which GSK-3α has been inactivated in either skeletal-muscle or liver displayed no differences in glucose tolerance or insulin sensitivity compared to wild type littermates. Given the strain differences in our original analyses, we examined the insulin and glucose sensitivity of global GSK-3α KO animals bred onto a C57BL/6 background. These animals also revealed no significant differences in glucose metabolism/insulin sensitivity compared to their wild type littermates. Furthermore, deletion of hepatic GSK-3α on the out-bred, ICR background failed to reproduce the insulin sensitivity manifested by the global deletion of this isoform. CONCLUSIONS/SIGNIFICANCE: From these data we conclude that the improved insulin sensitivity and hepatic glucose homeostasis phenotype observed upon global inactivation of GSK-3α is strain-specific. We surmise that the insulin

  19. What Is Hepatitis?

    Science.gov (United States)

    ... сский Español What is hepatitis? Online Q&A Reviewed July 2016 Q: What ... Question and answer archives Submit a question World Hepatitis Day Posters: Eliminate hepatitis World Hepatitis Day 2017 ...

  20. Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis.

    Science.gov (United States)

    Mir-Coll, Joan; Duran, Jordi; Slebe, Felipe; García-Rocha, Mar; Gomis, Ramon; Gasa, Rosa; Guinovart, Joan J

    2016-05-01

    Glycogen accumulation occurs in beta cells of diabetic patients and has been proposed to partly mediate glucotoxicity-induced beta cell dysfunction. However, the role of glycogen metabolism in beta cell function and its contribution to diabetes pathophysiology remain poorly understood. We investigated the function of beta cell glycogen by studying glucose homeostasis in mice with (1) defective glycogen synthesis in the pancreas; and (2) excessive glycogen accumulation in beta cells. Conditional deletion of the Gys1 gene and overexpression of protein targeting to glycogen (PTG) was accomplished by Cre-lox recombination using pancreas-specific Cre lines. Glucose homeostasis was assessed by determining fasting glycaemia, insulinaemia and glucose tolerance. Beta cell mass was determined by morphometry. Glycogen was detected histologically by periodic acid-Schiff's reagent staining. Isolated islets were used for the determination of glycogen and insulin content, insulin secretion, immunoblots and gene expression assays. Gys1 knockout (Gys1 (KO)) mice did not exhibit differences in glucose tolerance or basal glycaemia and insulinaemia relative to controls. Insulin secretion and gene expression in isolated islets was also indistinguishable between Gys1 (KO) and controls. Conversely, despite effective glycogen overaccumulation in islets, mice with PTG overexpression (PTG(OE)) presented similar glucose tolerance to controls. However, under fasting conditions they exhibited lower glycaemia and higher insulinaemia. Importantly, neither young nor aged PTG(OE) mice showed differences in beta cell mass relative to age-matched controls. Finally, a high-fat diet did not reveal a beta cell-autonomous phenotype in either model. Glycogen metabolism is not required for the maintenance of beta cell function. Glycogen accumulation in beta cells alone is not sufficient to trigger the dysfunction or loss of these cells, or progression to diabetes.

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

    Directory of Open Access Journals (Sweden)

    Joachim Nielsen

    Full Text Available 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 synthesis, as described by the product of glycogen particle size and number, is dependent on the time course of recovery after exercise and carbohydrate availability. In the present study, we investigated the subcellular distribution of glycogen in fibers with high (type I and low (type II mitochondrial content during post-exercise recovery from eccentric contractions. Analysis was completed on five male subjects performing an exercise bout consisting of 15 x 10 maximal eccentric contractions. Carbohydrate-rich drinks were subsequently ingested throughout a 48 h recovery period and muscle biopsies for analysis included time points 3, 24 and 48 h post exercise from the exercising leg, whereas biopsies corresponding to prior to and at 48 h after the exercise bout were collected from the non-exercising, control leg. Quantitative imaging by transmission electron microscopy revealed an early (post 3 and 24 h enhanced storage of intramyofibrillar glycogen (defined as glycogen particles located within the myofibrils of type I fibers, which was associated with an increase in the number of particles. In contrast, late in recovery (post 48 h, intermyofibrillar, intramyofibrillar and subsarcolemmal glycogen in both type I and II fibers were lower in the exercise leg compared with the control leg, and this was associated with a smaller size of the glycogen particles. We conclude that in the carbohydrate-supplemented state, the effect of eccentric contractions on glycogen metabolism depends on the subcellular localization, muscle fiber's oxidative capacity, and the time course of recovery. The early enhanced storage of intramyofibrillar glycogen after the eccentric

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

    Science.gov (United States)

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

    2014-01-01

    Epilepsy is a family of brain disorders with a largely unknown etiology and high percentage of pharmacoresistance. The clinical manifestations of epilepsy are seizures, which originate from aberrant neuronal synchronization and hyperexcitability. Reactive astrocytosis, a hallmark of the epileptic tissue, develops into loss-of-function of glutamine synthetase, impairment of glutamate-glutamine cycle and increase in extracellular and astrocytic glutamate concentration. Here, we argue that chronically elevated intracellular glutamate level in astrocytes is instrumental to alterations in the metabolism of glycogen and leads to the synthesis of polyglucosans. Unaccessibility of glycogen-degrading enzymes to these insoluble molecules compromises the glycogenolysis-dependent reuptake of extracellular K+ by astrocytes, thereby leading to increased extracellular K+ and associated membrane depolarization. Based on current knowledge, we propose that the deterioration in structural homogeneity of glycogen particles is relevant to disruption of brain K+ homeostasis and increased susceptibility to seizures in epilepsy. PMID:24643875

  3. Impaired expression of glycogen synthase mRNA in skeletal muscle of NIDDM patients

    DEFF Research Database (Denmark)

    Vestergaard, H; Bjørbaek, C; Andersen, P H

    1991-01-01

    Based on recent studies of the abnormal physiology and biochemistry of the glycogen synthesis in skeletal muscle of non-insulin-dependent diabetes mellitus (NIDDM) patients and their first-degree relatives, the key enzyme of this pathway, glycogen synthase (GS), is considered a candidate gene...... in the pathogenesis of insulin resistance. Comparing matched groups of 14 NIDDM patients with 14 control subjects, we found that impaired insulin-stimulated nonoxidative glucose metabolism of peripheral tissue (P less than 0.02) and reduced total GS activity (P less than 0.05) of vastus lateralis muscle from patients...... analysis of the entire coding sequence of the GS gene, we were unable to detect any genetic variants in a subset of eight NIDDM patients. We conclude that abnormal pretranslational regulation of the GS gene may contribute to impaired glycogen synthesis of muscle in NIDDM. Our studies give no evidence...

  4. 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...... were obtained from the lateral head of the gastrocnemius muscle before, immediately after, and 1, 2, and 7 days after the marathon, as were venous blood samples. Muscle GLUT-4 content was unaltered over the experimental period. Muscle glycogen concentration was 758 +/- 53 mmol/kg dry weight before......-race levels 7 days after the race. We conclude that the total GLUT-4 protein content is unaltered in the lateral gastrocnemius after a competitive marathon and that the slow recovery of muscle glycogen after the race apparently involves factors other than changes in the total content of this protein....

  5. Hepatitis B in pregnancy.

    OpenAIRE

    Arevalo, J A

    1989-01-01

    Chronic infection with the hepatitis B virus can result in the development of serious liver disease such as chronic active hepatitis, cirrhosis, and hepatocellular carcinoma. Vertical transmission from infected mothers to infants is thought to be partially responsible for the high prevalence of infection in certain high-risk groups. Immunoprophylaxis using hepatitis B vaccine and hepatitis immune globulin has been highly effective in decreasing the probability of chronic hepatitis B virus inf...

  6. Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation.

    Science.gov (United States)

    Holmes, Andrew P; Turner, Philip J; Carter, Paul; Leadbeater, Wendy; Ray, Clare J; Hauton, David; Buckler, Keith J; Kumar, Prem

    2014-10-15

    The view that the carotid body (CB) type I cells are direct physiological sensors of hypoglycaemia is challenged by the finding that the basal sensory neuronal outflow from the whole organ is unchanged in response to low glucose. The reason for this difference in viewpoint and how the whole CB maintains its metabolic integrity when exposed to low glucose is unknown. Here we show that, in the intact superfused rat CB, basal sensory neuronal activity was sustained during glucose deprivation for 29.1 ± 1.2 min, before irreversible failure following a brief period of excitation. Graded increases in the basal discharge induced by reducing the superfusate PO2 led to proportional decreases in the time to the pre-failure excitation during glucose deprivation which was dependent on a complete run-down in glycolysis and a fall in cellular energy status. A similar ability to withstand prolonged glucose deprivation was observed in isolated type I cells. Electron micrographs and immunofluorescence staining of rat CB sections revealed the presence of glycogen granules and the glycogen conversion enzymes glycogen synthase I and glycogen phosphorylase BB, dispersed throughout the type I cell cytoplasm. Furthermore, pharmacological attenuation of glycogenolysis and functional depletion of glycogen both significantly reduced the time to glycolytic run-down by ∼33 and 65%, respectively. These findings suggest that type I cell glycogen metabolism allows for the continuation of glycolysis and the maintenance of CB sensory neuronal output in periods of restricted glucose delivery and this may act as a key protective mechanism for the organ during hypoglycaemia. The ability, or otherwise, to preserve energetic status may thus account for variation in the reported capacity of the CB to sense physiological glucose concentrations and may even underlie its function during pathological states associated with augmented CB discharge. © 2014 The Authors. The Journal of Physiology © 2014

  7. Preexercise medium-chain triglyceride ingestion does not alter muscle glycogen use during exercise.

    Science.gov (United States)

    Horowitz, J F; Mora-Rodriguez, R; Byerley, L O; Coyle, E F

    2000-01-01

    This investigation determined whether ingestion of a tolerable amount of medium-chain triglycerides (MCT; approximately 25 g) reduces the rate of muscle glycogen use during high-intensity exercise. On two occasions, seven well-trained men cycled for 30 min at 84% maximal O(2) uptake. Exactly 1 h before exercise, they ingested either 1) carbohydrate (CHO; 0.72 g sucrose/kg) or 2) MCT+CHO [0.36 g tricaprin (C10:0)/kg plus 0.72 g sucrose/kg]. The change in glycogen concentration was measured in biopsies taken from the vastus lateralis before and after exercise. Additionally, glycogen oxidation was calculated as the difference between total carbohydrate oxidation and the rate of glucose disappearance from plasma (R(d) glucose), as measured by stable isotope dilution techniques. The change in muscle glycogen concentration was not different during MCT+CHO and CHO (42.0 +/- 4.6 vs. 38.8 +/- 4.0 micromol glucosyl units/g wet wt). Furthermore, calculated glycogen oxidation was also similar (331 +/- 18 vs. 329 +/- 15 micromol. kg(-1). min(-1)). The coingestion of MCT+CHO did increase (P < 0.05) R(d) glucose at rest compared with CHO (26.9 +/- 1.5 vs. 20.7 +/- 0. 7 micromol.kg(-1). min(-1)), yet during exercise R(d) glucose was not different during the two trials. Therefore, the addition of a small amount of MCT to a preexercise CHO meal did not reduce muscle glycogen oxidation during high-intensity exercise, but it did increase glucose uptake at rest.

  8. An Unusual Case of Locally Advanced Glycogen-Rich Clear Cell Carcinoma of the Breast

    Directory of Open Access Journals (Sweden)

    Beatriz Martín-Martín

    2011-09-01

    Full Text Available Glycogen-rich clear cell (GRCC is a rare subtype of breast carcinoma characterized by carcinoma cells containing an optically clear cytoplasm and intracytoplasmic glycogen. We present the case of a 55-year-old woman with a palpable mass in the right breast and clinical signs of locally advanced breast cancer (LABC. The diagnosis of GRCC carcinoma was based on certain histopathological characteristics of the tumor and immunohistochemical analysis. To our knowledge, this is the first case of GRCC LABC with intratumoral calcifications. There is no evidence of recurrence or metastatic disease after 14 months’ follow-up.

  9. Prevention of complications in glycogen storage disease type Ia with optimization of metabolic control.

    Science.gov (United States)

    Dambska, M; Labrador, E B; Kuo, C L; Weinstein, D A

    2017-08-01

    Prior to 1971, type Ia glycogen storage disease was marked by life-threatening hypoglycemia, lactic acidosis, severe failure to thrive, and developmental delay. With the introduction of continuous feeds in the 1970s and cornstarch in the 1980s, the prognosis improved, but complications almost universally developed. Changes in the management of type Ia glycogen storage disease have resulted in improved metabolic control, and this manuscript reviews the increasing evidence that complications can be delayed or prevented with optimal metabolic control as previously was seen in diabetes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Antibody-mediated enzyme replacement therapy targeting both lysosomal and cytoplasmic glycogen in Pompe disease.

