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International Journal of Molecular... Dec 2019The ability of 2-deoxy-d-glucose (2-DG) to interfere with d-glucose metabolism demonstrates that nutrient and energy deprivation is an efficient tool to suppress cancer... (Review)
Review
The ability of 2-deoxy-d-glucose (2-DG) to interfere with d-glucose metabolism demonstrates that nutrient and energy deprivation is an efficient tool to suppress cancer cell growth and survival. Acting as a d-glucose mimic, 2-DG inhibits glycolysis due to formation and intracellular accumulation of 2-deoxy-d-glucose-6-phosphate (2-DG6P), inhibiting the function of hexokinase and glucose-6-phosphate isomerase, and inducing cell death. In addition to glycolysis inhibition, other molecular processes are also affected by 2-DG. Attempts to improve 2-DG's drug-like properties, its role as a potential adjuvant for other chemotherapeutics, and novel 2-DG analogs as promising new anticancer agents are discussed in this review.
Topics: Cell Death; Combined Modality Therapy; Deoxyglucose; Glioblastoma; Glucose; Glucose-6-Phosphate; Glucose-6-Phosphate Isomerase; Glycolysis; Hexokinase; Humans
PubMed: 31905745
DOI: 10.3390/ijms21010234 -
Epilepsy & Behavior : E&B Mar 20232-deoxy-D-glucose (2DG) is a glucose analog differing from glucose only by removal of an oxygen atom at the 2 position, which prevents the isomerization of... (Review)
Review
2-deoxy-D-glucose (2DG) is a glucose analog differing from glucose only by removal of an oxygen atom at the 2 position, which prevents the isomerization of glucose-6-phosphate to fructose-6-phosphate, and thereby reversibly inhibits glycolysis. PET studies of regional brain glucose utilization positron-emitting 18F-2DG demonstrate that brain regions generating seizures have diminished glucose utilization during interictal conditions, but rapidly transition to markedly increased glucose delivery and utilization during seizures, particularly in status epilepticus (SE). 2-deoxy-D-glucose has acute antiseizure actions in multiple in vivo and in vitro seizure models, including models of SE induced by the chemo convulsants pilocarpine and kainic acid, suggesting that focal enhanced delivery of 2DG to ictal brain circuits is a potential novel anticonvulsant intervention for the treatment of SE.
Topics: Humans; Deoxyglucose; Status Epilepticus; Seizures; Glucose; Glycolysis; Pilocarpine
PubMed: 36804714
DOI: 10.1016/j.yebeh.2023.109108 -
In Vivo (Athens, Greece) 20231,5-Anhydro-d-fructose (1,5-AF, saccharide) and 1,5-anhydro-d-glucitol (1,5-AG) converted from 1,5-AF via the glycemic pathway have health benefits. However, this...
BACKGROUND/AIM
1,5-Anhydro-d-fructose (1,5-AF, saccharide) and 1,5-anhydro-d-glucitol (1,5-AG) converted from 1,5-AF via the glycemic pathway have health benefits. However, this metabolism has not been sufficiently elucidated. To clarify the in vivo metabolism of 1,5-AF to 1,5-AG, porcine (blood kinetics) and human (urinary excretion) studies were conducted.
MATERIALS AND METHODS
Microminipigs were administrated 1,5-AF orally or intravenously. Blood samples were obtained to analyse the kinetics of 1,5-AF and 1,5-AG. Urine samples were collected from human subjects who had orally ingested 1,5-AF, and the amounts of 1,5-AF and 1,5-AG excreted in the urine were analysed.
RESULTS
In blood kinetics analysis, the time to the maximum concentration of 1,5-AF after intravenous administration was 0.5 h, whereas 1,5-AF was not observed after oral administration. The times to the maximum concentration of 1,5-AG after intravenous and oral administration were 1.5 h and 2 h, respectively. In urinary excretion, the concentration of 1,5-AG in urine rapidly increased after the administration of 1,5-AF, peaked at 2 h, whereas 1,5-AF was not detected.
