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PubMedDate not supplied

Glycogen levels in human term placental disks, umbilical cords, and membranes.

Glycogen in the placenta and its appendages is important for fetal well-being. The precise location of the glycogen stores, however, is unknown. This study was initiated to quantitate glycogen levels at well-defined sampling sites in more than 641 samples from 10 uncomplicated pregnancies and to correlate these glycogen levels with clinical and morphological variables. By biochemical assay, glycogen levels were greatest in the midumbilical cord section (29.08 +/- 1.18 mg/g dry wt) and lowest in the amnionic membrane (2.31 +/- 0.08 mg/g dry wt). Within the placental disk, parenchymal glycogen levels were greatest near the cord insertion (9.31 +/- 2.68 mg/g dry wt) and lowest at the periphery (5.71 +/- 1.14 mg/g dry wt). The midumbilical cord glycogen level showed strong direct correlations (P < .001) with birth weight, umbilical cord weight, and total calculated umbilical cord glycogen and somewhat lower but significant (P < .037) direct correlations with the calculated mean umbilical cord glycogen level, total calculated placental glycogen content, and placental weight. The glycogen level in the middisk parenchymal section from the fetal surface correlated directly with gestational age. Periodic acid-Schiff stains showed that magenta glycogen granules were most abundant in the cytoplasm of the vascular smooth muscle cells. These data show significant variations in glycogen levels among sampling sites. Definition of the precise sampling site is important for clinicopathologic studies of placental glycogen and for interstudy correlations.

Extraembryonic Membranes↗
PubMed1998

[Effect of cadmium sulfate and strontium chloride on the glycogen content in hepatocytes of rats of various ages].

Cytophotometry and image analysis being used, hepatocyte glycogen contents were measured in periportal and pericentral zones of liver lobules at different stages (1, 7, 14, 21, 30, 90, 180 and 365 days) of postnatal development of both intact rats and rats exposed to chronic CdSO4 (1 mg/kg body weight) and SrSO4 (6.5 mg/kg body weight) intoxication. The glycogen content in hepatocytes of intact rats increased continuously in the course of development being most highest at the initial stage of development. The glycogen content ratio in cells of portal and central zones of liver lobules varied during ontogenesis. The maximum value of this ratio is reached on the 21st day after the rat birth, dropping sharply at later age to reach its minimum in adults. Intoxication of rats by Cd2+ and Sr2+ within 1-90 days interval reduced hepatocyte glycogen levels, compared to normal liver. The prolongation of rat treatment with heavy metals for 90-365 days led to glycogen accumulation in hepatocytes. Rat intoxication with heavy metals for 1 year brought about the increase in both glycogen content per cell and glycogen concentration. Cd2+ treatment for 30-90 days resulted in glycogen accumulation inhibition in both the investigated zones of liver lobules. Thereafter an increased glycogen accumulation took place in hepatocytes of the portal and central liver lobules. Following Cd2+ treatment, the value of the ratios of glycogen levels in the portal and central liver lobules was lower than in the normal liver on all stages of the postnatal rat development. The lowest value (< 1.0) of this ratio was reached in the cirrhotic liver. Distinct from Cd2+ treatment of rats, the treatment with Sr2+ does not lead to significant changes in glycogen levels in cells of different zones of liver lobules. Nevertheless certain destructive changes in glycogen-forming function of hepatocytes after Sr2+ treatment are apparent. This is suggested from the lower glycogen levels in the portal and central zones of liver lobules on 30-180 days interval compared to the normal liver. Besides, the values of ratios in glycogen levels in the portal and central zones of liver lobules in 14 and 21 days old rats was noticeably lower than in the intact rats of the same age.

Aging↗
PubMed1976

Biosynthesis of bacterial glycogen. Purification and properties of the Escherichia coli B ADPglucose:1,4-alpha-D-glucan 4-alpha-glucosyltransferase.

