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.

Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle

2008 ◽  
Vol 294 (1) ◽  
pp. E28-E35 ◽  
Author(s):  
Michale Bouskila ◽  
Michael F. Hirshman ◽  
Jørgen Jensen ◽  
Laurie J. Goodyear ◽  
Kei Sakamoto
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Glycogen Content ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Wild Type ◽  
Muscle Glycogen Synthesis ◽  
Mutant Forms

Insulin promotes dephosphorylation and activation of glycogen synthase (GS) by inactivating glycogen synthase kinase (GSK) 3 through phosphorylation. Insulin also promotes glucose uptake and glucose 6-phosphate (G-6- P) production, which allosterically activates GS. The relative importance of these two regulatory mechanisms in the activation of GS in vivo is unknown. The aim of this study was to investigate if dephosphorylation of GS mediated via GSK3 is required for normal glycogen synthesis in skeletal muscle with insulin. We employed GSK3 knockin mice in which wild-type GSK3α and -β genes are replaced with mutant forms (GSK3α/βS21A/S21A/S9A/S9A), which are nonresponsive to insulin. Although insulin failed to promote dephosphorylation and activation of GS in GSK3α/βS21A/S21A/S9A/S9Amice, glycogen content in different muscles from these mice was similar compared with wild-type mice. Basal and epinephrine-stimulated activity of muscle glycogen phosphorylase was comparable between wild-type and GSK3 knockin mice. Incubation of isolated soleus muscle in Krebs buffer containing 5.5 mM glucose in the presence or absence of insulin revealed that the levels of G-6- P, the rate of [14C]glucose incorporation into glycogen, and an increase in total glycogen content were similar between wild-type and GSK3 knockin mice. Injection of glucose containing 2-deoxy-[3H]glucose and [14C]glucose also resulted in similar rates of muscle glucose uptake and glycogen synthesis in vivo between wild-type and GSK3 knockin mice. These results suggest that insulin-mediated inhibition of GSK3 is not a rate-limiting step in muscle glycogen synthesis in mice. This suggests that allosteric regulation of GS by G-6- P may play a key role in insulin-stimulated muscle glycogen synthesis in vivo.

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.

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.

scholarly journals Transgenic overexpression of protein targeting to glycogen markedly increases adipocytic glycogen storage in mice

2007 ◽  
Vol 292 (3) ◽  
pp. E952-E963 ◽  
Author(s):  
Michael J. Jurczak ◽  
Arpad M. Danos ◽  
Victoria R. Rehrmann ◽  
Margaret B. Allison ◽  
Cynthia C. Greenberg ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Transgenic Animals ◽  
Glycogen Metabolism ◽  
Glycogen Storage ◽  
Fatty Acid Binding ◽  
Fat Depots

Adipocytes express the rate-limiting enzymes required for glycogen metabolism and increase glycogen synthesis in response to insulin. However, the physiological function of adipocytic glycogen in vivo is unclear, due in part to the low absolute levels and the apparent biophysical constraints of adipocyte morphology on glycogen accumulation. To further study the regulation of glycogen metabolism in adipose tissue, transgenic mice were generated that overexpressed the protein phosphatase-1 (PP1) glycogen-targeting subunit (PTG) driven by the adipocyte fatty acid binding protein (aP2) promoter. Exogenous PTG was detected in gonadal, perirenal, and brown fat depots, but it was not detected in any other tissue examined. PTG overexpression resulted in a modest redistribution of PP1 to glycogen particles, corresponding to a threefold increase in the glycogen synthase activity ratio. Glycogen synthase protein levels were also increased twofold, resulting in a combined greater than sixfold enhancement of basal glycogen synthase specific activity. Adipocytic glycogen levels were increased 200- to 400-fold in transgenic animals, and this increase was maintained to 1 yr of age. In contrast, lipid metabolism in transgenic adipose tissue was not significantly altered, as assessed by lipogenic rates, weight gain on normal or high-fat diets, or circulating free fatty acid levels after a fast. However, circulating and adipocytic leptin levels were doubled in transgenic animals, whereas adiponectin expression was unchanged. Cumulatively, these data indicate that murine adipocytes are capable of storing far higher levels of glycogen than previously reported. Furthermore, these results were obtained by overexpression of an endogenous adipocytic protein, suggesting that mechanisms may exist in vivo to maintain adipocytic glycogen storage at a physiological set point.

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 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.

Regulation of glycogenolysis in human muscle in response to epinephrine infusion

1983 ◽  
Vol 54 (1) ◽  
pp. 45-50 ◽  
Author(s):  
D. Chasiotis ◽  
K. Sahlin ◽  
E. Hultman
Keyword(s):  
Active Site ◽  
Inorganic Phosphate ◽  
Glycogen Phosphorylase ◽  
Glycogen Content ◽  
Glycogen Synthase ◽  
Human Muscle ◽  
Prolonged Infusion ◽  
Epinephrine Infusion ◽  
Resting Muscle

The regulation of glycogenolysis in human muscle during epinephrine infusion has been investigated. The content of cAMP in resting muscle was 2.7 +/- 0.7 (SD) mumol . kg dry muscle-1 and increased threefold during the first 5 min of infusion. Total glycogen phosphorylase and glycogen synthase activities were unchanged during the infusion. The proportion of phosphorylase in the a form in the basal state was estimated to be at least 22.5% and during infusion 80–90%. During infusion, synthase I activity decreased. The muscle glycogen content was 340 mmol . kg dry wt-1 and decreased during the first 2 min of infusion at a rate of 11.0 mmol glycosyl units . kg dry wt-1 . min-1. Prolonged infusion resulted in a much lower glycogenolytic rate, even though most of the phosphorylase was still in the a form. Accumulation of hexose monophosphates and lactate followed the changes in glycogen. It was concluded that despite the almost total transformation of phosphorylase to the a form, the in vivo activity was maintained at a low level. It is suggested that this may be due to a low concentration of inorganic phosphate at the active site of the enzyme.

