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.

SourceResearch connectionFrom yearThrough year

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

At least 109 records · Page 6Linked to original sources

PubMed1990

Labeling of hepatic glycogen after short- and long-term stimulation of glycogen synthesis in rats injected with 3H-galactose.

The effects of short- and long-term stimulation of glycogen synthesis elicited by dexamethasone were studied by light (LM) and electron (EM) microscopic radioautography (RAG) and biochemical analysis. Adrenalectomized rats were fasted overnight and pretreated for short- (3 hr) or long-term (14 hr) periods with dexamethasone prior to intravenous injection of tracer doses of 3H-galactose. Analysis of LM-RAGs from short-term rats revealed that about equal percentages (44%) of hepatocytes became heavily or lightly labeled 1 hr after labeling. The percentage of heavily labeled cells increased slightly 6 hr after labeling, and unlabeled glycogen became apparent in some hepatocytes. The percentage of heavily labeled cells had decreased somewhat 12 hr after labeling, and more unlabeled glycogen was evident. In the long-term rats 1 hr after labeling, a higher percentage of heavily labeled cells (76%) was observed compared to short-term rats, and most glycogen was labeled. In spite of the high amount of labeling seen initially, the percentage of heavily labeled hepatocytes had decreased considerably to 55% by 12 hr after injection; and sparsely labeled and unlabeled glycogen was prevalent. The EM-RAGs of both short- and long-term rats were similar. Silver grains were associated with glycogen patches 1 hr after labeling; 12 hr after labeling, the glycogen patches had enlarged; and label, where present, was dispersed over the enlarged glycogen clumps. Analysis of DPM/mg tissue corroborated the observed decrease in label 12 hr after administration in the long-term animals. The loss of label observed 12 hr after injection in the long-term pretreated rats suggests that turnover of glycogen occurred during this interval despite the net accumulation of glycogen that was visible morphologically and evident from biochemical measurement.

Animals↗

PubMed2000

Effects of supranormal liver glycogen content on hyperglucagonemia-induced liver glycogen breakdown.

The purpose of the present study was to test the hypothesis that a higher hepatic glycogen level is associated with higher glucagon-induced hepatic glycogen depletion. Four groups of anesthetized rats received three injections (at times 0, 30, and 60 min) of glucagon (intravenously, 20 [microg/kg). Among these groups, hepatic glycogen levels had previously been manipulated either by an overloading diet (Fast-refed), a reduction in food intake (1/2-fast), or exercise (75 min of running, 26 m/ min, 0% grade). A fourth group had normal hepatic glycogen levels. A fifth group of rats was injected only with saline (0.9% NaCl). Liver glycogen concentrations were measured every 30 min during the course of the 90-min experiment, using liver samples obtained from the open liver biopsy technique. Plasma glucagon concentrations were significantly higher (P < 0.05) in the glucagon-injected groups than in the saline-injected group. As expected, liver glycogen levels were significantly higher (P < 0.01; 1.6-fold) in the Fast-refed group than in all other groups. Glucagon-induced decreases in liver glycogen concentrations were similar in Fast-refed than in normally fed and exercised rats when the overall 90-min period was considered. However, during the course of the last 30-min period, liver glycogen was significantly (P < 0.01) decreased only in the Fast-refed group. The Fast-refed, normally fed, and exercised groups had a similar glucagon-induced hyperglycemia that was significantly more elevated (P < 0.01) than glucose levels measured in the saline-injected group. Glucagon-induced reactive hyperinsulinemia was observed only in the Fast-refed and normally fed rats, and not in the exercised and 1/2-fast rats. It is concluded that supranormal levels of liver glycogen may be associated with a larger hyperglucagonemia-induced liver glycogen breakdown.

Animal Nutritional Physiological Phenomena↗

PubMed1991

Long-term effects of insulin on the enzyme activity and messenger RNA of glycogen synthase in rat hepatoma H4 cells: an effect of insulin on glycogen synthase mRNA stability.

