Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GLYCOGEN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1997

Blood flow, lipid oxidation, and muscle glycogen synthesis after glycogen depletion by strenuous exercise.

UNLABELLED: We studied the interrelationship between blood flow, glycogen synthesis, and glucose and lipid utilization in 14 healthy men. A 4-h euglycemic insulin clamp with indirect calorimetry and muscle biopsies were done after a glycogen depletion (exercise) and after a resting day (control). In spite of the exercise induced decrease in leg muscle glycogen content (28% in the basal state, 22% after hyperinsulinemia, P < 0.05 in both as compared with the control study), basal or insulin stimulated glycogen synthase activity remained unchanged. In the basal state, glucose oxidation was 54% lower (P < 0.001) and lipid oxidation 108% higher (P < 0.001) after the glycogen depletion as compared with that in the control study. During the post-depletion insulin clamp, the glucose oxidation rate was 17% lower (P < 0.02) and lipid oxidation 169% higher (P < 0.01), while the whole body total glucose disposal was similar in both studies. Baseline forearm blood flow was similar and increased equally by over 40% during both insulin clamp studies (P < 0.05). Basal glucose extraction after glycogen depletion study was one third of that in the control study (P < 0.05). Both basal and insulin stimulated leg muscle glycogen content correlated inversely with basal forearm blood flow (r = -0.69, P < 0.01 and r = -0.82, P < 0.001, respectively) and basal lipid oxidation (r = -0.54, P < 0.05 and r = -0.64, P < 0.01, respectively) after glycogen depletion. Basal glycogen synthase fractional activity correlated positively with forearm blood flow (r = 0.78, P < 0.001) and forearm glucose uptake (r = 0.71, P < 0.05) during the insulin infusion. IN CONCLUSION: 1) the unchanged insulin sensitivity in the face of glycogen depletion is probably a result of increased lipid oxidation, and 2) blood flow is related inversely to muscle glycogen content and directly to glycogen synthase activity.

Adult↗
PubMed1992

Particulate glycogen of mammalian liver: specificity in binding phosphorylase and glycogen synthase.

The glycogen particle - glycogen metabolizing enzyme complex was investigated to gain some understanding of its physiological significance. Fractionations of populations of particles from mouse liver were carried out utilising open column and high performance liquid chromatography, and based either on the molecular weight of the particles or the hydrophobic interactions of the glycogen-associated proteins. The activities of glycogen phosphorylase and glycogen synthase were measured in these fractions. Fractionations were of tissue in different stages of glycogen deposition or mobilization. In animals fed ad libitum, glycogen synthase was associated with the whole spectrum of molecular weights, while the glycogen phosphorylase distribution was skewed in favour of the lower molecular weight species. Under conditions of glycogen mobilization, the phosphorylase distribution changed to include all molecular weights. The hydrophobic interaction separations demonstrated that glycogen synthase binds to a specific subpopulation of particles that is a minor proportion of the total. In general, there was a direct relationship of the total amount of phosphorylase and synthase bound during periods of mobilization and deposition, respectively. Two notable exceptions were the large amounts of glucose-6-P dependent synthase present during the early period of glycogen mobilization and the high amounts of active phosphorylase appearing shortly after food withdrawal, in spite of interim glycogen deposition from presumably already ingested food.

Animals↗
PubMed2000

Control of glycogen synthesis is shared between glucose transport and glycogen synthase in skeletal muscle fibers.