The Escherichia coli B glycogen synthase has been purified to apparent homogeneity with the use of a 4-aminobutyl-Sepharose column. Two fractions of the enzyme were obtained: glycogen synthase I with a specific activity of 380 mumol mg-1 and devoid of branching enzyme activity and glycogen synthase II having a specific activity of 505 mumol mg-1 and containing branching enzyme activity which was 0.1% of the activity observed for the glycogen synthase. Only one protein band was found in disc gel electrophoresis for each glycogen synthase fraction and they were coincident with glycogen synthase activity. One major protein band and one very faint protein band which hardly moved into the gel were observed in sodium dodecyl sulfate gel electrophoresis of the glycogen synthase fractions. The subunit molecular weight of the major protein band in sodium dodecyl sulfate gel electrophoresis of both glycogen synthase fractions was determined to be 49 000 +/- 2 000. The molecular weights of the native enzymes were determined by sucrose density gradient ultracentrifugation. Glycogen synthase I had a molecular weight of 93 000 while glycogen synthase II had a molecular weight of 200 000. On standing at 4 degrees C or at -85 degrees C both enzymes transform into species having molecular weights of 98 000, 135 000, and 185 000. Thus active forms of the E. coli B glycogen synthase can exist as dimers, trimers, and tetramers of the subunit. The enzyme was shown to catalyze transfer of glucose from ADPglucose to maltose and to higher oligosaccharides of the maltodextrin series but not to glucose. 1,5-Gluconolactone was shown to be a potent inhibitor of the glycogen synthase reaction. The glycogen synthase reaction was shown to be reversible. Formation of labeled ADPglucose occurred from either [14C]ADP or [14C]glycogen. The ratio of ADP to ADPglucose at equilibrium at 37 degrees C was determined and was found to vary threefold in the pH range of 5.27-6.82. From these data the ratio of ADP2- to ADPglucose at equilibrium was determined to be 45.8 +/- 4.5. Assuming that deltaF degrees of the hydrolysis of the alpha-1,4-glucosidic linkage is -4.0 kcal the deltaF degrees of hydrolysis of the glucosidic linkage in ADPglucose is -6.3 kcal.

Amylases↗
PubMed1993

Mechanisms of multisite phosphorylation and inactivation of rabbit muscle glycogen synthase.

Glycogen synthase, a rate-determining enzyme for glycogen biosynthesis, is regulated by complex multisite phosphorylation of its subunit. Previous work has suggested that phosphorylation by some protein kinases, casein kinase II and cyclic AMP-dependent protein kinase, potentiates the ability of other protein kinases, glycogen synthase kinase 3 and casein kinase I, respectively, to modify the enzyme. In the present study, active glycogen synthase was expressed in Escherichia coli using a pET vector. The purified recombinant glycogen synthase had specific activity and subunit M(r) similar to enzyme isolated from rabbit muscle. Prior phosphorylation by casein kinase II was found to be an obligate requirement for phosphorylation by glycogen synthase kinase 3, which introduced 4 mol phosphate/mol subunit. Casein kinase II action did not affect activity, whereas the phosphorylation catalyzed by glycogen synthase kinase 3 caused a potent inactivation, reducing the +/- glucose 6-phosphate activity ratio from 0.7 to 0.10. Casein kinase I alone phosphorylated the recombinant glycogen synthase, indicating that substrate phosphorylation was not an absolute requirement. However, the prior action of cyclic AMP-dependent protein kinase significantly potentiated the ability of casein kinase I to phosphorylate and inactivate glycogen synthase. All previous analyses of glycogen synthase phosphorylation have used enzyme purified from mammalian sources and containing residual covalent phosphate. By using recombinant substrate, the present study represents a rigorous assessment of the role of prior phosphorylation in the recognition of mammalian glycogen synthase by glycogen synthase kinase 3 and casein kinase I. The conclusion is that phosphorylation of glycogen synthase can involve the concerted action of multiple protein kinases.

Amino Acid Sequence↗
PubMed2000

Overexpression of the glycogen targeting (G(M)) subunit of protein phosphatase-1.

The G(M) glycogen-targeting subunit of protein phosphatase-1 (PP1) is believed to be involved in dephosphorylation of the enzymes of glycogen metabolism. To assess the roles of G(M) on glycogen metabolism, we created site-directed G(M) mutants and overexpressed them in Chinese hamster ovary (CHO) cells expressing human insulin receptor. Overexpressed G(M) recruited glycogen synthase as well as PP1 to the glycogen pellet, and upregulated basal glycogen synthase activity. Overexpressed G(M)-67A (Ser-67 replaced with alanine) exhibited decreased sensitivity to suppression of glycogen synthase activity by forskolin, while overexpression of G(M)-48A (Ser-48 replaced with alanine) preserved glycogen synthase activation in response to insulin. These observations indicate that in CHO cells overexpressing G(M); (1) G(M) translocates glycogen synthase to the glycogen pellet and affected basal glycogen synthase, (2) Ser-67 might be involved in the suppression of glycogen synthase activity by glycogenolytic agents, and (3) Ser-48 might not commit to activation of glycogen synthase by insulin.