Insulin induced glycogen synthase activity and decreased glycogen synthase mRNA concentrations in rat hepatoma H4 cells. Total enzyme activity measured with glucose 6-phosphate gradually increased during a 24-h insulin incubation. The time course of glycogen synthase activation measured by the activity ratio (low G-6-P/high G-6-P) in response to insulin was biphasic with the first peak at 15 min and the second peak at 4 to 6 h. When cells were incubated with insulin and cycloheximide, the first peak persisted while the second peak was abolished. These data suggest that the first activation peak derives from the classic effect of insulin via dephosphorylation and the second peak from an insulin-induced protein synthesis of a glycogen synthase activator. Ribonuclease protection assays with a cloned rat liver glycogen synthase cDNA were used to quantitate glycogen synthase mRNA. Insulin unexpectedly decreased glycogen synthase mRNA in a time- and a dose-dependent manner. After incubation with the RNA synthesis inhibitor, 5, 6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB) without and with insulin, the half time of glycogen synthase mRNA decreased from 6.0 +/- 0.80 to 3.9 +/- 0.75 h, respectively. Nuclear run-off experiments with isolated nuclei showed no change of transcription of glycogen synthase mRNA. These data suggest that insulin in this system affects glycogen synthase mRNA stability rather than transcription.

Animals↗

PubMed1986

Regulation of hepatic glycogen phosphorylase and glycogen synthase by calcium and diacylglycerol.

Incubation of rat hepatocytes with angiotensin II (1 nM) produced a time-dependent accumulation of 1, 2-diacylglycerol and inactivation of glycogen synthase with maximum effects at 10 min. The level of diacylglycerol then gradually declined and the activity of glycogen synthase I returned to control values at 30 min. In contrast, angiotensin II caused an increase in cytosolic Ca2+ and an activation of glycogen phosphorylase which were rapid and transient, reaching maximum values in less than 2 min and then returning to control levels at 15 min. There were excellent correlations between the changes in glycogen synthase I and diacylglycerol levels and between the changes in phosphorylase alpha and cytosolic Ca2+ in these time-course studies. However, there was no correlation between the changes in diacylglycerol and phosphorylase alpha or between the changes in cytosolic Ca2+ and glycogen synthase I. Norepinephrine also caused a slow increase in diacylglycerol and inactivation of glycogen synthase, and a rapid increase in cytosolic free Ca2+ and activation of glycogen phosphorylase. Addition of an alpha1-adrenergic blocker (prazosin or phentolamine) caused rapid decreases in cytosolic free Ca2+ and phosphorylase alpha, but only slowly reversed the inactivation of synthase and accumulation of diacylglycerol. The dose-response curves for norepinephrine and prazosin on glycogen synthase were well correlated with those on diacylglycerol. It is proposed that in liver cells, Ca2+-mobilizing hormones regulate phosphorylase a through a Ca2+-dependent mechanism and inactivate glycogen synthase through the generation of diacylglycerol, at least in part. The data provide additional support for the view that protein kinase C may be important in the regulation of glycogen synthase in liver.

Angiotensin II↗

PubMed1987

Liver glycogen metabolism in endotoxin shock. II. Endotoxin administration increases glycogen phosphorylase activities in dog livers.

The effects of E. coli endotoxin administration on hepatic glycogen phosphorylase activities in dogs were investigated. Hepatic glycogen phosphorylase activities in both control and endotoxic dogs were inactivated spontaneously by preincubation of enzyme preparations at 25 degrees C. Total glycogen phosphorylase activity was not significantly altered during preincubation. The activity of glycogen phosphorylase a was increased by 83 and 80% at 1 and 2 hr postendotoxin, respectively, without preincubation; and by 203 and 133% at 1 and 2 hr postendotoxin, respectively, after 30 min preincubation. Without preincubation, the glycogen phosphorylase percentage a activity was increased from the control value of 37 to 58% at 1 hr postendotoxin and to 53% at 2 hr postendotoxin. After 30 min preincubation, the glycogen phosphorylase percentage a activity was increased from the control value of 10 to 28% at 1 hr postendotoxin and to 20% at 2 hr postendotoxin. The time required for half maximum inactivation of percentage a activity was 16.5, 33, and 24 min for control, 1 and 2 hr postendotoxin, respectively. Although the Vmax and Km for glucose-1-P for total glycogen phosphorylase were not affected by endotoxin administration, the Vmax for glucose-1-P for glycogen phosphorylase a was increased by 57.3 and 42.7% at 1 and 2 hr postendotoxin, respectively, with no change in the Km values. Glucose inhibited glycogen phosphorylase a activity both in control and endotoxin-injected dogs, but the I50 value was increased by 35% in endotoxin-injected (2 hr) dogs. AMP activated glycogen phosphorylase b activity both in control and endotoxin-injected dogs with no change in A0.5 values between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Monophosphate↗