    Science.gov (United States)

    Yi, Haiqing; Sun, Tao; Armstrong, Dustin; Borneman, Scott; Yang, Chunyu; Austin, Stephanie; Kishnani, Priya S; Sun, Baodong

    2017-05-01

    Pompe disease is characterized by accumulation of both lysosomal and cytoplasmic glycogen primarily in skeletal and cardiac muscles. Mannose-6-phosphate receptor-mediated enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) targets the enzyme to lysosomes and thus is unable to digest cytoplasmic glycogen. Studies have shown that anti-DNA antibody 3E10 penetrates living cells and delivers "cargo" proteins to the cytosol or nucleus via equilibrative nucleoside transporter ENT2. We speculate that 3E10-mediated ERT with GAA will target both lysosomal and cytoplasmic glycogen in Pompe disease. A fusion protein (FabGAA) containing a humanized Fab fragment derived from the murine 3E10 antibody and the 110 kDa human GAA precursor was constructed and produced in CHO cells. Immunostaining with an anti-Fab antibody revealed that the Fab signals did not co-localize with the lysosomal marker LAMP2 in cultured L6 myoblasts or Pompe patient fibroblasts after incubation with FabGAA. Western blot with an anti-GAA antibody showed presence of the 150 kDa full-length FabGAA in the cell lysates, in addition to the 95- and 76 kDa processed forms of GAA that were also seen in the rhGAA-treated cells. Blocking of mannose-6-phosphate receptor with mannose-6-phosphate markedly reduced the 95- and the 76 kDa forms but not the 150 kDa form. In GAA-KO mice, FabGAA achieved similar treatment efficacy as rhGAA at an equal molar dose in reducing tissue glycogen contents. Our data suggest that FabGAA retains the ability of rhGAA to treat lysosomal glycogen accumulation and has the beneficial potential over rhGAA to reduce cytoplasmic glycogen storage in Pompe disease. FabGAA can be delivered to both the cytoplasm and lysosomes in cultured cells. FabGAA equally reduced lysosomal glycogen accumulation as rhGAA in GAA-KO mice. FabGAA has the beneficial potential over rhGAA to clear cytoplasmic glycogen. This study suggests a novel antibody-enzyme fusion protein therapy

  11. 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, ...

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

    Science.gov (United States)

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

    2017-01-05

    Glycogen and triglyceride are two major forms of energy storage in the body and provide the fuel during different phases of food deprivation. However, how glycogen metabolism is linked to fat deposition in adipose tissue has not been clearly characterized. We generated a mouse model with whole-body deletion of PPP1R3G, a glycogen-targeting subunit of protein phosphatase-1 required for glycogen synthesis. Upon feeding with high-fat diet, the body weight and fat composition are significantly reduced in the PPP1R3G-/- mice compared to the wild type controls. The metabolic rate of the mice as measured by O2 consumption and CO2 production is accelerated by PPP1R3G deletion. The high-fat diet-induced liver steatosis is also slightly relieved by PPP1R3G deletion. The glycogen level in adipose tissue is reduced by PPP1R3G deletion. In 3T3L1 cells, overexpression of PPP1R3G leads to increases of both glycogen and triglyceride levels. In conclusion, our study indicates that glycogen is actively involved in fat accumulation in adipose tissue and obesity development upon high-fat diet. Our study also suggests that PPP1R3G is an important player that links glycogen metabolism to lipid metabolism in vivo. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. 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

  14. 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

  15. Effect of supranutritional organic selenium supplementation on postpartum blood micronutrients, antioxidants, metabolites, and inflammation biomarkers in selenium-replete dairy cows.

    Science.gov (United States)

    Hall, Jean A; Bobe, Gerd; Vorachek, William R; Kasper, Katherine; Traber, Maret G; Mosher, Wayne D; Pirelli, Gene J; Gamroth, Mike

    2014-12-01

    Dairy cows have increased nutritional requirements for antioxidants postpartum. Supranutritional organic Se supplementation may be beneficial because selenoproteins are involved in regulating oxidative stress and inflammation. Our objective was to determine whether feeding Se-yeast above requirements to Se-replete dairy cows during late gestation affects blood micronutrients, antioxidants, metabolites, and inflammation biomarkers postpartum. During the last 8-weeks before calving, dairy cows at a commercial farm were fed either 0 (control) or 105 mg Se-yeast once weekly (supranutritional Se-yeast), in addition to Na selenite at 0.3 mg Se/kg dry matter in their rations. Concentrations of whole-blood (WB) Se and serum Se, erythrocyte glutathione (GSH), and serum albumin, cholesterol, α-tocopherol, haptoglobin, serum amyloid A (SAA), calcium, magnesium, phosphorus, non-esterified fatty acids, and β-hydroxybutyrate were measured directly after calving, at 48 h, and 14 days of lactation in 10 cows of each group. Supranutritional Se-yeast supplementation affected indicators of antioxidant status and inflammation. Cows fed a supranutritional Se-yeast supplement during the last 8-weeks of gestation had higher Se concentrations in WB (overall 52 % higher) and serum (overall 36 % higher) at all-time points, had higher SAA concentrations at 48 h (98 % higher), had higher erythrocyte GSH (38 % higher) and serum albumin concentrations (6.6 % higher) at 14 days, and had lower serum cholesterol concentrations and higher α-tocopherol/cholesterol ratios at calving and at 48 h compared with control cows. In conclusion, feeding Se-replete cows during late gestation a supranutritional Se-yeast supplement improves antioxidant status and immune responses after calving without negatively impacting other micronutrients and energy status.

  16. Acute phase response elicited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E status of vitamin-replete preruminant calves.

    Science.gov (United States)

    Nonnecke, B J; McGill, J L; Ridpath, J F; Sacco, R E; Lippolis, J D; Reinhardt, T A

    2014-09-01

    Studies in young animals have shown an association between vitamin deficiencies and increased risk of infectious disease; however, there is a paucity of information regarding the effect of acute infection on the vitamin status of the vitamin-replete neonate. To characterize the effects of acute infection on vitamin D and E status of the neonate, 6 vitamin-replete preruminant Holstein bull calves were experimentally infected with bovine viral diarrhea virus (BVDV; strain BVDV2-1373). Six mock-inoculated calves served as controls. Sustained pyrexia, leukopenia, and asynchronous increases in serum haptoglobin and serum amyloid A characterized the response of calves to infection with BVDV. Infection was also associated with increased serum IFN-γ, IL-2, and IL-6 concentrations. During the last 8 d of the 14-d postinoculation period, serum 25-hydroxyvitamin D and α-tocopherol concentrations in infected calves decreased by 51 and 82%, respectively. The observed inverse association between vitamin D and E status and serum amyloid A in infected calves suggests that the infection-induced acute phase response contributed to the reduced vitamin status of these animals. Additional studies are necessary to determine if the negative effect of infection on status are unique to this specific infection model or is representative of preruminant calf's response to acute infection. Studies are also needed to characterize mechanisms underlying infection-related changes in vitamin D and E status and to determine whether additional vitamin D or E supplementation during an acute infection diminishes disease severity and duration in the young animal. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  17. Glycogen synthase and phosphofructokinase protein and mRNA levels in skeletal muscle from insulin-resistant patients with non-insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Vestergaard, H; Lund, S; Larsen, F S

    1993-01-01

    -limiting enzymes in glycogen synthesis and glycolysis, glycogen synthase (GS) and phosphofructokinase (PFK), respectively. Analysis of biopsies of quadriceps muscle from 19 NIDDM patients and 19 control subjects showed in the basal state a 30% decrease (P

  18. Glycogen metabolism has a key role in the cancer microenvironment and provides new targets for cancer therapy.

    Science.gov (United States)

    Zois, Christos E; Harris, Adrian L

    2016-02-01

    Metabolic reprogramming is a hallmark of cancer cells and contributes to their adaption within the tumour microenvironment and resistance to anticancer therapies. Recently, glycogen metabolism has become a recognised feature of cancer cells since it is upregulated in many tumour types, suggesting that it is an important aspect of cancer cell pathophysiology. Here, we provide an overview of glycogen metabolism and its regulation, with a focus on its role in metabolic reprogramming of cancer cells under stress conditions such as hypoxia, glucose deprivation and anticancer treatment. The various methods to detect glycogen in tumours in vivo as well as pharmacological modulators of glycogen metabolism are also reviewed. Finally, we discuss the therapeutic value of targeting glycogen metabolism as a strategy for combinational approaches in cancer treatment.

  19. Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism.

    Science.gov (United States)

    Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemysław; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

    2015-10-29

    Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation.

  20. 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

    The number of people suffering from diabetes is hastily increasing and the condition is associated with altered brain glucose homeostasis. Brain glycogen is located in astrocytes and being a carbohydrate reservoir it contributes to glucose homeostasis. Furthermore, glycogen has been indicated...... to be important for proper neurotransmission under normal conditions. Previous findings from our laboratory suggested that glucose metabolism was reduced in type 2 diabetes, and thus we wanted to investigate more specifically how brain glycogen metabolism contributes to maintain energy status in the type 2...... 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...

  1. Cryo-chemical decellularization of the whole liver for mesenchymal stem cells-based functional hepatic tissue engineering.

    Science.gov (United States)

    Jiang, Wei-Cheng; Cheng, Yu-Hao; Yen, Meng-Hua; Chang, Yin; Yang, Vincent W; Lee, Oscar K

    2014-04-01

    Liver transplantation is the ultimate treatment for severe hepatic failure to date. However, the limited supply of donor organs has severely hampered this treatment. So far, great potentials of using mesenchymal stem cells (MSCs) to replenish the hepatic cell population have been shown; nevertheless, there still is a lack of an optimal three-dimensional scaffold for generation of well-transplantable hepatic tissues. In this study, we utilized a cryo-chemical decellularization method which combines physical and chemical approach to generate acellular liver scaffolds (ALS) from the whole liver. The produced ALS provides a biomimetic three-dimensional environment to support hepatic differentiation of MSCs, evidenced by expression of hepatic-associated genes and marker protein, glycogen storage, albumin secretion, and urea production. It is also found that hepatic differentiation of MSCs within the ALS is much more efficient than two-dimensional culture in vitro. Importantly, the hepatic-like tissues (HLT) generated by repopulating ALS with MSCs are able to act as functional grafts and rescue lethal hepatic failure after transplantation in vivo. In summary, the cryo-chemical method used in this study is suitable for decellularization of liver and create acellular scaffolds that can support hepatic differentiation of MSCs and be used to fabricate functional tissue-engineered liver constructs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Immunoglobulins for preventing hepatitis A

    DEFF Research Database (Denmark)

    Liu, Jian Ping; Nikolova, Dimitrinka; Fei, Yutong

    2009-01-01

    Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention.......Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention....

  3. Hepatitis Information for the Public

    Science.gov (United States)

    ... Hepatitis Contact Us Anonymous Feedback Quick Links to Hepatitis … A | B | C | D | E Viral Hepatitis Home ... Local Partners & Grantees Policy and Programs Resource Center Hepatitis Information for the Public Recommend on Facebook Tweet ...

  4. A widespread amino acid polymorphism at codon 905 of the glycogen-associated regulatory subunit of protein phosphatase-1 is associated with insulin resistance and hypersecretion of insulin

    DEFF Research Database (Denmark)

    Hansen, L; Hansen, T; Vestergaard, H

    1995-01-01

    The regulatory G-subunit of the glycogen-associated form of protein phosphatase 1 (PP1) plays a crucial part in muscle tissue glycogen synthesis and breakdown. As impaired insulin stimulated glycogen synthesis in peripheral tissues is considered to be a pathogenic factor in subsets of non-insulin...

  5. Hyperglycaemia normalises insulin action on glucose metabolism but not the impaired activation of AKT and glycogen synthase in the skeletal muscle of patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Vind, B F; Birk, J B; Vienberg, Sara Gry

    2012-01-01

    In type 2 diabetes, reduced insulin-stimulated glucose disposal, primarily glycogen synthesis, is associated with defective insulin activation of glycogen synthase (GS) in skeletal muscle. Hyperglycaemia may compensate for these defects, but to what extent it involves improved insulin signalling...... to glycogen synthesis remains to be clarified....

  6. Microbiological diagnostics of viral hepatitis

    OpenAIRE

    HASDEMİR, Ufuk

    2016-01-01

    Viral hepatitis is an infection that primarily affects the liverbut may also have systemic clinical manifestations. The vastmajority of viral hepatitis are caused by one of five hepatotropicviruses: hepatitis A virus (HAV), hepatitis B virus (HBV),hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), andhepatitis E virus (HEV) (Table I) [1]. HBV, HCV, and HDValso cause chronic hepatitis, whereas HAV does not. HEVcauses acute hepatitis in normal hosts but can cause protractedand chronic he...

  7. Dietary Tools To Modulate Glycogen Storage in Gilthead Seabream Muscle: Glycerol Supplementation

    DEFF Research Database (Denmark)

    Silva, Tomé S.; Matos, Elisabete; Cordeiro, Odete D.

    2012-01-01

    The quality and shelf life of fish meat products depend on the skeletal muscle’s energetic state at slaughter, as meat decomposition processes can be exacerbated by energy depletion. In this study, we tested dietary glycerol as a way of replenishing muscle glycogen reserves of farmed gilthead sea...

  8. Dietary Tools To Modulate Glycogen Storage In Fish Muscle: A Proteomic Assessment

    DEFF Research Database (Denmark)

    Silva, Tomé S.; Matos, Elisabete; Cordeire, Odete

    Post-mortem flesh deterioration is dependent on the energy reserves present at the time of death. Early depletion of muscle glycogen leads to the buildup of lactate and to the early onset of rigor mortis, resulting in the activation of endogenous proteases and the degradation of myofibrillar prot...