Animals↗
PubMed1993

Triiodo-L-thyronine stimulates glycogen synthesis in rat hepatocyte cultures.

The hyperthyroid state is associated with low hepatic glycogen levels, but paradoxically with a high activity of glycogen synthase and low activity of glycogen phosphorylase. We determined the effects of triiodo-L-thyronine (T3) on glycogen synthesis and glycogen synthase activity in rat hepatocytes in vitro. Culture of rat hepatocytes with T3 (100 nM-1 microM) for 16 h-40 h increases glycogen synthesis from glucose and gluconeogenic precursors. The stimulation of glycogen synthesis by T3 was associated with an increase in the activity of glycogen synthase and was additive with the long-term effects of insulin but not with the short-term stimulation of glycogen synthesis by insulin. Culture of hepatocytes with T3 (at concentrations up to 1 microM) did not affect the responsiveness of glycogen synthesis to short-term stimulation by insulin but culture with 10 microM-T3 decreased the responsiveness to insulin without affecting the basal rate. It is suggested that the high activity of glycogen synthase in the hyperthyroid state is due to a direct effect of T3 on the hepatocyte, but the low hepatic glycogen content is probably due to either secondary metabolite and/or endocrine changes or to impaired responsiveness to insulin. T3 may have an anabolic role in the control of hepatic glycogen storage in the euthyroid postprandial state.

Animals↗
PubMed1993

Maternal malnutrition does not affect fetal hepatic glycogen synthase ontogeny.

Maternal malnutrition late in pregnancy results in the reduced storage of fetal hepatic glycogen in the final days of gestation and an accentuation of normal birth-related hypoglycemia. It was of interest to determine whether or not low glycogen levels resulted when maternal malnutrition disrupted the normal ontogeny of fetal hepatic glycogen synthase, an important glycogenic enzyme. A defect in this enzyme would be expected to seriously affect prenatal and postnatal glycogen synthesis. For this study, livers were removed from fetuses from malnourished (50% of normal dietary intake) mice, as well as from ad libitum-fed mice, and used for the determination of hepatic glycogen, glycogen synthase activity, and glycogen synthase protein levels. In this paper we report that maternal dietary restriction late in pregnancy produces growth-retarded fetuses with severely reduced hepatic glycogen levels, but the normal ontogenic changes in the quantity and activity of hepatic glycogen synthase were not affected. It is especially significant that the accumulation of glycogen synthase occurred despite the minimal level of natural substrate available for the enzyme. These results suggest that the accumulation and activity of hepatic glycogen synthase during late gestation is related to developmental events rather than levels of substrate or glycogen.

Animals↗
PubMed2006

Beta(2)-Adrenergic activation increases glycogen synthesis in L6 skeletal muscle cells through a signalling pathway independent of cyclic AMP.