The effects of transgenic overexpression of glycogen synthase in different types of fast-twitch muscle fibers were investigated in individual fibers from the anterior tibialis muscle. Glycogen synthase was severalfold higher in all transgenic fibers, although the extent of overexpression was twofold greater in type IIB fibers. Effects of the transgene on increasing glycogen and phosphorylase and on decreasing UDP-glucose were also more pronounced in type IIB fibers. However, in any grouping of fibers having equivalent malate dehydrogenase activity (an index of oxidative potential), glycogen was higher in the transgenic fibers. Thus increasing synthase is sufficient to enhance glycogen accumulation in all types of fast-twitch fibers. Effects on glucose transport and glycogen synthesis were investigated in experiments in which diaphragm, extensor digitorum longus (EDL), and soleus muscles were incubated in vitro. Transport was not increased by the transgene in any of the muscles. The transgene increased basal [(14)C]glucose into glycogen by 2.5-fold in the EDL, which is composed primarily of IIB fibers. The transgene also enhanced insulin-stimulated glycogen synthesis in the diaphragm and soleus muscles, which are composed of oxidative fiber types. We conclude that increasing glycogen synthase activity increases the rate of glycogen synthesis in both oxidative and glycolytic fibers, implying that the control of glycogen accumulation by insulin in skeletal muscle is distributed between the glucose transport and glycogen synthase steps.

Animals↗
PubMed2005

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

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 sensitivities of these two enzymes may exemplify the adaptive strategies employed by liver and muscle cells to meet specific cellular demands.

Animals↗
PubMed1986

Glycogen synthase and phosphorylase activities during glycogen repletion in endotoxemic rats.

The activities of glycogen synthase and glycogen phosphorylase were quantitated in liver and skeletal muscle removed following glucose infusion in hemodynamically stable endotoxin-treated rats. Four hours after the IV injection of endotoxin or saline, rats were infused with 235 mumole/min/kg of glucose or saline for up to 4 additional hr. Saline-infused endotoxemic rats had lower basal glycogen content in muscle and liver, which was associated with an increased phosphorylase a activity in both tissues compared to controls. During the glucose infusion, the rate of glycogen repletion in muscle was similar in the two groups. Skeletal muscle phosphorylase a and glycogen synthase I & D activities were elevated above control values in endotoxemia, while glycogen synthase I activity remain unchanged. These changes in the activity of muscle phosphorylase and synthase are consistent with an increased flux of carbon into and out of glycogen and a normal rate of net glycogen synthesis during glucose infusion in endotoxin-treated rats. In contrast to muscle, hepatic glycogen synthesis by endotoxemic animals was reduced compared to glucose-infused controls. Hepatic glycogen repletion in control animals appeared to be mediated primarily by a glucose-induced suppression of phosphorylase a activity rather than an increased glycogen synthase activity. Glucose infusion failed to decrease phosphorylase a activity in endotoxin-treated rats, which may be causally related to the impaired ability of these animals to replete liver glycogen.

Animals↗
PubMed2000

Muscle glycogen does not interfere with a 13CO2 breath test to monitor liver glycogen oxidation.

Naturally 13C-enriched carbohydrate has been used to label the liver glycogen pool for metabolic studies. The utilization of this glycogen was then monitored by the appearance of 13CO2 in breath. Using this method, it is assumed that during sedentary fasting the contribution of muscle glycogen towards oxidation is negligible. We investigated the influence of a different level of 13C enrichment of muscle glycogen on the 13C enrichment of breath CO2 while the breath test was carried out. In six healthy volunteers, the muscle glycogen stores were grossly depleted by a cycling exercise prior to consumption of the 13C-enriched diet which was given over a 10 h period. The oxidation of liver glycogen was measured during an 18 h sedentary fast. The results were compared with a control group who had not depleted their muscle glycogen before labelling. A higher 13C enrichment of muscle glycogen did not interfere with two parameters of liver glycogen oxidation, i.e. the duration of the plateau phase of 13CO2 and the return to baseline time. It was also shown that the 13C-labelled muscle glycogen was still available after the 18 h fast because a strenuous exercise led to a rapid 13CO2 enrichment. It is concluded that muscle glycogen 13C enrichment does not invalidate a 13CO2 breath test to measure liver glycogen oxidation during a sedentary fast.

Adult↗
PubMed1998

Overexpression of protein targeting to glycogen (PTG) in rat hepatocytes causes profound activation of glycogen synthesis independent of normal hormone- and substrate-mediated regulatory mechanisms.

