Cytokine regulation of facilitated glucose transport in human articular chondrocytes

Glucose serves as the major energy substrate and the main precursor for the synthesis of glycosaminoglycans in chondrocytes. Facilitated glucose trans port represents the first rate-limiting step in glucose metabolism. This st udy examines molecular regulation of facilitated glucose transport in norma l human articular chondrocytes by proinflammatory cytokines. IL-1 beta and TNF-alpha, and to a lesser degree IL-6, accelerate facilitated glucose tran sport as measured by [H-3]2-deoxyglucose uptake. IL-1 beta induces an incre ased expression of glucose transporter (GLUT) 1 mRNA and protein, and GLUT9 mRNA. GLUT3 and GLUT8 mRNA are constitutively expressed in chondrocytes an d are not regulated by IL-1 beta. GLUT2 and GLUT4 mRNA are not detected in chondrocytes. IL-1 beta stimulates GLUT1 protein glycosylation and plasma m embrane incorporation. IL-1 beta regulation of glucose transport in chondro cytes depends on protein kinase C and p38 signal transduction pathways, and does not require phosphoinositide 3-kinase, extracellular signal-related k inase, or c-Jun N-terminal kinase activation. IL-1 beta -accelerated glucos e transport in chondrocytes is not mediated by endogenous NO or eicosanoids . These results demonstrate that stimulation of glucose transport represent s a component of the chondrocyte response to IL-1 beta. Two classes of GLUT s are identified in chondrocytes, constitutively expressed GLUT3 and GLUT8, and the inducible GLUT1 and GLUT9.