PubMed1972

Glycogen synthetase and the control of glycogen synthesis in the cellular slime mould Dictyostelium discoideum during cell differentiation.

1. The variation in cellular glycogen content of differentiating cells derived from myxamoebae that initially contained a wide range of glycogen contents (0.047-5.56mg of glycogen/10(8) myxamoebae) has been studied. 2. Myxamoebae that initially contained 0.047-3.62mg of glycogen/10(8) myxamoebae all gave rise to fruiting bodies that contained similar amounts of glycogen (0.06-0.11mg of glycogen/10(8) cells) but myxamoebae that initially contained 5.56mg of glycogen formed fruiting bodies containing 0.5mg of glycogen/10(8) cells. 3. Despite the high net rate of glycogen disappearance (during cell differentiation) from cells that contained more than 2mg of glycogen/10(8) cells initially, there were still significant variations in the rate of glycogen synthesis. The rate of glycogen synthesis reached a peak at the aggregation stage. 4. Evidence is presented showing that the rate of this synthesis of glycogen is controlled by factors other than the intracellular concentration of glycogen synthetase. 5. Our results are discussed in the context of the theory that the rates of glycogen synthesis and degradation act as a control mechanism for cell differentiation. 6. Criteria are discussed for deciding whether a biochemical event is causally or secondarily related to morphogenesis.

Cell Differentiation↗

PubMed1989

Pathways of glycogen synthesis from glucose during the glycogenic response to insulin in cultured foetal hepatocytes.

The pathways of glycogen synthesis from glucose were studied using double-isotope procedures in 18-day cultured foetal-rat hepatocytes in which glycogenesis is strongly stimulated by insulin. When the medium containing 4 mM-glucose was supplemented with [2-3H,U-14C]glucose or [3-3H,U-14C]glucose, the ratios of 3H/14C in glycogen relative to that in glucose were 0.23 +/- 0.04 (n = 6) and 0.63 +/- 0.09 (n = 8) respectively after 2 h. This indicates that more than 75% of glucose was first metabolized to fructose 6-phosphate, whereas 40% reached the step of the triose phosphates prior to incorporation into glycogen. The stimulatory effect of 10 nM-insulin on glycogenesis (4-fold) was accompanied by a significant increase in the (3H/14C in glycogen)/(3H/14C in glucose) ratio with 3H in the C-2 position (0.29 +/- 0.05, n = 6, P less than 0.001) or in the C-3 position (0.68 +/- 0.09, n = 8, P less than 0.01) of glucose, whereas the effect of a 12 mM-glucose load (3.5-fold) did not alter these ratios. Fructose (4 mM) displaced [U-14C]glucose during labelling of glycogen in the presence and absence of insulin by 50 and 20% respectively, and produced under both conditions a similar increase (45%) in the (3H/14C in glycogen)/(3H/14C in glucose) ratio when 3H was in the C-2 position. 3-Mercaptopicolinate (1 mM), an inhibitor of gluconeogenesis from lactate/pyruvate, further decreased the already poor labelling of glycogen from [U-14C]alanine, whereas it increased both glycogen content and incorporation of label from [U-14C]serine and [U-14C]glucose with no effect on the relative 3H/14C ratios in glycogen and glucose with 3H in the C-3 position of glucose. These results indicate that an alternative pathway in addition to direct glucose incorporation is involved in glycogen synthesis in cultured foetal hepatocytes, but that insulin preferentially favours the classical direct route. The alternative foetal pathway does not require gluconeogenesis from pyruvate-derived metabolites, contrary to the situation in the adult liver.

