scholarly journals Up-Regulation of Glycogen Synthesis and Degradation Enzyme Level Maintained Myocardial Glycogen in Huddling Brandt’s Voles Under Cool Environments

2021 ◽  
Vol 12 ◽  
Author(s):  
Jin-Hui Xu ◽  
Zhe Wang ◽  
Jun-Jie Mou ◽  
Chuan-Li Wang ◽  
Wei-Mei Huang ◽  
...  
Keyword(s):  
Glycogen Content ◽  
Glycogen Synthase ◽  
Enzyme Level ◽  
Glycogen Synthesis ◽  
Glycogen Accumulation ◽  
Cold Environments ◽  
Group 4 ◽  
Cool Environment ◽  
The Stability ◽  
Synthesis And Degradation

Small mammals exhibit limited glucose use and glycogen accumulation during hypothermia. Huddling is a highly evolved cooperative behavioral strategy in social mammals, allowing adaptation to environmental cooling. However, it is not clear whether this behavior affects the utilization of glycogen in cold environments. Here, we studied the effects of huddling on myocardial glycogen content in Brandt’s voles (Lasiopodomys brandtii) under a mild cold environment (15°C). Results showed that (1) Compared to the control (22°C) group (CON), the number of glycogenosomes more than tripled in the cool separated group (CS) in both males and females; whereas the number of glycogenosomes increased in females but was maintained in males in the cool huddling group (CH). (2) Glycogen synthase (GS) activity in the CS group remained unchanged, whereas glycogen phosphorylase (GYPL) activity decreased, which mediated the accumulation of glycogen content of the CS group. (3) Both GS and GYPL activity increased which may contribute to the stability of glycogen content in CH group. (4) The expression levels of glucose transporters GLUT1 and GLUT4 increased in the CS group, accompanied by an increase in glucose metabolism. These results indicate that the reduced glycogen degradation enzyme level and enhanced glucose transport may lead to an increase in myocardial glycogen content of the separated voles under cool environment; while the up-regulation of glycogen synthesis and degradation enzyme level maintained myocardial glycogen content in the huddling vole.

scholarly journals Huddling relieves myocardial glycogen synthesis of Brandt’s voles in mild cold environment

2020 ◽  
Author(s):  
Zhe Wang ◽  
Jun-jie Mou ◽  
Jin-hui Xu ◽  
Chuan-li Wang ◽  
Wei-mei Huang ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Cold Environment ◽  
Glycogen Accumulation ◽  
Treatment Groups ◽  
Cold Environments ◽  
Males And Females ◽  
Lasiopodomys Brandtii ◽  
Highly Evolved

Abstract Background:Small mammals have limited glucose use and limited glycogen accumulation during hypothermia. Huddling is a highly evolved cooperative behavioral strategy in social mammals, allowing adaptation to environmental cooling. As yet, however, is not clear whether this behavior affects the utilization of glycogen in cold environments. Here, we studied the effect of huddling on myocardial glycogen content in Brandt’s voles (Lasiopodomys brandtii) under a mild cold environment (15 °C). Results: Results showed that (1) Compared to the control (22 °C) group (CON), the number of glycogenosomes more than tripled in the cool separated group (CS) in both males and females; whereas the number of glycogenosomes increased in females but was maintained in males in the cool huddling group (CH). (2) The ratio of glycogen synthetase phosphorylation showed a similar trend as the change in glycogenosome number in the three treatment groups in both males and females. (3) Protein expression of glycogen phosphorylase remained stable in males in the three treatment groups but increased in CS group females compared with the CON group. Conclusion:These results indicate that huddling in voles alleviated the increase in myocardial glycogen content caused by the increase of glycogen synthesis under cool environments.

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

1996 ◽  
Vol 16 (8) ◽  
pp. 4357-4365 ◽  
Author(s):  
D Huang ◽  
I Farkas ◽  
P J Roach
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Kinase Activity ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Mutant Gene ◽  
Glycogen Synthase Kinase ◽  
Partial Purification ◽  
Glycogen Accumulation ◽  
Dependent Protein

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.

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.

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.

Control of glycogen synthesis is shared between glucose transport and glycogen synthase in skeletal muscle fibers

2000 ◽  
Vol 278 (2) ◽  
pp. E234-E243 ◽  
Author(s):  
Iñaki Azpiazu ◽  
Jill Manchester ◽  
Alexander V. Skurat ◽  
Peter J. Roach ◽  
John C. Lawrence
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Muscle Fibers ◽  
Fiber Types ◽  
Oxidative Potential ◽  
Glycogen Accumulation ◽  
Tibialis Muscle ◽  
Fast Twitch

The effects of transgenic overexpression of glycogen synthase in different types of fast-twitch muscle fibers were investigated in individual fibers from the anterior tibialis muscle. Glycogen synthase was severalfold higher in all transgenic fibers, although the extent of overexpression was twofold greater in type IIB fibers. Effects of the transgene on increasing glycogen and phosphorylase and on decreasing UDP-glucose were also more pronounced in type IIB fibers. However, in any grouping of fibers having equivalent malate dehydrogenase activity (an index of oxidative potential), glycogen was higher in the transgenic fibers. Thus increasing synthase is sufficient to enhance glycogen accumulation in all types of fast-twitch fibers. Effects on glucose transport and glycogen synthesis were investigated in experiments in which diaphragm, extensor digitorum longus (EDL), and soleus muscles were incubated in vitro. Transport was not increased by the transgene in any of the muscles. The transgene increased basal [14C]glucose into glycogen by 2.5-fold in the EDL, which is composed primarily of IIB fibers. The transgene also enhanced insulin-stimulated glycogen synthesis in the diaphragm and soleus muscles, which are composed of oxidative fiber types. We conclude that increasing glycogen synthase activity increases the rate of glycogen synthesis in both oxidative and glycolytic fibers, implying that the control of glycogen accumulation by insulin in skeletal muscle is distributed between the glucose transport and glycogen synthase steps.