Protein targeting to glycogen (PTG), also known as PPP1R5, is a widely expressed member of a growing family of proteins that target protein phosphatase-1 (PP-1) to glycogen particles. Because PTG also binds to glycogen synthase and phosphorylase kinase, it has been suggested that it serves as a "scaffold" for efficient activation of glycogen synthesis. However, very little is known about the metabolic effects of PTG. In this study, we have used recombinant adenovirus to overexpress PTG in primary rat hepatocytes, a cell type with high glycogenic capacity. We find that overexpression of PTG potently activates glycogen synthesis in cultured hepatocytes. Surprisingly, the glycogenic effect of PTG is observed even in the complete absence of carbohydrates or insulin in the culture medium. Furthermore, glycogenolytic agents such as forskolin or glucagon are largely ineffective at activating glycogen degradation in PTG overexpressing hepatocytes, even though large increases in cAMP levels are demonstrated. These metabolic effects of PTG overexpression are accompanied by a 3.6-fold increase in glycogen synthase activation state and a 40% decrease in glycogen phosphorylase activity. Our results are consistent with a model in which PTG overexpression "locks" the hepatocyte in a glycogenic mode, presumably via its ability to promote interaction of enzymes of glycogen metabolism with PP-1.

3T3 Cells↗
PubMed1986

Phosphorylation of the glycogen-binding subunit of protein phosphatase-1G by cyclic-AMP-dependent protein kinase promotes translocation of the phosphatase from glycogen to cytosol in rabbit skeletal muscle.

The glycogen-bound form of protein phosphatase-1 (termed protein phosphatase-1G) is composed of the catalytic (C) subunit complexed to a glycogen-binding (G) subunit that anchors the enzyme to glycogen [Strålfors et al. (1985) Eur. J. Biochem. 149, 295-303]. Incubation of purified protein phosphatase-1G with cyclic-AMP-dependent protein kinase and MgATP, which leads to stoichiometric phosphorylation of the G-subunit [Caudwell et al. (1986) FEBS Lett. 194, 85-90], was found to promote the release of the phosphatase from glycogen; similar observations were made using glycogen-protein particle preparations. An intravenous injection of adrenaline decreased protein phosphatase-1 activity associated with the glycogen-protein particles by 50% with a corresponding increase in the amount present in the cytosol. By contrast, adrenaline did not affect the distribution of glycogen synthase or glycogen phosphorylase which remained entirely bound to glycogen in these experiments. The specific release of protein phosphatase-1 from glycogen may facilitate its inactivation by inhibitor-1 in the cytosol, thereby preventing dephosphorylation of the glycogen metabolising enzymes. Translocation of protein phosphatase-1 may represent a novel mechanism for the activation of glycogenolysis and inhibition of glycogen synthesis by adrenaline.

Animals↗
PubMed1996

Insulin-like growth factor II affects the appearance and glycogen content of glycogen cells in the murine placenta.

The phenotype of mice with a targeted disruption of the insulin-like growth factor II gene (IGF-II null mice) is growth retardation of both fetus and placenta during the last two thirds of gestation (1). We have compared the placenta of IGF-II null and wild-type mice from days 9-18 of gestation. No morphological differences were detected until after day 12 of gestation, when a new population of placental cells, the glycogen cells, normally first appears. Fewer glycogen cells were present in the null placenta compared to the wild-type placenta on days 13, 15, and 18 of gestation. By day 15, glycogen cells constituted approximately 50% of the basal zone cells in the wild-type placenta, but only 20% of the basal zone cells in the null placenta (P < 0.01). By contrast, spongiotrophoblasts constituted 40% of the basal zone cells in the wild-type placenta and 70% of the basal zone cells in the null placenta. There were no differences in cell size at any time. These results suggest that glycogen cells do not efficiently differentiate in the absence of IGF-II. The differentiation of glycogen cells did not appear to be simply delayed in the null placenta, as the number of glycogen cells in the null placenta did not increase between days 15-18, and there was no change in the ratio of glycogen to spongiotrophoblasts in the basal zone (P > 0.50). The glycogen content of both spongiotrophoblasts and glycogen cells was significantly reduced in the null placenta, suggesting that IGF-II may be an important regulator of glycogen synthesis in the placenta. These results indicate that IGF-II regulates cell number in the placenta and may play an important role in the differentiation of glycogen cells and the production of glycogen by placental cells.