Animals↗

PubMed1996

NMR studies of muscle glycogen synthesis in insulin-resistant offspring of parents with non-insulin-dependent diabetes mellitus immediately after glycogen-depleting exercise.

To examine the impact of insulin resistance on the insulin-dependent and insulin-independent portions of muscle glycogen synthesis during recovery from exercise, we studied eight young, lean, normoglycemic insulin-resistant (IR) offspring of individuals with non-insulin-dependent diabetes mellitus and eight age-weight matched control (CON) subjects after plantar flexion exercise that lowered muscle glycogen to approximately 25% of resting concentration. After approximately 20 min of exercise, intramuscular glucose 6-phosphate and glycogen were simultaneously monitored with 31P and 13C NMR spectroscopies. The postexercise rate of glycogen resynthesis was nonlinear. Glycogen synthesis rates during the initial insulin independent portion (0-1 hr of recovery) were similar in the two groups (IR, 15.5 +/- 1.3 mM/hr and CON, 15.8 +/- 1.7 mM/hr); however, over the next 4 hr, insulin-dependent glycogen synthesis was significantly reduced in the IR group [IR, 0.1 +/- 0.5 mM/hr and CON, 2.9 +/- 0.2 mM/hr; (P < or = 0.001)]. After exercise there was an initial rise in glucose 6-phosphate concentrations that returned to baseline after the first hour of recovery in both groups. In summary, we found that following muscle glycogen-depleting exercise, IR offspring of parents with non-insulin-dependent diabetes mellitus had (i) normal rates of muscle glycogen synthesis during the insulin-independent phase of recovery from exercise and (ii) severely diminished rates of muscle glycogen synthesis during the subsequent recovery period (2-5 hr), which has previously been shown to be insulin-dependent in normal CON subjects. These data provide evidence that exercise and insulin stimulate muscle glycogen synthesis in humans by different mechanisms and that in the IR subjects the early response to stimulation by exercise is normal.

Adult↗

PubMed1968

Rabbit skeletal muscle glycogen. A morphological and biochemical study of glycogen beta-particles isolated by the precipitation-centrifugation method.

Glycogen in its particulate beta-form is localized in the sarcoplasm close to the sarcoplasmic reticulum. Some particles are in close contact with the membranes, on the outer side of the vesicles. The mild technique of differential precipitation-centrifugation has been adapted to the preparation of glycogen from adult skeletal muscle. A preliminary low-speed centrifugation which eliminates the contractile protein structures and the cell debris is followed by a high-speed centrifugation which produces pellets containing glycogen mixed with smooth-walled vesicles, the glycogen-sarcovesicular fraction. The glycogen obtained after treatment of this fraction with deoxycholate and two washings contains 3% protein. A similar protein content contaminates glycogen banded in a linear sucrose gradient. The glycogen-sarcovesicular fraction and the purified glycogen have been examined, under the electron microscope, in sections of fixed and embedded material or with the negative staining technique. The glycogen beta-particles in negatively stained preparations have an average diameter of 39.4 mmicro. The largest particles present irregular outlines, suggesting the presence of conglomerated subunits, about 20 mmicro in diameter. These subunits seem to fall apart under the influence of concentrated potassium hydroxide. The mean sedimentation coefficients calculated for infinite dilution vary from 115 to 135S. The spectrophotometric analysis of the glycogen-iodine complex indicates the presence of long end-chains in the molecule.

Animals↗

PubMed1989

The glycogen-binding subunit of protein phosphatase-1G from rabbit skeletal muscle. Further characterisation of its structure and glycogen-binding properties.