AIMS/HYPOTHESIS: In skeletal muscle, the storage of glycogen by insulin is regulated by glycogen synthase, which is regulated by glycogen synthase kinase 3 (GSK3). Here we examined whether adrenergic receptor activation, which can increase glucose uptake, regulates glycogen synthesis in L6 skeletal muscle cells. METHODS: We used L6 cells and measured glycogen synthesis (as incorporation of D: -[U-(14)C]glucose into glycogen) and GSK3 phosphorylation following adrenergic activation. RESULTS: Insulin (negative logarithm of median effective concentration [pEC(50)] 8.2 +/- 0.3) and the beta-adrenergic agonist isoprenaline (pEC(50) 7.5 +/- 0.3) induced a twofold increase in glycogen synthesis in a concentration-dependent manner. The alpha(1)-adrenergic agonist cirazoline and alpha(2)-adrenergic agonist clonidine had no effect. Both insulin and isoprenaline phosphorylated GSK3. The beta-adrenergic effect on glycogen synthesis is mediated by beta(2)-adrenoceptors and not beta(1)-/beta(3)-adrenoceptors, and was not mimicked by 8-bromo-cyclic AMP or cholera toxin, and also was insensitive to pertussis toxin, indicating no involvement of cyclic AMP or inhibitory G-protein (G(i)) signalling in the beta(2)-adrenergic effect on glycogen synthesis. 12-O-tetra-decanoylphorbol-13-acetate (TPA) increased glycogen synthesis 2.5-fold and phosphorylated GSK3 fourfold. Inhibition of protein kinase C (PKC) isoforms with 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrollo(3,4-c)-carbazole (Gö6976; inhibits conventional and novel PKCs) or 2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide (Gö6983; inhibits conventional, novel and atypical PKCs) inhibited the stimulatory TPA effect, but did not significantly inhibit glycogen synthesis mediated by insulin or isoprenaline. Inhibition of phosphatidylinositol 3-kinase (PI3K) with wortmannin inhibited the effects of insulin and isoprenaline on glycogen synthesis. CONCLUSIONS/INTERPRETATION: These results demonstrate that in L6 skeletal muscle cells adrenergic stimulation through beta(2)-adrenoceptors, but not involving cyclic AMP or G(i), activates a PI3K pathway that stimulates glycogen synthesis through GSK3.

AMP-Activated Protein Kinases↗
PubMed1995

Phosphorylation and inactivation of rat heart glycogen synthase by cAMP-dependent and cAMP-independent protein kinases.

The regulation of cardiac muscle glycogen metabolism is not well understood. Previous studies have indicated that heart glycogen synthase is heavily phosphorylated in vivo on multiple sites. Using purified enzymes, we have investigated the effect of phosphorylation of different sites on the activity of rat heart glycogen synthase. A convenient procedure was developed for the purification of rat heart glycogen synthase. The enzyme was phosphorylated by selected kinases, and glycogen synthase activity, extent of phosphorylation, and phosphopeptide maps were analyzed. Rat heart glycogen synthase, purified to apparent homogeneity (M(r) 87,000 on SDS-PAGE), had a specific activity of 18 U/mg protein and had an activity ratio of 0.74 (activity in the absence divided by the activity in the presence of glucose 6-P). cAMP-dependent protein kinase, glycogen synthase kinase 3, Ca2+/calmodulin-dependent protein kinase II, protein kinase C, and phosphorylase kinase phosphorylated the enzyme with a concomitant decrease in the activity ratio to values ranging from 0.1 to 0.4. Casein kinase II phosphorylated but did not inactivate glycogen synthase. Six tryptic phosphopeptides, obtained from heart glycogen synthase phosphorylated by the various kinases, were separated by reverse-phase chromatography. The phosphopeptide(s) obtained with each kinase eluted at the same position(s) as corresponding phosphopeptides obtained from rat skeletal muscle glycogen synthase. The study shows that the pattern of phosphorylation and effects on activity are very similar for cardiac and skeletal muscle glycogen synthase. It is suggested that the well known differences in heart and glycogen metabolism may be due to the interplay of kinases and phosphatases which could lead to different phosphorylation and activity states of glycogen synthase.

Animals↗
PubMed1999

Rapid normalization of hepatic glycogen metabolism in rats with long-term bile duct ligation after biliodigestive anastomosis.

BACKGROUND/AIMS: Rats with chronic bile duct ligation have reduced hepatic glycogen stores and decreased activities of enzyme involved in glycogen metabolism. In the current studies, the reversibility of these changes following reversal of biliary obstruction by Roux-en-Y anastomosis (RY) was investigated. METHODS: Rats were studied after bile duct ligation for 4 weeks (BDL rats), or 5 or 14 days after relief of biliary obstruction by RY. Control rats were pair-fed to treated rats, and all rats were studied in the fed state. RESULTS: The liver glycogen content was decreased in BDL rats (198+/-167 vs. 753+/-315 mg/liver in BDL vs. control rats) and normalized within 5 days after RY. The total activities of glycogen synthase and phosphorylase were both reduced by 51% in BDL as compared to control rats. Five days after RY, the activity of glycogen synthase had increased significantly in comparison to BDL rats, whereas glycogen phosphorylase had remained unchanged. Fourteen days after RY, both enzyme activities had completely normalized. Northern blots revealed reduced hepatic mRNA levels in BDL rats, for glycogen synthase and phosphorylase. While the mRNA level for glycogen synthase normalized within 5 days after RY, the level for glycogen phosphorylase increased but did not normalize completely within 14 days after RY. CONCLUSIONS: Hepatic glycogen stores are decreased in BDL rats but recover rapidly after relief of biliary obstruction. Reduced activity and mRNA levels of glycogen synthase suggest that impaired glycogen synthesis is the principal mechanism for decreased hepatic glycogen stores in BDL rats.

