GO:0010828 positive regulation of D-glucose transmembrane transport: Regulation, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0010828 describes any process that increases the frequency, rate, or extent of glucose transport across a membrane, a critical control point in cellular energy homeostasis.
• Key molecular players include glucose transporters such as GLUT1 (SLC2A1), whose activity and membrane localization are regulated by post-translational modifications like S-palmitoylation.
• Dysregulation of glucose transport contributes to cancer metabolism, as seen in glioblastoma where DHHC9-mediated GLUT1 palmitoylation promotes glycolysis and tumorigenesis.
• CFTR modulators can influence glucose homeostasis in cystic fibrosis-related diabetes, highlighting the clinical relevance of glucose transport regulation.
• Research methods to study this process include genetic knockout, point mutations, knock-in reporters, overexpression, and CRISPR library screening [1,2].
• Understanding GO:0010828 provides mechanistic insights into metabolic diseases, cancer, and potential therapeutic targets [1,8].
Description
Positive regulation of D-glucose transmembrane transport (GO:0010828) is a biological process that increases the movement of glucose across cellular membranes. This process is fundamental for maintaining energy balance, as glucose is a primary metabolic fuel for most cells. The regulation occurs at multiple levels, including transporter expression, trafficking, and post-translational modifications, ensuring that glucose uptake matches cellular demands. Researchers study this term to understand how cells adapt to fluctuating glucose availability and how dysregulation contributes to diseases such as cancer and diabetes [1,8]. In glioblastoma, for example, enhanced glucose transport supports the high glycolytic rate required for rapid tumor growth. Similarly, in cystic fibrosis-related diabetes, impaired glucose homeostasis is linked to defects in CFTR function and glucose transport regulation. Thus, GO:0010828 represents a convergence point for metabolic, signaling, and disease-related pathways.
positive regulation of D-glucose transmembrane transport At A Glance
| GO ID | GO:0010828 |
|---|---|
| GO term | positive regulation of D-glucose transmembrane transport |
| Ontology | biological_process |
| Synonym | positive regulation of glucose transmembrane transport; positive regulation of glucose transport |
| Major function | Increases the frequency, rate, or extent of glucose transport across a membrane |
| Related transporters | GLUT1 (SLC2A1), GLUT4 (SLC2A4), and other facilitative glucose transporters |
| Key regulatory mechanisms | Post-translational modifications (e.g., S-palmitoylation), trafficking, and signaling pathways |
| Disease relevance | Cancer (e.g., glioblastoma), cystic fibrosis-related diabetes, metabolic disorders |
What Is GO:0010828?
GO:0010828, positive regulation of D-glucose transmembrane transport, is defined as any process that increases the frequency, rate, or extent of glucose transport across a membrane. Glucose transport itself is the directed movement of the hexose monosaccharide glucose into, out of, or within a cell, or between cells, mediated by transporters or pores. This term encompasses molecular events that upregulate the activity, abundance, or efficiency of glucose transport systems, thereby enhancing glucose flux across membranes.
Why Is positive regulation of D-glucose transmembrane transport Important in Cell Biology?
Positive regulation of D-glucose transmembrane transport is essential for cellular energy homeostasis and survival. It ensures that cells can rapidly increase glucose uptake in response to high energy demand, such as during proliferation or stress. Dysregulation of this process is a hallmark of many diseases, including cancer, where enhanced glucose transport supports the Warburg effect and tumor growth. In cystic fibrosis-related diabetes, impaired glucose homeostasis is associated with defects in CFTR function and glucose transport regulation. Therefore, understanding the mechanisms that positively regulate glucose transport is critical for developing targeted therapies for metabolic diseases and cancer.
• Supports rapid energy supply for proliferating cells, including cancer cells.
• Plays a key role in the Warburg effect and tumor metabolism.
• Contributes to glucose homeostasis in normal physiology and disease.
• Dysregulation is linked to cystic fibrosis-related diabetes.
• Provides potential therapeutic targets for cancer and metabolic disorders [1,8].
• Involves post-translational modifications like S-palmitoylation that can be targeted.