The glycogen-bound form of protein phosphatase-1 (PP-1G) was previously purified as a heterodimer composed of a 37-kDa catalytic (C) subunit and a proteolytically sensitive 103-kDa glycogen-binding (G) subunit [Stråhlfors, P., Hiraga, A. & Cohen, P. (1985) Eur. J. Biochem. 149, 295-303]. In this paper we demonstrate by a variety of criteria that the intact G subunit is a 161-kDa protein, and that the 103-kDa species (now termed G') is itself a product of proteolysis. A second phosphorylation site for cAMP-dependent protein kinase (termed site 2) was identified on the G subunit. The site 2 serine was phosphorylated at a comparable rate to site 1, and near stoichiometric phosphorylation could be achieved in the presence and absence of glycogen. Site 2 was dephosphorylated by PP-1 at a slow rate, whereas site 1 was resistant to autodephosphorylation. PP-1G, as well as the proteolytic activity responsible for degradation of the G subunit, remained tightly associated with glycogen-protein particles during washing with a variety of solvents. The PP-1G holoenzyme was released from glycogen-protein particles by dilution, with a dissociation half point corresponding to about 10 nM PP-1G. Binding experiments with purified PP-1G and glycogen indicated a bimolecular process with Kapp values corresponding to about 8 nM glycogen and 4 nM PP-1G. Binding was not significantly affected by increasing ionic strength to 0.5 M or variation of pH from 6 to 8. The results are consistent with a high-affinity glycogen-binding domain on the G subunit, and indicate that a physiological concentrations of phosphatase and glycogen, PP-1G should be almost entirely bound to glycogen.

Animals↗

PubMed2006

Increased sensitivity of glycogen synthesis to phosphorylase-a and impaired expression of the glycogen-targeting protein R6 in hepatocytes from insulin-resistant Zucker fa/fa rats.

Hepatic insulin resistance in the leptin-receptor defective Zucker fa/fa rat is associated with impaired glycogen synthesis and increased activity of phosphorylase-a. We investigated the coupling between phosphorylase-a and glycogen synthesis in hepatocytes from fa/fa rats by modulating the concentration of phosphorylase-a. Treatment of hepatocytes from fa/fa rats and Fa/? controls with a selective phosphorylase inhibitor caused depletion of phosphorylase-a, activation of glycogen synthase and stimulation of glycogen synthesis. The flux-control coefficient of phosphorylase on glycogen synthesis was glucose dependent and at 10 mm glucose was higher in fa/fa than Fa/? hepatocytes. There was an inverse correlation between the activities of glycogen synthase and phosphorylase-a in both fa/fa and Fa/? hepatocytes. However, fa/fa hepatocytes had a higher activity of phosphorylase-a, for a corresponding activity of glycogen synthase. This defect was, in part, normalized by expression of the glycogen-targeting protein, PTG. Hepatocytes from fa/fa rats had normal expression of the glycogen-targeting proteins G(L) and PTG but markedly reduced expression of R6. Expression of R6 protein was increased in hepatocytes from Wistar rats after incubation with leptin and insulin. Diminished hepatic R6 expression in the leptin-receptor defective fa/fa rat may be a contributing factor to the elevated phosphorylase activity and/or its high control strength on glycogen synthesis.

Animals↗

PubMed2004

Mutations in the gal83 glycogen-binding domain activate the snf1/gal83 kinase pathway by a glycogen-independent mechanism.

The yeast Snf1 kinase and its mammalian ortholog, AMP-activated protein kinase (AMPK), regulate responses to metabolic stress. Previous studies identified a glycogen-binding domain in the AMPK beta1 subunit, and the sequence is conserved in the Snf1 kinase beta subunits Gal83 and Sip2. Here we use genetic analysis to assess the role of this domain in vivo. Alteration of Gal83 at residues that are important for glycogen binding of AMPK beta1 abolished glycogen binding in vitro and caused diverse phenotypes in vivo. Various Snf1/Gal83-dependent processes were upregulated, including glycogen accumulation, expression of RNAs encoding glycogen synthase, haploid invasive growth, the transcriptional activator function of Sip4, and activation of the carbon source-responsive promoter element. Moreover, the glycogen-binding domain mutations conferred transcriptional regulatory phenotypes even in the absence of glycogen, as determined by analysis of a mutant strain lacking glycogen synthase. Thus, mutation of the glycogen-binding domain of Gal83 positively affects Snf1/Gal83 kinase function by a mechanism that is independent of glycogen binding.

Amino Acid Sequence↗

PubMed1975

Determination of the glycogen content in single neutrophil leukocytes using a micromodel of leukocyte glycogen.

