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
This article has been cited 14 times.- Temre MK, Kumar A, Singh SM. An appraisal of the current status of inhibition of glucose transporters as an emerging antineoplastic approach: Promising potential of new pan-GLUT inhibitors.. Front Pharmacol 2022;13:1035510.
- Wu X, Fan X, Crawford R, Xiao Y, Prasadam I. The Metabolic Landscape in Osteoarthritis.. Aging Dis 2022 Jul 11;13(4):1166-1182.
- Mou Y, Du Y, Zhou L, Yue J, Hu X, Liu Y, Chen S, Lin X, Zhang G, Xiao H, Dong B. Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging.. Front Immunol 2022;13:796288.
- Maleckar MM, Clark RB, Votta B, Giles WR. The Resting Potential and K(+) Currents in Primary Human Articular Chondrocytes.. Front Physiol 2018;9:974.
- Chen LY, Lotz M, Terkeltaub R, Liu-Bryan R. Modulation of matrix metabolism by ATP-citrate lyase in articular chondrocytes.. J Biol Chem 2018 Aug 3;293(31):12259-12270.
- Mejia EM, Zinko JC, Hauff KD, Xu FY, Ravandi A, Hatch GM. Glucose Uptake and Triacylglycerol Synthesis Are Increased in Barth Syndrome Lymphoblasts.. Lipids 2017 Feb;52(2):161-165.
- Selesniemi K, Albers RE, Brown TL. Id2 Mediates Differentiation of Labyrinthine Placental Progenitor Cell Line, SM10.. Stem Cells Dev 2016 Jul 1;25(13):959-74.
- Lane RS, Fu Y, Matsuzaki S, Kinter M, Humphries KM, Griffin TM. Mitochondrial respiration and redox coupling in articular chondrocytes.. Arthritis Res Ther 2015 Mar 10;17(1):54.
- Lacombe VA. Expression and regulation of facilitative glucose transporters in equine insulin-sensitive tissue: from physiology to pathology.. ISRN Vet Sci 2014;2014:409547.
- Rufino AT, Rosa SC, Judas F, Mobasheri A, Lopes MC, Mendes AF. Expression and function of K(ATP) channels in normal and osteoarthritic human chondrocytes: possible role in glucose sensing.. J Cell Biochem 2013 Aug;114(8):1879-89.
- Mobasheri A. Glucose: an energy currency and structural precursor in articular cartilage and bone with emerging roles as an extracellular signaling molecule and metabolic regulator.. Front Endocrinol (Lausanne) 2012;3:153.
- Reddy AB, Srivastava SK, Ramana KV. Aldose reductase inhibition prevents lipopolysaccharide-induced glucose uptake and glucose transporter 3 expression in RAW264.7 macrophages.. Int J Biochem Cell Biol 2010 Jun;42(6):1039-45.
- Skovgaard D, Kjaer M, El-Ali H, Kjaer A. 18F-fluorodeoxyglucose and PET/CT for noninvasive study of exercise-induced glucose uptake in rat skeletal muscle and tendon.. Eur J Nucl Med Mol Imaging 2009 May;36(5):859-68.
- Willis LM, Small BJ, Bickford PC, Umphlet CD, Moore AB, Granholm AC. Dietary blueberry supplementation affects growth but not vascularization of neural transplants.. J Cereb Blood Flow Metab 2008 Jun;28(6):1150-64.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
