scholarly journals Regulation of glycogen synthase activity and phosphorylation by exercise

2004 ◽  
Vol 63 (2) ◽  
pp. 233-237 ◽  
Author(s):  
Jakob N. Nielsen ◽  
Jørgen F. P. Wojtaszewski
Keyword(s):  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Relative Strength ◽  
Energy Utilization ◽  
Rate Limiting Step ◽  
Glycogen Repletion ◽  
Response To Exercise ◽  
Rate Limiting ◽  
Glycogen Synthase Activity ◽  
Glycogen Breakdown

Glycogen synthase (GS) catalyses the rate-limiting step of UDP-glucose incorporation into glycogen. Exercise is a potent regulator of GS activity, leading to activation of GS immediately after exercise promoting glycogen repletion by mechanisms independent of insulin. The incorporation of UDP-glucose is energy demanding, and during intense exercise GS is deactivated, diminishing energy utilization but also increasing the potential for glycogen breakdown. An apparent activation of GS is observed during moderate exercise, which could be considered as a potential waste of energy, although the cellular capacity for glycogen breakdown is considerably higher than that for glycogen synthesis. The understanding of this complex regulation of GS activity in response to exercise is just at its beginning. In the present review potential mechanisms by which exercise regulates GS activity are described, factors that may promote GS activation and factors that may deactivate GS are discussed, pointing to the view that GS activity during exercise is the result of the relative strength of these opposing factors.

Cytochemical localization of glycogen synthase activity in rat liver

1992 ◽  
Vol 50 (1) ◽  
pp. 804-805
Author(s):  
John E. Michaels ◽  
Robert R. Cardell
Keyword(s):  
Glycogen Synthase ◽  
Periodic Acid ◽  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Periodic Acid Schiff ◽  
Cytochemical Localization ◽  
Phosphorylation State ◽  
Rate Limiting ◽  
Glycogen Synthase Activity ◽  
Product Control

Glycogen synthase (GS) is the rate limiting enzyme for liver glycogen synthesis and its activity varies with the phosphorylation state of the enzyme. The current study focused on changes in the intralobular patterns of distribution of cytochemically localized GS activity during glycogen synthesis.Normal and adrenalectomized (ADX) rats were fasted overnight to reduce liver glycogen to minimal levels. Fasted ADX rats received 2 mg dexamethasone (DEX) 0-8 h prior to sacrifice to stimulate glycogen synthesis. Liver was removed, rapidly frozen in isopentane cooled in liquid nitrogen, then cryostat sectioned. GS activity was localized histochemically by 3 h incubation in medium containing both UDP-glucose and glucose 6-phosphate. Glycogen was formed as reaction product. Control incubations omitted the substrate. Two stains were used to identify glycogen: 1) iodine staining of the incubated sections was rather specific for the newly formed glycogen (Figs. 1-6), whereas 2) periodic acid-Schiff (PAS) stained both native and nascent glycogen.

scholarly journals Role of nuclear glycogen synthase and cytoplasmic UDP glucose pyrophosphorylase in the biosynthesis of nuclear glycogen in HD33 Ehrlich-Lettré ascites tumor cells.

1981 ◽  
Vol 89 (3) ◽  
pp. 475-484 ◽  
Author(s):  
C Granzow ◽  
M Kopun ◽  
H P Zimmermann
Keyword(s):  
Tumor Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Membrane System ◽  
Ascites Tumor ◽  
Cell Nuclei ◽  
Electron Microscopic ◽  
Intact Cells ◽  
Isolated Nuclei ◽  
Glycogen Synthase Activity

