Cytokine Regulation of Facilitated Glucose Transport in Human Articular Chondrocytes

Shikhman, Alexander R.; Brinson, Diana C.; Valbracht, Jean; Lotz, Martin

doi:10.4049/jimmunol.167.12.7001

Cited by 144 publications

(137 citation statements)

References 77 publications

(52 reference statements)

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“…The IL-1-dependent increase in glucose transport by ovarian cells was found to be mediated via up-regulation of GLUT3 expression (Kol et al 1997), while the IL-1-induced increase in glucose transport by porcine synovial fibroblasts depended on the up-regulation of erythrocyte GLUT1. In human articular chondrocytes, IL-1 had no effect on GLUT3 and GLUT8 expression, whereas GLUT1 and GLUT9 were up-regulated (Shikhman et al 2001). In the present study, we have shown that IL-1, TNF-and IFN-down-regulate the expression of GLUT8 in Leydig cells.…”

supporting

confidence: 49%

Expression and regulation of glucose transporter 8 in rat Leydig cells

Chen

Nagpal²,

Lin

2003

Journal of Endocrinology

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Basal and LH/human chorionic gonadotropin (hCG)-stimulated testosterone formation by Leydig cells is dependent on ambient glucose levels. Inhibition of glucose uptake is associated with decreased testosterone formation. Recently, glucose transporter 8 (GLUT8) has been shown to be highly expressed in the testis. In the present study, we have investigated the expression and regulation of the GLUT8 gene in rat Leydig cells. Primers were designed by using sequences that are not conserved in GLUT1 to GLUT5 and that contain the glycosylation region of GLUT8. This yielded an amplicon of 186 bp. The tissue-specific expression experiments in adult rat (55-to 65-day-old) tissues revealed that GLUT8 is expressed predominantly in the testis, in smaller amounts in heart and kidney, and in negligible amounts in liver and spleen. Furthermore, GLUT8 mRNA was found to be highly expressed in crude interstitial cells, Leydig cells and testicular and epididymal germ cells. In prepubertal rat (20-day-old) tissues, GLUT8 expression was comparatively much lower than in the adult rat tissues. By comparative RT-PCR, hCG caused dose-and timedependent increases of GLUT8 mRNA levels. hCG and IGF-I had synergistic effects on GLUT8 mRNA and protein expression. GLUT1 and GLUT3 were also found to be expressed in Leydig cells. However, neither GLUT1 nor GLUT3 were affected by treatments with hCG, IGF-I or hCG and IGF-I combined. The addition of murine interleukin-1 (mIL-1 ; 10 ng/ml), murine tumor necrosis factor-(mTNF-; 10 ng/ml), murine interferon-(mIFN-; 500 U/ml) separately or in combination decreased hCG-induced GLUT8 mRNA levels significantly. In conclusion, GLUT8 mRNA in Leydig cells was positively regulated by hCG and IGF-I and downregulated by cytokines, mIL-1 , mTNF-and mIFN-. These results indicate that hCG, growth factors and cytokines affect Leydig cell steroidogenesis by modulating GLUT8 expression.

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supporting

confidence: 49%

Expression and regulation of glucose transporter 8 in rat Leydig cells

Chen

Nagpal²,

Lin

2003

Journal of Endocrinology

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“…These authors demonstrated that treating 3T3-L1 adipocytes with recombinant murine IL-6 for 5 h increased basal glucose transport by ~20%. An increase in IL-6-stimulated basal glucose transport has also been observed in both smooth muscle [67] and chondrocytes [68], although this effect is not always seen, as two studies have found no effect of IL-6 on basal glucose transport in 3T3 L1 adipocytes [55,69].…”

Section: Interaction Between Il-6 and Glucose Transport In Vitromentioning

confidence: 92%

Interleukin-6 and insulin sensitivity: friend or foe?

2004

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“…One plausible explanation for this observation is an increase in the translocation of preexisting GLUT1 protein from subcellular compartment to the cell membrane 20 in an extremely hypoxic environment. It is also possible that other glucose transporters, such as GLUT3 and GLUT9, which have recently been shown to be expressed in chondrocytes, 14,34 are involved in this process. GLUT3 is known to be a high-affinity glucose transporter, 13 and could have a role in regulating glucose transport under such stimuli where chondrocytes have a very high metabolic demand to maintain their matrix synthesis function.…”

Section: Discussionmentioning

confidence: 99%

Effects of hypoxia on glucose transport in primary equine chondrocytes in vitro and evidence of reduced GLUT1 gene expression in pathologic cartilage in vivo

Peansukmanee¹,

Vaughan-Thomas²,

Carter³

et al. 2009

Journal Orthopaedic Research

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Articular chondrocytes exist in an environment lacking in oxygen and nutrients due to the avascular nature of cartilage. The main source of metabolic energy is glucose, which is taken up by glucose transporters (GLUTs). In diseased joints, oxygen tensions and glucose availability alter as a result of inflammation and changes in vascularisation. Accordingly, in this study we examined the effects of hypoxia and the hypoxia mimetic cobalt chloride (CoCl 2 ) on glucose transport in equine chondrocytes and compared expression of the hypoxia responsive GLUT1 gene in normal and diseased cartilage. Monolayers of equine chondrocytes were exposed to 20% O 2 , 1% O 2 , CoCl 2 (75 mM), or a combination of 1% O 2 and CoCl 2 . Glucose uptake was measured using 2-deoxy-D-[2,6-3 H] glucose. GLUT1 protein and mRNA expression were determined by FACS analysis and qPCR, respectively. GLUT1 mRNA expression in normal and diseased cartilage was analyzed using explants derived from normal, OA, and OCD cartilage. Chondrocytes under hypoxic conditions exhibited a significantly increased glucose uptake as well as upregulated GLUT1 protein expression. GLUT1 mRNA expression significantly increased in combined hypoxia-CoCl 2 treatment. Analysis of clinical samples indicated a significant reduction in GLUT1 mRNA in OA samples. In OCD samples GLUT1 expression also decreased but did not reach statistical significance. The increase in glucose uptake and GLUT1 expression under hypoxic conditions confirms that hypoxia alters the metabolic requirements of chondrocytes. The altered GLUT1 mRNA expression in diseased cartilage with significance in OA suggests that reduced GLUT1 may contribute to the failure of OA cartilage repair. ß

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Cytokine Regulation of Facilitated Glucose Transport in Human Articular Chondrocytes

Cited by 144 publications

References 77 publications

Expression and regulation of glucose transporter 8 in rat Leydig cells

Expression and regulation of glucose transporter 8 in rat Leydig cells

Interleukin-6 and insulin sensitivity: friend or foe?

Effects of hypoxia on glucose transport in primary equine chondrocytes in vitro and evidence of reduced GLUT1 gene expression in pathologic cartilage in vivo

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