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Biochemistry. Biokhimiia Nov 20183-Deoxyglucosone (3DG) is a highly reactive dicarbonyl species, and its accumulation evokes carbonyl and oxidative stress. Our recent data reveal the role of 3DG as an...
3-Deoxyglucosone (3DG) is a highly reactive dicarbonyl species, and its accumulation evokes carbonyl and oxidative stress. Our recent data reveal the role of 3DG as an independent factor for the development of prediabetes and suggest that intestine could be its novel target tissue. The present study investigated whether exogenous 3DG increases intestinal permeability by triggering carbonyl and oxidative stress, thus contributing to β-cell dysfunction. Rats were administered 3DG for two weeks by gastric gavage. Then levels of insulin, ROS, MDA, SOD, NLRP3, TNF-α and IL-1β in blood plasma as well as the ROS level and content of TNF-α and IL-1β in pancreas were assessed. Also, the expression of E-cadherin and ZO-1 as well as levels of 3DG, protein carbonylation, ROS, TNF-α and IL-1β in colon were determined. The 3DG-treated rats showed an elevation in systemic oxidative stress (ROS, MDA and SOD) and in inflammation (TNF-α and IL-1β), decreased plasma insulin level 15 min after the glucose load, and increased levels of TNF-α, IL-1β and ROS in pancreatic tissue. In colon tissues of the 3DG-treated rats, decreased E-cadherin expression and increased ROS production as well as an elevation of TNF-α and IL-1β levels were observed. Interestingly, elevation of colon protein carbonylation was observed in the 3DG-treated rats that displayed 3DG deposition in colon tissues. We revealed for the first time that 3DG deposition in colon triggers carbonyl and oxidative stress and, as a consequence, impairs gut permeability. The enhanced intestinal permeability caused by 3DG deposition in colon results in systemic and pancreatic oxidative stress and inflammatory process, contributing to the development of β-cell dysfunction.
Topics: Animals; Colon; Deoxyglucose; Gene Expression Regulation; Insulin-Secreting Cells; Permeability; Protein Carbonylation; Rats; Rats, Sprague-Dawley
PubMed: 30482147
DOI: 10.1134/S0006297918110068 -
Cellular and Molecular Neurobiology Jul 2020Cerebral glycogen is principally localized in astrocytes rather than in neurons. Glycogen metabolism has been implicated in higher brain functions, including learning...
Cerebral glycogen is principally localized in astrocytes rather than in neurons. Glycogen metabolism has been implicated in higher brain functions, including learning and memory, yet the distribution patterns of glycogen in different types of astrocytes have not been fully described. Here, we applied a method based on the incorporation of 2-NBDG, a D-glucose fluorescent derivative that can trace glycogen, to investigate glycogen's distribution in the brain. We identified two types of astrocytes, namely, 2-NBDG (glycogen-deficient) and 2-NBDG (glycogen-rich) cells. Whole-cell patch-clamp and fluorescence-activated cell sorting (FACS) were used to separate 2-NBDG astrocytes from 2-NBDG astrocytes. The expression levels of glycogen metabolic enzymes were analyzed in 2-NBDG and 2-NBDG astrocytes. We found unique glycogen metabolic patterns between 2-NBDG and 2-NBDG astrocytes. We also observed that 2-NBDG astrocytes were mainly identified as fibrous astrocytes but not protoplasmic astrocytes. Our data reveal cell type-dependent glycogen distribution and metabolism patterns, suggesting diverse functions of these different astrocytes.
Topics: 4-Chloro-7-nitrobenzofurazan; Animals; Astrocytes; Cells, Cultured; Cerebral Cortex; Deoxyglucose; Glucose; Glycogen; Mice; Mice, Inbred C57BL; Neurons; Single-Cell Analysis
PubMed: 31863221
DOI: 10.1007/s10571-019-00775-4 -
PLoS Neglected Tropical Diseases Jul 20222-Deoxy-D-glucose (2-DG) is a glucose analog used as a promising anticancer agent. It exerts its effects by inhibiting the glycolytic energy metabolism to deplete cells...
2-Deoxy-D-glucose and combined 2-Deoxy-D-glucose/albendazole exhibit therapeutic efficacy against Echinococcus granulosus protoscoleces and experimental alveolar echinococcosis.
