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Differential regulation of the GLUT1 and GLUT3 glucose transporters by growth factors and pro-inflammatory cytokines in equine articular chondrocytes.
Abstract: Glucose serves as the major energy substrate for articular chondrocytes and as the main precursor for the synthesis of extracellular matrix glycosaminoglycans in cartilage. Chondrocytes have been shown to express several glucose transporter (GLUT) isoforms including GLUT1 and GLUT3. The aim of this investigation was to determine the effects of endocrine and cytokine factors on the capacity of equine articular chondrocytes for transporting 2-deoxy-d-[2,6-3H] glucose and on the expression levels of GLUT1 and GLUT3. Chondrocytes maintained in monolayer culture were stimulated for 24 h with TNF-alpha (100 ng mL(-1)), IL-1beta (100 ng mL(-1)), IGF-I (20 ng mL(-1)), TGF-beta (20 ng mL(-1)) and insulin (12.5 microg mL(-1)) before measuring uptake of non-metabolizable 2-deoxyglucose in the presence and absence of the glucose transport inhibitor cytochalasin B. Polyclonal antibodies to GLUT1 and GLUT were used to compare GLUT1 and GLUT3 expression in stimulated and un-stimulated alginate encapsulated chondrocytes by Western blotting. Results indicated that 2-deoxyglucose uptake was inhibited by up to 95% in the presence of cytochalasin B suggesting that glucose uptake into equine chondrocytes is GLUT-mediated. Insulin had no effect on glucose uptake, but treatment with IGF-I, TGF-beta, IL-1beta and TNF-alpha resulted in a significant increase (>65%) in 2-deoxyglucose uptake compared to control values. GLUT1 was found to be increased in chondrocytes stimulated with all the growth factors and cytokines but GLUT 3 was only upregulated by IGF-I. The data presented support a critical role for glucose in the responses of equine articular chondrocytes to pro-inflammatory cytokines and anabolic endocrine factors.
Publication Date: 2005-02-25 PubMed ID: 15727913DOI: 10.1016/j.tvjl.2004.01.026Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article investigates the impact of certain hormones and cytokines on the ability of equine articular chondrocytes, cells in the horse’s cartilage, to transport glucose for energy and the synthesis of key components of cartilage. The study further explored how these hormones and cytokines affect the expression of two isoforms of the glucose transporter (GLUT): GLUT1 and GLUT3.
Objective of Research
- This study was set out to determine the effects of endocrine (hormone) and cytokine (protein molecules involved in cell signaling) factors on the glucose transport capability of equine articular chondrocytes and how they influence the expression levels of GLUT1 and GLUT3, two specific forms of the glucose transporter protein.
Methodology
- The researchers maintained chondrocytes in a monolayer culture and stimulated them using various cytokines and hormones, including TNF-alpha, IL-1beta, IGF-I, TGF-beta, and insulin.
- They measured the uptake of a non-metabolizable form of glucose in both the presence and absence of the glucose transport inhibitor, cytochalasin B. This step was critical to determine whether glucose uptake in these cells was mediated by GLUT proteins.
- The scientists also compared the expression levels of GLUT1 and GLUT3 in stimulated and unstimulated chondrocytes by using a technique known as Western blotting, which helps identify specific proteins in a sample.
Results and Findings
- The study revealed that the glucose inhibitor cytochalasin B could suppress glucose uptake in chondrocytes by up to 95%. This finding suggested that glucose uptake in these cells was mediated by GLUT transporters.
- Insulin did not affect glucose uptake; however, it was found that IGF-I, TGF-beta, IL-1beta, and TNF-alpha increased glucose uptake by more than 65% compared to control values.
- Increased expression of GLUT1 was observed in chondrocytes stimulated with all tested growth factors and cytokines. However, GLUT3 was only upregulated by IGF-I.
Conclusion
- The data supported a significant role for glucose in the responses of equine articular chondrocytes to pro-inflammatory cytokines and anabolic endocrine factors. It suggests that understanding glucose uptake and GLUT expression in chondrocytes could be important in understanding and potentially managing inflammatory conditions affecting horse cartilage.
Cite This Article
APA
Phillips T, Ferraz I, Bell S, Clegg PD, Carter SD, Mobasheri A.
(2005).
Differential regulation of the GLUT1 and GLUT3 glucose transporters by growth factors and pro-inflammatory cytokines in equine articular chondrocytes.
Vet J, 169(2), 216-222.
https://doi.org/10.1016/j.tvjl.2004.01.026 Publication
Researcher Affiliations
- Connective Tissue and Molecular Pathogenesis Research Groups, Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, UK.
MeSH Terms
- Animals
- Blotting, Western
- Cartilage, Articular / metabolism
- Chondrocytes / cytology
- Chondrocytes / metabolism
- Cytokines / pharmacology
- Gene Expression Regulation
- Glucose / metabolism
- Glucose Transporter Type 1
- Glucose Transporter Type 3
- Horses / metabolism
- Insulin / pharmacology
- Insulin-Like Growth Factor I / pharmacology
- Interleukin-1 / pharmacology
- Monosaccharide Transport Proteins / genetics
- Monosaccharide Transport Proteins / metabolism
- Nerve Tissue Proteins / genetics
- Nerve Tissue Proteins / metabolism
- Signal Transduction / drug effects
- Stifle / metabolism
- Transforming Growth Factor beta / pharmacology
- Transforming Growth Factors / pharmacology
- Tumor Necrosis Factor-alpha / pharmacology
Citations
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