GO:0010907 positive regulation of glucose metabolic process: Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0010907 describes any process that increases the rate, frequency or extent of glucose metabolism, the chemical reactions and pathways involving glucose.
• Positive regulation of glucose metabolism is essential for immune cell memory formation, as a Pck1-directed glycogen metabolic program supports memory CD8+ T cells.
• Glucose transporter 2 (GLUT2) senses environmental glucose and regulates CD8+ T cell function, linking glucose metabolism to immune responses.
• The Alamandine/MrgD axis prevents TGF-beta1-mediated fibroblast activation by regulating aerobic glycolysis and mitophagy.
• Hepatic TGF-beta1 and Foxo1 reciprocally regulate gluconeogenesis and energy expenditure, highlighting crosstalk between signaling and glucose metabolism.
• CARM1-mediated OGT arginine methylation stabilizes OGT and promotes non-small cell lung cancer glycolysis, connecting glucose metabolism to cancer progression.
Description
Glucose metabolism is a fundamental cellular process that provides energy and biosynthetic precursors. The Gene Ontology term GO:0010907, positive regulation of glucose metabolic process, encompasses any process that increases the rate, frequency or extent of glucose metabolism, which includes the chemical reactions and pathways involving glucose. This term is critical for understanding how cells adapt to changing nutrient availability, such as in immune responses, cancer, and metabolic disorders. For researchers, GO:0010907 provides a framework to study the molecular mechanisms that upregulate glucose utilization, including glycolysis, gluconeogenesis, and glycogen metabolism. Key regulators such as Pck1, GLUT2, and Foxo1 have been shown to modulate glucose metabolic processes in diverse physiological contexts [1,3,4]. Understanding positive regulation of glucose metabolism is essential for developing therapeutic strategies targeting metabolic reprogramming in diseases like cancer and diabetes.
positive regulation of glucose metabolic process At A Glance
| GO ID | GO:0010907 |
|---|---|
| GO term | positive regulation of glucose metabolic process |
| Ontology | biological_process |
| Synonym | positive regulation of glucose metabolism |
| Major function | Upregulation of glucose metabolism, including glycolysis, gluconeogenesis, and glycogen metabolism |
| Related processes | Cellular response to nutrient levels, energy homeostasis, immune cell function |
| Key regulators | Pck1, GLUT2, Foxo1, TGF-beta1, OGT, CARM1 |
| Disease relevance | Cancer, metabolic disorders, immune dysfunction |
What Is GO:0010907?
GO:0010907 is defined as any biological process that increases the rate, frequency or extent of glucose metabolism. Glucose metabolic processes are the chemical reactions and pathways involving glucose, the aldohexose gluco-hexose. This term is a child of positive regulation of metabolic process and is involved in cellular responses to nutrient status.
Why Is positive regulation of glucose metabolic process Important in Cell Biology?
Positive regulation of glucose metabolism is central to cellular energy homeostasis and biosynthetic capacity. It enables cells to rapidly adapt to increased energy demands, such as during immune activation or tumor growth. Dysregulation of this process contributes to diseases including cancer, diabetes, and immune disorders, making it a key area for therapeutic intervention [1,2,4,6].
• Supports memory CD8+ T cell formation and maintenance via Pck1-directed glycogen metabolism.
• Regulates CD8+ T cell function through GLUT2-mediated environment sensing.
• Prevents TGF-beta1-mediated fibroblast activation via the Alamandine/MrgD axis and aerobic glycolysis.
• Controls hepatic gluconeogenesis and energy expenditure through reciprocal regulation of TGF-beta1 and Foxo1.
• Promotes non-small cell lung cancer glycolysis via CARM1-mediated OGT stabilization.
• Involved in nutrient sensing and mTORC1 regulation through KICSTOR and GATOR1.
• Modulates glucose uptake under hyperosmotic stress.
• Essential for feto-placental metabolism and fetal growth.
What Happens During positive regulation of glucose metabolic process?
Initiation by Nutrient and Hormonal Signals
In simple terms: The process starts when cells sense nutrients or hormones that signal a need for more glucose metabolism.
Positive regulation of glucose metabolism is initiated by extracellular signals such as nutrients, hormones, and growth factors. For example, TGF-beta1 and Foxo1 reciprocally regulate hepatic gluconeogenesis in response to metabolic status. Hyperosmotic stress can positively or negatively regulate glucose uptake depending on the cellular context. The Alamandine/MrgD axis responds to TGF-beta1 to modulate aerobic glycolysis and mitophagy in fibroblasts.
Transcriptional and Post-translational Control of Metabolic Enzymes
In simple terms: Cells adjust the amounts and activities of enzymes that break down or produce glucose.
