Distinct pathways regulate facilitated glucose transport in human articular chondrocytes during anabolic and catabolic responses

1 Division of Arthritis Research, The Scripps Research Institute, and 2 Division of Rheumatology, Scripps Clinic, La Jolla, California 92037 Submitted 30 May 2003 ; accepted in final form 16 January 2004 Articular cartilage is an avascular, non-insulin-sensitive tissue that utilizes glucose as the main energy source, a precursor for glycosaminoglycan synthesis, and a regulator of gene expression. Facilitated glucose transport represents the first rate-limiting step in glucose metabolism. Previously, we demonstrated that glucose transport in chondrocytes is regulated by proinflammatory cytokines via upregulation of GLUT mRNA and protein expression. The objective of the present study was to determine differences in molecular mechanisms regulating glucose transport in chondrocytes stimulated with the anabolic transforming growth factor- 1 (TGF- 1) vs. the catabolic and proinflammatory cytokine IL-1 . Both TGF- 1 and IL-1 accelerate glucose transport in chondrocytes. Although both IL-1 and TGF- 1 enhance glucose transport in chondrocytes to a similar magnitude, IL-1 induces significantly higher levels of lactate. TGF- 1-stimulated glucose transport is not associated with increased expression or membrane incorporation of GLUT1, -3, -6, -8, and -10 and depends on PKC and ERK activation. In contrast, IL-1 -stimulated glucose transport is accompanied by increased expression and membrane incorporation of GLUT1 and -6 and depends upon activation of PKC and p38 MAP kinase. In conclusion, anabolic and catabolic stimuli regulate facilitated glucose transport in human articular chondrocytes via different effector and signaling mechanisms, and they have distinct effects on glycolysis. chondrocytes; glucose transporter proteins; interleukin-1 ; transforming growth factor- 1 Address for reprint requests and other correspondence: A. R. Shikhman, Division of Arthritis Research, The Scripps Research Institute, MEM 161, 10550 North Torrey Pines Road, La Jolla, CA 92037 (E-mail: shikhman{at}scripps.edu ).