• Affects mitochondrial function and reprogramming through glucose-mediated signals.
• Can be studied using CRISPR-based genetic models to dissect causal roles [1,2].
What Happens During positive regulation of D-glucose transmembrane transport?
Glucose transporter expression and localization
In simple terms: Cells make more glucose transporters and move them to the cell surface to take in more glucose.
Positive regulation often begins with increased expression of glucose transporters such as GLUT1 (SLC2A1) or GLUT4 (SLC2A4). Transcriptional upregulation and enhanced trafficking to the plasma membrane elevate the number of active transporters, thereby increasing glucose uptake capacity. In glioblastoma, DHHC9-mediated S-palmitoylation of GLUT1 at Cys207 promotes its localization to the plasma membrane and enhances glycolysis.
Post-translational modifications of transporters
In simple terms: Chemical tags added to transporters can change how well they work or where they go.
Post-translational modifications, such as S-palmitoylation, regulate transporter stability, trafficking, and activity. DHHC9 palmitoylates GLUT1, which is required for its plasma membrane localization and function in glioblastoma cells. This modification enhances glucose transport and supports tumorigenesis, illustrating how a single modification can positively regulate the process.
Signaling pathways that stimulate glucose transport
In simple terms: Hormones and growth signals tell cells to take in more glucose.
Signaling cascades, including insulin and growth factor pathways, can rapidly increase glucose transport by promoting transporter translocation and activation. In cancer cells, oncogenic signaling often upregulates glucose transport to meet metabolic demands. Additionally, glucose-mediated mitochondrial reprogramming via cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites highlights cross-talk between glucose transport and organelle function.
Membrane dynamics and transporter recycling
In simple terms: Transporters are constantly recycled between the inside of the cell and the surface.
The balance between endocytosis and exocytosis of glucose transporters determines the steady-state level at the plasma membrane. Positive regulation can involve enhanced exocytosis or reduced endocytosis, leading to increased surface retention of transporters. This dynamic regulation allows cells to rapidly adjust glucose uptake in response to changing conditions.
Key Genes Involved in GO:0010828 positive regulation of D-glucose transmembrane transport
The following genes and proteins are central to the positive regulation of D-glucose transmembrane transport, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC2A1 (GLUT1) | Facilitative glucose transporter; mediates basal glucose uptake | Target for cancer metabolism; S-palmitoylation by DHHC9 enhances its function |
| SLC2A4 (GLUT4) | Insulin-responsive glucose transporter in muscle and adipose tissue | Key regulator of whole-body glucose homeostasis; studied in diabetes |
| DHHC9 (ZDHHC9) | Palmitoyltransferase that modifies GLUT1 | Promotes glioblastoma glycolysis and tumorigenesis via GLUT1 S-palmitoylation |
| TM4SF5 | Tetraspanin involved in mitochondrial-lysosomal contact sites | Mediates glucose-mediated mitochondrial reprogramming |
| CFTR | Chloride channel; affects glucose homeostasis | Modulator effects on glucose homeostasis in cystic fibrosis-related diabetes |
| INSR | Insulin receptor; initiates signaling for glucose uptake | Central to insulin-stimulated glucose transport |
| AKT2 | Serine/threonine kinase; promotes GLUT4 translocation | Key node in insulin signaling and glucose transport |
| TBC1D4 (AS160) | Rab GTPase-activating protein; regulates GLUT4 trafficking | Important for insulin-stimulated glucose transport |
| SLC2A2 (GLUT2) | Bidirectional glucose transporter in liver and pancreas | Involved in glucose sensing and homeostasis |
| SLC2A3 (GLUT3) | High-affinity glucose transporter in neurons | Critical for neuronal glucose uptake |
| HIF1A | Hypoxia-inducible factor; upregulates GLUT1 expression | Links hypoxia to increased glucose transport in cancer |
| MYC | Oncogenic transcription factor; promotes glycolysis and glucose transport | Drives metabolic reprogramming in tumors |
| PIK3CA | Catalytic subunit of PI3K; activates AKT signaling | Frequently mutated in cancers; enhances glucose uptake |
| PTEN | Lipid phosphatase; negative regulator of PI3K/AKT | Loss leads to increased glucose transport |
| RAB8A | Rab GTPase involved in vesicle trafficking | May regulate GLUT4 translocation |
| RAB10 | Rab GTPase; facilitates GLUT4 vesicle transport | Implicated in insulin-stimulated glucose uptake |
| SNAP23 | SNARE protein; mediates GLUT4 vesicle fusion | Essential for GLUT4 translocation to plasma membrane |
| VAMP2 | Vesicle-associated membrane protein; involved in GLUT4 exocytosis | Key component of GLUT4 trafficking machinery |
How Is positive regulation of D-glucose transmembrane transport Regulated?
