scholarly journals Regulation of glycogen synthesis in rat skeletal muscle after glycogen-depleting contractile activity: effects of adrenaline on glycogen synthesis and activation of glycogen synthase and glycogen phosphorylase

1999 ◽  
Vol 344 (1) ◽  
pp. 231-235 ◽  
Author(s):  
Jesper FRANCH ◽  
Rune ASLESEN ◽  
Jørgen JENSEN
Keyword(s):  
Skeletal Muscles ◽  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Contractile Activity ◽  
Glycogen Synthesis ◽  
High Rate ◽  
Rat Skeletal Muscle ◽  
Lower Activation ◽  
Glycogen Stores

We investigated the effects of insulin and adrenaline on the rate of glycogen synthesis in skeletal muscles after electrical stimulation in vitro. The contractile activity decreased the glycogen concentration by 62%. After contractile activity, the glycogen stores were fully replenished at a constant and high rate for 3 h when 10 m-i.u./ml insulin was present. In the absence of insulin, only 65% of the initial glycogen stores was replenished. Adrenaline decreased insulin-stimulated glycogen synthesis. Surprisingly, adrenaline did not inhibit glycogen synthesis stimulated by glycogen-depleting contractile activity. In agreement with this, the fractional activity of glycogen synthase was high when adrenaline was present after exercise, whereas adrenaline decreased the fractional activity of glycogen synthase to a low level during stimulation with insulin. Furthermore, adrenaline activated glycogen phosphorylase almost completely during stimulation with insulin, whereas a much lower activation of glycogen phosphorylase was observed after contractile activity. Thus adrenaline does not inhibit contraction-stimulated glycogen synthesis.

scholarly journals Activation of Glycogen Phosphorylase in Blood Platelets

Blood ◽  
1967 ◽  
Vol 30 (3) ◽  
pp. 321-330 ◽  
Author(s):  
ROBERT B. SCOTT ◽  
LaVerne W. Cooper
Keyword(s):  
Glycogen Phosphorylase ◽  
Blood Platelets ◽  
Glycogen Synthesis ◽  
Phosphorylase Kinase ◽  
Clot Retraction ◽  
Total Enzyme Activity ◽  
Glycogen Stores ◽  
Total Enzyme ◽  
Glycogen Breakdown

Abstract 1. In platelets incubated in vitro, glycogen phosphorylase was activated, and the degree of activation roughly corresponds to the degree of manipulation of the platelets and is greatest in the least physiologic incubation medium. 2. Activation proceeds with an increasing proportion of enzyme which is active in the absence of AMP, suggesting the action of the phosphorylase-activating enzyme, phosphorylase kinase, in platelets. 3. Total enzyme activity (activity with AMP) likewise increases and continues to increase while the AMP-independent fraction begins to decrease again, suggesting more than one activating mechanism. 4. During glycogen breakdown, and during coagulation and clot retraction induced by thrombin, glycogen synthesis was shown to continue in vitro. Clot retraction was found to be more dependent on adequate glycogen stores than was coagulation.

scholarly journals Diverse effects of two allosteric inhibitors on the phosphorylation state of glycogen phosphorylase in hepatocytes

2002 ◽  
Vol 368 (1) ◽  
pp. 309-316 ◽  
Author(s):  
Theodore LATSIS ◽  
Birgitte ANDERSEN ◽  
Loranne AGIUS
Keyword(s):  
Glycogen Phosphorylase ◽  
Potent Inhibitor ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Small Degree ◽  
Allosteric Inhibitors ◽  
Phosphorylation State ◽  
Stimulation Of

