Distinct pathways regulate facilitated glucose transport in human articular chondrocytes during anabolic and catabolic responses.
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-beta1 (TGF-beta1) vs. the catabolic and proinflammatory cytokine IL-1beta. Both TGF-beta1 and IL-1beta accelerate glucose transport in chondrocytes. Although both IL-1beta and TGF-beta1 enhance glucose transport in chondrocytes to a similar magnitude, IL-1beta induces significantly higher levels of lactate. TGF-beta1-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-1beta-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.
Shikhman
Alexander R
AR
Division of Arthritis Research, The Scripps Research Institute, MEM 161, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. shikhman@scripps.edu
Brinson
Diana C
DC
Lotz
Martin K
MK
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002358:Cartilage, Articular / Q000166:cytology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D007375:Interleukin-1; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; C430746:SLC2A10 protein, human; C495687:SLC2A3 protein, human; C405325:SLC2A8 protein, human; C411811:SLC2A9 protein, human; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D005947:Glucose