- |||||||||| deoxyglucose / Generic mfg., olanzapine / Generic mfg.
Interactions Between Insulin and Dopamine in the Brain: Implications for Metabolism Across Health and Disease (Grand Canyon 3-5) - Oct 31, 2022 - Abstract #ACNP2022ACNP_1072;
Mahavir Agarwal is implementing preclinical [1-14C]2-deoxy-D-glucose autoradiography procedures to examine the effects of insulin on brain-wide glucose uptake...Providing a necessary clinical connection, he has further evidence that the olanzapine, a commonly prescribed antipsychotic (AP) with high metabolic liability and dopamine D2 antagonist properties, abolishes the effect of insulin on cerebral glucose uptake in the same brain regions...Dr. Mahavir Agarwal (University of Toronto) leverages autoradiography techniques, commonly used as an index of local neural activity, to directly measure localized glucose uptake, revealing the effects of antipsychotic-induced brain insulin resistance.
- |||||||||| deoxyglucose / Generic mfg.
Worth the Risk? Effects of Development and Early Care Quality on Lateral Habenula Involvement in Infant Social Behavior Flexibility (Grand Sonoran C-D) - Oct 31, 2022 - Abstract #ACNP2022ACNP_829;
PN18/ PN28 rat pups were injected with 14C 2-deoxyglucose (2-DG, 20 μCi/100 g, s.c.) and then received mild tail shocks (0.5mA) or no shocks, alone or with a social partner present every 5 mins for 40 mins, followed by brain removal for autoradiography...Conclusions Development and early care influence LHb involvement in processing social and threat cues. Whereas weaning typically triggers habenula-dependent inhibition of social approach under threat, early adversity engages LHb-inhibited approach even in the absence of threat.
- |||||||||| deoxyglucose / Generic mfg., clozapine / Generic mfg.
Journal: Impact of somatostatin interneurons on interactions between barrels in plasticity induced by whisker deprivation. (Pubmed Central) - Oct 29, 2022
To visualize the deprivation-induced plasticity, [C]-2-deoxyglucose mapping of cortical functional representation of the spared whisker was performed at the end of the deprivation...SOM-IN activation did not affect plasticity. These data show that SOM-IN activity is part of cortical circuitry that affects interbarrel interactions underlying deprivation-induced plasticity in adult mice.
- |||||||||| cerulenin / Fermentek
Journal: Role of Glycolysis and Fatty Acid Synthesis in the Activation and T Cell-Modulating Potential of Dendritic Cells Stimulated with a TLR5-Ligand Allergen Fusion Protein. (Pubmed Central) - Oct 28, 2022
In vitro pretreatment of mDCs with cerulenin (inhibitor of fatty acid biosynthesis) led to a decrease in both rFlaA:Betv1-induced anti-inflammatory cytokine Interleukin (IL) 10 and T helper cell type (TH) 1-related cytokine IL-12p70, while the pro-inflammatory cytokine IL 1β was unaffected...Inhibition of the glycolytic enzyme hexokinase-2 by 2-deoxyglucose led to a decrease in all investigated cytokines (IL-10, IL-12p70, and IL-1β)...In co-cultures of rFlaA:Betv1-stimulated mDCs with CD4+ T cells, the suppression of Bet v 1-specific TH2 responses was shown to depend on fatty acid synthesis. The effector function of rFlaA:Betv1-activated mDCs mainly relies on glycolysis, with fatty acid synthesis also significantly contributing to rFlaA:Betv1-mediated cytokine secretion, the production of antimicrobial molecules, and the modulation of T cell responses.
- |||||||||| deoxyglucose / Generic mfg.
Journal: TCA-phospholipid-glycolysis targeted triple therapy effectively suppresses ATP production and tumor growth in glioblastoma. (Pubmed Central) - Oct 25, 2022
Cellular oxygen consumption rate (OCR) and the total proton efflux rate (PER), as well as ATP concentration, were tracked to study metabolic responses to specifically targeted inhibitors, including EPIC-0412, arachidonyl trifluoromethyl ketone (AACOCF3), and 2 deoxy-D-glucose (2-DG)...We demonstrated that the combination therapy effectively extended the survival of cerebral tumor-bearing mice. Our findings indicate that the TCA-phospholipid-glycolysis metabolism axis can be blocked by specific inhibitors that significantly disrupt the tumor energy metabolism and suppress tumor proliferation in vitro and in vivo, suggesting that targeting ATP synthesis inhibition in cancer cells might be an attractive therapeutic avenue in GBM management.