Animals↗
PubMed1973

Effects of endotoxin on gluconeogenesis, glycogen synthesis, and liver glycogen synthase in mice.

This study was undertaken to characterize the nature of carbohydrate loss due to endotoxin poisoning in mice and to elucidate mechanisms responsible for the changes. Female ICR mice, fasted overnight, were injected intraperitoneally with a mean lethal dose of endotoxin extracted from Salmonella typhimurium strain SR-11. Liver glycogen levels, alanine-U-(14)C and pyruvate-2-(14)C incorporation into blood glucose and liver glycogen, glucose-U-(14)C incorporation into liver glycogen, and liver glycogen synthase activities were measured at intervals after treatment. Liver glycogen in fasted mice given endotoxin was diminished significantly as early as 1 h after treatment. Liver glycogen synthase was significantly decreased in poisoned mice at 17 h. The use of actinomycin D showed that the induction of this enzyme due to fasting or hydrocortisone, or both, was inhibited by endotoxin. The incorporation of the (14)C-label from alanine-U-(14)C, pyruvate-2-(14)C, or glucose-U-(14)C into blood glucose and liver glycogen was substantially impaired in endotoxemic animals at 12 h. Decreases in incorporation occurred as early as 4 h after treatment. The progressive increase in glycogen synthase activity observed in fasted controls was not seen in endotoxin-poisoned mice. The administration of a glucose or pyruvate load to endotoxin-treated mice did not restore gluconeogenesis, glycogen synthesis, or liver glycogen synthase activity to normal levels. The in vivo activation of glycogen synthase by glucose was significantly reduced in endotoxemic animals. These changes indicate reduced carbohydrate synthesis as a probable cause for rapid sugar loss during endotoxemia in mice.

Alanine↗
PubMed2006

Inhibition of glycogen synthesis by increased lipid availability is associated with subcellular redistribution of glycogen synthase.

Increased lipid availability is associated with diminished insulin-stimulated glucose uptake and glycogen synthesis in muscle, but it is not clear whether alterations in glycogen synthase activity itself play a direct role. Because intracellular localization of this enzyme is involved in its regulation, we investigated whether fat oversupply causes an inhibitory redistribution. We examined the recovery of glycogen synthase in subcellular fractions from muscle of insulin-resistant, fat-fed rats and chow-fed controls, either maintained in the basal state or after a euglycaemic-hyperinsulinaemic clamp. Although glycogen synthase protein and activity were mostly recovered in an insoluble fraction, insulin caused translocation of activity from the smaller soluble pool to the insoluble fraction. Fat-feeding, which led to a reduction in glycogen synthesis during the clamp, was associated with a depletion in the soluble pool, consistent with an important role for this component. A similar depletion was also observed in cytosolic fractions of muscles from obese db/db mice, another model of lipid-induced insulin resistance. To investigate this in more detail, we employed lipid-pretreated L6 myotubes, which exhibited a reduction in insulin-stimulated glycogen synthesis independently of alterations in glucose flux or insulin signalling through protein kinase B. In control cells, insulin caused redistribution of a minor cytosolic pool of glycogen synthase to an insoluble fraction, which was again forestalled by lipid pretreatment. Glycogen synthase recovered in the insoluble fraction from pre-treated cells exhibited a low fractional velocity that was not increased in response to insulin. Our results suggest that the initial localization of glycogen synthase in a soluble pool plays an important role in glycogen synthesis, and that its sequestration in an insulin-resistant insoluble pool may explain in part the reduced glycogen synthesis caused by lipid oversupply.

Animals↗
PubMed1991

Amylin activates glycogen phosphorylase and inactivates glycogen synthase via a cAMP-independent mechanism.