The positive regulation of D-glucose transmembrane transport is controlled by a complex network of signaling pathways and post-translational modifications. Insulin signaling through the PI3K/AKT pathway promotes GLUT4 translocation to the plasma membrane, enhancing glucose uptake in muscle and adipose tissue. In cancer cells, oncogenic signaling and hypoxia-inducible factors upregulate GLUT1 expression and activity. Additionally, S-palmitoylation of GLUT1 by DHHC9 is a critical regulatory modification that enhances its plasma membrane localization and function. Glucose itself can also feed back to regulate mitochondrial function and cholesterol export at mitochondria-lysosome contact sites, as shown for TM4SF5. These layers of regulation ensure that glucose transport is tightly coupled to cellular energy status and environmental cues.
positive regulation of D-glucose transmembrane transport and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC2A1 (GLUT1) | Glioblastoma, cancer metabolism | Knockout or point mutation of palmitoylation site (Cys207) in glioblastoma cell lines |
| DHHC9 | Glioblastoma tumorigenesis | Knockout or overexpression in glioblastoma cells to assess GLUT1 palmitoylation |
| TM4SF5 | Metabolic reprogramming, mitochondrial function | Knockout in hepatocytes or cancer cells to study mitochondria-lysosome contact sites |
| CFTR | Cystic fibrosis-related diabetes | CFTR modulator treatment in patient-derived cells; knock-in of common mutations [7,8] |
| INSR | Diabetes, insulin resistance | Knockout or point mutation in muscle cells to study glucose transport |
Cancer metabolism and glioblastoma
In glioblastoma, DHHC9-mediated S-palmitoylation of GLUT1 promotes its plasma membrane localization, enhancing glucose uptake and glycolysis. This supports tumorigenesis and highlights GLUT1 as a potential therapeutic target. The positive regulation of glucose transport is therefore a key driver of cancer metabolic reprogramming.
Cystic fibrosis-related diabetes
CFTR modulators can affect glucose homeostasis in children and young adults with cystic fibrosis-related diabetes. Studies show that improvements in CFTR function may influence glucose transport regulation, although the relationship is modified by adiposity and other factors [7,8]. This underscores the clinical importance of glucose transport regulation in cystic fibrosis.
Mitochondrial dysfunction and metabolic reprogramming
Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites links glucose transport to organelle function. Dysregulation of this process may contribute to metabolic disorders and cancer.