Anastomosis, Roux-en-Y↗
PubMed1998

Effects of dichloroacetate on glycogen metabolism in B6C3F1 mice.

Dichloroacetate (DCA) is a by-product of drinking water chlorination. Administration of DCA in drinking water results in accumulation of glycogen in the liver of B6C3F1 mice. To investigate the processes affecting liver glycogen accumulation, male B6C3F1 mice were administered DCA in drinking water at levels varying from 0.1 to 3 g/l for up to 8 weeks. Liver glycogen synthase (GS) and glycogen phosphorylase (GP) activities, liver glycogen content, serum glucose and insulin levels were analyzed. To determine whether effects were primary or attributable to increased glycogen synthesis, some mice were fasted and administered a glucose challenge (20 min before sacrifice). DCA treatments in drinking water caused glycogen accumulation in a dose-dependent manner. The DCA treatment in drinking water suppressed the activity ratio of GS measured in mice sacrificed at 9:00 AM, but not at 3:00 AM. However, net glycogen synthesis after glucose challenge was increased with DCA treatments for 1-2 weeks duration, but the effect was no longer observed at 8 weeks. Degradation of glycogen by fasting decreased progressively as the treatment period was increased, and no longer occurred at 8 weeks. A shift of the liver glycogen-iodine spectrum from DCA-treated mice was observed relative to that of control mice, suggesting a change in the physical form of glycogen. These data suggest that DCA-induced glycogen accumulation at high doses is related to decreases in the degradation rate. When DCA was administered by single intraperitoneal (i.p.) injection to naïve mice at doses of 2-200 mg/kg at the time of glucose challenge, a biphasic response was observed. Doses of 10-25 mg/kg increased both plasma glucose and insulin concentrations. In contrast, very high i.p. doses of DCA (> 75 mg/kg) produced progressive decreases in serum glucose and glycogen deposition in the liver. Since the blood levels of DCA produced by these higher i.p. doses were significantly higher than observed with drinking water treatment, we conclude that apparent differences with data of previous investigations is related to substantial differences in systemic dose and/or dose-time relations.

Administration, Oral↗
PubMed1998

Re-feeding after starvation involves a temporal shift in the control site of glycogen synthesis in rat muscle.

The starved-to-fed transition is accompanied by rapid glycogen deposition in skeletal muscles. On the basis of recent findings [Bräu, Ferreira, Nikolovski, Raja, Palmer and Fournier (1997) Biochem. J. 322, 303-308] that during recovery from exercise there is a shift from a glucose 6-phosphate/phosphorylation-based control of glycogen synthesis to a phosphorylation-based control alone, this paper seeks to establish whether a similar shift occurs in muscle during re-feeding after starvation in the rat. Chow re-feeding after 48 h of starvation resulted in glycogen deposition in all muscles examined (white, red and mixed quadriceps, soleus and diaphragm) to levels higher than those in the fed state. Although the early phase of re-feeding was associated with increases in glucose 6-phosphate levels in all muscles, there was no accompanying increase in the fractional velocity of glycogen synthase except in the white quadriceps muscle. This finding, together with the observation that the fractional velocity of glycogen synthase in most muscles was already high in the starved state, suggests that in the initial phase of glycogen deposition the phosphorylation state of the enzyme may be adequate to support net glycogen synthesis. In the later phase of re-feeding, the progressive decrease in the fractional velocity of glycogen synthase in association with a decrease in the rate of glycogen deposition suggests that glycogen synthesis is controlled primarily by changes in the phosphorylation state of glycogen synthase. In conclusion, this study suggests that there is a temporal shift in the site of control of glycogen synthesis as glycogen deposition progresses during re-feeding after starvation.

Animals↗
PubMed1997

Glycogen biogenesis in rat 1 fibroblasts expressing rabbit muscle glycogenin.