Muscle-specific overexpression of wild type and R225Q mutant AMP-activated protein kinase γ3-subunit differentially regulates glycogen accumulation

2006 ◽  
Vol 291 (3) ◽  
pp. E557-E565 ◽  
Author(s):  
Haiyan Yu ◽  
Michael F. Hirshman ◽  
Nobuharu Fujii ◽  
Jason M. Pomerleau ◽  
Lauren E. Peter ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Glycogen Content ◽  
Specific Activity ◽  
Glycogen Synthase ◽  
Underlying Mechanism ◽  
Wild Type ◽  
Glycogen Accumulation ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) is a heterotrimeric complex that works as an energy sensor to integrate nutritional and hormonal signals. The naturally occurring R225Q mutation in the γ3-subunit in pigs is associated with abnormally high glycogen content in skeletal muscle. Becauses skeletal muscle accounts for most of the body's glucose uptake, and γ3 is specifically expressed in skeletal muscle, it is important to understand the underlying mechanism of this mutation in regulating glucose and glycogen metabolism. Using skeletal muscle-specific transgenic mice overexpressing wild type γ3 (WTγ3) and R225Q mutant γ3 (MUTγ3), we show that both WTγ3 and MUTγ3 mice have 1.5- to 2-fold increases in muscle glycogen content. In WTγ3 mice, increased glycogen content was associated with elevated total glycogen synthase activity and reduced glycogen phosphorylase activity, whereas alterations in activities of these enzymes could not explain elevated glycogen in MUTγ3 mice. Basal, 5-aminoimidazole- AICAR- and phenformin-stimulated AMPKα2 isoform-specific activities were decreased only in MUTγ3 mice. Basal rates of 2-DG glucose uptake were decreased in both WTγ3 and MUTγ3 mice. However, AICAR- and phenformin-stimulated 2-DG glucose uptake were blunted only in MUTγ3 mice. In conclusion, expression of either wild type or mutant γ3-subunit of AMPK results in increased glycogen concentrations in muscle, but the mechanisms underlying this alteration appear to be different. Furthermore, mutation of the γ3-subunit is associated with decreases in AMPKα2 isoform-specific activity and impairment in AICAR- and phenformin-stimulated skeletal muscle glucose uptake.

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.

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

2004 ◽  
Vol 23 (16) ◽  
pp. 3196-3205 ◽  
Author(s):  
Alejandro Buschiazzo ◽  
Juan E Ugalde ◽  
Marcelo E Guerin ◽  
William Shepard ◽  
Rodolfo A Ugalde ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Synthesis And Degradation

scholarly journals Heating after intense repeated contractions inhibits glycogen accumulation in mouse EDL muscle: role of phosphorylase in postexercise glycogen metabolism

2018 ◽  
Vol 315 (5) ◽  
pp. C706-C713 ◽  
Author(s):  
Sarah J. Blackwood ◽  
Ester Hanya ◽  
Abram Katz
Keyword(s):  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Type Ii ◽  
Muscle Type ◽  
Phosphorylase Activity ◽  
Glycogen Accumulation ◽  
Longus Muscle ◽  
Edl Muscle

The effects of heating on glycogen synthesis (incorporation of [14C]glucose into glycogen) and accumulation after intense repeated contractions were investigated. Isolated mouse extensor digitorum longus muscle (type II) was stimulated electrically to perform intense tetanic contractions at 25°C. After 120 min recovery at 25°C, glycogen accumulated to almost 80% of basal, whereas after recovery at 35°C, glycogen remained low (~25% of basal). Glycogen synthesis averaged 0.97 ± 0.07 µmol·30 min−1·g wet wt−1 during recovery at 25°C and 1.48 ± 0.08 during recovery at 35°C ( P < 0.001). There were no differences in phosphorylase and glycogen synthase total activities nor in phosphorylase fractional activity, whereas glycogen synthase fractional activity was increased by ~50% after recovery at 35°C vs. 25°C. Inorganic phosphate (Pi, substrate for phosphorylase) was markedly increased (~300% of basal) following contraction but returned to control levels after 120 min recovery at 25°C. In contrast, Pi remained elevated after recovery at 35°C (>2-fold higher than recovery at 25°C). Estimates of glycogen breakdown indicated that phosphorylase activity (either via inhibition at 25°C or activation at 35°C) was responsible for ~60% of glycogen accumulation during recovery at 25°C and ~45% during recovery at 35°C. These data demonstrate that despite the enhancing effect of heating on glycogen synthesis during recovery from intense contractions, glycogen accumulation is inhibited owing to Pi-mediated activation of phosphorylase. Thus phosphorylase can play a quantitatively important role in glycogen biogenesis during recovery from repeated contractions in isolated type II muscle.

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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