From positive regulation of D-glucose transmembrane transport-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does DHHC9-mediated GLUT1 palmitoylation regulate glucose transport? | Point mutation of GLUT1 Cys207 (palmitoylation-deficient) via CRISPR knock-in |
| What is the role of TM4SF5 in glucose-mediated mitochondrial reprogramming? | TM4SF5 knockout cells and rescue with wild-type or mutant TM4SF5 |
| How do CFTR modulators affect glucose homeostasis? | Patient-derived intestinal organoids or cell lines with CFTR mutations treated with modulators [7,8] |
| Is GLUT1 overexpression sufficient to drive glycolysis? | CRISPR-mediated overexpression of GLUT1 in cancer cell lines |
| What genes regulate glucose transport in a genome-wide manner? | CRISPR library screening for glucose uptake regulators [1,2] |
| Can we visualize GLUT1 trafficking in live cells? | Knock-in of fluorescent tag (e.g., GFP) at endogenous SLC2A1 locus |
How to Study the positive regulation of D-glucose transmembrane transport Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Loss-of-function effects on glucose transport | Identify essential genes for glucose uptake |
| Point mutation knock-in | Effect of specific amino acid modifications | Test palmitoylation site requirement in GLUT1 |
| Fluorescent tagging knock-in | Subcellular localization and trafficking | Visualize GLUT1 dynamics in live cells |
| Overexpression | Gain-of-function effects | Assess sufficiency of a gene to enhance transport |
| CRISPR library screening | Genome-wide identification of regulators | Discover novel genes controlling glucose transport [1,2] |
| RNA-seq | Transcriptional changes in transporters and regulators | Profile gene expression under different glucose conditions |
| Proteomics | Protein abundance and modifications | Detect S-palmitoylation of GLUT1 |
| Metabolic assays | Glucose uptake and lactate production | Measure functional impact of genetic perturbations |
CRISPR knockout and point mutation
CRISPR-Cas9 knockout of candidate genes (e.g., DHHC9, SLC2A1) can determine their necessity for glucose transport. Point mutations, such as GLUT1 Cys207 to alanine, can specifically abolish palmitoylation and assess its impact on transport and tumorigenesis.
Knock-in reporters and tagging
Knock-in of fluorescent tags (e.g., GFP) at endogenous loci allows real-time imaging of transporter trafficking and localization. This approach can reveal how positive regulation affects plasma membrane abundance of GLUT1.
Overexpression and rescue experiments
Overexpression of wild-type or mutant transporters can test sufficiency, while rescue experiments in knockout backgrounds confirm specificity. For example, overexpressing DHHC9 increases GLUT1 palmitoylation and glucose uptake.
CRISPR library screening and bioinformatics
Genome-wide CRISPR screens can identify novel regulators of glucose transport. Bioinformatics analysis of screen hits, combined with transcriptomic and proteomic data, can uncover pathways and networks controlling GO:0010828 [1,2].
How CRISPR Can Be Used to Study GO:0010828 positive regulation of D-glucose transmembrane transport
Knockout
CRISPR knockout of genes such as DHHC9 or SLC2A1 can abolish glucose transport regulation, revealing their essential roles. For example, DHHC9 knockout reduces GLUT1 palmitoylation and glucose uptake in glioblastoma cells.
Point Mutation
Point mutations, such as GLUT1 Cys207Ala, can specifically disrupt palmitoylation without affecting other functions. This allows precise dissection of post-translational regulation in glucose transport.
Knock-in
Knock-in of tags or reporters (e.g., GFP) at endogenous loci enables tracking of transporter localization and dynamics. This can show how positive regulation increases plasma membrane GLUT1.
Overexpression
CRISPR-mediated overexpression of candidate genes (e.g., DHHC9, GLUT1) can test whether increased expression is sufficient to enhance glucose transport and downstream phenotypes like tumorigenesis.
How EDITGENE Supports positive regulation of D-glucose transmembrane transport Research
Researchers studying positive regulation of D-glucose transmembrane transport-related genes often need to determine whether a candidate gene is causally involved in glucose uptake, how specific modifications affect transporter function, and whether targeting these pathways can reverse disease phenotypes. EDITGENE provides comprehensive CRISPR-based services to address these questions with precision and reproducibility.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of D-glucose transmembrane transport research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
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| ZDHHC7 Knockout HEK293 Cell Line | EDJ-KQ3630 | Human | 55625 | Details Get a Quote |
| C3 Knockout HEK293 Cell Line | EDJ-KQ3837 | Human | 718 | Details Get a Quote |
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| NR4A3 Knockout HEK293 Cell Line | EDJ-KQ6158 | Human | 8013 | Details Get a Quote |
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| CLIP3 Knockout HEK293 Cell Line | EDJ-KQ8347 | Human | 25999 | Details Get a Quote |
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| BRAF Knockout HEK293 Cell Line | EDJ-KQ17804 | Human | 673 | Details Get a Quote |
| BRAF Knockout HCT 116 Cell Line | EDJ-KQ18183 | Human | 673 | Details Get a Quote |
| BRAF Knockout A-549 Cell Line | EDC07532 | Human | 673 | Details Get a Quote |
| BRAF Knockout HeLa Cell Line | EDJ-KQ19077 | Human | 673 | Details Get a Quote |
| C3 Knockout A-549 Cell Line | EDJ-KQ25992 | Human | 718 | Details Get a Quote |
| C3 Knockout HeLa Cell Line | EDJ-KQ25993 | Human | 718 | Details Get a Quote |
| NR4A3 Knockout A-549 Cell Line | EDJ-KQ29967 | Human | 8013 | Details Get a Quote |
| NR4A3 Knockout HeLa Cell Line | EDJ-KQ29968 | Human | 8013 | Details Get a Quote |
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Frequently Asked Questions About positive regulation of D-glucose transmembrane transport
What is GO:0010828?
