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Structure-Function Elucidation of Flavonoids by Modern Technologies
Published in Dilip Ghosh, Pulok K. Mukherjee, Natural Medicines, 2019
Ritu Varshney, Neeladrisingha Das, Rutusmita Mishra, Partha Roy
There are several methods to quantify cellular glucose uptake and these differ mainly in terms of the substrate for glucose transport. Upon transport glucose is shuttled to various pathways, so non-metabolizable analogues are used in these assays. These methods can be divided into two categories: (1) detection of accumulated intracellular 2-[3H] deoxy-d-glucose-6-phosphate (3H-2DG6P) by radioactive method and (2) enzymatic detection of 2-deoxy-d-glucose-6-phosphate (2DG6P) by colorimetric/fluorometric/luminometric methods (Saito et al. 2011; Fan et al. 2013; Boucher et al. 2014). Of these methods, the non-radioactive enzymatic detection of 2DG6P has been widely used because of its simplicity and the lack of any need to handle or dispose of radioactive materials. In this method, 2-deoxy-d-glucose (the glucose analogue), is added to cells and taken up by glucose transporters, which is then further phosphorylated to 2DG6P by hexokinase. However, 2DG6P cannot be metabolized further and thus accumulates in the cells, which is directly proportional to 2-deoxy-d-glucose taken up by cells. The accumulated 2-deoxy-d-glucose can be further detected by colorimetric/fluorometric/luminometric enzymatic assay methods (Saito et al. 2011; Fan et al. 2013; Valley et al. 2016).
Nuclei of the Solitary Tract and Regulation of Glycemia
Published in I. Robin A. Barraco, Nucleus of the Solitary Tract, 2019
Cesar Timo-Iaria, Edson Carlos Fraga da Silva, Naomi Shinomiya Hell
Some glucose analogs, such as 2-deoxy-d-glucose and 3-O-methylglucose, instead cause hyperglycemia, but as with insulin, they increase digestive secretions and motility and augment food intake. The explanation for such a paradox lies in activation of the glucoreceptors, mentioned above, that sense cytoglucopenia. 2-Deoxy-d-glucose (2-DG), which has been used for decades as a probe to disclose mechanisms involved in regulation or carbohydrate and fatty acid metabolism and food intake, is phosphorylated in the cells but cannot be metabolized further to fructose-6-phosphate nor can it be a substrate for glucose-6-phosphate dehydrogenase because of the lack of a hydroxyl group in the carbon-2 position. Thus, it is kept attached to those enzymes, blocking their action on glucose-6-phosphate. This condition, which takes hours to be reversed, leads to a lack of metabolizable glucose in the intracellular medium (functional cytoglucopenia).
Recent Advances in Technology
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Depending on the radiotracer used, different aspects of tissue metabolism can be studied, such as distribution of blood flow, oxygen utilization and protein synthesis. The overwhelming majority of clinical studies are in conjunction with an analogue of glucose, 2-[18 F] fluoro-2-deoxy-D-glucose (FDG), which reflects glucose metabolism. Cancer cells have a greater avidity for glucose than normal cells. Otto Warburg and colleagues made this observation in the 1920s.4 FDG can be used to exploit the differences in glucose metabolism between cancer cells and normal cells.