- |||||||||| deoxyglucose / Generic mfg.
Journal: Hyperglycemia Enhances Immunosuppression and Aerobic Glycolysis of Pancreatic Cancer Through Upregulating Bmi1-UPF1-HK2 Pathway. (Pubmed Central) - Oct 25, 2022
Our findings indicate that the TCA-phospholipid-glycolysis metabolism axis can be blocked by specific inhibitors that significantly disrupt the tumor energy metabolism and suppress tumor proliferation in vitro and in vivo, suggesting that targeting ATP synthesis inhibition in cancer cells might be an attractive therapeutic avenue in GBM management. Our results suggest that the previously unreported Bmi1-UPF1-HK2 pathway contributes to PC progression and immunosuppression, which may bring in new targets for developing effective therapies to treat patients with PC.
- |||||||||| deoxyglucose / Generic mfg.
Journal: The ROS/NF-κB/HK2 axis is involved in the arsenic-induced Warburg effect in human L-02 hepatocytes. (Pubmed Central) - Oct 21, 2022
Further study indicated that arsenic-induced accumulation of reactive oxygen species (ROS) activated the nuclear factor kappa B (NF-κB) signaling pathway by phosphorylation of p65 at the Ser536 and Ser276 sites, leading to upregulated expression of HK2. We therefore concluded that the ROS/NF-κB/HK2 axis contributes to the Warburg effect and cell proliferation induced by low doses of arsenic.AbbreviationsROS, Reactive oxygen species; NAC, N-acetyl-L-cysteine; 2-DG, 2-deoxy-D-glucose; 2-NBDG, 2-Deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose.
- |||||||||| deoxyglucose / Generic mfg.
Review, Journal: Multifaceted entrancing role of glucose and its analogue, 2-deoxy-D-glucose in cancer cell proliferation, inflammation, and virus infection. (Pubmed Central) - Oct 14, 2022
It promotes the formation of anti-inflammatory mediators, and macrophage polarization, and also modulates immune function, which decreases inflammation. 2-DG inhibits PI3K/Akt/mTOR and upregulates the AMPK pathway, causing activation of the SIRT-4 gene that reduces lipogenesis, glucose uptake, nucleotide formation, and alters viral replication thus reducing the chances of infection.
- |||||||||| deoxyglucose / Generic mfg.
Trial completion date, Trial primary completion date: Safety and Pharmacokinetic Study of Intranasal 2-DG in Healthy Volunteers (clinicaltrials.gov) - Oct 12, 2022
P1, N=45, Recruiting,
2-DG inhibits PI3K/Akt/mTOR and upregulates the AMPK pathway, causing activation of the SIRT-4 gene that reduces lipogenesis, glucose uptake, nucleotide formation, and alters viral replication thus reducing the chances of infection. Trial completion date: Oct 2022 --> Mar 2023 | Trial primary completion date: Aug 2022 --> Dec 2022
- |||||||||| deoxyglucose / Generic mfg.
Convergent modulation of feeding and stress by an ascending catecholamine pathway (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_11690;
We targeted axon-GCaMP6s to NTSDBH and found that 2-deoxyglucose induced hypoglycemia robustly activates NTSDBH→PVH projections...These experiments revealed that NTSDBH activates and inhibits an equal proportion of PVHMC4R (~25%) and these connections are mediated, in part, by alpha-adrenergic receptors. Taken together these studies show that adrenergic NTSDBH→PVHMC4R connections contributes to feeding and stress response.