  9. Iliopsoas abscess as a complication of glycogen storage disease 1b

    Directory of Open Access Journals (Sweden)

    Marcos Prada-Arias

    2017-01-01

    Full Text Available We present a case of iliopsoas abscess secondary to inflammatory bowel disease associated to glycogen storage disease 1b in a 12-year-old boy. To the best of our knowledge, a similar case has not been reported in medical literature.

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

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Ørtenblad, Niels

    2013-01-01

    , topological, and dynamic organization of skeletal muscle fibers. In summary, the distribution of glycogen within skeletal muscle fibers has been shown to depend on the fiber phenotype, individual training status, short-term immobilization, and exercise and to influence both muscle contractility...

  11. In vitro cytocompatibility of porcine type I atelocollagen crosslinked by oxidized glycogen.

    Science.gov (United States)

    Rousseau, Cécile F; Gagnieu, Christian H

    2002-03-01

    Oxidized glycogen is used as collagen crosslinker to obtain materials with defined crosslinking degrees. These materials are characterized by their swelling ratio. calorimetric properties and the crosslinking level. Direct and indirect cytotoxicities of the materials obtained as sheets, are evaluated in vitro in cultures of human fibroblasts. The crosslinking degree depends on the ratio CHO glycogen/NH2 glycogen, but whatever this ratio (4.0, 2.0 or 0.4), an important percentage of the introduced CHO groups remains free and these groups are responsible for the cytotoxicity observed with the strongly crosslinked materials. This cytotoxicity appears in cell shape modification and in significant reduction of cell growth. Whatever the crosslinking degree, this toxicity can be suppressed by a single treatment with sodium borohydride, which reduced the remaining free CHO groups in OH functions and stabilizes the materials by a concomitant reduction of the crosslinking imine bonds. After reduction, all materials allow cellular adhesion and proliferation. This new crosslinking method of the collagen by the oxidized glycogen could be promising in the preparation of matrix for in vitro and in vivo tissue regeneration.

  12. The Role of Post-Exercise Nutrient Administration on Muscle Protein Synthesis and Glycogen Synthesis

    Science.gov (United States)

    Poole, Chris; Wilborn, Colin; Taylor, Lem; Kerksick, Chad

    2010-01-01

    Nutrient administration following an exercise bout vastly affects anabolic processes within the human body, irrespective of exercise mode. Of particular importance are protein and carbohydrates whereby these two macronutrients portray distinct functions as anabolic agents. It has been confirmed that protein and/or amino acid ingestion following resistance training is required to reach a positive protein/nitrogen balance, and carbohydrate intake during recovery is the most important consideration to replenish glycogen stores from an exhaustive exercise bout. Several factors play significant roles in determining the effectiveness of protein and carbohydrate supplementation on post-exercise protein and glycogen synthesis. Improper application of these factors can limit the body’s ability to reach an anabolic status. The provided evidence clearly denotes the importance these two macronutrients have in regards to post-exercise nutrition and anabolism. Therefore, the purpose of this review is to discuss the impact of dietary protein and carbohydrate intake during the recovery state on muscle protein synthesis and glycogen synthesis. Key points Post-exercise nutrient intake is essential for promoting protein synthesis and glycogen synthesis. The timing and amount of protein and/or carbohydrate ingested affects the rate and amount of synthesis. The type/form of protein and/or carbohydrate ingested after exercise alters anabolic processes during the recovery period. PMID:24149627

  13. Mutation detection in glycogen storage disease type II by RT-PCR and automated sequencing

    NARCIS (Netherlands)

    M.M.P. Hermans (Monique); D. van Leenen (Dik); M.A. Kroos (Marian); A.J.J. Reuser (Arnold)

    1997-01-01

    textabstractA new method is described for detection of mutations in the lysosomal a-glucosidase gene (GAA) leading to Glycogen Storage Disease type II (GSDII). A key feature of the method is isolation and reverse transcription of mRNA followed by PCR amplification of lysosomal a-glucosidase cDNA

  14. The Drosophila NR4A nuclear receptor DHR38 regulates carbohydrate metabolism and glycogen storage.

    Science.gov (United States)

    Ruaud, Anne-Françoise; Lam, Geanette; Thummel, Carl S

    2011-01-01

    Animals balance nutrient storage and mobilization to maintain metabolic homeostasis, a process that is disrupted in metabolic diseases like obesity and diabetes. Here, we show that DHR38, the single fly ortholog of the mammalian nuclear receptor 4A family of nuclear receptors, regulates glycogen storage during the larval stages of Drosophila melanogaster. DHR38 is expressed and active in the gut and body wall of larvae, and its expression levels change in response to nutritional status. DHR38 null mutants have normal levels of glucose, trehalose (the major circulating form of sugar), and triacylglycerol but display reduced levels of glycogen in the body wall muscles, which constitute the primary storage site for carbohydrates. Microarray analysis reveals that many metabolic genes are mis-regulated in DHR38 mutants. These include phosphoglucomutase, which is required for glycogen synthesis, and the two genes that encode the digestive enzyme amylase, accounting for the reduced amylase enzyme activity seen in DHR38 mutant larvae. These studies demonstrate that a critical role of nuclear receptor 4A receptors in carbohydrate metabolism has been conserved through evolution and that nutritional regulation of DHR38 expression maintains the proper uptake and storage of glycogen during the growing larval stage of development.

  15. Use of modified cornstarch therapy to extend fasting in glycogen storage disease types Ia and Ib

    NARCIS (Netherlands)

    Correia, Catherine E.; Bhattacharya, Kaustuv; Lee, Philip J.; Shuster, Jonathan J.; Theriaque, Douglas W.; Shankar, Meena N.; Smit, G. Peter A.; Weinstein, David A.

    2008-01-01

    Background: Type I glycogen storage disease (GSD) is caused by a deficiency of glucose-6-phosphatase resulting in severe fasting hypoglycemia. Objective: We compared the efficacy of a new modified starch with the currently used cornstarch therapy in patients with type Ia and Ib GSD. Design: This was

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

    Science.gov (United States)

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

    2017-02-01

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

  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. The role of post-exercise nutrient administration on muscle protein synthesis and glycogen synthesis.

    Science.gov (United States)

    Poole, Chris; Wilborn, Colin; Taylor, Lem; Kerksick, Chad

    2010-01-01

    Nutrient administration following an exercise bout vastly affects anabolic processes within the human body, irrespective of exercise mode. Of particular importance are protein and carbohydrates whereby these two macronutrients portray distinct functions as anabolic agents. It has been confirmed that protein and/or amino acid ingestion following resistance training is required to reach a positive protein/nitrogen balance, and carbohydrate intake during recovery is the most important consideration to replenish glycogen stores from an exhaustive exercise bout. Several factors play significant roles in determining the effectiveness of protein and carbohydrate supplementation on post-exercise protein and glycogen synthesis. Improper application of these factors can limit the body's ability to reach an anabolic status. The provided evidence clearly denotes the importance these two macronutrients have in regards to post-exercise nutrition and anabolism. Therefore, the purpose of this review is to discuss the impact of dietary protein and carbohydrate intake during the recovery state on muscle protein synthesis and glycogen synthesis. Key pointsPost-exercise nutrient intake is essential for promoting protein synthesis and glycogen synthesis.The timing and amount of protein and/or carbohydrate ingested affects the rate and amount of synthesis.The type/form of protein and/or carbohydrate ingested after exercise alters anabolic processes during the recovery period.

  20. Expression and characterization of thermostable glycogen branching enzyme from Geobacillus mahadia Geo-05

    Directory of Open Access Journals (Sweden)

    Nur Syazwani Mohtar

    2016-12-01

    Full Text Available The glycogen branching enzyme (EC 2.4.1.18, which catalyses the formation of α-1,6-glycosidic branch points in glycogen structure, is often used to enhance the nutritional value and quality of food and beverages. In order to be applicable in industries, enzymes that are stable and active at high temperature are much desired. Using genome mining, the nucleotide sequence of the branching enzyme gene (glgB was extracted from the Geobacillus mahadia Geo-05 genome sequence provided by the Malaysia Genome Institute. The size of the gene is 2013 bp, and the theoretical molecular weight of the protein is 78.43 kDa. The gene sequence was then used to predict the thermostability, function and the three dimensional structure of the enzyme. The gene was cloned and overexpressed in E. coli to verify the predicted result experimentally. The purified enzyme was used to study the effect of temperature and pH on enzyme activity and stability, and the inhibitory effect by metal ion on enzyme activity. This thermostable glycogen branching enzyme was found to be most active at 55 °C, and the half-life at 60 °C and 70 °C was 24 h and 5 h, respectively. From this research, a thermostable glycogen branching enzyme was successfully isolated from Geobacillus mahadia Geo-05 by genome mining together with molecular biology technique.

  1. A possible relationship between gluconeogenesis and glycogen metabolism in rabbits during myocardial ischemia

    Directory of Open Access Journals (Sweden)

    RAQUEL R. DE AGUIAR

    2017-08-01

    Full Text Available ABSTRACT Ischemia is responsible for many metabolic abnormalities in the heart, causing changes in organ function. One of modifications occurring in the ischemic cell is changing from aerobic to anaerobic metabolism. This change causes the predominance of the use of carbohydrates as an energy substrate instead of lipids. In this case, the glycogen is essential to the maintenance of heart energy intake, being an important reserve to resist the stress caused by hypoxia, using glycolysis and lactic acid fermentation. In order to study the glucose anaerobic pathways utilization and understand the metabolic adaptations, New Zealand white rabbits were subjected to ischemia caused by Inflow occlusion technique. The animals were monitored during surgery by pH and lactate levels. Transcription analysis of the pyruvate kinase, lactate dehydrogenase and phosphoenolpyruvate carboxykinase enzymes were performed by qRT-PCR, and glycogen quantification was determined enzymatically. Pyruvate kinase transcription increased during ischemia, followed by glycogen consumption content. The gluconeogenesis increased in control and ischemia moments, suggesting a relationship between gluconeogenesis and glycogen metabolism. This result shows the significant contribution of these substrates in the organ energy supply and demonstrates the capacity of the heart to adapt the metabolism after this injury, sustaining the homeostasis during short-term myocardial ischemia.

  2. Function of trehalose and glycogen in cell cycle progression and cell viability in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Silljé, H H; Paalman, J W; ter Schure, E G; Olsthoorn, S Q; Verkleij, A J; Boonstra, Johannes; Verrips, C T

    Trehalose and glycogen accumulate in Saccharomyces cerevisiae when growth conditions deteriorate. It has been suggested that aside from functioning as storage factors and stress protectants, these carbohydrates may be required for cell cycle progression at low growth rates under carbon limitation.

  3. Trehalose, glycogen and ethanol metabolism in the gcr1 mutant of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Seker, Tamay; Hamamci, H.

    2003-01-01

    Since Gcr1p is pivotal in controlling the transcription of glycolytic enzymes and trehalose metabolism seems to be one of the control points of glycolysis, we examined trehalose and glycogen synthesis in response to 2 % glucose pulse during batch growth in gcr1 (glucose regulation-1) mutant lacking...

  4. Early alterations in soleus GLUT-4, glucose transport, and glycogen in voluntary running rats

    Science.gov (United States)

    Henriksen, Erik J.; Halseth, Amy E.

    1994-01-01

    Voluntary wheel running (WR) by juvenile female rats was used as a noninterventional model of soleus muscle functional overload to study the regulation of insulin-stimulated glucose transport activity by the glucose transporter (GLUT-4 isoform) protein level and glycogen concentration. Soleus total protein content was significantly greater (+18%;P greater than 0.05) than in age-matched controls after 1 wk of WR, and this hypertrophic response continued in weeks 2-4 (+24-32%). GLUT-4 protein was 39% greater than in controls in 1-wk WR soleus, and this adaptation was accompanied by a similar increase in in vitro insulin-stimulated glucose transport activity(+29%). After 2 and 4 wk of WR, however, insulin-stimulated glucose transport activity had returned to control levels, despite a continued elevation (+25-28%) of GLUT-4 protein. At these two time points, glycogen concentration was significantly enhanced in WR soleus (+21-42%), which coincided with significant reductions in glycogen synthase activity ratios (-23 to-41%). These results indicate that, in this model of soleus muscle functional overload, the GLUT-4 protein level may initially regulate insulin-stimulated glucose transport activity in the absence of changes in other modifying factors. However,this regulation of glucose transport activity by GLUT-4 protein may be subsequently overridden by elevated glycogen concentration.

  5. Glycogen synthase kinase 3α regulates urine concentrating mechanism in mice

    DEFF Research Database (Denmark)

    Nørregaard, Rikke; Tao, Shixin; Nilsson, Line

    2015-01-01

    In mammals, glycogen synthase kinase (GSK)3 comprises GSK3α and GSK3β isoforms. GSK3β has been shown to play a role in the ability of kidneys to concentrate urine by regulating vasopressin-mediated water permeability of collecting ducts, whereas the role of GSK3α has yet to be discerned. To inves...

  6. 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

  7. High versus low glycemic index 3-h recovery diets following glycogen-depleting exercise has no effect on subsequent 5-km cycling time trial performance.