scholarly journals Muscle-Specific Deletion of the Glut4 Glucose Transporter Alters Multiple Regulatory Steps in Glycogen Metabolism

2005 ◽  
Vol 25 (21) ◽  
pp. 9713-9723 ◽  
Author(s):  
Young-Bum Kim ◽  
Odile D. Peroni ◽  
William G. Aschenbach ◽  
Yasuhiko Minokoshi ◽  
Ko Kotani ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Glycogen Phosphorylase ◽  
Glucose Transporter ◽  
Glycogen Content ◽  
Glycogen Synthase ◽  
Hexokinase Ii ◽  
Phosphorylase Activity ◽  
Fasted State ◽  
Glycogen Phosphorylase Activity ◽  
Glycogen Synthase Activity

ABSTRACT Mice with muscle-specific knockout of the Glut4 glucose transporter (muscle-G4KO) are insulin resistant and mildly diabetic. Here we show that despite markedly reduced glucose transport in muscle, muscle glycogen content in the fasted state is increased. We sought to determine the mechanism(s). Basal glycogen synthase activity is increased by 34% and glycogen phosphorylase activity is decreased by 17% (P < 0.05) in muscle of muscle-G4KO mice. Contraction-induced glycogen breakdown is normal. The increased glycogen synthase activity occurs in spite of decreased signaling through the insulin receptor substrate 1 (IRS-1)-phosphoinositide (PI) 3-kinase-Akt pathway and increased glycogen synthase kinase 3β (GSK3β) activity in the basal state. Hexokinase II is increased, leading to an approximately twofold increase in glucose-6-phosphate levels. In addition, the levels of two scaffolding proteins that are glycogen-targeting subunits of protein phosphatase 1 (PP1), the muscle-specific regulatory subunit (RGL) and the protein targeting to glycogen (PTG), are strikingly increased by 3.2- to 4.2-fold in muscle of muscle-G4KO mice compared to wild-type mice. The catalytic activity of PP1, which dephosphorylates and activates glycogen synthase, is also increased. This dominates over the GSK3 effects, since glycogen synthase phosphorylation on the GSK3-regulated site is decreased. Thus, the markedly reduced glucose transport in muscle results in increased glycogen synthase activity due to increased hexokinase II, glucose-6-phosphate, and RGL and PTG levels and enhanced PP1 activity. This, combined with decreased glycogen phosphorylase activity, results in increased glycogen content in muscle in the fasted state when glucose transport is reduced.

Glycogen content and contraction regulate glycogen synthase phosphorylation and affinity for UDP-glucose in rat skeletal muscles

2007 ◽  
Vol 293 (6) ◽  
pp. E1622-E1629 ◽  
Author(s):  
Yu-Chiang Lai ◽  
Jorid Thrane Stuenæs ◽  
Chia-Hua Kuo ◽  
Jørgen Jensen
Keyword(s):  
Skeletal Muscles ◽  
Glycogen Content ◽  
Glycogen Synthase ◽  
Dry Weight ◽  
Kinetic Properties ◽  
Glycogen Accumulation ◽  
Specific Antibodies ◽  
Phosphorylation Pattern ◽  
Gsk 3Β

Glycogen content and contraction strongly regulate glycogen synthase (GS) activity, and the aim of the present study was to explore their effects and interaction on GS phosphorylation and kinetic properties. Glycogen content in rat epitrochlearis muscles was manipulated in vivo. After manipulation, incubated muscles with normal glycogen [NG; 210.9 ± 7.1 mmol/kg dry weight (dw)], low glycogen (LG; 108.1 ± 4.5 mmol/ kg dw), and high glycogen (HG; 482.7 ± 42.1 mmol/kg dw) were contracted or rested before the studies of GS kinetic properties and GS phosphorylation (using phospho-specific antibodies). LG decreased and HG increased GS Km for UDP-glucose (LG: 0.27 ± 0.02 < NG: 0.71 ± 0.06 < HG: 1.11 ± 0.12 mM; P < 0.001). In addition, GS fractional activity inversely correlated with glycogen content ( R = −0.70; P < 0.001; n = 44). Contraction decreased Km for UDP-glucose (LG: 0.14 ± 0.01 = NG: 0.16 ± 0.01 < HG: 0.33 ± 0.03 mM; P < 0.001) and increased GS fractional activity, and these effects were observed independently of glycogen content. In rested muscles, GS Ser641 and Ser7 phosphorylation was decreased in LG and increased in HG compared with NG. GSK-3β Ser9 and AMPKα Thr172 phosphorylation was not modulated by glycogen content in rested muscles. Contraction decreased phosphorylation of GS Ser641 at all glycogen contents. However, contraction increased GS Ser7 phosphorylation even though GS was strongly activated. In conclusion, glycogen content regulates GS affinity for UDP-glucose and low affinity for UDP-glucose in muscles with high glycogen content may reduce glycogen accumulation. Contraction increases GS affinity for UDP-glucose independently of glycogen content and creates a unique phosphorylation pattern.

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