Key enzymes such as Pck1 (phosphoenolpyruvate carboxykinase 1) are transcriptionally regulated to direct glycogen metabolic programs in memory CD8+ T cells. Foxo1 controls gluconeogenic gene expression in the liver. Post-translational modifications, such as CARM1-mediated arginine methylation of OGT, stabilize OGT and promote glycolysis in non-small cell lung cancer.
Glucose Uptake and Transport
In simple terms: Glucose must enter the cell before it can be metabolized.
Glucose transporter 2 (GLUT2) senses environmental glucose and regulates CD8+ T cell function. Hyperosmotic stress can modulate glucose uptake through positive and negative regulatory mechanisms. In the feto-placental unit, glucose transport and metabolism are essential for fetal growth.
Integration with Cellular Energy and Biosynthetic Pathways
In simple terms: Glucose metabolism is linked to other pathways that produce energy and building blocks.
The KICSTOR complex recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1, which in turn promotes anabolic processes including glucose metabolism. Pck1-directed glycogen metabolism supports memory CD8+ T cell formation and maintenance. The Alamandine/MrgD axis regulates aerobic glycolysis and mitophagy, linking glucose metabolism to mitochondrial quality control.
Key Genes Involved in GO:0010907 positive regulation of glucose metabolic process
The following genes and proteins are key players in the positive regulation of glucose metabolic process, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| Pck1 | Directs glycogen metabolic program in memory CD8+ T cells | Memory T cell formation and maintenance |
| GLUT2 (SLC2A2) | Glucose transporter and environment sensor in CD8+ T cells | T cell function and glucose sensing |
| Foxo1 | Reciprocally regulates hepatic gluconeogenesis with TGF-beta1 | Hepatic glucose metabolism and energy expenditure |
| TGF-beta1 | Regulates gluconeogenesis and fibroblast activation | Liver metabolism and fibrosis [2,4] |
| OGT | Stabilized by CARM1-mediated arginine methylation to promote glycolysis | Non-small cell lung cancer glycolysis |
| CARM1 | Methylates OGT to stabilize it and promote glycolysis | Cancer metabolism |
| MrgD | Receptor for Alamandine that prevents TGF-beta1-mediated fibroblast activation | Fibroblast activation and aerobic glycolysis |
| KICSTOR | Recruits GATOR1 to lysosome for nutrient-dependent mTORC1 regulation | Nutrient sensing and mTORC1 signaling |
| GATOR1 | Inhibits mTORC1 in response to nutrient status | mTORC1 regulation and glucose metabolism |
| mTORC1 | Promotes anabolic processes including glucose metabolism | Cell growth and metabolism |
| Alamandine | Peptide that activates MrgD to regulate glycolysis and mitophagy | Fibroblast activation and metabolism |
| PGC-1alpha | Transcriptional coactivator of gluconeogenic genes | Hepatic glucose metabolism |
| PEPCK | Enzyme catalyzing gluconeogenesis | Glucose production |
| GSK3 | Kinase that regulates glycogen synthase | Glycogen metabolism |
| HIF-1alpha | Transcription factor that upregulates glycolytic genes | Cancer glycolysis |
| c-Myc | Transcription factor that promotes glycolysis | Cancer metabolism |
| AMPK | Energy sensor that regulates glucose metabolism | Cellular energy homeostasis |
How Is positive regulation of glucose metabolic process Regulated?
Positive regulation of glucose metabolic process is controlled by multiple signaling pathways. The KICSTOR complex recruits GATOR1 to the lysosome, which is necessary for nutrients to regulate mTORC1, a master regulator of anabolic metabolism including glucose utilization. TGF-beta1 and Foxo1 reciprocally regulate hepatic gluconeogenesis and energy expenditure. The Alamandine/MrgD axis modulates aerobic glycolysis and mitophagy in response to TGF-beta1. Additionally, hyperosmotic stress can positively or negatively regulate glucose uptake.
positive regulation of glucose metabolic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| Pck1 | Memory CD8+ T cell formation | Knockout mouse models, T cell-specific deletion |
| GLUT2 | T cell function and glucose sensing | Conditional knockout in T cells |
| Foxo1 | Hepatic gluconeogenesis and diabetes | Liver-specific knockout or overexpression |
| CARM1/OGT | Non-small cell lung cancer glycolysis | Cancer cell lines with knockout or point mutations |
| MrgD | Fibroblast activation and fibrosis | Knockout mice or fibroblast-specific deletion |
Cancer Metabolism
Positive regulation of glucose metabolism is a hallmark of cancer, where tumor cells often exhibit increased glycolysis (Warburg effect). CARM1-mediated OGT arginine methylation promotes non-small cell lung cancer glycolysis by stabilizing OGT. Targeting this pathway may offer therapeutic opportunities.