    Science.gov (United States)

    Brown, Laura J S; Midgley, Adrian W; Vince, Rebecca V; Madden, Leigh A; McNaughton, Lars R

    2013-09-01

    Some athletes train/compete multiple times in a single day and rapid restoration of muscle and hepatic glycogen stores is therefore important for athletic performance. Randomised, counterbalanced, crossover, single blinded study investigated the effects of low/high glycaemic index (GI) meals on the physiological responses to a 3-h recovery period and subsequent 5-km cycling time trial (TT). Seven male cyclists completed glycogen-depleting exercise followed by a 3-h recovery period, when participants consumed either a high or low GI meal providing 2gkg(-1) BM of carbohydrate. Participants then performed a 5-km cycling TT. Blood samples were analysed for glucose insulin, free fatty acid (FFA) and triglyceride. There was no significant difference between the median (IQR) cycling TT time of 8.5 (3.0) min in the LGI condition and 8.4 (1.8) min in the HGI condition (p=0.45). Serum insulin was significantly higher in the HGI condition throughout the 3-h recovery period (p=0.025), FFA concentrations were higher in the HGI condition only at 30min into recovery (p=0.008). The respiratory exchange ratio (p=0.028) and carbohydrate oxidation rate (p=0.015) increased over time in the HGI condition, whereas the rate of fat oxidation demonstrated the opposite response (p=0.001). No significant differences between conditions were observed for any physiological variables at the end of the 5-km TT. Although the GI of the two meals indicated important metabolic differences during the recovery period, there was no evidence suggesting these differences influenced subsequent 5-km TT performance. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  8. Glycogen Synthase Kinase-3 regulates IGFBP-1 gene transcription through the Thymine-rich Insulin Response Element

    Directory of Open Access Journals (Sweden)

    Marquez Rodolfo

    2004-09-01

    Full Text Available Abstract Background Hepatic expression of several gene products involved in glucose metabolism, including phosphoenolpyruvate carboxykinase (PEPCK, glucose-6-phosphatase (G6Pase and insulin-like growth factor binding protein-1 (IGFBP-1, is rapidly and completely inhibited by insulin. This inhibition is mediated through the regulation of a DNA element present in each of these gene promoters, that we call the Thymine-rich Insulin Response Element (TIRE. The insulin signalling pathway that results in the inhibition of these gene promoters requires the activation of phosphatidylinositol 3-kinase (PI 3-kinase. However, the molecules that connect PI 3-kinase to these gene promoters are not yet fully defined. Glycogen Synthase Kinase 3 (GSK-3 is inhibited following activation of PI 3-kinase. We have shown previously that inhibitors of GSK-3 reduce the activity of two TIRE-containing gene promoters (PEPCK and G6Pase, whose products are required for gluconeogenesis. Results In this report we demonstrate that in H4IIE-C3 cells, four distinct classes of GSK-3 inhibitor mimic the effect of insulin on a third TIRE-containing gene, IGFBP-1. We identify the TIRE as the minimum requirement for inhibition by these agents, and demonstrate that the target of GSK-3 is unlikely to be the postulated TIRE-binding protein FOXO-1. Importantly, overexpression of GSK-3 in cells reduces the insulin regulation of TIRE activity as well as endogenous IGFBP-1 expression. Conclusions These results implicate GSK-3 as an intermediate in the pathway from the insulin receptor to the TIRE. Indeed, this is the first demonstration of an absolute requirement for GSK-3 inhibition in insulin regulation of gene transcription. These data support the potential use of GSK-3 inhibitors in the treatment of insulin resistant states such as Type 2 diabetes mellitus, but suggest that it will be important to identify all TIRE-containing genes to assess potential side effects of these agents.

  9. Effect of lung fibrosis on glycogen content in different extrapulmonary tissues.

    Science.gov (United States)

    Borges, Elizabeth Lage; de Barros Pinheiro, Marina; Prata, Luana Oliveira; Sales, Wesley Araújo; Silva, Yuri Augusto Junqueira Belém; Caliari, Marcelo Vidigal; Rodrigues-Machado, Maria Glória; da Glória Rodrigues-Machado, Maria

    2014-02-01

    Patients with pulmonary fibrosis often exhibit reduced lung function and diminished health-related quality of life. Studies have shown that paraquat-induced, extrapulmonary, acute lung injury affects the metabolic profile of glycogen content in different tissues. The purpose of the present study was to investigate whether the process of pulmonary fibrosis induced by continuous exposure to the toxic herbicide paraquat or by a local insult from bleomycin affects the glycogen content in tissues. In the paraquat experiment, Wistar rats (n = 5 per group) received either saline (controls) or an intraperitoneal injection of a paraquat solution (7.0 mg/kg; experimental group) once a week for 4 weeks. In the bleomycin experiment, Balb/c mice (n = 5 per group) received either saline (controls) or 6.25 U/kg of bleomycin through intratracheal instillation in single dose (experimental group). Glycogen content in different tissues (mg/g tissue) was measured using the anthrone reagent. The lungs submitted to histopathological and quantitative analyses of fibrosis. Paraquat-induced fibrosis led to lower glycogen content in the gastrocnemius muscle (2.7 ± 0.1 vs. 3.4 ± 0.1; 79 %) compared with the controls, whereas no changes in glycogen content were found in the diaphragm or heart. Bleomycin-induced fibrosis led to lower glycogen content in the diaphragm (0.43 ± 0.02 vs. 0.79 ± 0.09, 54 %), gastrocnemius muscle (0.62 ± 0.11 vs. 1.18 ± 0.06, 52 %), and heart (0.68 ± 0.11 vs. 1.39 ± 0.1, 49 %) compared with the controls (p < 0.05). Moreover, the area of fibrous connective tissue (μm(2)) in the lungs was significantly increased in paraquat-induced fibrosis (3,463 ± 377 vs. 565 ± 89) and bleomycin-induced fibrosis (3,707 ± 433.9 vs. 179 ± 51.28) compared with the controls. The findings suggest that the effects of fibrogenesis in the lungs are not limited to local alterations but also lead to a reduction in glycogen content in the heart

  10. [Viral hepatitis in travellers].

    Science.gov (United States)

    Abreu, Cândida

    2007-01-01

    Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

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

    Science.gov (United States)

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

    2017-03-01

    Deficiency of glycogen branching enzyme (GBE) causes glycogen storage disease type IV (GSD IV), which is characterized by the accumulation of a less branched, poorly soluble form of glycogen called polyglucosan (PG) in multiple tissues. This study evaluates the efficacy of gene therapy with an adeno-associated viral (AAV) vector in a mouse model of adult form of GSD IV (Gbe1ys/ys). An AAV serotype 9 (AAV9) vector containing a human GBE expression cassette (AAV-GBE) was intravenously injected into 14-day-old Gbe1ys/ys mice at a dose of 5 × 1011 vector genomes per mouse. Mice were euthanized at 3 and 9 months of age. In the AAV-treated mice at 3 months of age, GBE enzyme activity was highly elevated in heart, which is consistent with the high copy number of the viral vector genome detected. GBE activity also increased significantly in skeletal muscles and the brain, but not in the liver. The glycogen content was reduced to wild-type levels in muscles and significantly reduced in the liver and brain. At 9 months of age, though GBE activity was only significantly elevated in the heart, glycogen levels were significantly reduced in the liver, brain, and skeletal muscles of the AAV-treated mice. In addition, the AAV treatment resulted in an overall decrease in plasma activities of alanine transaminase, aspartate transaminase, and creatine kinase, and a significant increase in fasting plasma glucose concentration at 9 months of age. This suggests an alleviation of damage and improvement of function in the liver and muscles by the AAV treatment. This study demonstrated a long-term benefit of a systemic injection of an AAV-GBE vector in Gbe1ys/ys mice.

  12. A STUDY ON ENDOMETRIAL MORPHOLOGY AND GLYCOGEN CONTENT IN INFERTILE WOMEN

    Directory of Open Access Journals (Sweden)

    Swayam Prava Pradhan

    2017-01-01

    Full Text Available BACKGROUND Infertility is a common problem in day-to-day practice. Therefore, the common uterine pathology should be excluded while investigating infertility. Endometrial biopsy plays an important role in diagnosing infertility and assessing the glycogen content of endometrium, which is essential for implantation of fertilised ovum. The aim of the study is to find out endometrial pathologies and glycogen content of endometrium as causes of infertility. MATERIALS AND METHODS A study of 139 cases of primary and secondary infertility was carried out in the Department of Pathology, M.K.C.G. Medical College, Berhampur. Women with history of infertility were subjected to premenstrual endometrial biopsy. Routine haematoxylin and eosin staining was done for dating endometrium. Endometrial specimens were evaluated in the light of menstrual history to find out various endometrial changes in them. Periodic Acid-Schiff stain was done to detect amount of glycogen in the endometrium. RESULTS Primary infertility was detected in 85.6% of cases (n=119 and secondary infertility in 14.4% (n=20 of cases. Maximum incidence of infertility was seen among patients between 23 and 27 years of age. Anovulatory cycles were seen in 29.5% (n=41 of cases. Glycogen deficiency was seen in 28.88% (n=26 of cases. Tubercular endometritis was found in 3.9% (n=4 of cases and cystic glandular hyperplasia seen in 2.5% (n=3 of cases of primary infertility. CONCLUSION Endometrial pathologies are important causes of infertility and depletion of glycogen results in inadequate preparation of endometrium, which maybe one of the causes of infertility.

  13. 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.

  14. Pyruvate incubation enhances glycogen stores and sustains neuronal function during subsequent glucose deprivation.

    Science.gov (United States)

    Shetty, Pavan K; Sadgrove, Matthew P; Galeffi, Francesca; Turner, Dennis A

    2012-01-01

    The use of energy substrates, such as lactate and pyruvate, has been shown to improve synaptic function when administered during glucose deprivation. In the present study, we investigated whether prolonged incubation with monocarboxylate (pyruvate or lactate) prior rather than during glucose deprivation can also sustain synaptic and metabolic function. Pyruvate pre-incubation(3-4h) significantly prolonged (>25 min) the tolerance of rat hippocampal slices to delayed glucose deprivation compared to control and lactate pre-incubated slices, as revealed by field excitatory post synaptic potentials (fEPSPs); pre-incubation with pyruvate also reduced the marked decrease in NAD(P)H fluorescence resulting from glucose deprivation. Moreover, pyruvate exposure led to the enhancement of glycogen stores with time, compared to glucose alone (12 μmol/g tissue at 4h vs. 3.5 μmol/g tissue). Prolonged resistance to glucose deprivation following exogenous pyruvate incubation was prevented by glycogenolysis inhibitors, suggesting that enhanced glycogen mediates the delay in synaptic activity failure. The application of an adenosine A1 receptor antagonist enhanced glycogen utilization and prolonged the time to synaptic failure, further confirming this hypothesis of the importance of glycogen. Moreover, tissue levels of ATP were also significantly maintained during glucose deprivation in pyruvate pretreated slices compared to control and lactate. In summary, these experiments indicate that pyruvate exposure prior to glucose deprivation significantly increased the energy buffering capacity of hippocampal slices, particularly by enhancing internal glycogen stores, delaying synaptic failure during glucose deprivation by maintaining ATP levels, and minimizing the decrease in the levels of NAD(P)H. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. 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.

  16. Genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction.

    Science.gov (United States)

    Guan, Lili; Feng, Haiyan; Gong, Dezheng; Zhao, Xu; Cai, Li; Wu, Qiong; Yuan, Bo; Yang, Mei; Zhao, Jie; Zou, Yuan

    2013-12-01

    Insulin resistance (IR) increases with age and plays a key role in the pathogenesis of type 2 diabetes mellitus. Oxidative stress and mitochondrial dysfunction are supposed to be major factors leading to age-related IR. Genipin, an extract from Gardenia jasminoides Ellis fruit, has been reported to stimulate insulin secretion in pancreatic islet cells by regulating mitochondrial function. In this study, we first investigated the effects of genipin on insulin sensitivity and the potential mitochondrial mechanisms in the liver of aging rats. The rats were randomly assigned to receive intraperitoneal injections of either 25mg/kg genipin or vehicle once daily for 12days. The aging rats showed hyperinsulinemia and hyperlipidemia, and insulin resistance as examined by the decreased glucose decay constant rate during insulin tolerance test (kITT). The hepatic tissues showed steatosis and reduced glycogen content. Hepatic malondialdehyde level and mitochondrial reactive oxygen species (ROS) were higher, and levels of mitochondrial membrane potential (MMP) and ATP were lower as compared with the normal control rats. Administration of genipin ameliorated systemic and hepatic insulin resistance, alleviated hyperinsulinemia, hyperglyceridemia and hepatic steatosis, relieved hepatic oxidative stress and mitochondrial dysfunction in aging rats. Furthermore, genipin not only improved insulin sensitivity by promoting insulin-stimulated glucose consumption and glycogen synthesis, inhibited cellular ROS overproduction and alleviated the reduction of levels of MMP and ATP, but also reversed oxidative stress-associated JNK hyperactivation and reduced Akt phosphorylation in palmitate-treated L02 hepatocytes. In conclusion, genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction. © 2013.

  17. Hepatitis virus panel

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003558.htm Hepatitis virus panel To use the sharing features on this page, please enable JavaScript. The hepatitis virus panel is a series of blood tests used ...

  18. Hepatitis A - children

    Science.gov (United States)

    ... attends day care: Make sure the children and staff at the day care center have had their hepatitis A vaccine. Inspect the area where diapers are changed to ensure that proper hygiene is followed. If your child gets hepatitis A, ...