- |||||||||| lovastatin / Generic mfg., deoxyglucose / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Journal: Hyperactive Akt1 Signaling Increases Tumor Progression and DNA Repair in Embryonal Rhabdomyosarcoma RD Line and Confers Susceptibility to Glycolysis and Mevalonate Pathway Inhibitors. (Pubmed Central) - Oct 1, 2022
Furthermore, we found that pronounced Akt1 signaling increased the susceptibility to cell apoptosis after treatments with 2-deoxy-D-glucose (2-DG) and lovastatin, enzymatic inhibitors of hexokinase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), especially in combination with radiotherapy and doxorubicin. In conclusion, these data suggest that restriction of glucose metabolism and the mevalonate pathway, in combination with standard therapy, may increase therapy success in RMS tumors characterized by a dysregulated Akt signaling.
- |||||||||| deoxyglucose / Generic mfg.
Journal: Dynamic glucose uptake, storage and release by human microvascular endothelial cells. (Pubmed Central) - Sep 29, 2022
To illuminate mechanisms, we tracked [H]-2-deoxyglucose (2-DG) in human adipose-tissue microvascular endothelial cells...Thus, by utilizing radioactive and fluorescent glucose derivatives, we identified two parallel routes of entry: uptake into the cytosol through dedicated glucose transporters and endocytosis. This reveals aspects of the complex glucose handling by endothelial cells that may contribute to glucose delivery to tissues.
- |||||||||| deoxyglucose / Generic mfg., donepezil / Generic mfg.
Journal: Thymidine and 2'-deoxyuridine reduce microglial activation and improve oxidative stress damage by modulating glycolytic metabolism on the Aβ-induced brain injury. (Pubmed Central) - Sep 29, 2022
Donepezil (Do, 10 mg/kg/d), Thy (20 mg/kg/d), and 2'-De (20 mg/kg/d) were administered for 4 weeks after the injection of Aβ peptides (200 μM, i.c.v.) to mice...Moreover, 2-Deoxy-D-glucose (2-DG), a glycolysis inhibitor, was added to explore the mechanisms underlying the effects of Thy and 2'-De on Aβ-induced N9 cells...Moreover, 2-DG enhanced the effects of drugs, reduced microglial activation, and attenuated oxidative stress to interfere with Aβ-induced N9 cells. In conclusion, Thy and 2'-De reduced microglial activation and improved oxidative stress damage by modulating glycolytic metabolism on the Aβ-induced brain injury.
- |||||||||| metformin / Generic mfg., deoxyglucose / Generic mfg., temozolomide / Generic mfg.
Primary oligodendroglioma cell culture viability: an in vitro study with metabolic modulators (West/Central Hall) - Sep 28, 2022 - Abstract #SNO2022SNO_1156;
Standard treatment with temozolomide (TMZ, 200 µM) was also performed...Glycolytic inhibitor 2DG resulted effective against oligodendroglioma cells. Whereas further studies are needed to validate these results, a better understanding of metabolic susceptibility could allow the development of better-targeted and more-effective therapeutic approaches.
- |||||||||| deoxyglucose / Generic mfg.
Preclinical, Journal: Enteral glucose, absorbed and metabolized, potently enhances mesenteric lymph flow in chow and high fat fed rats. (Pubmed Central) - Sep 24, 2022
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)...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.
- |||||||||| deoxyglucose / Generic mfg.
Journal: Lactate-induced lactylation in skeletal muscle is associated with insulin resistance in humans. (Pubmed Central) - Sep 20, 2022
Inhibition of glycolysis (with 2-deoxy-d-glucose) or LDH-A (with sodium oxamate or LDH-A siRNA) for 24 h reduced HSkMC lactylation which paralleled reductions in culture media lactate accumulation. This study identified the existence of a lactate-derived post-translational modification in human skeletal muscle and suggests skeletal muscle lactylation could provide additional insight into the regulation of skeletal muscle metabolism, including insulin resistance.
- |||||||||| deoxyglucose / Generic mfg.
Journal: Aroylhydrazone Glycoconjugate Prochelators Exploit Glucose Transporter 1 (GLUT1) to Target Iron in Cancer Cells. (Pubmed Central) - Sep 20, 2022
Cellular assays showed that the glycoconjugates rely on the GLUT1 transporter for uptake, lead to intracellular iron deprivation, and present antiproliferative activity. Ectopic overexpression of GLUT1 in malignant and normal cells increased the uptake and toxicity of the glycoconjugated prochelators, demonstrating that these compounds are well suited for targeting cells overexpressing glucose transporters and therefore for selective iron sequestration in malignant cells.