CONCLUSION
1,5-AF was rapidly metabolized to 1.5-AG in vivo in swine and human.
Topics: Humans; Animals; Swine; Sorbitol; Deoxyglucose; Fructose
PubMed: 37103066
DOI: 10.21873/invivo.13176 -
Biochemical and Biophysical Research... Mar 2015Dicarbonyl stress is the abnormal accumulation of dicarbonyl metabolites leading to increased protein and DNA modification contributing to cell and tissue dysfunction in... (Review)
Review
Dicarbonyl stress is the abnormal accumulation of dicarbonyl metabolites leading to increased protein and DNA modification contributing to cell and tissue dysfunction in ageing and disease. Enzymes metabolising dicarbonyls, glyoxalase 1 and aldoketo reductases, provide an efficient and stress-response enzyme defence against dicarbonyl stress. Dicarbonyl stress is produced by increased formation and/or decreased metabolism of dicarbonyl metabolites, and by exposure to exogenous dicarbonyls. It contributes to ageing, disease and activity of cytototoxic chemotherapeutic agents.
Topics: Aging; Aldehydes; Cardiovascular Diseases; Deoxyglucose; Diabetes Mellitus; Glyoxal; Humans; Inflammation; Kidney Diseases; Models, Biological; Oxidative Stress; Pyruvaldehyde; Stress, Physiological
PubMed: 25666945
DOI: 10.1016/j.bbrc.2015.01.140 -
American Journal of Physiology.... Oct 2022A portion of absorbed dietary triglycerides (TG) is retained in the intestine after the postprandial period, within intracellular and extracellular compartments. This...
A portion of absorbed dietary triglycerides (TG) is retained in the intestine after the postprandial period, within intracellular and extracellular compartments. This pool of TG can be mobilized in response to several stimuli, including oral glucose. The objective of this study was to determine whether oral glucose must be absorbed and metabolized to mobilize TG in rats and whether high-fat feeding, a model of insulin resistance, alters the lipid mobilization response to glucose. Lymph flow, TG concentration, TG output, and apolipoprotein B48 (apoB48) concentration and output were assessed after an intraduodenal lipid bolus in rats exposed to the following intraduodenal administrations 5 h later: saline (placebo), glucose, 2-deoxyglucose (2-DG, absorbed but not metabolized), or glucose + phlorizin (intestinal glucose absorption inhibitor). Glucose alone, but not 2-DG or glucose + phlorizin treatments, stimulated lymph flow, TG output, and apoB48 output compared with placebo. The effects of glucose in high-fat-fed rats were similar to those in chow-fed rats. In conclusion, glucose must be both absorbed and metabolized to enhance lymph flow and intestinal lipid mobilization. This effect is qualitatively and quantitatively similar in high-fat- and chow-fed rats. The precise signaling mechanism whereby enteral glucose enhances lymph flow and mobilizes enteral lipid remains to be determined. Glucose potently enhances mesenteric lymph flow in chow- and high-fat-fed rats. The magnitude of glucose effect on lymph flow is no different in chow- and high-fat-fed rats. Glucose must be absorbed and metabolized to enhance lymph flow and mobilize intestinal lipid.
Topics: Animals; Apolipoprotein B-48; Chylomicrons; Deoxyglucose; Glucose; Lymph; Phlorhizin; Rats; Triglycerides
PubMed: 35916412
DOI: 10.1152/ajpgi.00095.2022 -
Journal of Cancer Research and... Sep 2009The glucose analog 2-deoxy-D-glucose (2-DG), an inhibitor of glucose transport and glycolytic ATP production, is the most widely investigated metabolic inhibitor for... (Review)
Review
The glucose analog 2-deoxy-D-glucose (2-DG), an inhibitor of glucose transport and glycolytic ATP production, is the most widely investigated metabolic inhibitor for targeting glucose metabolism. Besides depleting energy in cells, 2-DG has also been found to alter N-linked glycosylation leading to unfolded protein responses and induce changes in gene expression and phosphorylation status of proteins involved in signaling, cell cycle control, DNA repair, calcium influx, and apoptosis. Inhibition of cell proliferation and induction of apoptosis have been observed as cytotoxic effects in a wide variety of tumor cells in vitro, while sensitization of tumor cells to ionizing radiation and certain chemotherapeutic drugs is associated with enhanced mitotic as well as apoptotic cell death induced by the primary therapeutic agent. Therefore, there has been a considerable amount of interest in developing 2-DG as a therapeutic agent or adjuvant in the radiotherapy and chemotherapy of tumors.