Although the novel pancreatic peptide amylin has been shown to induce insulin resistance and decrease glucose uptake, the mechanism of amylin's actions is unknown. The following study evaluated the effect of amylin on glycogen metabolism in isolated soleus muscles in the presence and absence of insulin (200 microU/ml). Total glycogen, glycogen phosphorylase and glycogen synthases activities, and cAMP levels were measured. Total glycogen levels were significantly decreased by amylin (100 nM) in fed or fasted muscles under conditions of insulin stimulation. Amylin (100 nM) activated glycogen phosphorylase by as much as 100% and decreased glycogen synthase activity by over 60%, depending on the metabolic state of the muscles. These effects where comparable to those of the beta adrenergic agonist isoproterenol. A lower concentration of amylin (1 nM) did not significantly affect glycogen levels, glycogen phosphorylase, or glycogen synthase activity. Cyclic AMP levels were increased two-fold by isoproterenol but were unaffected by amylin. In conclusion, amylin induces glycogenolysis by decreasing glycogen synthesis and increasing breakdown. The effect of amylin on enzyme activity is consistent with a phosphorylation-dependent mechanism. It is likely that these events are mediated via a cAMP independent protein kinase.

Amyloid↗
PubMed2003

Overexpression of glycogen synthase in mouse muscle results in less branched glycogen.

Glycogen, a branched polymer of glucose, serves as an energy reserve in many organisms. The degree of branching likely reflects the balance between the activities of glycogen synthase and branching enzyme. Mice overexpressing constitutively active glycogen synthase in skeletal muscle (GSL30) have elevated muscle glycogen. To test whether excess glycogen synthase activity affected glycogen branching, we examined the glycogen from skeletal muscle of GSL30 mice. The absorption spectrum of muscle glycogen determined in the presence of iodine was shifted to higher wavelengths in the GSL30 animals, consistent with a decrease in the degree of branching. As judged by Western blotting, the levels of glycogenin and the branching enzyme were also elevated. Branching enzyme activity also increased approximately threefold. However, this compared with an increase in glycogen synthase of some 50-fold, so that the increase in branching enzyme in response to overexpression of glycogen synthase was insufficient to synthesize normally branched glycogen.

1,4-alpha-Glucan Branching Enzyme↗
PubMed2003

Protein targeting to glycogen overexpression results in the specific enhancement of glycogen storage in 3T3-L1 adipocytes.

Protein phosphatase-1 (PP1) plays an important role in the regulation of glycogen synthesis by insulin. Protein targeting to glycogen (PTG) enhances glycogen accumulation by increasing PP1 activity against glycogen-metabolizing enzymes. However, the specificity of PTG's effects on cellular dephosphorylation and glucose metabolism is unclear. Overexpression of PTG in 3T3-L1 adipocytes using a doxycycline-controllable adenoviral construct resulted in a 10-20-fold increase in PTG levels and an 8-fold increase in glycogen levels. Inclusion of 1 microg/ml doxycycline in the media suppressed PTG expression, and fully reversed all PTG-dependent effects. Infection of 3T3-L1 adipocytes with the PTG adenovirus caused a marked dephosphorylation and activation of glycogen synthase. The effects of PTG seemed specific, because basal and insulin-stimulated phosphorylation of a variety of signaling proteins was unaffected. Indeed, glycogen synthase was the predominant protein whose phosphorylation state was decreased in 32P-labeled cells. PTG overexpression did not alter PP1 protein levels but increased PP1 activity 6-fold against phosphorylase in vitro. In contrast, there was no change in PP1 activity measured using myelin basic protein, suggesting that PTG overexpression specifically directed PP1 activity against glycogen-metabolizing enzymes. To investigate the metabolic consequences of altering PTG levels, glucose uptake and storage in 3T3-L1 adipocytes was measured. PTG overexpression did not affect 2-deoxy-glucose transport rates in basal and insulin-stimulated cells but dramatically enhanced glycogen synthesis rates under both conditions. Despite the large increases in cellular glucose flux upon PTG overexpression, basal and insulin-stimulated glucose incorporation into lipid were unchanged. Cumulatively, these data indicate that PTG overexpression in 3T3-L1 adipocytes discretely stimulates PP1 activity against glycogen synthase and phosphorylase, resulting in a marked and specific increase in glucose uptake and storage as glycogen.

3T3 Cells↗