The kinetics of the periodic acid oxidation as part of the periodic acid-Schiff reaction was studied by combined microinterferometry and microspectrophotometry in micromodel systems of liver glycogen and leukocyte glycogen as well as in neutrophil leukocytes. The initial formation of Schiff-positive chromogens was more rapid in neutrophil leukocytes than in liver or leukocyte glycogen. The chromogen formation was, however, practically complete within 60 min in both neutrophil leukocytes and leukocyte glycogen, but this did not appear to be the case in liver glycogen. Differences in the rate of chromogen formation may depend on various factors such as differences in the source and treatment of the glycogen. The complete periodic acid-Schiff reaction appears to be a measure of the glycogen amount in neutrophil leukocytes and the microdroplet system of leukocyte glycogen is considered to be an appropriate model for the estimation of the glycogen amount in single neutrophil leukocytes. A mean value of 13.3 10-12 g glycogen per normal human neutrophil was found.

Glycogen↗

PubMed2000

Overexpression of glutamine:fructose-6-phosphate amidotransferase in rat-1 fibroblasts enhances glucose-mediated glycogen accumulation via suppression of glycogen phosphorylase activity.

The hexosamine biosynthesis pathway (HBP) mediates many of the adverse effects of excess glucose. We have shown previously that glucose down-regulates basal and insulin-stimulated glycogen synthase (GS) activity. Overexpression of the rate-limiting enzyme in the HBP, glutamine:fructose-6-phosphate amidotransferase (GFA), mimics these effects of high glucose and renders the cells more sensitive to glucose. Here we examine the role of the HBP in regulating cellular glycogen content. Glycogen content and glycogen phosphorylase (GP) activity were determined in Rat-1 fibroblasts that overexpress GFA. In both GFA and controls there was a dose-dependent increase in glycogen content (approximately 8-fold) in cells cultured in increasing glucose concentrations (1-20 mM). There was a shift to the left in the glucose dose-response curve for glycogen content in GFA cells (ED50 for glycogen content = 5.80+/-1.05 vs. 8.84+/-0.87 mM glucose, GFA vs. control). Inhibition of GFA reduced glycogen content by 28.4% in controls cultured in 20 mM glucose. In a dose-dependent manner, glucose resulted in a more than 35% decrease in GP activity in controls. GP activity in GFA cells was suppressed compared with that in controls, and there was no glucose-induced down-regulation of GP activity. Glucosamine and uridine mimicked the effects of glucose on glycogen content and GP activity. However, chronic overexpression of GFA is a unique model of hexosamine excess, as culturing control cells in low dose glucosamine (0.1-0.25 mM) did not suppress GP activity and did not eliminate the glucose-mediated down-regulation of GP activity. We conclude that increased flux through the HBP results in enhanced glycogen accumulation due to suppression of GP activity. These results demonstrate that the HBP is an important regulator of cellular glucose metabolism and supports its role as a cellular glucose/satiety sensor.

Animals↗

PubMed2004

Crystal structure of glycogen synthase: homologous enzymes catalyze glycogen synthesis and degradation.

Glycogen and starch are the major readily accessible energy storage compounds in nearly all living organisms. Glycogen is a very large branched glucose homopolymer containing about 90% alpha-1,4-glucosidic linkages and 10% alpha-1,6 linkages. Its synthesis and degradation constitute central pathways in the metabolism of living cells regulating a global carbon/energy buffer compartment. Glycogen biosynthesis involves the action of several enzymes among which glycogen synthase catalyzes the synthesis of the alpha-1,4-glucose backbone. We now report the first crystal structure of glycogen synthase in the presence and absence of adenosine diphosphate. The overall fold and the active site architecture of the protein are remarkably similar to those of glycogen phosphorylase, indicating a common catalytic mechanism and comparable substrate-binding properties. In contrast to glycogen phosphorylase, glycogen synthase has a much wider catalytic cleft, which is predicted to undergo an important interdomain 'closure' movement during the catalytic cycle. The structures also provide useful hints to shed light on the allosteric regulation mechanisms of yeast/mammalian glycogen synthases.

Adenosine Diphosphate↗

PubMed2002

Glucose transport rate and glycogen synthase activity both limit skeletal muscle glycogen accumulation.