Two distinct allosteric inhibitors of glycogen phosphorylase, 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) and CP-91149 (an indole-2-carboxamide), were investigated for their effects on the phosphorylation state of the enzyme in hepatocytes in vitro. CP-91149 induced inactivation (dephosphorylation) of phosphorylase in the absence of hormones and partially counteracted the phosphorylation caused by glucagon. Inhibition of glycogenolysis by CP-91149 can be explained by dephosphorylation of phosphorylase a. This was associated with activation of glycogen synthase and stimulation of glycogen synthesis. DAB, in contrast, induced a small degree of phosphorylation of phosphorylase. This was associated with inactivation of glycogen synthase and inhibition of glycogen synthesis. Despite causing phosphorylation (activation) of phosphorylase, DAB is a very potent inhibitor of glycogenolysis in both the absence and presence of glucagon. This is explained by allosteric inhibition of phosphorylase a, which overrides the increase in activation state. In conclusion, two potent phosphorylase inhibitors exert different effects on glycogen metabolism in intact hepatocytes as a result of opposite effects on the phosphorylation state of both phosphorylase and glycogen synthase.

Autoregulation of myocardial glycogen concentration during intermittent hypoxia

1996 ◽  
Vol 271 (2) ◽  
pp. R311-R319 ◽  
Author(s):  
P. H. McNulty ◽  
C. Ng ◽  
W. X. Liu ◽  
D. Jagasia ◽  
G. V. Letsou ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Cardiac Work ◽  
Perfused Heart ◽  
Systemic Hypoxia ◽  
Glycogen Stores ◽  
Glycogen Breakdown ◽  
Intact Rats

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.

scholarly journals Antagonistic Controls of Autophagy and Glycogen Accumulation by Snf1p, the Yeast Homolog of AMP-Activated Protein Kinase, and the Cyclin-Dependent Kinase Pho85p

2001 ◽  
Vol 21 (17) ◽  
pp. 5742-5752 ◽  
Author(s):  
Zhong Wang ◽  
Wayne A. Wilson ◽  
Marie A. Fujino ◽  
Peter J. Roach
Keyword(s):  
Protein Kinase ◽  
Stationary Phase ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glycogen Storage ◽  
Wild Type ◽  
Gene Encoding ◽  
Glycogen Accumulation ◽  
Yeast Homolog ◽  
Glycogen Stores

ABSTRACT In the yeast Saccharomyces cerevisiae, glycogen is accumulated as a carbohydrate reserve when cells are deprived of nutrients. Yeast mutated in SNF1, a gene encoding a protein kinase required for glucose derepression, has diminished glycogen accumulation and concomitant inactivation of glycogen synthase. Restoration of synthesis in an snf1 strain results only in transient glycogen accumulation, implying the existence of otherSNF1-dependent controls of glycogen storage. A genetic screen revealed that two genes involved in autophagy, APG1and APG13, may be regulated by SNF1. Increased autophagic activity was observed in wild-type cells entering the stationary phase, but this induction was impaired in ansnf1 strain. Mutants defective for autophagy were able to synthesize glycogen upon approaching the stationary phase, but were unable to maintain their glycogen stores, because subsequent synthesis was impaired and degradation by phosphorylase, Gph1p, was enhanced. Thus, deletion of GPH1 partially reversed the loss of glycogen accumulation in autophagy mutants. Loss of the vacuolar glucosidase, SGA1, also protected glycogen stores, but only very late in the stationary phase. Gph1p and Sga1p may therefore degrade physically distinct pools of glycogen. Pho85p is a cyclin-dependent protein kinase that antagonizes SNF1control of glycogen synthesis. Induction of autophagy inpho85 mutants entering the stationary phase was exaggerated compared to the level in wild-type cells, but was blocked in apg1 pho85 mutants. We propose that Snf1p and Pho85p are, respectively, positive and negative regulators of autophagy, probably via Apg1 and/or Apg13. Defective glycogen storage in snf1cells can be attributed to both defective synthesis upon entry into stationary phase and impaired maintenance of glycogen levels caused by the lack of autophagy.

scholarly journals Overexpression of SH2-Containing Inositol Phosphatase 2 Results in Negative Regulation of Insulin-Induced Metabolic Actions in 3T3-L1 Adipocytes via Its 5′-Phosphatase Catalytic Activity