Metabolic Disorders
Dysregulation of glucose metabolism contributes to type 2 diabetes and obesity. Hepatic TGF-beta1 and Foxo1 reciprocally regulate gluconeogenesis and energy expenditure, and their imbalance can lead to hyperglycemia. Understanding these mechanisms is crucial for developing treatments for metabolic diseases.
Immune Cell Function and Memory
Glucose metabolism is essential for T cell activation and memory formation. Pck1-directed glycogen metabolism regulates memory CD8+ T cell formation and maintenance. GLUT2 senses environmental glucose to regulate CD8+ T cell function. Defects in these pathways can impair immune responses.
Fibrosis and Tissue Remodeling
The Alamandine/MrgD axis prevents TGF-beta1-mediated fibroblast activation by regulating aerobic glycolysis and mitophagy. This suggests that positive regulation of glucose metabolism plays a role in fibrotic diseases, and modulating it could be therapeutic.
From positive regulation of glucose metabolic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does Pck1 regulate memory CD8+ T cell formation? | Pck1 knockout mice or T cell-specific deletion |
| How does GLUT2 sense glucose in T cells? | GLUT2 knockout or point-mutation knock-in in T cells |
| What is the role of Foxo1 in hepatic gluconeogenesis? | Liver-specific Foxo1 knockout or overexpression |
| Does CARM1-mediated OGT methylation promote cancer glycolysis? | CARM1 knockout or OGT point-mutation in cancer cells |
| How does Alamandine/MrgD regulate fibroblast activation? | MrgD knockout or Alamandine treatment in fibroblasts |
| Does KICSTOR regulate mTORC1 in response to nutrients? | KICSTOR knockout cells and nutrient starvation |
How to Study the positive regulation of glucose metabolic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| 13C-glucose flux analysis | Rate of glucose metabolism through pathways | Quantifying glycolysis and TCA cycle activity [1,6] |
| RNA-seq | Transcriptional changes in metabolic genes | Identifying upregulated glucose metabolism genes [1,4] |
| Proteomics | Protein expression and modifications | Detecting OGT methylation and other PTMs |
| CRISPR knockout | Loss-of-function effects on glucose metabolism | Testing causal roles of Pck1, GLUT2, etc. [1,3] |
| CRISPR knock-in | Introduction of specific mutations or tags | Studying point mutations in metabolic enzymes [4,6] |
| Live-cell biosensors | Real-time metabolite dynamics | Monitoring glucose uptake and ATP levels [3,8] |
| Seahorse assay | Extracellular acidification and oxygen consumption | Measuring glycolysis and oxidative phosphorylation |
| Western blot | Protein expression and phosphorylation | Validating signaling changes in glucose metabolism [2,4] |
Metabolic Flux Analysis
Metabolic flux analysis using isotope-labeled glucose (e.g., 13C-glucose) allows researchers to measure the rate of glucose metabolism through glycolysis, the TCA cycle, and other pathways. This is essential for quantifying positive regulation of glucose metabolic process in response to genetic or environmental changes [1,6].
Transcriptomics and Proteomics
RNA-seq and proteomics can identify changes in gene and protein expression that accompany positive regulation of glucose metabolism. For example, Pck1 and Foxo1 target genes can be assessed in memory T cells or liver tissue [1,4]. Post-translational modifications like arginine methylation of OGT can be detected by mass spectrometry.
Genetic Knockout and Knock-in Models
CRISPR-Cas9-mediated knockout or knock-in of key genes such as Pck1, GLUT2, Foxo1, CARM1, and OGT enables causal testing of their roles in glucose metabolism. These models can be used in cell lines or primary cells to study metabolic phenotypes [1,3,4,6].
Live-Cell Imaging and Biosensors
Genetically encoded fluorescent biosensors (e.g., for ATP, NADH, or glucose) allow real-time monitoring of glucose metabolism in living cells. This approach can reveal dynamic changes in response to stimuli that positively regulate glucose metabolism [3,8].
How CRISPR Can Be Used to Study GO:0010907 positive regulation of glucose metabolic process
Knockout
CRISPR knockout of genes such as Pck1, GLUT2, Foxo1, CARM1, or OGT can reveal their essential roles in positive regulation of glucose metabolism. For example, Pck1 knockout impairs memory CD8+ T cell formation, and GLUT2 knockout alters T cell function. These models are valuable for target validation.
Point Mutation
Point mutations can be introduced to study specific residues critical for enzyme activity or regulation. For instance, mutation of the arginine methylation site on OGT can prevent CARM1-mediated stabilization and reduce glycolysis in cancer cells. Similarly, point mutations in Foxo1 can affect its DNA-binding and gluconeogenic activity.
