Glycogen Accumulation in Trichomonas is Driven by the Availability of Extracellular Glucose

This study aims to evaluate the bioactive components, in vitro bioactivities, and in vivo hypoglycemic effect of P. frutescens leaf, which is a traditional medicine-food homology plant. P. frutescens methanol crude extract and its fractions (petroleum ether, chloroform, ethyl acetate, n-butanol fractions, and aqueous phase residue) were prepared by ultrasound-enzyme assisted extraction and liquid–liquid extraction. Among the samples, the ethyl acetate fraction possessed the high total phenolic (440.48 μg GAE/mg DE) and flavonoid content (455.22 μg RE/mg DE), the best antioxidant activity (the DPPH radical, ABTS radical, and superoxide anion scavenging activity, and ferric reducing antioxidant power were 1.71, 1.14, 2.40, 1.29, and 2.4 times higher than that of control Vc, respectively), the most powerful α-glucosidase inhibitory ability with the IC50 value of 190.03 μg/mL which was 2.2-folds higher than control acarbose, the strongest proliferative inhibitory ability against MCF-7 and HepG2 cell with the IC50 values of 37.92 and 13.43 μg/mL, which were considerable with control cisplatin, as well as certain inhibition abilities on acetylcholinesterase and tyrosinase. HPLC analysis showed that the luteolin, rosmarinic acid, rutin, and catechin were the dominant components of the ethyl acetate fraction. Animal experiments further demonstrated that the ethyl acetate fraction could significantly decrease the serum glucose level, food, and water intake of streptozotocin-induced diabetic SD rats, increase the body weight, modulate their serum levels of TC, TG, HDL-C, and LDL-C, improve the histopathology and glycogen accumulation in liver and intestinal tissue. Taken together, P. frutescens leaf exhibits excellent hypoglycemic activity in vitro and in vivo, and could be exploited as a source of natural antidiabetic agent.

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Modeling CNS Involvement in Pompe Disease Using Neural Stem Cells Generated from Patient-Derived Induced Pluripotent Stem Cells

Cells ◽

10.3390/cells10010008 ◽

2020 ◽

Vol 10 (1) ◽

pp. 8

Author(s):

Yu-Shan Cheng ◽

Shu Yang ◽

Junjie Hong ◽

Rong Li ◽

Jeanette Beers ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Pompe Disease ◽

Drug Efficacy ◽

Cns Involvement ◽

Glycogen Accumulation ◽

Induced Pluripotent ◽

Alpha Glucosidase

Pompe disease is a lysosomal storage disorder caused by autosomal recessive mutations in the acid alpha-glucosidase (GAA) gene. Acid alpha-glucosidase deficiency leads to abnormal glycogen accumulation in patient cells. Given the increasing evidence of central nervous system (CNS) involvement in classic infantile Pompe disease, we used neural stem cells, differentiated from patient induced pluripotent stem cells, to model the neuronal phenotype of Pompe disease. These Pompe neural stem cells exhibited disease-related phenotypes including glycogen accumulation, increased lysosomal staining, and secondary lipid buildup. These morphological phenotypes in patient neural stem cells provided a tool for drug efficacy evaluation. Two potential therapeutic agents, hydroxypropyl-β-cyclodextrin and δ-tocopherol, were tested along with recombinant human acid alpha-glucosidase (rhGAA) in this cell-based Pompe model. Treatment with rhGAA reduced LysoTracker staining in Pompe neural stem cells, indicating reduced lysosome size. Additionally, treatment of diseased neural stem cells with the combination of hydroxypropyl-β-cyclodextrin and δ-tocopherol significantly reduced the disease phenotypes. These results demonstrated patient-derived Pompe neural stem cells could be used as a model to study disease pathogenesis, to evaluate drug efficacy, and to screen compounds for drug discovery in the context of correcting CNS defects.

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Effects of Nutrient Intake Timing on Post-Exercise Glycogen Accumulation and its Related Signaling Pathways in Mouse Skeletal Muscle

Nutrients ◽

10.3390/nu11112555 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2555 ◽

Cited By ~ 1

Author(s):

Takahashi ◽

Matsunaga ◽

Banjo ◽

Takahashi ◽

Sato ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Glycogen ◽

Nutrient Intake ◽

Matched Control ◽

Control Group ◽

Glycogen Depletion ◽

Post Exercise ◽

Glycogen Accumulation ◽

Matched Control Group ◽

Significant Difference

We investigated the effects of nutrient intake timing on glycogen accumulation and its related signals in skeletal muscle after an exercise that did not induce large glycogen depletion. Male ICR mice ran on a treadmill at 25 m/min for 60 min under a fed condition. Mice were orally administered a solution containing 1.2 mg/g carbohydrate and 0.4 mg/g protein or water either immediately (early nutrient, EN) or 180 min (late nutrient, LN) after the exercise. Tissues were harvested at 30 min after the oral administration. No significant difference in blood glucose or plasma insulin concentrations was found between the EN and LN groups. The plantaris muscle glycogen concentration was significantly (p < 0.05) higher in the EN group—but not in the LN group—compared to the respective time-matched control group. Akt Ser473 phosphorylation was significantly higher in the EN group than in the time-matched control group (p < 0.01), while LN had no effect. Positive main effects of time were found for the phosphorylations in Akt substrate of 160 kDa (AS160) Thr642 (p < 0.05), 5'-AMP-activated protein kinase (AMPK) Thr172 (p < 0.01), and acetyl-CoA carboxylase Ser79 (p < 0.01); however, no effect of nutrient intake was found for these. We showed that delayed nutrient intake could not increase muscle glycogen after endurance exercise which did not induce large glycogen depletion. The results also suggest that post-exercise muscle glycogen accumulation after nutrient intake might be partly influenced by Akt activation. Meanwhile, increased AS160 and AMPK activation by post-exercise fasting might not lead to glycogen accumulation.