GO:0010828 is the Gene Ontology term for positive regulation of D-glucose transmembrane transport, describing any process that increases the frequency, rate, or extent of glucose movement across a membrane.
What genes are involved in positive regulation of D-glucose transmembrane transport?
Key genes include SLC2A1 (GLUT1), DHHC9, SLC2A4 (GLUT4), TM4SF5, and CFTR, among others [1,2,8].
How is glucose transport regulated?
Glucose transport is regulated by signaling pathways (e.g., insulin/PI3K/AKT), post-translational modifications (e.g., S-palmitoylation), and transporter trafficking.
What diseases are associated with dysregulated glucose transport?
Dysregulated glucose transport is linked to cancer (e.g., glioblastoma), cystic fibrosis-related diabetes, and metabolic disorders [1,8].
What is the role of GLUT1 in cancer?
GLUT1 is often overexpressed in cancer cells to support high glucose uptake and glycolysis; its S-palmitoylation by DHHC9 enhances its function in glioblastoma.
How can CRISPR be used to study glucose transport?
CRISPR can create knockouts, point mutations, knock-ins, and overexpression models to dissect gene function in glucose transport [1,2].
What is S-palmitoylation and how does it affect glucose transport?
S-palmitoylation is the addition of palmitate to cysteine residues; it regulates GLUT1 membrane localization and activity, thereby enhancing glucose transport.
What methods are used to measure glucose transport?
Methods include glucose uptake assays, metabolic flux analysis, and imaging of fluorescently tagged transporters.
Can CFTR modulators affect glucose homeostasis?
Yes, CFTR modulators may improve glucose homeostasis in cystic fibrosis-related diabetes, though effects are modified by adiposity and other factors [7,8].
What is the connection between TM4SF5 and glucose transport?
TM4SF5 is involved in glucose-mediated mitochondrial reprogramming at mitochondria-lysosome contact sites, linking glucose transport to organelle function.
Conclusion
Positive regulation of D-glucose transmembrane transport (GO:0010828) is a fundamental biological process that ensures adequate glucose supply for cellular metabolism. Its dysregulation contributes to cancer, diabetes, and other metabolic diseases. Advances in CRISPR-based models and screening technologies are enabling precise dissection of the molecular players and regulatory mechanisms. EDITGENE provides a comprehensive suite of services to support research in this area, from knockout and point mutation models to library screening and bioinformatics.
References
- 1. Zhang Z et al.. 2021. DHHC9-mediated GLUT1 S-palmitoylation promotes glioblastoma glycolysis and tumorigenesis.. Nat Commun 12(1):5872 PMID: 34620861
- 2. Kim JE et al.. 2024. Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites.. Cancer Commun (Lond) 44(1):47-75 PMID: 38133457
- 7. Gonzalez Ramirez LA et al.. 2025. Relationship between skeletal muscle indicators and clinical outcomes in cystic fibrosis is modified by adiposity and CFTR modulator use: a cross-sectional analysis.. Am J Clin Nutr 122(5):1479-1488 PMID: 40972870
- 8. Giordano P et al.. 2025. Effect of CFTR modulators on glucose homeostasis in children and young adults with cystic fibrosis-related diabetes: a systematic review.. Front Endocrinol (Lausanne) 16:1623654 PMID: 40842499