  19. Delta agent (Hepatitis D)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000216.htm Hepatitis D (Delta agent) To use the sharing features on this page, please enable JavaScript. Hepatitis D is a viral infection caused by the ...

  20. Hepatitis B Vaccination Protection

    Science.gov (United States)

    Fact Sheet Hepatitis B Vaccination Protection Hepatitis B virus (HBV) is a pathogenic microorganism that can cause potentially life- threatening disease in humans. HBV infection is transmitted through exposure ...

  1. Hepatitis B Foundation Newsletter: B Informed

    Science.gov (United States)

    ... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  2. Hepatitis viruses overview

    African Journals Online (AJOL)

    Hepatitis is major cause of morbidity or mortality worldwide, particularly in the developing world. The major causes of infective hepatitis are hepatitis viruses. A, B, C, D or E. In the acute phase, there are no clinical features that can reliably differentiate between these viruses. Infection may be asymptomatic or can present as.

  3. Know More Hepatitis

    Science.gov (United States)

    ... death. In fact, Hepatitis C is a leading cause of liver cancer and the #1 cause of liver transplants. Many people can get lifesaving care and treatment. Knowing you have Hepatitis C can help you make important decisions about your health. Successful treatments can eliminate the ... “Hepatitis C: Did You Know?” Watch this video ...

  4. Hepatitis E Virus

    African Journals Online (AJOL)

    Abstract. Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the developing world. It is a waterborne virus that can cause epidemics in the face of overcrowding and poor sanitation. Although the hepatitis illness is usually self-limiting, it has a high mortality in pregnant women and can become a ...

  5. Hepatitis B and Hepatitis C in Pregnancy

    Science.gov (United States)

    ... who are infected never get rid of the hepatitis B virus. This is called chronic infection. These people keep the virus for the rest of their lives. They are known as carriers . Most carriers do not have ... and early death. Can hepatitis B virus infection be cured? There is no ...

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Christopher M Carmean

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

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

    Science.gov (United States)

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

    2013-01-01

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

  9. Seasonal Changes in Glycogen Contents in Various Tissues of the Edible Bivalves, Pen Shell Atrina lischkeana, Ark Shell Scapharca kagoshimensis, and Manila Clam Ruditapes philippinarum in West Japan

    Directory of Open Access Journals (Sweden)

    Tatsuya Yurimoto

    2015-01-01

    Full Text Available The types of tissues accumulating glycogen and seasonal changes in glycogen content were investigated in the following shell species: pen shell Atrina lischkeana, ark shell Scapharca kagoshimensis, and Manila clam Ruditapes philippinarum. Comparison of the results showed that the adductor muscle or foot was the main glycogen reservoir and the levels varied seasonally. The adductor muscle in the pen shell showed higher glycogen content during spring and lower content during autumn. The ark shell, on the other hand, showed higher content during winter and spring and lower content during summer and autumn, while the Manila clam showed higher glycogen content during spring and summer and lower content during autumn and winter. These results revealed that the adductor muscle in pen shells and the foot in ark shells and Manila clams act as the main storage tissues for glycogen in the three species studied and that these tissues are suitable to analyze glycogen prevalence to estimate individual physiological condition.

  10. Expression of glycogen synthase and phosphofructokinase in muscle from type 1 (insulin-dependent) diabetic patients before and after intensive insulin treatment

    DEFF Research Database (Denmark)

    Vestergaard, H; Andersen, P H; Lund, S

    1994-01-01

    glycogen storage and glycolysis: glycogen synthase and phosphofructokinase, respectively. In nine diabetic patients biopsies of quadriceps muscle were taken before and 24-h after intensified insulin therapy and compared to findings in eight control subjects. Subcutaneous injections of rapid acting insulin...... diabetic patients showed a normal total glycogen synthase activity but a 48% decrease (p = 0.006) in glycogen synthase fractional velocity (0.1 mmol/l glucose 6-phosphate) (FV0.1) and a 45% increase (p = 0.01) in the half-maximal activation constant of glycogen synthase (A0.5). The activity...... of phosphofructokinase and the specific mRNA and immunoreactive protein levels of both glycogen synthase and phosphofructokinase were similar in the two groups. The 2.8-fold increase in serum insulin levels and the halving of the plasma glucose level for at least 15 h were associated with a normalization of glycogen...

  11. 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...

  12. Alcoholic hepatitis.

    Science.gov (United States)

    Damgaard Sandahl, Thomas

    2014-10-01

    Alcoholic hepatitis (AH) is an acute inflammatory syndrome causing significant morbidity and mortality. The prognosis is strongly dependent on disease severity, as assessed by clinical scoring systems. Reliable epidemiological data as well as knowledge of the clinical course of AH are essential for planning and resource allocation within the health care system. Likewise, individual evaluation of risk is desirable in the clinical handling of patients with AH as it can guide treatment, improve patient information, and serve as strata in clinical trials. The present PhD thesis is based on three studies using a cohort of nearly 2000 patients diagnosed with AH in Denmark from 1999 to 2008 as a cohort, in a population-based study design. The aims of this thesis were as follows. (1) To describe the incidence and short- and long-term mortality, of AH in Denmark (Study I). (2) To validate and compare the ability of the currently available prognostic scores to predict mortality in AH (Study II). (3) To investigate the short- and long-term causes of death of patients with AH (Study III). During the study decade, the annual incidence rate in the Danish population rose from 37 to 46 per 106 for men and from 24 to 34 per 106 for women. Both short- and long-term mortality rose for men and women, and the increase in short-term mortality was attributable to increasing patient age and prevalence of cirrhosis. Our evaluation of the most commonly used prognostic scores for predicting the mortality of patients with AH showed that all scores performed similarly, with Area under the Receiver Operator Characteristics curves giving values between 0.74 and 0.78 for 28-day mortality assessed on admission. Our study on causes of death showed that in the short-term (information about AH that shows increasing incidence and mortality rates. Consequently, it reiterates the fact that AH is a life-threatening disease and suggests that AH is an increasing public health concern. The most widely used

  13. Involvement of glycogen synthase kinase-3β in liver ischemic conditioning induced cardioprotection against myocardial ischemia and reperfusion injury in rats.

    Science.gov (United States)

    Yang, Shuai; Abbott, Geoffrey W; Gao, Wei Dong; Liu, Jin; Luo, Chaozhi; Hu, Zhaoyang

    2017-05-01

    Remote ischemic conditioning has been convincingly shown to render the myocardium resistant to a subsequent more severe sustained episode of ischemia. Compared with other organs, little is known regarding the effect of transient liver ischemic conditioning. We proposed the existence of cardioprotection induced by remote liver conditioning. Male Sprague-Dawley rats were divided into sham-operated control (no further hepatic intervention) and remote liver ischemic conditioning groups. For liver ischemic conditioning, three cycles of 5 min of liver ischemia-reperfusion stimuli were conducted before-(liver preconditioning), post-myocardial ischemia (liver postconditioning), or in combination of both (liver preconditioning + liver postconditioning). Rats were exposed to 45 min of left anterior descending coronary artery occlusion, followed by 3 h of reperfusion thereafter. ECG and hemodynamics were measured throughout the experiment. The coronary artery was reoccluded at the end of reperfusion for infarct size determination. Blood samples were taken for serum lactate dehydrogenase and creatine kinase-MB test. Heart tissues were taken for apoptosis measurements and Western blotting. Our data demonstrate that liver ischemic preconditioning, postconditioning, or a combination of both, offered strong cardioprotection, as evidenced by reduction in infarct size and cardiac tissue damage, recovery of cardiac function, and inhibition of apoptosis after ischemia-reperfusion. Moreover, liver ischemic conditioning increased cardiac (not hepatic) glycogen synthase kinase-3β (GSK-3β) phosphorylation. Accordingly, inhibition of GSK-3β mimicked the cardioprotective action of liver conditioning. These results demonstrate that remote liver ischemic conditioning protected the heart against ischemia and reperfusion injury via GSK-3β-dependent cell-survival signaling pathway.NEW & NOTEWORTHY Remote ischemic conditioning protects hearts against ischemia and reperfusion (I/R) injury

  14. Pathogenesis of Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Irena Ciećko-Michalska

    2012-01-01

    Full Text Available Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy.

  15. Pathogenesis of Hepatic Encephalopathy

    Science.gov (United States)

    Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

    2012-01-01

    Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

  16. Comparative analyses of DHA-Phosphatidylcholine and recombination of DHA-Triglyceride with Egg-Phosphatidylcholine or Glycerylphosphorylcholine on DHA repletion in n-3 deficient mice.

    Science.gov (United States)

    Wu, Fang; Wang, Dan-Dan; Wen, Min; Che, Hong-Xia; Xue, Chang-Hu; Yanagita, Teruyoshi; Zhang, Tian-Tian; Wang, Yu-Ming

    2017-12-08

    Docosahexaenoic acid (DHA) is important for optimal neurodevelopment and brain function during the childhood when the brain is still under development. The effects of DHA-Phosphatidylcholine (DHA-PC) and the recombination of DHA-Triglyceride with egg PC (DHA-TG + PC) or α-Glycerylphosphorylcholine (DHA-TG + α-GPC) were comparatively analyzed on DHA recovery and the DHA accumulation kinetics in tissues including cerebral cortex, erythrocyte, liver, and testis were evaluated in the weaning n-3 deficient mice. The concentration of DHA in weaning n-3 deficient mice could be recovered rapidly by dietary DHA supplementation, in which DHA-PC exhibited the better efficacy than the recombination of DHA-Triglyceride with egg PC or α-GPC. Interestingly, DHA-TG + α-GPC exhibited the greater effect on DHA accumulation than DHA-TG + PC in cerebral cortex and erythrocyte (p DHA-PC. Meanwhile, DHA-TG + PC showed a similar effect to DHA-PC on DHA repletion in testis, which was better than that of DHA-TG + α-GPC (p DHA supplements could be applied targetedly based on the DHA recovery in different tissues, although the supplemental effects of the recombination of DHA-Triglyceride with egg PC or α-GPC were not completely equivalent to that of DHA-PC, which could provide some references to develop functional foods to support brain development and function.

  17. Zn-depleted mice absorb more of an intragastric Zn solution by a metallothionein-enhanced process than do Zn-replete mice.

    Science.gov (United States)

    Coyle, P; Philcox, J C; Rofe, A M

    2000-04-01

    The influence of metallothionein (MT)(2) on Zn absorption was investigated in MT-null (MT-/-) and normal (MT+/+) mice fed Zn-depleted (ZnD) diets for 7 d and compared with those fed Zn-replete (ZnR) diets in a previous study. Mice were starved for 20 h, then administered an oral gavage of aqueous (65)ZnSO(4) solution at doses of 154, 770 or 1540 nmol of Zn, and the amount transferred into nongut tissues was determined 4 h later. (65)Zn transfer did not differ between genotypes in ZnR mice. However ZnD MT+/+ mice had a 30-40% greater transfer from the 154 and 770 Zn doses compared to ZnR MT+/+ mice. This was not observed in MT-/- mice. In MT+/+ mice, Zn depletion enhanced the induction of MT by Zn in the intestine and pancreas. (65)Zn uptakes in the liver and pancreas were greater in MT+/+ than MT-/- mice, and this was greater (50%) at the 154 and 770 doses in mice fed ZnD diets. Plasma Zn concentrations were raised to a similar extent in ZnR and ZnD MT-/- mice. ZnR MT+/+ mice had significantly lower plasma Zn levels than MT-/-mice; this difference was less marked in the ZnD mice. We conclude that a MT-facilitated enhancement in Zn absorption occurs in response to dietary Zn deficiency.

  18. Altered Wnt signalling in the teenage suicide brain: focus on glycogen synthase kinase-3β and β-catenin

    National Research Council Canada - National Science Library

    Ren, Xinguo; Rizavi, Hooriyah S; Khan, Mansoor A; Dwivedi, Yogesh; Pandey, Ghanshyam N

    2013-01-01

    Glycogen synthase kinase (GSK)-3β and β-catenin are important components of the Wnt signalling pathway, which is involved in numerous physiological functions such as cognition, brain development and cell survival...

  19. Altered Wnt signalling in the teenage suicide brain: focus on glycogen synthase kinase-3[beta] and [beta]-catenin

    National Research Council Canada - National Science Library

    Xinguo Ren; Hooriyah S Rizavi; Mansoor A Khan; Yogesh Dwivedi; Ghanshyam N Pandey

    2013-01-01

      Abstract Glycogen synthase kinase (GSK)-3[beta] and [beta]-catenin are important components of the Wnt signalling pathway, which is involved in numerous physiological functions such as cognition, brain development and cell survival...

  20. RELATIVE DEGREE OF STIMULATION-EVOKED GLYCOGEN DEGRADATION IN MUSCLE-FIBERS OF DIFFERENT TYPE IN RAT GASTROCNEMIUS

    NARCIS (Netherlands)

    KERNELL, D; LIND, A; VANDIEMEN, ABJP; DEHAAN, A

    1995-01-01

    1. The relative degree of glycogen degradation, caused in different fibre types by supramaximal electrical activation of the muscle nerve, was investigated in m. gastrocnemius medialis of young adult rats under general pentobarbitone anaesthesia. Pour different protocols of intermittent maximal

  1. 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.