2001 ◽  
Vol 21 (5) ◽  
pp. 1633-1646 ◽  
Author(s):  
Tsutomu Wada ◽  
Toshiyasu Sasaoka ◽  
Makoto Funaki ◽  
Hiroyuki Hori ◽  
Shihou Murakami ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Uptake ◽  
Phosphatase Activity ◽  
Insulin Signaling ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Dominant Negative ◽  
Inositol Phosphatase

ABSTRACT Phosphatidylinositol (PI) 3-kinase plays an important role in various metabolic actions of insulin including glucose uptake and glycogen synthesis. Although PI 3-kinase primarily functions as a lipid kinase which preferentially phosphorylates the D-3 position of phospholipids, the effect of hydrolysis of the key PI 3-kinase product PI 3,4,5-triphosphate [PI(3,4,5)P3] on these biological responses is unknown. We recently cloned rat SH2-containing inositol phosphatase 2 (SHIP2) cDNA which possesses the 5′-phosphatase activity to hydrolyze PI(3,4,5)P3 to PI 3,4-bisphosphate [PI(3,4)P2] and which is mainly expressed in the target tissues of insulin. To study the role of SHIP2 in insulin signaling, wild-type SHIP2 (WT-SHIP2) and 5′-phosphatase-defective SHIP2 (ΔIP-SHIP2) were overexpressed in 3T3-L1 adipocytes by means of adenovirus-mediated gene transfer. Early events of insulin signaling including insulin-induced tyrosine phosphorylation of the insulin receptor β subunit and IRS-1, IRS-1 association with the p85 subunit, and PI 3-kinase activity were not affected by expression of either WT-SHIP2 or ΔIP-SHIP2. Because WT-SHIP2 possesses the 5′-phosphatase catalytic region, its overexpression marked by decreased insulin-induced PI(3,4,5)P3 production, as expected. In contrast, the amount of PI(3,4,5)P3 was increased by the expression of ΔIP-SHIP2, indicating that ΔIP-SHIP2 functions in a dominant-negative manner in 3T3-L1 adipocytes. Both PI(3,4,5)P3 and PI(3,4)P2 were known to possibly activate downstream targets Akt and protein kinase Cλ in vitro. Importantly, expression of WT-SHIP2 inhibited insulin-induced activation of Akt and protein kinase Cλ, whereas these activations were increased by expression of ΔIP-SHIP2 in vivo. Consistent with the regulation of downstream molecules of PI 3-kinase, insulin-induced 2-deoxyglucose uptake and Glut4 translocation were decreased by expression of WT-SHIP2 and increased by expression of ΔIP-SHIP2. In addition, insulin-induced phosphorylation of GSK-3β and activation of PP1 followed by activation of glycogen synthase and glycogen synthesis were decreased by expression of WT-SHIP2 and increased by the expression of ΔIP-SHIP2. These results indicate that SHIP2 negatively regulates metabolic signaling of insulin via the 5′-phosphatase activity and that PI(3,4,5)P3 rather than PI(3,4)P2 is important for in vivo regulation of insulin-induced activation of downstream molecules of PI 3-kinase leading to glucose uptake and glycogen synthesis.

scholarly journals The effect of insulin-like growth factor II on glucose uptake and metabolism in rat skeletal muscle in vitro

1992 ◽  
Vol 286 (2) ◽  
pp. 561-565 ◽  
Author(s):  
S J Bevan ◽  
M Parry-Billings ◽  
E Opara ◽  
C T Liu ◽  
D B Dunger ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Insulin Like Growth Factor ◽  
Rat Skeletal Muscle ◽  
Factor Ii ◽  
Igf Binding ◽  
Uptake And Metabolism

The effect of insulin-like growth factor II (IGF II) on the rates of lactate formation, glycogen synthesis and glucose transport in the presence of a range of concentrations of insulin were investigated using an isolated preparation of rat skeletal muscle. IGF II, at a concentration of 65 ng/ml, caused a small but significant increase in the rates of these processes at a basal physiological insulin concentration (10 muunits/ml), but was without effect in the presence of 1, 100, 1000 or 10,000 muunits of insulin/ml. Hence IGF II increased the insulin sensitivity of this tissue. This effect was removed if the incubation medium was supplemented with an equimolar concentration of IGF binding protein 1 (BP1). It is suggested that changes in the concentration of IGF II and/or BP1 may regulate glucose uptake and metabolism in skeletal muscle and have physiological significance in the control of blood glucose level.