Quercetin acts via the G3BP1/YWHAZ axis to inhibit glycolysis and proliferation in oral squamous cell carcinoma
Published in Toxicology Mechanisms and Methods, 2023
Meng Hu, Hong-yan Song, Ling Chen
The naturally occurring polyphenolic quercetin can inhibit glycolysis in several types of tumor cells (Li et al. 2019; Xu et al. 2021), including oral squamous cell carcinoma, thereby slowing cancer growth (Huang et al. 2013; Shi et al. 2019; Tu et al. 2021). Extensive observations have demonstrated that quercetion can repress glycolysis in cancer cells by modulating Akt/mTOR pathway-mediated autophagy and hexokinase 2 (Jia et al. 2018; Wu et al. 2019). Therefore, we postulated that quercetin may be effective against oral squamous cell carcinoma because it inhibits glycolysis via the G3BP1/YWHAZ axis. We tested these hypotheses by analyzing glycolysis, cell proliferation, and G3BP1/YWHAZ signaling in oral squamous cell carcinoma cells stably over- or underexpressing G3BP1 or YWHAZ. We also examined the effects of treating cells with the glycolysis inhibitor 2-deoxy-d-glucose (2-DG). We hope that G3BP1 may be a new therapeutic target for oral squamous cell carcinoma, and simultaneous inhibition of glycolysis may become a new effective therapeutic mechanism for quercetin in this cancer.
Current and future pharmacotherapy options for drug-resistant epilepsy
Published in Expert Opinion on Pharmacotherapy, 2022
2-Deoxy-D-glucose is a glucose analog which reversibly inhibits glycolysis and reduces metabolic flux in the glycolytic pathway. Its effects were initially discovered whilst investigating mechanisms of carbohydrate restriction which underpin the efficacy of the ketogenic diet [66,67]. 2-Deoxy-D-glucose has demonstrated protective activity across several preclinical animal models including acute seizures, chronic epilepsy and traumatic brain injury. Acute experimental seizure models have shown promise in rat models of status epilepticus, with a reduction of the duration and severity of status epilepticus [68]. Here, 2-Deoxy-D-glucose is preferentially delivered into neural circuits underlying status epilepticus. These neural circuits have higher metabolic demands and focal increased blood flow which can be targeted using 2-Deoxy-D-glucose. Compared to current ASMs, this offers a novel therapeutic avenue for seizure control. 2-Deoxy-D-glucose has also been shown to have antiepileptogenic effects in chronic-kindling models of experimental epilepsy demonstrating efficacy up to 10–15 minutes following seizure induction [67]. In models of post-traumatic epilepsy, 2-Deoxy-D-glucose has demonstrated protective effects against secondary neurological damage and behavioral effects in rodent models [69]. Phase 2 clinical trials to assess safety, tolerability, and pharmacokinetics of acute 2-Deoxy-D-glucose in patients with epilepsy are planned.
Microglia as therapeutic targets after neurological injury: strategy for cell therapy
Published in Expert Opinion on Therapeutic Targets, 2021
M. Collins Scott, Supinder S. Bedi, Scott D. Olson, Candice M. Sears, Charles S. Cox
When stimulated by an inflammatory insult, microglia uses anaerobic metabolism, in particular glycolysis, for rapid energy production. Gimeno-Bayón et al. performed in vitro analysis of BV-2 microglia by inducing the M1 inflammatory state with lipopolysaccharides (LPS) and IFN-γ. After stimulation, the BV-2 cells increased glucose consumption, hexokinase activity, and lactate production. While there was no change in the inner membrane potential of mitochondria, the glucose:lactate ratio increased, indicating a shift to anaerobic metabolism by BV-2 microglia [70]. Holland et al obtained similar results in mice when stimulating microglia with IFN-γ; they also demonstrated that expression of the isozyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKB3) increased in microglia after IFN-γ stimulation. PFKB3 is an important allosteric activator of phosphofructokinase-1, the rate-limiting enzyme of glycolysis [71]. To cope with the increased glucose demand, BV-2 microglia will increase expression of glucose-uptake membrane transporters (GLUT), in particular, GLUT1 and GLUT4 [70,72]. Microglia increase GLUT expression in response to increased glucose requirements in the M1 state. Inhibition of glycolysis can attenuate the pro-inflammatory response of stimulated microglia. In vitro studies have demonstrated this with 2-deoxy-D-glucose (2-DG), a glycolytic inhibitor. 2-DG treatment decreases microglial secretion of certain inflammatory cytokines in mice, like TNF-α, IL-1β, and IL-6 [73,74]