  2. Functional importance of the astrocytic glycogen-shunt and glycolysis for maintenance of an intact intra/extracellular glutamate gradient

    DEFF Research Database (Denmark)

    Schousboe, Arne; Sickmann, Helle M; Walls, Anne B

    2010-01-01

    It has been proposed that a considerable fraction of glucose metabolism proceeds via the glycogen-shunt consisting of conversion of glucose units to glycogen residues and subsequent production of glucose-1-phosphate to be metabolized in glycolysis after conversion to glucose-6-phosphate. The impo......It has been proposed that a considerable fraction of glucose metabolism proceeds via the glycogen-shunt consisting of conversion of glucose units to glycogen residues and subsequent production of glucose-1-phosphate to be metabolized in glycolysis after conversion to glucose-6-phosphate....... The importance of this as well as the significance of ATP formed in glycolysis versus that formed by the concerted action of the tricarboxylic acid (TCA) cycle processes and oxidative phosphorylation for maintenance of glutamate transport capacity in astrocytes is discussed. It is argued that glycolytically...

  3. Developmental changes in hepatic glucose metabolism in a newborn piglet model: A comparative analysis for suckling period and early weaning period.

    Science.gov (United States)

    Xie, Chunyan; Wang, Qinhua; Wang, Jing; Tan, Bie; Fan, Zhiyong; Deng, Ze-yuan; Wu, Xin; Yin, Yulong

    2016-02-19

    The liver glucose metabolism, supplying sufficient energy for glucose-dependent tissues, is important in suckling or weaned animals, although there are few studies with piglet model. To better understand the development of glucose metabolism in the piglets during suckling period and early weaning period, we determined the hepatic glycogen content, and investigated the relative protein expression of key enzymes of glucogenesis (GNG) and mRNA levels of some glucose metabolism-related genes. During suckling period, the protein level of G6Pase in the liver of suckling piglets progressively declined with day of age compared with that of newborn piglets (at 1 day of age), whereas the PEPCK level stabilized until day 21 of age, indicating that hepatic GNG capacity gradually weakened in suckling piglets. The synthesis of hepatic glycogen, which was consistent with the fluctuation of glycolytic key genes PFKL and PKLR that gradually decreased after birth and was more or less steady during latter suckling period, although both the mRNA levels of GCK and key glucose transporter GLUT2 presented uptrend in suckling piglets. However, early weaning significantly suppressed the hepatic GNG in the weaned piglets, especially at d 3-5 of weaning period, then gradually recovered at d 7 of weaning period. Meanwhile, PFKL, PKLR and GLUT2 showed the similar trend during weaning period. On the contrast, the hepatic glycogen reached the maximum value when the G6Pase and PEPCK protein expression were at the lowest level, although the GCK level maintained increasing through 7 days of weaning period. Altogether, our study provides evidence that hepatic GNG and glycolysis in newborn piglets were more active than other days during suckling period, and early weaning could significantly suppressed glucose metabolism in liver, but this inhibition would progressively recover at day 7 after weaning. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Influência das formas de carboidratos no treinamento físico e na supercompensação glicogênica de ratos Influence of carbohydrates forms of in physical training and glycogen overcompensation in rats

    Directory of Open Access Journals (Sweden)

    Hesses Marani Lima

    2003-06-01

    , observou-se o aumento gradual dos teores dos lipídios totais, a cada hora, independentemente da forma de CHO consumida pelos animais.Two carbohydrates forms, sucrose and corn starch, were utilized, in the physical training of rats, having as basis the “classic” method of overcompensation of glycogen which includes the depletion of tissue glycogen followed by carbohydrate load. The analyzed parameters were body weight gain, feed conversion, feed efficiency, tissue muscle and hepatic glycogen levels, plasma glucose and serum total lipids. Wistar male rats were utilized, consuming diets with simples carbohydrates (CHOs and complex carbohydrates (CHOc. The experiment consisted of three phases: 1st phase- adaptation to the liquid medium, 2nd Phase- training, where the physical training program was established, in these phases 1 and 2 the groups were fed diets containing 75% of carbohydrates and finally in the 3rd phase- of “glycogen overcompensation”, a shift in the concentration of carbohydrates was done. Proceeding this phase, the groups were submitted to one day called the “event”, where all the groups swam for about 2 and a half hours and at the end of this, the replenishment of the tissue stores of glycogen in the following times 0, 6, 12, 24, 48 and 72 hours was monitored. The main results point out that: (a the physical training for rats raised the tissue glycogen levels; (b the forms of carbohydrates simple (sucrose or complex (corn starch, did not intervene in tissue glycogen, plasma glucose and serum total lipids; (c the overcompensation of glycogen rise higher store of glycogen in tissue hepatic rats as compared with tissue muscle; (d the greatest replenishment of glycogen in all tissues occurred within 12 hours consuming diets with either simple or complex diets; (e the complex form did not provide reduced levels of serum glucose in the 9-hour post-fasting; (f With advancing time, the gradual increase of the contents of the total lipids every hour

  5. Involvement of Glycogen Synthase Kinase-3 in the Mechanisms of Conditioned Food Aversion Memory Reconsolidation.

    Science.gov (United States)

    Nikitin, V P; Solntseva, S V; Kozyrev, S A

    2017-02-01

    Experiments were performed on the snails trained in conditioned food aversion for 3 days. Injection of TDZD-8 (glycogen synthase kinase-3 inhibitor, 2 mg/kg) in combination with reminder (presentation of a conditioned food stimulus) led to memory impairment developing 3 days after inhibitor/reminder exposure and followed by spontaneous recovery in 10 days. Injections of TDZD-8 in a dose of 4 or 20 mg/kg before reminder were shown to cause amnesia that persisted for more than 10 days. Memory recovery during repeated training was observed at the earlier period than after initial training. The impairment of memory reconsolidation by TDZD-8 after training of snails for 1 day was less pronounced than under standard training conditions (3 days). The effect of a glycogen synthase kinase-3 inhibitor during memory reconsolidation is probably followed by impairment of memory retrieval and/or partial loss, which can be compensated spontaneously or after repeated training.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-05-01

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

  7. Insight into "Consensus recommendations for diagnosis and treatment of glycogen storage disease typeⅡ"

    Directory of Open Access Journals (Sweden)

    Hong-zhi GUAN

    2014-05-01

    Full Text Available Glycogen storage disease typeⅡ (GSDⅡ is a rare progressive lysosomal storage disease caused by deficiency of acid α-glucosidase (GAA. The gene is located in 17q25.3. Diagnosis has been classically made by means of muscular biopsy. Nowadays it is more convenient to screen GAA in dried blood sample followed by GAA assessment in lymphocytes or fibroblasts or by the genetic analysis of mutations. Besides non-specific multiprofessional management, there is a specific enzyme replacement therapy (ERT since 2006 which compensates for the missing enzyme by administration of recombinant produced enzyme. "Consensus recommendations for diagnosis and treatment of glycogen storage disease type Ⅱ", published on Natl Med J China in 2013, gives us a novel and compressive insight into this rare disease. doi: 10.3969/j.issn.1672-6731.2014.05.003

  8. The Action of Antidiabetic Plants of the Canadian James Bay Cree Traditional Pharmacopeia on Key Enzymes of Hepatic Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    Abir Nachar

    2013-01-01

    Full Text Available We determined the capacity of putative antidiabetic plants used by the Eastern James Bay Cree (Canada to modulate key enzymes of gluconeogenesis and glycogen synthesis and key regulating kinases. Glucose-6-phosphatase (G6Pase and glycogen synthase (GS activities were assessed in cultured hepatocytes treated with crude extracts of seventeen plant species. Phosphorylation of AMP-dependent protein kinase (AMPK, Akt, and Glycogen synthase kinase-3 (GSK-3 were probed by Western blot. Seven of the seventeen plant extracts significantly decreased G6Pase activity, Abies balsamea and Picea glauca, exerting an effect similar to insulin. This action involved both Akt and AMPK phosphorylation. On the other hand, several plant extracts activated GS, Larix laricina and A. balsamea, far exceeding the action of insulin. We also found a significant correlation between GS stimulation and GSK-3 phosphorylation induced by plant extract treatments. In summary, three Cree plants stand out for marked effects on hepatic glucose homeostasis. P. glauca affects glucose production whereas L. laricina rather acts on glucose storage. However, A. balsamea has the most promising profile, simultaneously and powerfully reducing G6Pase and stimulating GS. Our studies thus confirm that the reduction of hepatic glucose production likely contributes to the therapeutic potential of several antidiabetic Cree traditional medicines.

  9. ¹³C MRS reveals a small diurnal variation in the glycogen content of human thigh muscle.

    Science.gov (United States)

    Takahashi, Hideyuki; Kamei, Akiko; Osawa, Takuya; Kawahara, Takashi; Takizawa, Osamu; Maruyama, Katsuya

    2015-06-01

    There is marked diurnal variation in the glycogen content of skeletal muscles of animals, but few studies have addressed such variations in human muscles. (13)C MRS can be used to noninvasively measure the glycogen content of human skeletal muscle, but no study has explored the diurnal variations in this parameter. This study aimed to investigate whether a diurnal variation in glycogen content occurs in human muscles and, if so, to what extent it can be identified using (13)C MRS. Six male volunteers were instructed to maintain their normal diet and not to perform strenuous exercise for at least 3 days before and during the experiment. Muscle glycogen and blood glucose concentrations were measured six times in 24 h under normal conditions in these subjects. The glycogen content in the thigh muscle was determined noninvasively by natural abundance (13)C MRS using a clinical MR system at 3 T. Nutritional analysis revealed that the subjects' mean carbohydrate intake was 463 ± 137 g, being approximately 6.8 ± 2.4 g/kg body weight. The average sleeping time was 5.9 ± 1.0 h. The glycogen content in the thigh muscle at the starting point was 64.8 ± 20.6 mM. Although absolute and relative individual variations in muscle glycogen content were 7.0 ± 2.1 mM and 11.3 ± 4.6%, respectively, no significant difference in glycogen content was observed among the different time points. This study demonstrates that normal food intake (not fat and/or carbohydrate rich), sleep and other daily activities have a negligible influence on thigh muscle glycogen content, and that the diurnal variation of the glycogen content in human muscles is markedly smaller than that in animal muscles. Moreover, the present results also support the reproducibility and availability of (13)C MRS for the evaluation of the glycogen content in human muscles. Copyright © 2015 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

  12. Molar mass and solution conformation of branched alpha(1 - 4), alpha(1 - 6) Glucans. Part I: Glycogens in water

    OpenAIRE

    Morris, Gordon; Ang, S.; Hill, S. E.; Lewis, S.; Schafer, B.; Nobbmann, U.; Harding, S. E.

    2008-01-01

    Solution molar masses and conformations of glycogens from different sources (rabbit, oyster, mussel and bovine) were analysed using sedimentation velocity in the analytical ultracentrifuge, size-exclusion chromatography coupled to multi-angle laser light scattering (SEC-MALLS), size-exclusion chromatography coupled to a differential pressure viscometer and dynamic light scattering. Rabbit, oyster and mussel glycogens consisted of one population of high molar mass (weight averages ranging from...

  13. Biological characterization of a novel hybrid copolymer carrier system based on glycogen

    Czech Academy of Sciences Publication Activity Database

    Jirátová, M.; Pospíšilová, Aneta; Rabyk, Mariia; Pařízek, Martin; Kovář, J.; Gálisová, A.; Hrubý, Martin; Jirák, D.

    2018-01-01

    Roč. 8, č. 1 (2018), s. 73-82 ISSN 2190-393X R&D Projects: GA MZd(CZ) NV15-25781A; GA ČR(CZ) GA13-08336S; GA ČR(CZ) GAP108/12/1168 Institutional support: RVO:61389013 ; RVO:67985823 Keywords : glycogen * polymers * drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Pharmacology and pharmacy Impact factor: 3.094, year: 2016

  14. Molecular Mechanisms of Allosteric Inhibition of Brain Glycogen Phosphorylase by Neurotoxic Dithiocarbamate Chemicals.

    Science.gov (United States)

    Mathieu, Cécile; Bui, Linh-Chi; Petit, Emile; Haddad, Iman; Agbulut, Onnik; Vinh, Joelle; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2017-02-03

    Dithiocarbamates (DTCs) are important industrial chemicals used extensively as pesticides and in a variety of therapeutic applications. However, they have also been associated with neurotoxic effects and in particular with the development of Parkinson-like neuropathy. Although different pathways and enzymes (such as ubiquitin ligases or the proteasome) have been identified as potential targets of DTCs in the brain, the molecular mechanisms underlying their neurotoxicity remain poorly understood. There is increasing evidence that alteration of glycogen metabolism in the brain contributes to neurodegenerative processes. Interestingly, recent studies with N,N-diethyldithiocarbamate suggest that brain glycogen phosphorylase (bGP) and glycogen metabolism could be altered by DTCs. Here, we provide molecular and mechanistic evidence that bGP is a target of DTCs. To examine this system, we first tested thiram, a DTC pesticide known to display neurotoxic effects, observing that it can react rapidly with bGP and readily inhibits its glycogenolytic activity (kinact = 1.4 × 105 m-1 s-1). Using cysteine chemical labeling, mass spectrometry, and site-directed mutagenesis approaches, we show that thiram (and certain of its metabolites) alters the activity of bGP through the formation of an intramolecular disulfide bond (Cys318-Cys326), known to act as a redox switch that precludes the allosteric activation of bGP by AMP. Given the key role of glycogen metabolism in brain functions and neurodegeneration, impairment of the glycogenolytic activity of bGP by DTCs such as thiram may be a new mechanism by which certain DTCs exert their neurotoxic effects. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Rapid Detection of Glycogen Synthase Kinase-3 Activity in Mouse Sperm Using Fluorescent Gel Shift Electrophoresis

    OpenAIRE

    Hoseok Choi; Bomi Choi; Ju Tae Seo; Kyung Jin Lee; Myung Chan Gye; Young-Pil Kim

    2016-01-01

    Assaying the glycogen synthase kinase-3 (GSK3) activity in sperm is of great importance because it is closely implicated in sperm motility and male infertility. While a number of studies on GSK3 activity have relied on labor-intensive immunoblotting to identify phosphorylated GSK3, here we report the simple and rapid detection of GSK3 activity in mouse sperm using conventional agarose gel electrophoresis and a fluorescent peptide substrate. When a dye-tethered and prephosphorylated (primed) p...