2-Deoxy-D-glucose (2-DG) is a glucose analog used as a promising anticancer agent. It exerts its effects by inhibiting the glycolytic energy metabolism to deplete cells of energy. The larval stage of Echinococcus relies on glycolysis for energy production. Therefore, in this study, we investigated the in vitro and in vivo efficacy of 2-DG against the larval stage of Echinococcus granulosus and E. multilocularis. 2-DG exhibited significant time- and dose-dependent effects against in vitro cultured E. granulosus protoscoleces and E. multilocularis metacestodes. A daily oral administration of 500 mg/kg 2-DG in E. multilocularis-infected mice effectively reduced the weight of metacestodes. Notably, the combination treatment, either 2-DG (500 mg/kg/day) + albendazole (ABZ) (200 mg/kg/day) or 2-DG (500 mg/kg/day) + half-dose of ABZ (100 mg/kg/day), exhibited a potent therapeutic effect against E. multilocularis, significantly promoting the reduction of metacestodes weight compared with the administration of 2-DG or ABZ alone. Furthermore, the combination significantly promoted apoptosis of the cells of metacestodes and inhibited glycolysis in metacestodes, compared with the administration of 2-DG or ABZ alone. In conclusion, 2-DG exerts an effective activity against the larval stage of Echinococcus. Thus, it may be a promising anti-Echinococcus drug, and its combination with ABZ may provide a new strategy for the treatment of echinococcosis in humans.
Topics: Albendazole; Animals; Deoxyglucose; Echinococcosis; Echinococcus granulosus; Echinococcus multilocularis; Glucose; Humans; Larva; Mice
PubMed: 35849619
DOI: 10.1371/journal.pntd.0010618 -
Journal of Nuclear Medicine : Official... Jun 1995The clinical utility of FDG-PET imaging in the evaluation of patients with cardiac, oncologic and neurologic diseases is well documented. The major disadvantages of PET... (Comparative Study)
Comparative Study
UNLABELLED
The clinical utility of FDG-PET imaging in the evaluation of patients with cardiac, oncologic and neurologic diseases is well documented. The major disadvantages of PET continue to be its high cost and limited availability.
METHODS
With the goal of providing equivalent diagnostic information using a widely available, less expensive modality, we evaluated the clinical utility of FDG-SPECT imaging with a conventional dual-headed camera as compared to PET in 21 patients.
RESULTS
To compare the image quality of the two modalities, major physical parameters and phantom determinations were obtained. By using the 511-keV collimators, we achieved resolution and system volume sensitivity that were less than those for PET by factors of 2.6 and 8, respectively. The SPECT system, on the other hand, could easily resolve 2 x 0.5-cm cold defects in the heart phantom and 2-cm hot lesions in a 22-cm cylindrical phantom with a target-to-background ratio of 5:1. FDG-SPECT imaging of nine patients with heart disease yielded similar diagnostic information of the amount of viable myocardium present when compared to PET. In seven of eight patients, malignant tissue visualized with FDG-PET was seen equally well with SPECT. The lesions not visualized with FDG-SPECT were either small (< or = 1.5 cm) or benign. SPECT imaging of four patients with cerebral lesions was inconclusive due to the small sample size but seemed promising.
CONCLUSION
FDG-SPECT with 511-keV collimation is less expensive, more available and technically simpler than PET. We believe that FDG-SPECT has achieved sufficient sensitivity and resolution to detect myocardial viability and diagnose malignant tumors > or = 2 cm in diameter.
Topics: Adult; Aged; Brain; Deoxyglucose; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Heart; Humans; Male; Middle Aged; Neoplasms; Sensitivity and Specificity; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon
PubMed: 7769457
DOI: No ID Found -
International Journal of Molecular... Aug 2018Cancer metabolism is characterized by extensive glucose consumption through aerobic glycolysis. No effective therapy exploiting this cancer trait has emerged so far, in...
Cancer metabolism is characterized by extensive glucose consumption through aerobic glycolysis. No effective therapy exploiting this cancer trait has emerged so far, in part, due to the substantial side effects of the investigated drugs. In this study, we examined the side effects of a combination of isocaloric ketogenic diet (KD) with the glycolysis inhibitor 2-deoxyglucose (2-DG). Two groups of eight athymic nude mice were either fed a standard diet (SD) or a caloric unrestricted KD with a ratio of 4 g fat to 1 g protein/carbohydrate. 2-DG was investigated in commonly employed doses of 0.5 to 4 g/kg and up to 8 g/kg. Ketosis was achieved under KD (ketone bodies: SD 0.5 ± 0.14 mmol/L, KD 1.38 ± 0.28 mmol/L, < 0.01). The intraperitoneal application of 4 g/kg of 2-DG caused a significant increase in blood glucose, which was not prevented by KD. Sedation after the 2-DG treatment was observed and a behavioral test of spontaneous motion showed that KD reduced the sedation by 2-DG ( < 0.001). A 2-DG dose escalation to 8 g/kg was lethal for 50% of the mice in the SD and for 0% of the mice in the KD group ( < 0.01). A long-term combination of KD and an oral 1 or 2 g 2-DG/kg was well-tolerated. In conclusion, KD reduces the sedative effects of 2-DG and dramatically increases the maximum tolerated dose of 2-DG. A continued combination of KD and anti-glycolytic therapy is feasible. This is, to our knowledge, the first demonstration of increased tolerance to glycolysis inhibition by KD.