Topics: Animals; Antineoplastic Agents; Deoxyglucose; Humans; In Vitro Techniques; Neoplasms; Radiation Tolerance; Radiation-Sensitizing Agents; Radiotherapy
PubMed: 20009290
DOI: 10.4103/0973-1482.55137 -
International Journal of Molecular... Feb 2017Molecular pathological pathways leading to multi-organ failure in critical illness are progressively being unravelled. However, attempts to modulate these pathways have... (Review)
Review
Molecular pathological pathways leading to multi-organ failure in critical illness are progressively being unravelled. However, attempts to modulate these pathways have not yet improved the clinical outcome. Therefore, new targetable mechanisms should be investigated. We hypothesize that increased dicarbonyl stress is such a mechanism. Dicarbonyl stress is the accumulation of dicarbonyl metabolites (i.e., methylglyoxal, glyoxal, and 3-deoxyglucosone) that damages intracellular proteins, modifies extracellular matrix proteins, and alters plasma proteins. Increased dicarbonyl stress has been shown to impair the renal, cardiovascular, and central nervous system function, and possibly also the hepatic and respiratory function. In addition to hyperglycaemia, hypoxia and inflammation can cause increased dicarbonyl stress, and these conditions are prevalent in critical illness. Hypoxia and inflammation have been shown to drive the rapid intracellular accumulation of reactive dicarbonyls, i.e., through reduced glyoxalase-1 activity, which is the key enzyme in the dicarbonyl detoxification enzyme system. In critical illness, hypoxia and inflammation, with or without hyperglycaemia, could thus increase dicarbonyl stress in a way that might contribute to multi-organ failure. Thus, we hypothesize that increased dicarbonyl stress in critical illness, such as sepsis and major trauma, contributes to the development of multi-organ failure. This mechanism has the potential for new therapeutic intervention in critical care.
Topics: Biomarkers; Comorbidity; Critical Care; Critical Illness; Deoxyglucose; Glyoxal; Humans; Hypoxia; Inflammation; Multiple Organ Failure; Pyruvaldehyde; Stress, Physiological
PubMed: 28178202
DOI: 10.3390/ijms18020346 -
Journal of Nuclear Medicine : Official... Sep 1988
Topics: Brain Neoplasms; Data Interpretation, Statistical; Deoxyglucose; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Humans; Tomography, Emission-Computed
PubMed: 3261788
DOI: No ID Found -
IUBMB Life Feb 2014Through the eons of time, out of all possible configurations, nature has selected glucose not only as a vital source of energy to sustain life but also as the molecule...
Through the eons of time, out of all possible configurations, nature has selected glucose not only as a vital source of energy to sustain life but also as the molecule who's structure supplies the appropriate elements required for a cell to grow and multiply. This understanding, at least in part, explains the profound effects that the analog of glucose, 2-deoxy-d-glucose, has been shown to have on as common and widespread diseases as cancer, viral infection, aging-related morbidity, epilepsy, and others. This review is confined to summarizing some of the salient findings of this remarkable compound as they relate mainly to cancer.
Topics: Apoptosis; Autophagy; Deoxyglucose; Endoplasmic Reticulum Stress; Glycosylation; Humans; Hypoxia; Neoplasms; Virus Replication
PubMed: 24578297
DOI: 10.1002/iub.1251 -
Journal of Nuclear Medicine : Official... Mar 1993
Topics: Cell Division; Deoxyglucose; Flow Cytometry; Fluorodeoxyglucose F18; Humans; Neoplasms; Tomography, Emission-Computed
PubMed: 8441033
DOI: No ID Found