  16. Clinical study of respiratory function in patients with late-onset glycogen storage disease typeⅡ

    Directory of Open Access Journals (Sweden)

    Wei-na JIN

    2014-05-01

    Full Text Available Background Late-onset glycogen storage disease typeⅡ(GSDⅡ, Pompe disease is an autosomal recessive disease exhibiting progressive proximal skeletal muscle weakness and respiratory muscle involvement, caused by deficiency of the lysosomal enzyme acid α-glucosidase (GAA. Most of patients died of respiratory failure.  Methods Eleven patients with late-onset glycogen storage disease type Ⅱ underwent respiratory function evaluation, whose diagnosis was confirmed by muscle pathology, GAA activity assay and gene analysis. Respiratory function evaluation included upright and supine position of forced vital capacity (FVC, forced expiratory volume at the first second (FEV1, maximal inspiratory pressure (MIP, maximal expiratory pressure (MEP and cough peak flow (CPF. All data were compared with predicted value. The decreased value between upright and supine position FVC ( △ FVC were calculated. The correlation between respiratory function and the age of onset, disease course, motor function, GAA activity were analyzed.  Results All of 11 patients with late-onset glycogen storage disease type Ⅱ showed declined respiratory function compared with predicted value. The upright FVC, upright FEV1, △ FVC, MIP, MEP and CPF declined in 10, 10, 8, 11, 10, and 10 patients, respectively. All patients had normal FEV1/FVC in both upright and supine position. There was no correlation between upright FVC, △ FVC and the onset age, disease course, motor function, GAA activity statistically.  Conclusions Pulmonary dysfunction is common in late-onset glycogen storage disease type Ⅱ, with restrictive ventilatory impairment more predominant, which is caused by inspiratory muscle weakness. doi: 10.3969/j.issn.1672-6731.2014.05.007

  17. 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.

  18. 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...

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

    Science.gov (United States)

    Sickmann, Helle M; Waagepetersen, Helle S

    2015-02-01

    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 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 understanding of how brain energy and neurotransmitter metabolism is affected in diabetes. There will be a particular focus on the role of brain glycogen to support glycolytic and TCA cycle activity as well as glutamate-glutamine cycle in type 1 and type 2 diabetes.

  20. A plastid-localized glycogen synthase kinase 3 modulates stress tolerance and carbohydrate metabolism.

    Science.gov (United States)

    Kempa, Stefan; Rozhon, Wilfried; Samaj, Jozef; Erban, Alexander; Baluska, Frantisek; Becker, Thomas; Haselmayer, Joachim; Schleiff, Enrico; Kopka, Joachim; Hirt, Heribert; Jonak, Claudia

    2007-03-01

    Glycogen synthase kinase 3 (GSK-3) was originally identified as a regulator of glycogen synthesis in mammals. Like starch in plants, glycogen is a polymer of glucose, and serves as an energy and carbon store. Starch is the main carbohydrate store in plants. Regulation of starch metabolism, in particular in response to environmental cues, is of primary importance for carbon and energy flow in plants but is still obscure. Here, we provide evidence that MsK4, a novel Medicago sativa GSK-3-like kinase, connects stress signalling with carbon metabolism. MsK4 was found to be a plastid-localized protein kinase that is associated with starch granules. High-salt stress rapidly induced the in vivo kinase activity of MsK4. Metabolic profiling of MsK4 over-expressor lines revealed changes in sugar metabolism, including increased amounts of maltose, the main degradation product of starch in leaves. Plants over-expressing MsK4 showed improved tolerance to salt stress. Moreover, under high-salinity conditions, MsK4-over-expressing plants accumulated significantly more starch and showed modified carbohydrate content compared with wild-type plants. Overall, these data indicate that MsK4 is an important regulator that adjusts carbohydrate metabolism to environmental stress.

  1. THE ROLE OF POST-EXERCISE NUTRIENT ADMINISTRATION ON MUSCLE PROTEIN SYNTHESIS AND GLYCOGEN SYNTHESIS

    Directory of Open Access Journals (Sweden)

    Chris Poole

    2010-09-01

    Full Text Available Nutrient administration following an exercise bout vastly affects anabolic processes within the human body, irrespective of exercise mode. Of particular importance are protein and carbohydrates whereby these two macronutrients portray distinct functions as anabolic agents. It has been confirmed that protein and/or amino acid ingestion following resistance training is required to reach a positive protein/nitrogen balance, and carbohydrate intake during recovery is the most important consideration to replenish glycogen stores from an exhaustive exercise bout. Several factors play significant roles in determining the effectiveness of protein and carbohydrate supplementation on post-exercise protein and glycogen synthesis. Improper application of these factors can limit the body's ability to reach an anabolic status. The provided evidence clearly denotes the importance these two macronutrients have in regards to post-exercise nutrition and anabolism. Therefore, the purpose of this review is to discuss the impact of dietary protein and carbohydrate intake during the recovery state on muscle protein synthesis and glycogen synthesis

  2. The Csr System Regulates Escherichia coli Fitness by Controlling Glycogen Accumulation and Energy Levels

    Directory of Open Access Journals (Sweden)

    Manon Morin

    2017-10-01

    Full Text Available In the bacterium Escherichia coli, the posttranscriptional regulatory system Csr was postulated to influence the transition from glycolysis to gluconeogenesis. Here, we explored the role of the Csr system in the glucose-acetate transition as a model of the glycolysis-to-gluconeogenesis switch. Mutations in the Csr system influence the reorganization of gene expression after glucose exhaustion and disturb the timing of acetate reconsumption after glucose exhaustion. Analysis of metabolite concentrations during the transition revealed that the Csr system has a major effect on the energy levels of the cells after glucose exhaustion. This influence was demonstrated to result directly from the effect of the Csr system on glycogen accumulation. Mutation in glycogen metabolism was also demonstrated to hinder metabolic adaptation after glucose exhaustion because of insufficient energy. This work explains how the Csr system influences E. coli fitness during the glycolysis-gluconeogenesis switch and demonstrates the role of glycogen in maintenance of the energy charge during metabolic adaptation.

  3. Body metal concentrations and glycogen reserves in earthworms (Dendrobaena octaedra) from contaminated and uncontaminated forest soil

    Energy Technology Data Exchange (ETDEWEB)

    Holmstrup, Martin, E-mail: martin.holmstrup@dmu.d [National Environmental Research Institute, Aarhus University, Department of Terrestrial Ecology, Vejlsovej 25, DK-8600 Silkeborg (Denmark); Sorensen, Jesper G. [National Environmental Research Institute, Aarhus University, Department of Terrestrial Ecology, Vejlsovej 25, DK-8600 Silkeborg (Denmark); Overgaard, Johannes; Bayley, Mark [Zoophysiology, Department of Biological Sciences, Aarhus University, Building 131, DK-8000 Aarhus C (Denmark); Bindesbol, Anne-Mette [National Environmental Research Institute, Aarhus University, Department of Terrestrial Ecology, Vejlsovej 25, DK-8600 Silkeborg (Denmark); Zoophysiology, Department of Biological Sciences, Aarhus University, Building 131, DK-8000 Aarhus C (Denmark); Slotsbo, Stine; Fisker, Karina V.; Maraldo, Kristine [National Environmental Research Institute, Aarhus University, Department of Terrestrial Ecology, Vejlsovej 25, DK-8600 Silkeborg (Denmark); Waagner, Dorthe [National Environmental Research Institute, Aarhus University, Department of Terrestrial Ecology, Vejlsovej 25, DK-8600 Silkeborg (Denmark); Zoophysiology, Department of Biological Sciences, Aarhus University, Building 131, DK-8000 Aarhus C (Denmark); Labouriau, Rodrigo [Aarhus University, Faculty of Agricultural Sciences, Department of Genetics and Biotechnology, Research Centre Foulum, Blichers Alle 20, P.O. Box 50, DK-8830 Tjele (Denmark); Asmund, Gert [National Environmental Research Institute, Aarhus University, Department of Arctic Environment, Frederiksborgvej 399, DK-4000 Roskilde (Denmark)

    2011-01-15

    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. - Detoxification and accumulation of cadmium and lead by earthworms carries little energetic expenses whereas strict internal regulation of aluminium and nickel has energetic costs.

  4. Leucine-Enriched Essential Amino Acids Augment Muscle Glycogen Content in Rats Seven Days after Eccentric Contraction

    Directory of Open Access Journals (Sweden)

    Hiroyuki Kato

    2017-10-01

    Full Text Available Eccentric contractions induce muscle damage, which impairs recovery of glycogen and adenosine tri-phosphate (ATP content over several days. Leucine-enriched essential amino acids (LEAAs enhance the recovery in muscles that are damaged after eccentric contractions. However, the role of LEAAs in this process remains unclear. We evaluated the content in glycogen and high energy phosphates molecules (phosphocreatine (PCr, adenosine di-phosphate (ADP and ATP in rats that were following electrically stimulated eccentric contractions. Muscle glycogen content decreased immediately after the contraction and remained low for the first three days after the stimulation, but increased seven days after the eccentric contraction. LEAAs administration did not change muscle glycogen content during the first three days after the contraction. Interestingly, however, it induced a further increase in muscle glycogen seven days after the stimulation. Contrarily, ATP content decreased immediately after the eccentric contraction, and remained lower for up to seven days after. Additionally, LEAAs administration did not affect the ATP content over the experimental period. Finally, ADP and PCr levels did not significantly change after the contractions or LEAA administration. LEAAs modulate the recovery of glycogen content in muscle after damage-inducing exercise.

  5. Hepatic sarcoidosis complicating treatment-naive viral hepatitis

    OpenAIRE

    Aravinthan, Aloysious; Gelson, William; Limbu, Anita; Brais, Rebecca; Richardson, Paul

    2012-01-01

    Hepatic sarcoidosis is usually asymptomatic but rarely leads to adverse liver-related outcome. Co-existence of viral hepatitis and hepatic sarcoidosis is a rare, but recognised phenomenon. Obtaining a balance between immune suppression and anti-viral therapy may be problematic. Immunosuppression in the presence of viral hepatitis can lead to rapid deterioration of liver disease. Similarly, anti-viral therapy may exacerbate granulomatous hepatitis. Here we present two cases of viral hepatitis ...

  6. Autophagy in Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Yang Song

    2014-01-01

    Full Text Available Hepatic fibrosis is a leading cause of morbidity and mortality worldwide. Hepatic fibrosis is usually associated with chronic liver diseases caused by infection, drugs, metabolic disorders, or autoimmune imbalances. Effective clinical therapies are still lacking. Autophagy is a cellular process that degrades damaged organelles or protein aggregation, which participates in many pathological processes including liver diseases. Autophagy participates in hepatic fibrosis by activating hepatic stellate cells and may participate as well through influencing other fibrogenic cells. Besides that, autophagy can induce some liver diseases to develop while it may play a protective role in hepatocellular abnormal aggregates related liver diseases and reduces fibrosis. With a better understanding of the potential effects of autophagy on hepatic fibrosis, targeting autophagy might be a novel therapeutic strategy for hepatic fibrosis in the near future.