We varied rates of glucose transport and glycogen synthase I (GS-I) activity (%GS-I) in isolated rat epitrochlearis muscle to examine the role of each process in determining the rate of glycogen accumulation. %GS-I was maintained at or above the fasting basal range during 3 h of incubation with 36 mM glucose and 60 microU/ml insulin. Lithium (2 mM LiCl) added to insulin increased glucose transport rate and muscle glycogen content compared with insulin alone. The glycogen synthase kinase-3beta inhibitor GF-109203 x (GF; 10 microM) maintained %GS-I about twofold higher than insulin with or without lithium but did not increase glycogen accumulation. When %GS-I was lowered below the fasting range by prolonged incubation with 36 mM glucose and 2 mU/ml insulin, raising rates of glucose transport with bpV(phen) or of %GS-I with GF produced additive increases in glycogen concentration. Phosphorylase activity was unaffected by GF or bpV(phen). In muscles of fed animals, %GS-I was approximately 30% lower than in those of fasted rats, and insulin-stimulated glycogen accumulation did not occur unless %GS-I was raised with GF. We conclude that the rate of glucose transport is rate limiting for glycogen accumulation unless %GS-I is below the fasting range, in which case both glucose transport rate and GS activity can limit glycogen accumulation.

Animals↗

PubMed2003

Regulation of glycogen synthase by glucose and glycogen: a possible role for AMP-activated protein kinase.

We report here use of human myoblasts in culture to study the relationships between cellular glycogen concentrations and the activities of glycogen synthase (GS) and AMP-activated protein kinase (AMPK). Incubation of cells for 2 h in the absence of glucose led to a 25% decrease in glycogen content and a significant decrease in the fractional activity of GS. This was accompanied by stimulation of both the alpha1 and alpha2 isoforms of AMPK, without significant alterations in the ratios of adenine nucleotides. When glucose was added to glycogen-depleted cells, a rapid and substantial increase in GS activity was accompanied by inactivation of AMPK back to basal values. Inclusion of the glycogen phosphorylase inhibitor, CP-91149, prevented the loss of glycogen during glucose deprivation but not the activation of AMPK. However, in the absence of prior glycogen breakdown, glucose treatment failed to activate GS above control values, indicating the crucial role of glycogen content. Activation of AMPK by either 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR) or hydrogen peroxide was also associated with a decrease in the activity ratio of GS. AICAR treatment had no effect on total cellular glycogen content but led to a modest increase in glucose uptake. These data support a role for AMPK in both stimulating glucose uptake and inhibiting GS in intact cells, thus promoting glucose flux through glycolysis.

AMP-Activated Protein Kinases↗

PubMed2002

Epinephrine control of glycogen metabolism in glycogen-associated protein phosphatase PP1G/R(GL) knockout mice.

The glycogen-associated protein phosphatase (PP1G/ R(GL))may play a central role in the hormonal control of glycogen metabolism in the skeletal muscle. Here, we investigated the in vivo epinephrine effect of glycogen metabolism in the skeletal muscle of the wild-type and R(GL) knockout mice. The administration of epinephrine increased blood glucose levels from 200 +/- +/- 20 to 325 +/- 20 mg/dl in both wild-type and knockout mice. Epinephrine decreased the glycogen synthase -/+ G6P ratio from 0.24 +/- 0.04 to 0.10 +/- 0.02 in the wild-type, and from 0.17 +/- 0.02 to 0.06 +/- 0.01 in the knockout mice. Conversely, the glycogen phosphorylase activity ratio increased from 0.21 +/- 0.04 to 0.65 +/- 0.07 and from 0.30 +/- 0.04 to 0.81 +/- 0.06 in the epinephrine treated wild-type and knockout mice respectively. The glycogen content of the knockout mice was substantially lower (27 percent) than that of both wild-type mice; and epinephrine decreased glycogen content in the wild-type and knockout mice. Also, in Western blot analysis there was no compensation of the other glycogen targeting components PTG/R5 and R6 in the knockout mice compared with the wild-type. Therefore, R(GL) is not required for the epinephrine stimulation of glycogen metabolism, and rather another phosphatase and/or regulatory subunit appears to be involved.

Animals↗