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Effect of Oral D-Tagatose on Liver Volume and Hepatic Glycogen Accumulation in Healthy Male Volunteers

Regulatory Toxicology and Pharmacology ◽

10.1006/rtph.2001.1470 ◽

2001 ◽

Vol 33 (2) ◽

pp. 257-267 ◽

Cited By ~ 14

Author(s):

Chris Boesch ◽

Michael Ith ◽

Bruno Jung ◽

Karin Bruegger ◽

Sidona Erban ◽

...

Keyword(s):

Liver Volume ◽

Hepatic Glycogen ◽

Healthy Male ◽

Glycogen Accumulation ◽

Healthy Male Volunteers ◽

Male Volunteers

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Glycogen synthesis in the perfused liver of adrenalectomized rats

Biochemical Journal ◽

10.1042/bj1560585 ◽

1976 ◽

Vol 156 (3) ◽

pp. 585-592 ◽

Cited By ~ 17

Author(s):

P D Whitton ◽

D A Hems

Keyword(s):

Intact Animal ◽

Glycogen Synthesis ◽

Hepatic Metabolism ◽

Hepatic Glycogen ◽

Perfused Liver ◽

Short Term ◽

Glycogen Accumulation ◽

Glycogen Deposition ◽

Adrenalectomized Rats

1. A total loss of capacity for net glycogen synthesis was observed in experiments with the perfused liver of starved adrenalectomized rats. 2. This lesion was corrected by insulin or cortisol in vivo (over 2-5h), but not by any agent tested in perfusion. 3. The activity of glycogen synthetase a, and its increase during perfusion, in the presence of glucose plus glucogenic substrates, were proportional to the rate of net glycogen accumulation. 4. This complete inherent loss of capacity for glycogen synthesis after adrenalectomy is greater than any defect in hepatic metabolism yet reported in this situation, and is not explicable by a decrease in the rate of gluconegenesis (which supports glycogen synthesis in the liver of starved rats). The short-term (2-5h) stimulatory effect of glucocorticoids in the intact animal, on hepatic glycogen deposition, may be mediated partly through insulin action, although neither insulin or cortisol appear to act directly on the liver to stimulate glycogen synthesis.

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PKC-mediated toxicity of elevated glucose concentration on cardiomyocyte function

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00894.2013 ◽

2014 ◽

Vol 307 (4) ◽

pp. H587-H597 ◽

Cited By ~ 7

Author(s):

Mark W. Sims ◽

James Winter ◽

Sean Brennan ◽

Robert I. Norman ◽

G. André Ng ◽

...

Keyword(s):

Blood Glucose ◽

Glucose Concentration ◽

Contractile Function ◽

Blood Glucose Concentration ◽

Specific Inhibitor ◽

Wistar Rat ◽

Patch Clamp Recording ◽

Electrical Stability ◽

Extracellular Glucose Concentration ◽

Extracellular Glucose

While it is well established that mortality risk after myocardial infarction (MI) increases in proportion to blood glucose concentration at the time of admission, it is unclear whether there is a direct, causal relationship. We investigated potential mechanisms by which increased blood glucose may exert cardiotoxicity. Using a Wistar rat or guinea-pig isolated cardiomyocyte model, we investigated the effects on cardiomyocyte function and electrical stability of alterations in extracellular glucose concentration. Contractile function studies using electric field stimulation (EFS), patch-clamp recording, and Ca2+ imaging were used to determine the effects of increased extracellular glucose concentration on cardiomyocyte function. Increasing glucose from 5 to 20 mM caused prolongation of the action potential and increased both basal Ca2+ and variability of the Ca2+ transient amplitude. Elevated extracellular glucose concentration also attenuated the protection afforded by ischemic preconditioning (IPC), as assessed using a simulated ischemia and reperfusion model. Inhibition of PKCα and β, using Gö6976 or specific inhibitor peptides, attenuated the detrimental effects of glucose and restored the cardioprotected phenotype to IPC cells. Increased glucose concentration did not attenuate the cardioprotective role of PKCε, but rather activation of PKCα and β masked its beneficial effect. Elevated extracellular glucose concentration exerts acute cardiotoxicity mediated via PKCα and β. Inhibition of these PKC isoenzymes abolishes the cardiotoxic effects and restores IPC-mediated cardioprotection. These data support a direct link between hyperglycemia and adverse outcome after MI. Cardiac-specific PKCα and β inhibition may be of clinical benefit in this setting.

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

Molecular and Cellular Biology ◽

10.1128/mcb.16.8.4357 ◽

1996 ◽

Vol 16 (8) ◽

pp. 4357-4365 ◽

Cited By ~ 64

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.

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