  7. Hepatitis isquémica Ischemic hepatitis

    Directory of Open Access Journals (Sweden)

    Marcos Amuchástegui (h

    2006-10-01

    Full Text Available La hepatitis isquémica es una complicación sumamente infrecuente de cirugía cardiovascular. Las biopsias muestran necrosis centrolobulillar. El término de "hepatitis" fue propuesto debido al aumento de transaminasas similar a aquellas de origen infeccioso, e "isquémica" por falla en la perfusión hepática. Posteriormente se definió el término de hepatitis isquémica como cuadro de elevación aguda y reversible (dentro de las 72 horas de transaminasas de hasta 20 veces el valor normal, asociado a trastornos en la perfusión hepática, luego de haber excluido otras causas de hepatitis aguda o daño hepatocelular. Se describe el caso de un paciente de 53 años que consulta por dolor epigástrico de 12 h de evolución sin fiebre, náuseas ni vómitos, resistente a la medicación. Tenía antecedentes inmediatos de reemplazo de válvula aórtica, y estaba anticoagulado. Evolucionó con shock y fallo multiorgánico. El examen evidenció marcada ictericia y signos de taponamiento pericárdico, asociado a un aumento considerable de enzimas hepáticas. Un ecocardiograma informó signos de taponamiento cardíaco y ausencia de disección aórtica. Se decidió pericardiocentesis, extrayéndose 970 cc. de líquido sanguinolento, y hemodiálisis, con notable mejoría de su estado hemodinámico. Los valores enzimáticos disminuyeron. Los marcadores virales fueron negativos.Ischemic hepatitis is an uncommon cardiovascular surgery complication. Hepatic biopsies show centrolobulillar necrosis. The term "hepatitis" was proposed because of a raise in hepatic enzymes similar with infectious disease, and "ischemic" because of failure in hepatic perfusion. Ischemic hepatitis was then defined as an acute and reversible elevation of hepatic enzymes (within 72 h, associated with disturbance in hepatic perfusion after excluding other causes of acute hepatitis. A 53 year-old male presented complaining of a 12 h epigastric pain, without nausea or vomiting, resistant

  8. Hepatitis E Virus

    Directory of Open Access Journals (Sweden)

    Christina Levick

    2014-05-01

    Full Text Available Hepatitis E virus (HEV is the most common cause of acute viral hepatitis in the developing world. It is a waterborne virus that can cause epidemics in the face of overcrowding and poor sanitation. Although the hepatitis illness is usually self-limiting, it has a high mortality in pregnant women and can become a chronic infection in the immunosuppressed. Treatment is mostly supportive and prevention is by good water hygiene.

  9. Preventing hepatitis B or C

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000401.htm Preventing hepatitis B or C To use the sharing features on this page, please enable JavaScript. Hepatitis B and hepatitis C infections cause irritation and ...

  10. Bone repair in calcium-deficient rats: comparison of xylitol+calcium carbonate with calcium carbonate, calcium lactate and calcium citrate on the repletion of calcium.

    Science.gov (United States)

    Hämäläinen, M M

    1994-06-01

    The potential value of xylitol in calcium therapy was evaluated by comparing the effect of dietary xylitol (50 g/kg diet) + calcium carbonate with the effects of calcium carbonate, calcium lactate and calcium citrate on bone repair of young male rats after the rats consumed for 3 wk a calcium-deficient diet (0.2 g Ca/kg diet). After this calcium-depletion period, the rats were fed for 2 wk one of four diets, each containing 5 g Ca/kg diet as one of the four dietary calcium sources. The diet of the control animals was supplemented with CaCO3 (5 g Ca/kg diet) throughout the study. The Ca-deficient rats showed low bone mass, low serum calcium and high serum 1,25-dihydroxycholecalciferol, parathyroid hormone (1-34 fraction) and osteocalcin concentrations. They also excreted magnesium, phosphate and hydroxyproline in the urine in high concentrations, and had high bone alkaline phosphatase and tartrate-resistant acid phosphatase activities. Most of these changes were reversed by the administered of the calcium salts. The highest recoveries of femoral dry weight, calcium, magnesium and phosphate were observed in the groups receiving xylitol+CaCO3 and calcium lactate. Calcium lactate and calcium citrate caused low serum phosphate concentration compared with rats receiving CaCO3 and with the age-matched Ca-replete controls. Xylitol-treated rats excreted more calcium and magnesium in urine than did the other rats, probably due to increased absorption of these minerals from the gut. These results suggest that dietary xylitol improves the bioavailability of calcium salts.

  11. Dietary repletion with ω3 fatty acid or with COX inhibition reverses cognitive effects in F3 ω3 fatty-acid-deficient mice.

    Science.gov (United States)

    Hafandi, Ahmad; Begg, Denovan P; Premaratna, Shirmila D; Sinclair, Andrew J; Jois, Mark; Weisinger, Richard S

    2014-04-01

    Dietary deficiency of ω3 fatty acid during development leads to impaired cognitive function. However, the effects of multiple generations of ω3 fatty-acid deficiency on cognitive impairment remain unclear. In addition, we sought to test the hypothesis that the cognitive impairments of ω3 fatty-acid-deficient mice are mediated through the arachidonic acid-cyclooxygenase (COX) pathway. To address these issues, C57BL/6J mice were bred for 3 generations and fed diets either deficient (DEF) or sufficient (SUF) in ω3 fatty acids. At postnatal day 21, the F3 offspring remained on the dam's diet or were switched to the opposite diet, creating 4 groups. In addition, 2 groups that remained on the dam's diet were treated with a COX inhibitor. At 19 wk of age, spatial-recognition memory was tested on a Y-maze. Results showed that 16 wk of SUF diet reversed the cognitive impairment of F3 DEF mice. However, 16 wk of ω3 fatty-acid-deficient diet impaired the cognitive performance of the F3 SUF mice, which did not differ from that of the F3 DEF mice. These findings suggest that the cognitive deficits after multigenerational maintenance on ω3 fatty-acid-deficient diet are not any greater than are those after deficiency during a single generation. In addition, treatment with a COX inhibitor prevented spatial-recognition deficits in F3 DEF mice. Therefore, cognitive impairment due to dietary ω3 fatty-acid deficiency appears to be mediated by the arachidonic acid-COX pathway and can be prevented by 16 wk of dietary repletion with ω3 fatty acids or COX inhibition.

  12. Hepatitis C: Information on Testing and Diagnosis

    Science.gov (United States)

    HEPATITIS C Information on Testing & Diagnosis What is Hepatitis C? Hepatitis C is a serious liver disease that results from infection with the Hepatitis C virus. Hepatitis C has been called a silent ...

  13. Production of polyhydroxyalkanoates from fermented sugar cane molasses by a mixed culture enriched in glycogen accumulating organisms.

    Science.gov (United States)

    Bengtsson, Simon; Pisco, Ana R; Reis, Maria A M; Lemos, Paulo C

    2010-02-01

    Batch production of polyhydroxyalkanoates (PHAs) under aerobic conditions by an open mixed culture enriched in glycogen accumulating organisms (GAOs) with fermented sugar cane molasses as substrate was studied. The produced polymers contained five types of monomers, namely 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV), 3-hydroxy-2-methylbutyrate (3H2MB), 3-hydroxy-2-methylvalerate (3H2MV) and the medium chain length monomer 3-hydroxyhexanoate (3HHx). With fermented molasses as substrate, PHA was produced under concurrent consumption of stored glycogen with yields of 0.47-0.66 C-mol PHA per C-mol of total carbon substrate and with rates up to 0.65 C-mol/C-molX h. In order to investigate the role of glycogen during aerobic PHA accumulation in GAOs, synthetic single volatile fatty acids (VFAs) were used as substrates and it was found that the fate of glycogen was dependent on the type of VFA being consumed. Aerobic PHA accumulation occurred under concurrent glycogen consumption with acetate as substrate and under minor concurrent glycogen production with propionate as substrate. With butyrate and valerate as substrates, PHA accumulation occurred with the glycogen pool unaffected. The composition of the PHA was dependent on the VFA composition of the fermented molasses and was 56-70 mol-% 3HB, 13-43 mol-% 3HV, 1-23 mol-% 3HHx and 0-2 mol-% 3H2MB and 3H2MV. The high polymer yields and production rates suggest that enrichment of GAOs can be a fruitful strategy for mixed culture production of PHA from waste substrates. Copyright 2009 Elsevier B.V. All rights reserved.

  14. THE EFFECT OF INSULIN AND CARBOHYDRATE SUPPLEMENTATION ON GLYCOGEN REPLENISHMENT AMONG DIFFERENT HINDLIMB MUSCLES IN RATS FOLLOWING PROLONGED SWIMMING

    Directory of Open Access Journals (Sweden)

    Mei-Chich Hsu

    2012-04-01

    Full Text Available In the present study we investigated the interactive effects of insulin and carbohydrate on glycogen replenishment in different rat hindlimb muscles. Forty male Sprague Dawley rats were assigned to 5 groups, including 1 sedentary control with carbohydrate supplement (2 g glucose · kg body wt-1, 2 sedentary rats with 16 hours recovery, carbohydrate and insulin (0.5 U · kg body wt-1, 3 swimming without recovery, 4 swimming with 16 hours recovery and carbohydrate supplement, and 5 swimming with 16 hours recovery, carbohydrate and insulin. The swimming protocol consisted of two 3 h swimming sections, which were separated by a 45 min rest. The insulin and carbohydrate were administered to the rats immediately after exercise. At the end of the experiment, the soleus (S, plantaris (P, quadriceps (Q and gastrocnemius (G were surgically excised to evaluate glycogen utilization and replenishment. We observed that glycogen utilization was significantly lower in G and Q than S and P during swimming (p <0.05, and S showed the greatest capacity of glycogen resynthesis after post-exercise recovery (p <0.05. In the sedentary state, the glycogen synthesis did not differ among hindlimb muscles during insulin and carbohydrate treatments. Interestingly, with insulin and carbohydrate, the glycogen resynthesis in S and P were significantly greater than in Q and G following post-exercise recovery (p <0.05. We therefore concluded that the soleus and plantaris are the primary working muscles during swimming, and the greatest glycogen replenishment capacity of the soleus during post-exercise recovery is likely due to its highest insulin sensitivity.

  15. Engraftment Potential of Spheroid-Forming Hepatic Endoderm Derived from Human Embryonic Stem Cells

    Science.gov (United States)

    Kim, Sung-Eun; An, Su Yeon; Woo, Dong-Hun; Han, Jiyou; Kim, Jong Hyun; Jang, Yu Jin; Son, Jeong Sang; Yang, Hyunwon; Cheon, Yong Pil

    2013-01-01

    Transplantation and drug discovery programs for liver diseases are hampered by the shortage of donor tissue. While recent studies have shown that hepatic cells can be derived from human embryonic stem cells (hESCs), few cases have shown selective enrichment of hESC-derived hepatocytes and their integration into host liver tissues. Here we demonstrate that the dissociation and reaggregation procedure after an endodermal differentiation of hESC produces spheroids mainly consisted of cells showing hepatic phenotypes in vitro and in vivo. A combined treatment with Wnt3a and bone morphogenic protein 4 efficiently differentiated hESCs into definitive endoderm in an adherent culture. Dissociation followed by reaggregation of these cells in a nonadherent condition lead to the isolation of spheroid-forming cells that preferentially expressed early hepatic markers from the adherent cell population. Further differentiation of these spheroid cells in the presence of the hepatocyte growth factor, oncostatin M, and dexamethasone produced a highly enriched population of cells exhibiting characteristics of early hepatocytes, including glycogen storage, indocyanine green uptake, and synthesis of urea and albumin. Furthermore, we show that grafted spheroid cells express hepatic features and attenuate the serum aspartate aminotransferase level in a model of acute liver injury. These data suggest that hepatic progenitor cells can be enriched by the spheroid formation of differentiating hESCs and that these cells have engraftment potential to replace damaged liver tissues. PMID:23373441

  16. 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...... dephosphorylated state. In a search for genetic defects responsible for the decreased insulin stimulated glycogen synthesis seen in patients with non-insulin-dependent diabetes mellitus (NIDDM) and their glucose-tolerant first-degree relatives we have performed mutational analysis of the coding region of the 2...

  17. Hepatic adenomatosis: rapid sequence MR imaging following gadolinium enhancement: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Brummett, D. [Dept. of Radiology, Medical College of Georgia, Augusta (United States); Burton, E.M. [Dept. of Radiology, Medical College of Georgia, Augusta (United States)]|[Dept. of Pediatrics, Medical College of Georgia, Augusta (United States); Sabio, H. [Dept. of Pediatrics, Medical College of Georgia, Augusta (United States)

    1999-04-01

    Hepatic adenomas are primary liver tumors usually associated with underlying metabolic disease or with anabolic steroid or oral contraceptive use. Hepatic adenomatosis (HA) is defined as the presence of more than four adenomas. Only 13 cases of HA have been reported in patients without glycogen storage disease or steroid use. We report a case of HA imaged by postcontrast T1-weighted images obtained during a breath-holding series. The lesions were most conspicuous 3-4 min after contrast administration; 4 of the 5 tumors were not identified on T2-weighted images. Unlike previous reports of HA in which the lesions remained hyperintense during sequential postcontrast imaging, the smaller lesions in this case demonstrated contrast washout, thereby distinguishing them from hemangiomata. (orig.) With 3 figs., 10 refs.

  18. Hepatitis E og graviditet

    DEFF Research Database (Denmark)

    Mannheimer, Ebba Elisabeth; Harritshøj, Lene Holm; Katzenstein, Terese Lea

    2016-01-01

    Hepatitis E virus (HEV) infection among pregnant women is severe, often leading to fulminant hepatic failure and death, with mortality rates up to 15-25%. Studies suggest that differences in genotypes/subgenotypes, hormonal and immunological changes during pregnancy may contribute to the severe...

  19. hy viral hepatitis?

    African Journals Online (AJOL)

    randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional. Therapy Group. N Engl J Med 1990; 323: 295-301. 14. Ncayiyana DJ. Coming to grips with the future of health care - the ANC National. Health Plan. 5 Air Med J 1994; ...

  20. Cytomegalovirus Hepatitis During Pregnancy

    Directory of Open Access Journals (Sweden)

    Ying Chan

    1995-01-01

    Full Text Available Background: Although cytomegalovirus (CMV is an uncommon cause of viral hepatitis during pregnancy, a definitive diagnosis is important because of the potential for congenital CMV. In the case reported here, a diagnosis of hepatitis caused by CMV was made after the more common viral pathogens had been ruled out.