- |||||||||| deoxyglucose / Generic mfg.
Preclinical, Journal: In vitro storage of boar spermatozoa increases the demand of ATP for reactivation of motility. (Pubmed Central) - Sep 20, 2022
Storage of boar spermatozoa increases the demand of adenosine triphosphate for reactivation of spermatozoa towards fast, non-linear, and hyperactivation-like motility patterns upon rewarming. Maintenance of glycolysis seems to be decisive for sperm function after long-term storage in vitro.
- |||||||||| Mekinist (trametinib) / Novartis, Somavert (pegvisomant) / Pfizer, navitoclax (ABT 263) / AbbVie
Review, Journal: Therapeutics That Can Potentially Replicate or Augment the Anti-Aging Effects of Physical Exercise. (Pubmed Central) - Sep 18, 2022
The current scientific evidence on the anti-aging effect of these drugs and supplements is still scarce and no recommendation of their generalized use can be made at this stage. Further studies are warranted to determine which therapies display a geroprotective effect and are capable of emulating the benefits of physical exercise.
- |||||||||| deoxyglucose / Generic mfg.
The Physiological Ketone Body Beta-Hydroxybutyrate Potently Neutralizes APS-Associated NETosis (Virtual Poster Hall) - Sep 17, 2022 - Abstract #ACRConvergence2022ACR_CONVERGENCE_2693;
Furthermore, APS IgG-induced NETosis was highly susceptible to the effects of beta-hydroxybutyrate, laying the foundation for examining ketosis as a possible treatment paradigm. Experiments, including mouse thrombosis models, are now underway to better understand the therapeutic potential suggested by these preclinical data
- |||||||||| deoxyglucose / Generic mfg.
Preclinical, Journal: Early alterations in brain glucose metabolism and vascular function in a transgenic rat model of Alzheimer's disease. (Pubmed Central) - Sep 10, 2022
To assess brain glucose uptake, rats were fasted overnight and then challenged with an intravenous infusion of 2-deoxy-D-glucose (2DG)...TgAD rats also showed a 59±42% increase in total choline level in the hippocampus, suggesting increased membrane turnover. In combination with our earlier findings of impaired electrophysiological metrics at this early stage of AD pathology progression, our findings suggest that subtle neuronal function alterations that would be difficult to assess in a clinical population may be accompanied by MRI-detectable changes in brain glucose metabolism and cerebrovascular function.
- |||||||||| deoxyglucose / Generic mfg., thyroxine / Generic mfg.
Biomarker, Journal: Trimester-specific phthalate exposures in pregnancy are associated with circulating metabolites in children. (Pubmed Central) - Sep 7, 2022
In combination with our earlier findings of impaired electrophysiological metrics at this early stage of AD pathology progression, our findings suggest that subtle neuronal function alterations that would be difficult to assess in a clinical population may be accompanied by MRI-detectable changes in brain glucose metabolism and cerebrovascular function. Metabolomics biomarkers may reflect sex- and exposure timing-specific responses to prenatal phthalate exposures manifesting in childhood that may not be detected using standard clinical markers of cardiometabolic risk.
- |||||||||| deoxyglucose / Generic mfg.
Journal: Glycolysis and the Pentose Phosphate Pathway Promote LPS-Induced NOX2 Oxidase- and IFN-β-Dependent Inflammation in Macrophages. (Pubmed Central) - Aug 27, 2022
Here, we show that LPS treatment of macrophages increased the classical oxidative burst response via the NADPH oxidase (NOX) 2 enzyme, which was blocked by 2-deoxyglucose (2-DG) inhibition of glycolysis...Moreover, recombinant IFN-β increased NOX2 oxidase-dependent ROS production, as well as NOX2 and p47phox expression. Our findings identify a previously undescribed molecular mechanism where both glycolysis and the pentose phosphate pathway are required to promote LPS-induced inflammation in macrophages.
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