ArticleEuropean journal of nuclear medicine and molecular imaging2019
Obligatory role of endoplasmic reticulum in brain FDG uptake.
Article in European journal of nuclear medicine and molecular imaging, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
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- Fundamental Role of Pentose Phosphate Pathway within the Endoplasmic Reticulum in Glutamine Addiction of Triple-Negative Breast Cancer Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Mitochondrial Generated Redox Stress Differently Affects the Endoplasmic Reticulum of Circulating Lymphocytes and Monocytes in Treatment-Naïve Hodgkin's Lymphoma.Antioxidants (Basel, Switzerland) · 2022Article
- Opportunistic skeletal muscle metrics as prognostic tools in metastatic castration-resistant prostate cancer patients candidates to receive Radium-223.Annals of nuclear medicine · 2022Article
- Chemotherapy-induced Cardiac18F-FDG Uptake in Patients with Lymphoma: An Early Metabolic Index of Cardiotoxicity?Arquivos brasileiros de cardiologia · 2022Article
- If It Works, Don't Touch It? A Cell-Based Approach to Studying 2-[Pharmaceuticals (Basel, Switzerland) · 2021Article
- The Role of Endoplasmic Reticulum in the Differential Endurance against Redox Stress in Cortical and Spinal Astrocytes from the Newborn SOD1Antioxidants (Basel, Switzerland) · 2021Article
- Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside?Biomolecules · 2021Review
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
purposeThe endoplasmic reticulum (ER) contains hexose-6P-dehydrogenase (H6PD). This enzyme competes with glucose-6P-phosphatase for processing a variety of phosphorylated hexoses including 2DG-6P. The present study aimed to verify whether this ER glucose-processing machinery contributes to brain FDG uptake.
methodsEffect of the H6PD inhibitor metformin on brain 18F-FDG accumulation was studied, in vivo, by microPET imaging. These data were complemented with the in vitro estimation of the lumped constant (LC). Finally, reticular accumulation of the fluorescent 2DG analogue 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2NBDG) and its response to metformin was studied by confocal microscopy in cultured neurons and astrocytes.
resultsMetformin halved brain 18F-FDG accumulation without altering whole body tracer clearance. Ex vivo, this same response faced the doubling of both glucose consumption and lactate release. The consequent fall in LC was not explained by any change in expression or activity of its theoretical determinants (GLUTs, hexokinases, glucose-6P-phosphatase), while it agreed with the drug-induced inhibition of H6PD function. In vitro, 2NBDG accumulation selectively involved the ER lumen and correlated with H6PD activity being higher in neurons than in astrocytes, despite a lower glucose consumption.
conclusionsThe activity of the reticular enzyme H6PD profoundly contributes to brain 18F-FDG uptake. These data challenge the current dogma linking 2DG/FDG uptake to the glycolytic rate and introduce a new model to explain the link between 18-FDG uptake and neuronal activity.
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