Glycogenin, a self-glucosylating protein involved in the initiation of glycogen biosynthesis, varies in intracellular concentration from barely detectable in liver to a high level in muscle. The effect of increasing the glycogenin level on glycogen synthesis was studied in rat 1 fibroblasts stably overexpressing rabbit muscle glycogenin. In the presence of glucose, all of the expressed glycogenin was attached to polysaccharide and the free protein could only be detected by western blot analysis after incubation of cells in a glucose-depleted medium or treatment of the cell extract with alpha-amylase. In control cells, increased extracellular glucose concentrations promoted translocation of glycogen synthase from the soluble to the pellet fraction with an increase in the associated glycogen. Overexpression of glycogenin did not affect total intracellular glycogen and glycogen synthase levels at any concentration of glucose but significantly reduced glucose-induced accumulation of insoluble glycogen and translocation of glycogen synthase. Immunofluorescence analysis revealed a diffuse cytoplasmic distribution of glycogenin expressed in rat 1 cells. In rat 1 cells incubated with glucose, discrete deposits of glycogen were detected by staining with HIO4/Schiff but this was eliminated by overexpressing glycogenin. Analysis of [14C]glucose- or [35S]methionine-labeled extracts from glycogenin-expressing cells by continuous polyacrylamide gel electrophoresis and by two-dimensional gel electrophoresis revealed a continuum of glycogenin-containing species from low molecular mass to sizes significantly greater than 400 kDa. We conclude that (a) overexpression of glycogenin does not enhance glycogen synthesis but causes production of more, smaller, glycogen molecules with a concomitant change in their intracellular localization; (b) glycogenin and elevated glucose have opposing effects on the distribution of glycogenin and glycogen synthase in rat 1 cells; and (c) the biogenesis of glycogen in rat 1 cells occurs without the accumulation of any major intermediate form.

Animals↗
PubMed1996

Pho85p, a cyclin-dependent protein kinase, and the Snf1p protein kinase act antagonistically to control glycogen accumulation in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, nutrient levels control multiple cellular processes. Cells lacking the SNF1 gene cannot express glucose-repressible genes and do not accumulate the storage polysaccharide glycogen. The impaired glycogen synthesis is due to maintenance of glycogen synthase in a hyperphosphorylated, inactive state. In a screen for second site suppressors of the glycogen storage defect of snf1 cells, we identified a mutant gene that restored glycogen accumulation and which was allelic with PHO85, which encodes a member of the cyclin-dependent kinase family. In cells with disrupted PHO85 genes, we observed hyperaccumulation of glycogen, activation of glycogen synthase, and impaired glycogen synthase kinase activity. In snf1 cells, glycogen synthase kinase activity was elevated. Partial purification of glycogen synthase kinase activity from yeast extracts resulted in the separation of two fractions by phenyl-Sepharose chromatography, both of which phosphorylated and inactivated glycogen synthase. The activity of one of these, GPK2, was inhibited by olomoucine, which potently inhibits cyclin-dependent protein kinases, and contained an approximately 36-kDa species that reacted with antibodies to Pho85p. Analysis of Ser-to-Ala mutations at the three potential Gsy2p phosphorylation sites in pho85 cells implicated Ser-654 and/or Thr-667 in PHO85 control of glycogen synthase. We propose that Pho85p is a physiological glycogen synthase kinase, possibly acting downstream of Snf1p.

Alleles↗
PubMed1996

Autoregulation of myocardial glycogen concentration during intermittent hypoxia.

During hypoxia, the heart consumes glycogen to generate ATP. Tolerance of repetitive hypoxia logically requires prompt replenishment of glycogen, a process whose regulation is not fully understood. To examine this, we imposed a defined hypoxic stimulus on the rat heart while varying its workload. In intact rats, hypoxia reduced myocardial glycogen approximately 30% and increased both the fraction of glycogen synthase in its physiologically active (GS I) form (from 0.24 +/- 0.06 to 0.82 +/- 0.07; P < 0.005) and glycogen synthesis (from 0.087 +/- 0.011 to 0.375 +/- 0.046 mumol.g-1.min-1; P < 0.005). Reducing cardiac work (with propranolol or heterotopic transplantation) reduced glycogen breakdown, glycogen synthase activation, and glycogen synthesis in parallel, stepwise fashion in intact rats. Correspondingly, hypoxia increased GS I activity in the perfused heart in vitro, but only under conditions where glycogen was consumed. This suggests myocardial glycogen synthase is activated by systemic hypoxia and catalyzes rapid posthypoxic glycogen synthesis. Hypoxic glycogen synthase activation appears to be a proportionate, wholly intrinsic response to local glycogenolysis, operating to preserve myocardial glycogen stores independent of any extracardiac mediator of carbohydrate metabolism.