Biochemical and autoradiographic evidence show both glycogen synthesis and the presence of glycogen synthase (UDP glucose [UDPG]: glycogen 4-alpha-D-glucosyltransferase; EC 2.4.1.11) in isolated nuclei of Ehrlich-Lettré mouse ascites tumor cells of the mutant subline HD33. 5 d after tumor transplantation, glycogen (average 5-7 pg/cell) is stored mainly in the cell nuclei. The activity of glycogen synthase in isolated nuclei is 14.5 mU/mg protein. At least half of the total cellular glycogen synthase activity is present in the nuclei. The nuclear glycogen synthase activity exists almost exclusively in its b form. The Km value for (a + b) glycogen synthase is 1 x 10(-3) M UDPG, the activation constant is 5 x 10(-3) M glucose-6-phosphate (Glc-6-P). Light and electron microscopic autoradiographs of isolated nuclei incubated with UDP-[1-3H]glucose show the highest activity of glycogen synthesis not only in the periphery of glycogen deposits but also in interchromatin regions unrelated to detectable glycogen particles. Together with earlier findings on nuclear glycogen synthesis in intact HD33 ascites tumor cells (Zimmermann, H.-P., V. Granzow, and C. Granzow. 1976. J. Ultrastruct. Res. 54:115-123), the results of tests on isolated nuclei suggest a predominantly appositional mode of nuclear glycogen deposition, without participation of the nuclear membrane system. In intact cells, synthesis of UDPG for nuclear glycogen synthesis depends on the activity of the exclusively cytoplasmic UDPG pyrophosphorylase (UTP: alpha-D-glucose-1-phosphate uridylyltransferase; EC 2.7.7.9). However, we conclude that glycogen synthesis is not exclusively a cytoplasmic function and that the mammalian cell nucleus is capable of synthesizing glycogen.

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

2002 ◽  
Vol 282 (6) ◽  
pp. E1214-E1221 ◽  
Author(s):  
Jonathan S. Fisher ◽  
Lorraine A. Nolte ◽  
Kentaro Kawanaka ◽  
Dong-Ho Han ◽  
Terry E. Jones ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Muscle Glycogen ◽  
Glycogen Synthase ◽  
Transport Rate ◽  
Prolonged Incubation ◽  
Glycogen Accumulation ◽  
Gf 109203X ◽  
Rate Limiting ◽  
Glycogen Synthase Activity

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 μU/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-3β inhibitor GF-109203x (GF; 10 μM) 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 ∼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.

Glycogen Metabolism in Psoriatic Epidermis and in Regenerating Epidermis

1984 ◽  
Vol 67 (3) ◽  
pp. 291-298 ◽  
Author(s):  
C. S. Harmon ◽  
P. J. R. Phizackerley
Keyword(s):  
Glycogen Content ◽  
Glycogen Synthase ◽  
Quantitative Estimation ◽  
Glycogen Synthesis ◽  
Pentose Phosphate ◽  
Normal Epithelium ◽  
Glycogen Synthase Activity ◽  
Psoriatic Lesions ◽  
Wound Epithelium

1. The observation that the glycogen content of epidermis from psoriatic lesions and from regenerating wound epithelium is increased has been confirmed by quantitative estimation. 2. In epidermis from psoriatic lesions, although the proportion of glycogen synthase in the I form is only about 5% of the total and similar to control values, total glycogen synthase activity is increased approximately 4-fold and hence glycogen synthase I activity is increased to the same extent. In contrast, total phosphorylase activity is only slightly increased and, since the proportion of the enzyme in the a form is reduced, phosphorylase a activity is similar to control values. 3. In epidermis from psoriatic lesions, the concentration of UDP-glucose is approximately doubled, and the concentrations of fructose 1,6-bisphosphate and of 6-phosphogluconate are increased approximately 5-fold. It is concluded that rates of glycogen synthesis, of glycolysis and of the pentose phosphate pathway are all enhanced in vivo and in consequence the rate of glucose uptake by psoriatic epidermis must be increased. 4. In the non-involved epidermis of psoriatic patients the glycogen content is within normal limits, and although total glycogen synthase activity is increased the ratio of glycogen synthase I to phosphorylase a is maintained at normal levels by the appropriate phosphorylation of both enzymes. 5. In regenerating wound epithelium in the pig, the changes in enzyme activity and in metabolite concentration closely resemble those found in epithelium from psoriatic lesions except that in wound epithelium the proportion of phosphorylase in the a form is increased relative to normal epithelium.