scholarly journals Increase in Subcellular GSK-3 Clusters in Insulin- and Adrenaline-treated Differentiated Rat Skeletal Muscle Fibres

2020 ◽  
Author(s):  
Katja Fink ◽  
Mateja Lobe Prebil ◽  
Nina Vardjan ◽  
Jorgen Jensen ◽  
Robert Zorec ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Metabolic Regulation ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase 3 ◽  
Muscle Fibres ◽  
Optical Section ◽  
Rat Skeletal Muscle ◽  
Average Size ◽  
Skeletal Muscle Fibres

Glycogen synthase kinase 3 (GSK-3) plays an important role in metabolic regulation in skeletal muscles, and both insulin and adrenaline stimulate   GKS-3 phosphorylation. The aim of the present study was to study the effect of insulin and adrenaline on GSK-3 localisation in skeletal muscles.We characterized subcellular localization of (GSK-3) signal protein in fully differentiated muscle fibre by immunofluorescence and confocal microscopy. We stimulated muscle fibres with insulin and/or adrenaline. Images were analysed by segmentation of single central optical section of the muscle.We found GSK-3 to be localised in clusters. The number of GSK-3 clusters and their average size were increased after stimulation with insulin and/or adrenaline. Average GSK-3 particle size is linearly related to their quantity.We conclude that subcellular GSK-3 in isolated skeletal muscle fibres is localized in clusters and clustering increased after stimulation with insulin and/or adrenaline.

Is resting muscle oxygen uptake controlled by oxygen availability to cells?

1989 ◽  
Vol 66 (1) ◽  
pp. 253-260 ◽  
Author(s):  
A. E. Chinet ◽  
J. Mejsnar
Keyword(s):  
Skeletal Muscles ◽  
Oxidative Capacity ◽  
Albumin Solution ◽  
Rat Skeletal Muscle ◽  
Flow Rates ◽  
Muscle Oxygen ◽  
Rate Dependent ◽  
Resting Muscle

To estimate oxidative capacity of noncontracting rat skeletal muscle, the isolated gracilis muscle was perfused at various high flow rates with high-PO2 (88 kPa) saline-albumin solution and simultaneously perifused at either low (6.3 kPa) or high PO2 in a calorimeter at 28 degrees C. Under low-PO2 perifusion, specific O2 consumption and heat production rates (MO2 and E, respectively) were flow-rate dependent. E values were all larger than those obtained on blood-perfused preparations at 28 degrees C. MO2 reached 0.47 mumol.min-1.g muscle-1 and E reached 4 mW/g. Normalized to 36 degrees C by means of activation energies determined from 30 and 36 degrees C measurements on nonperfused gracilis strips, these maxima correspond to three times the largest MO2 measured by other authors in blood-autoperfused gracilis. Increasing perifusion PO2 from 6.3 to 88 kPa sharply decreased MO2. These results confirm that MO2 of blood-perfused skeletal muscles in vitro (and a fortiori in vivo) is kept much below its maximum for a noncontracting organ; they also suggest that this maximum MO2 is not necessarily an effect of unphysiologically high PO2 in the tissue cells.

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

1998 ◽  
Vol 329 (2) ◽  
pp. 341-347 ◽  
Author(s):  
P. Anthony JAMES ◽  
B. Carrie FLYNN ◽  
L. Sioned JONES ◽  
T. Norman PALMER ◽  
A. Paul FOURNIER
Keyword(s):  
Skeletal Muscles ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Quadriceps Muscle ◽  
Control Site ◽  
Temporal Shift ◽  
Fed State ◽  
Phosphorylation State ◽  
Glycogen Deposition ◽  
Later Phase

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.

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