Knock-in
Knock-in of reporter genes or tags (e.g., GFP, luciferase) allows tracking of gene expression and protein localization in real time. Knock-in of a tagged OGT or Pck1 can help visualize their dynamics during glucose metabolism [1,6]. This approach is also useful for creating disease-relevant mutations.
Overexpression
Overexpression of genes like Pck1, GLUT2, or CARM1 can enhance glucose metabolism and may be used to study gain-of-function phenotypes. For example, overexpression of CARM1 increases OGT stabilization and promotes glycolysis in lung cancer cells. Overexpression models are useful for identifying downstream effects and potential therapeutic targets.
How EDITGENE Supports positive regulation of glucose metabolic process Research
Researchers studying positive regulation of glucose metabolic process-related genes often need to determine whether a candidate gene is causally involved in metabolic reprogramming. EDITGENE provides comprehensive CRISPR-based services to accelerate this research, from knockout to knock-in and library screening.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of glucose metabolic process research.
Frequently Asked Questions About positive regulation of glucose metabolic process
What is GO:0010907?
GO:0010907 is the Gene Ontology term for positive regulation of glucose metabolic process, defined as any process that increases the rate, frequency or extent of glucose metabolism.
What genes are involved in positive regulation of glucose metabolic process?
Key genes include Pck1, GLUT2, Foxo1, CARM1, OGT, and TGF-beta1, among others [1,3,4,6].
How does Pck1 regulate glucose metabolism?
Pck1 directs a glycogen metabolic program that regulates formation and maintenance of memory CD8+ T cells.
What is the role of GLUT2 in glucose metabolism?
GLUT2 is a glucose transporter that senses environmental glucose and regulates CD8+ T cell function.
How does CARM1 affect glucose metabolism in cancer?
CARM1-mediated OGT arginine methylation stabilizes OGT and promotes non-small cell lung cancer glycolysis.
What diseases are associated with dysregulated glucose metabolism?
Cancer, diabetes, fibrosis, and immune disorders are linked to dysregulation of glucose metabolic processes [1,2,4,6].
How can I study positive regulation of glucose metabolic process?
Researchers use CRISPR knockout, knock-in, metabolic flux analysis, and biosensors to study this process [1,3,6].
What is the Alamandine/MrgD axis?
The Alamandine/MrgD axis prevents TGF-beta1-mediated fibroblast activation by regulating aerobic glycolysis and mitophagy.
How does mTORC1 regulate glucose metabolism?
mTORC1 promotes anabolic processes including glucose metabolism, and its activity is controlled by nutrients via KICSTOR and GATOR1.
What CRISPR services does EDITGENE offer for glucose metabolism research?
EDITGENE provides knockout, point mutation, knock-in, overexpression cell models, CRISPR library screening, and bioinformatics services for glucose metabolism research.
Conclusion
Positive regulation of glucose metabolic process (GO:0010907) is a critical biological process that governs cellular energy homeostasis and biosynthetic capacity. Its dysregulation is implicated in cancer, metabolic disorders, and immune dysfunction. Understanding the molecular players such as Pck1, GLUT2, Foxo1, CARM1, and OGT provides opportunities for therapeutic intervention. EDITGENE offers comprehensive CRISPR solutions to accelerate research in this field.
References
- 1. Ma R et al.. 2018. A Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8(+) T cells.. Nat Cell Biol 20(1):21-27 PMID: 29230018
- 2. Wang W et al.. 2023. Alamandine/MrgD axis prevents TGF-β1-mediated fibroblast activation via regulation of aerobic glycolysis and mitophagy.. J Transl Med 21(1):24 PMID: 36635651
- 3. Fu H et al.. 2023. The glucose transporter 2 regulates CD8(+) T cell function via environment sensing.. Nat Metab 5(11):1969-1985 PMID: 37884694
- 4. Pan Q et al.. 2023. Reciprocal Regulation of Hepatic TGF-β1 and Foxo1 Controls Gluconeogenesis and Energy Expenditure.. Diabetes 72(9):1193-1206 PMID: 37343276
- 5. Gual P et al.. 2003. Positive and negative regulation of glucose uptake by hyperosmotic stress.. Diabetes Metab 29(6):566-75 PMID: 14707885
- 6. Lin L et al.. 2024. CARM1-mediated OGT arginine methylation promotes non-small cell lung cancer glycolysis by stabilizing OGT.. Cell Death Dis 15(12):927 PMID: 39715739
- 7. Ward JW et al.. 2004. Ovine feto-placental metabolism.. J Physiol 554(Pt 2):529-41 PMID: 14594988
- 8. Wolfson RL et al.. 2017. KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1.. Nature 543(7645):438-442 PMID: 28199306