Effect of hypercorticism on regulation of skeletal muscle glycogen metabolism by insulin

1992 ◽  
Vol 262 (4) ◽  
pp. E427-E433 ◽  
Author(s):  
L. Coderre ◽  
A. K. Srivastava ◽  
J. L. Chiasson
Keyword(s):  
Muscle Glycogen ◽  
Glycogen Content ◽  
Activity Ratio ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Dexamethasone Treatment ◽  
Muscle Glycogen Content ◽  
Glycogen Synthase Activity ◽  
Muscle Glycogen Concentration

The effects of hypercorticism on the regulation of glycogen metabolism by insulin in skeletal muscles was examined by using the hindlimb perfusion technique. Rats were injected daily with either saline or dexamethasone (0.4 mg.kg-1.day-1) for 14 days and were studied in the fed or fasted (24 h) state under saline or insulin (1 mU/ml) treatment. In fed controls, insulin resulted in glycogen synthase activation and in enhanced glycogen synthesis. In dexamethasone-treated animals, basal muscle glycogen concentration remained normal, but glycogen synthase activity ratio was decreased in white and red gastrocnemius and plantaris muscles. Furthermore, insulin failed to activate glycogen synthase and glycogen synthesis. In the controls, fasting was associated with decreased glycogen concentrations and with increased glycogen synthase activity ratio in all four groups of muscles (P less than 0.01). Dexamethasone treatment, however, completely abolished the decrease in muscle glycogen content as well as the augmented glycogen synthase activity ratio associated with fasting. Insulin infusion stimulated glycogen synthesis in fasted controls but not in dexamethasone-treated rats. These data therefore indicate that dexamethasone treatment inhibits the stimulatory effect of insulin on glycogen synthase activity and on glycogen synthesis. Furthermore, hypercorticism suppresses the decrease in muscle glycogen content associated with fasting.

Adenosine exerts a glycogen-sparing action in contracting rat skeletal muscle

1997 ◽  
Vol 272 (5) ◽  
pp. E762-E768 ◽  
Author(s):  
L. Vergauwen ◽  
E. A. Richter ◽  
P. Hespel
Keyword(s):  
Skeletal Muscle ◽  
Glycogen Synthase ◽  
Fiber Type ◽  
Fiber Types ◽  
Adrenergic Stimulation ◽  
Receptor Antagonism ◽  
Glycogen Synthase Activity ◽  
Glycogen Sparing ◽  
Glycogen Breakdown

The role of adenosine in regulating glycogen breakdown during electrically induced muscle contractions was investigated in isolated rat hindquarters perfused with a standard medium either lacking or containing 100 microU/ml insulin and/or 1.67 nM isoprenaline. Nonselective A1/A2-adenosine receptor antagonism via caffeine enhanced (P < 0.05) glycogen breakdown in contracting fast-oxidative (FO) fibers by 40%, provided they were exposed to both insulin and isoprenaline. Combined A1/A2-receptor antagonism by 8-cyclopentyl-1,3-dipropylxanthine (CPDPX) plus 3,7-dimethyl-1-proparglyxanthine (DMPX) fully reproduced (P < 0.05) this stimulatory effect. Furthermore, CPDPX plus DMPX also enhanced (P < 0.05) glycogenolysis during contractions in soleus but not in white gastrocnemius muscle. In contrast, CPDPX or DMPX alone did not affect glycogenolysis in either fiber type. Muscle adenosine 3',5'-cyclic monophosphate concentration during contractions was increased (P < 0.05) by CPDPX plus DMPX in both fiber types, whereas glycogen synthase fractional activity was depressed (P < 0.05). Phosphorylase activity was not changed by CPDPX plus DMPX. It is concluded that adenosine exerts a glycogen-sparing action in oxidative skeletal muscle exposed to both insulin and beta-adrenergic stimulation during contraction, presumably via stimulation of glycogen synthase activity.