Topics: Animals; Antimetabolites; Blood Glucose; Deoxyglucose; Diet, Ketogenic; Female; Glucose; Glycolysis; Ketone Bodies; Ketosis; Mice, Nude; Neoplasms
PubMed: 30127309
DOI: 10.3390/ijms19082462 -
The Western Journal of Medicine Oct 1994
Review
Topics: Deoxyglucose; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Humans; Neoplasms; Tomography, Emission-Computed
PubMed: 7817554
DOI: No ID Found -
Magnetic Resonance in Medicine Aug 2018Glucose uptake and metabolism can be measured by chemical exchange-sensitive spin-lock (CESL) MRI with an administration of glucose or its analogs. This study...
PURPOSE
Glucose uptake and metabolism can be measured by chemical exchange-sensitive spin-lock (CESL) MRI with an administration of glucose or its analogs. This study investigates the sensitivity, the spatiotemporal characteristics, and the signal source of glucoCESL with a 9L rat brain tumor model.
METHODS
Dynamic CESL MRI with intravenous injection of D-glucose, 2-deoxy-D-glucose (2DG), and L-glucose were measured and compared with gadolinium-based dynamic contrast-enhanced (DCE) MRI.
RESULTS
The CESL signals with an injection of glucose or analogs have faster and larger changes in tumors than normal brain tissue. In tumors, the CESL signal with 2DG injection has larger and slower peak response than that with D-glucose due to the accumulation of 2DG and 2DG-6-phosphate in the intracellular compartment, whereas L-glucose, which cannot be transported intracellularly by glucose transporters, only induces a small change. The initial glucoCESL maps (< 4 minutes) are qualitatively similar to DCE maps, whereas later maps (> 4 minutes) show more widespread responses. The rise times of D-glucose-CESL and 2DG-CESL signals in the tumor are slower than that of DCE. Our data suggest that the initial CESL contrast primarily reflects a passive increase of glucose content in the extracellular space of tumors due to a higher vascular permeability, whereas the later period may have a significant contribution from the uptake/metabolism of glucose in the intracellular compartment.
CONCLUSIONS
Our results demonstrate that glucoCESL MRI has both extracellular and intracellular contributions, and can be a useful tool for measurements of both vascular permeability and glucose uptake in tumors.
Topics: Animals; Brain; Brain Chemistry; Brain Neoplasms; Deoxyglucose; Glucose; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Rats; Rats, Inbred F344
PubMed: 29569739
DOI: 10.1002/mrm.27183 -
PloS One 2017Vaccination is a safe and effective approach to prevent deadly diseases. To increase vaccine production, we propose that a mechanical stimulation can enhance protein...
Vaccination is a safe and effective approach to prevent deadly diseases. To increase vaccine production, we propose that a mechanical stimulation can enhance protein production. In order to prove this hypothesis, Sf9 insect cells were used to evaluate the increase in the expression of a fusion protein from hepatitis B virus (HBV S1/S2). We discovered that the ultrasound stimulation at a frequency of 1.5 MHz, intensity of 60 mW/cm2, for a duration of 10 minutes per day increased HBV S1/S2 by 27%. We further derived a model for transport through a cell membrane under the effect of ultrasound waves, tested the key assumptions of the model through a molecular dynamics simulation package, NAMD (Nanoscale Molecular Dynamics program) and utilized CHARMM force field in a steered molecular dynamics environment. The results show that ultrasound waves can increase cell permeability, which, in turn, can enhance nutrient / waste exchange thus leading to enhanced vaccine production. This finding is very meaningful in either shortening vaccine production time, or increasing the yield of proteins for use as vaccines.
Topics: 4-Chloro-7-nitrobenzofurazan; Animals; Blotting, Western; Cell Membrane Permeability; Deoxyglucose; Hepatitis B Vaccines; Molecular Dynamics Simulation; Phosphatidylcholines; Proteins; Sf9 Cells; Sonication; Thermodynamics; Ultrasonic Waves
PubMed: 29176801
DOI: 10.1371/journal.pone.0187048 -
Antiviral Research Sep 1982
Review
Topics: Antiviral Agents; Biological Transport; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Deoxyglucose; Endoplasmic Reticulum; Epitopes; Fluorodeoxyglucose F18; Glucosamine; Glycoproteins; Herpes Simplex; Humans; Hydrazones; Oligosaccharides; Peptide Hydrolases; Tunicamycin; Viral Envelope Proteins; Viral Proteins; Viruses
PubMed: 6184015
DOI: 10.1016/0166-3542(82)90041-9 -
Journal of Nuclear Medicine : Official... Mar 1992
Topics: Deoxyglucose; Fluorodeoxyglucose F18; Glycolysis; Humans; Neoplasms; Tomography, Emission-Computed
PubMed: 1740699
DOI: No ID Found