Animals↗
PubMed1986

Glucose feeding and exercise in trained rats: mechanisms for glycogen sparing.

This investigation studied the effect of an oral glucose feeding on glycogen sparing during exercise in non-glycogen-depleted and glycogen-depleted endurance-trained rats. The non-glycogen-depleted rats received via a stomach tube 2 ml of a 20% glucose solution labeled with [U-14C]glucose just prior to exercise (1 h at 25 m/min). Another group of rats ran for 40 min at higher intensity to deplete glycogen stores, after which they received the same glucose feeding and continued running for 1 h at 25 m/min. The initial 40-min run depleted glycogen in heart, skeletal muscle, and liver. In the non-glycogen-depleted rats the glucose feeding spared glycogen in the liver, primarily from the oxidation of blood-borne glucose in muscle. In the glycogen-depleted rats, muscle glycogen was repleted after the feeding, but sources other than the administered glucose also contributed to glycogen synthesis. The results suggest that glycogen depletion rather than the glucose feeding per se stimulates glycogen resynthesis in muscle during exercise in endurance-trained rats.

Animals↗
PubMed1989

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

The time course of glycogen changes in soleus muscle recovering from 3 days of nonweight bearing by hindlimb suspension was investigated. Within 15 min and up to 2 h, muscle glycogen decreased. Coincidentally, muscle glucose 6-phosphate and the fractional activity of glycogen phosphorylase, measured at the fresh muscle concentrations of AMP, increased. Increased fractional activity of glycogen synthase during this time was likely the result of greater glucose 6-phosphate and decreased glycogen. From 2 to 4 h, when the synthase activity remained elevated and the phosphorylase activity declined, glycogen levels increased (glycogen supercompensation). A further increase of glycogen up to 24 h did not correlate with the enzyme activities. Between 24 and 72 h, glycogen decreased to control values, possibly initiated by high phosphorylase activity at 24 h. At 12 and 24 h, the inverse relationship between glycogen concentration and the synthase activity ratio was lost, indicating that reloading transiently uncoupled glycogen control of this enzyme. These data suggest that the activities of glycogen synthase and phosphorylase, when measured at physiological effector levels, likely provide the closest approximation to the actual enzyme activities in vivo. Measurements made in this way effectively explained the majority of the changes in the soleus glycogen content during recovery from nonweight bearing.

Adenosine Monophosphate↗
PubMed1985

Insulin, not glucose, controls hepatocellular glycogen deposition. A re-evaluation of the role of both agents in cultured liver cells.

The direct effects of insulin and glucose on glycogen accumulation were compared using monolayers of chicken embryo hepatocytes which, when cultured in chemically defined medium without hormones, retain viability for several days but become depleted of glycogen. The data strongly suggest that insulin is the major direct signal for hepatic glycogen synthesis, while glucose supports glycogen accumulation primarily in its role as a substrate. Insulin alone, when added to the cells in physiological concentrations, either shortly after isolation or throughout culture, restored glycogen to the maximal levels found in the liver of the fed chicken. Addition of increasing amounts of glucose in the absence of insulin, in contrast, yielded proportional but limited increases in glycogen deposition attaining not more than 30% of the maximal storage capacity of the cells. This hormone-independent glycogenesis was characterized by a 30-min burst of glycogen deposition immediately following a stepped increase of glucose, with no detectable change in glycogen synthase activity. Insulin-dependent glycogenesis evidenced a much slower rate of glycogen deposition and was accompanied by a near tripling of glycogen synthase activity. Insulin-induced glycogen stores were broken down following removal of the hormone, even when glucose was present in great excess, indicating that the cells require insulin to maintain as well as build up maximal levels of glycogen. In the presence of glucagon, insulin-induced glycogen stores were rapidly degraded, but glucose-induced glycogenesis was not inhibited. The actions of insulin and glucose in this system are both qualitatively and quantitatively similar to those that have been observed in the diabetic animal.

Animals↗