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Updated: Jul 31, 2025
Extracellular Glucose Depletion as an Indirect Measure of Glucose Uptake in Cells and Tissues Ex Vivo
Published on: April 6, 2022
Transcriptome Analysis Reveals Organ-Specific Effects of 2-Deoxyglucose Treatment in Healthy Mice
Objective:
Glycolytic inhibition via 2-deoxy-D-glucose (2DG) has potential therapeutic benefits for a range of diseases, including cancer, epilepsy, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), and COVID-19, but the systemic effects of 2DG on gene function across different tissues are unclear.
Methods:
This study analyzed the transcriptional profiles of nine tissues from C57BL/6J mice treated with 2DG to understand how it modulates pathways systemically. Principal component analysis (PCA), weighted gene co-network analysis (WGCNA), analysis of variance, and pathway analysis were all performed to identify modules altered by 2DG treatment.
Results:
PCA revealed that samples clustered predominantly by tissue, suggesting that 2DG affects each tissue uniquely. Unsupervised clustering and WGCNA revealed six distinct tissue-specific modules significantly affected by 2DG, each with unique key pathways and genes. 2DG predominantly affected mitochondrial metabolism in the heart, while in the small intestine, it affected immunological pathways.
Conclusions:
These findings suggest that 2DG has a systemic impact that varies across organs, potentially affecting multiple pathways and functions. The study provides insights into the potential therapeutic benefits of 2DG across different diseases and highlights the importance of understanding its systemic effects for future research and clinical applications.
Insights
Glycolytic inhibition using 2-deoxy-D-glucose (2DG) impacts gene function differently across mouse tissues. This research clarifies 2DG
Area of Science:
- Metabolic pathway modulation
- Systems biology
- Pharmacogenomics
Background:
- 2-deoxy-D-glucose (2DG) is investigated for therapeutic potential in diseases like cancer, SLE, and RA.
- Systemic effects of 2DG on gene expression across diverse tissues remain largely uncharacterized.
Approach:
- Transcriptional profiling of nine C57BL/6J mouse tissues after 2DG treatment.
- Utilized Principal Component Analysis (PCA), Weighted Gene Co-network Analysis (WGCNA), ANOVA, and pathway analysis.
- Identified tissue-specific gene expression modules and pathways modulated by 2DG.
Key Points:
- PCA indicated tissue-unique responses to 2DG.
- Six distinct tissue-specific modules were significantly altered by 2DG.
- 2DG differentially impacted mitochondrial metabolism in the heart and immunological pathways in the small intestine.
Conclusions:
- 2DG exerts a systemic influence on gene function that is organ-dependent.
- Understanding tissue-specific effects is crucial for optimizing 2DG's therapeutic applications.
- This study provides foundational insights into 2DG's complex biological impact.