Effect of hepatic nerves on disposition of an intraduodenal glucose load

1993 ◽  
Vol 265 (3) ◽  
pp. E487-E496 ◽  
Author(s):  
M. C. Moore ◽  
G. I. Shulman ◽  
A. Giaccari ◽  
M. J. Pagliassotti ◽  
G. Cline ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Glucose Infusion ◽  
Hepatic Glycogen ◽  
Indirect Pathway ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake ◽  
Hepatic Nerves ◽  
Glycogen Synthase Activity

We examined the disposition of a continuous 4-h intraduodenal glucose infusion (8 mg.kg-1 x min-1, labeled with [1-13C]glucose and [3-3H]glucose) in nine conscious hepatic-denervated dogs. Cumulative net hepatic uptakes (in grams of glucose equivalents) were 13.7 +/- 2.5 glucose, 3.1 +/- 0.6 gluconeogenic amino acids, and 0.8 +/- 0.1 glycerol. Net hepatic glycogen synthesis totalled 11.0 +/- 0.9 g, 55-62% via the direct pathway. All values were similar to those in hepatic-innervated dogs. Glycogen synthase activity and rate of glycogen synthesis were positively correlated (r2 = 0.913, P < 0.05). Variability in net hepatic glycogen synthesis and the mass of glycogen synthesized via the indirect pathway was reduced in hepatic-denervated dogs (P < 0.05). In conclusion, the glycemic response and rate of net glycogen synthesis during an intraduodenal glucose infusion was no different in hepatic-denervated and -innervated dogs. Net hepatic glucose uptake was sufficient to account for all net hepatic glycogen synthesis and lactate production, consistent with an intrahepatic source of gluconeogenic precursors for glycogen synthesis via the indirect pathway. Hepatic nerves appear responsible for much of the variability in net hepatic glycogen synthesis and in the mass of glycogen synthesized via the indirect pathway in normal dogs.

More marked stimulation by lithium than insulin of the glycogenic pathway in rat skeletal muscle.

1997 ◽  
Vol 273 (3) ◽  
pp. E514 ◽  
Author(s):  
C Fürnsinn ◽  
C Noe ◽  
R Herdlicka ◽  
M Roden ◽  
P Nowotny ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Zucker Rats ◽  
Kinase Activation ◽  
Insulin Resistant ◽  
Primary Deficit ◽  
Rat Soleus Muscle ◽  
Glycogen Synthase Activity

Lithium's impact on glucose metabolism was compared with that of insulin in isolated rat soleus muscle. Lithium chloride (20 mmol/l) induced a 4.8-fold more pronounced increment over basal glycogen synthase activity than insulin (10 nmol/l) (nmol UDP-glucose into glycogen in synthase activity assay.g-1.min-1: lithium, +22.1 +/- 1.8 vs. insulin, +4.6 +/- 3.9; P < 0.01). In parallel, lithium was less efficient than insulin in stimulating glucose transport (counts per minute 2-deoxy-D-[3H]glucose.mg-1.h-1: lithium, +211 +/- 19 vs. insulin, +311 +/- 57; P < 0.05) and lactate release (mumol.g-1.h-1: lithium, +1.0 +/- 0.5 vs. insulin, +3.9 +/- 0.5; P < 0.01), and similar increments were induced in glycogen synthesis (mumol glucose into glycogen.g-1.h-1: lithium, +3.32 +/- 0.43 vs. insulin, +3.46 +/- 0.47; not significant). Full additivity of glycogenic effects and divergent dependency on phosphatidylinositol 3-kinase activation provided further evidence for different mechanisms of action. In muscle from insulin-resistant obese Zucker rats (fa/fa), failure of lithium to reverse deficits in glucose metabolism suggested a primary deficit in muscle glucose uptake rather than glycogen synthesis. Hence lithium distinctly stimulates glycogen synthase activity in skeletal muscle and may therefore be regarded as a candidate for the treatment of disorders associated with primary deficits in the glycogenic pathway.

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