title: Cytokine regulation of facilitated glucose transport in human articular chondrocytes.
abstract: Glucose serves as the major energy substrate and the main precursor for the synthesis of glycosaminoglycans in chondrocytes. Facilitated glucose transport represents the first rate-limiting step in glucose metabolism. This study examines molecular regulation of facilitated glucose transport in normal human articular chondrocytes by proinflammatory cytokines. IL-1beta and TNF-alpha, and to a lesser degree IL-6, accelerate facilitated glucose transport as measured by [(3)H]2-deoxyglucose uptake. IL-1beta induces an increased expression of glucose transporter (GLUT) 1 mRNA and protein, and GLUT9 mRNA. GLUT3 and GLUT8 mRNA are constitutively expressed in chondrocytes and are not regulated by IL-1beta. GLUT2 and GLUT4 mRNA are not detected in chondrocytes. IL-1beta stimulates GLUT1 protein glycosylation and plasma membrane incorporation. IL-1beta regulation of glucose transport in chondrocytes depends on protein kinase C and p38 signal transduction pathways, and does not require phosphoinositide 3-kinase, extracellular signal-related kinase, or c-Jun N-terminal kinase activation. IL-1beta-accelerated glucose transport in chondrocytes is not mediated by endogenous NO or eicosanoids. These results demonstrate that stimulation of glucose transport represents a component of the chondrocyte response to IL-1beta. Two classes of GLUTs are identified in chondrocytes, constitutively expressed GLUT3 and GLUT8, and the inducible GLUT1 and GLUT9.
authors.affiliation: Division of Arthritis Research, The Scripps Research Institute, La Jolla, CA 92037, USA. ashikman@scrippsclinic.com
authors.forename: A R
authors.initials: AR
authors.lastname: Shikhman
authors.forename: D C
authors.initials: DC
authors.lastname: Brinson
authors.forename: J
authors.initials: J
authors.lastname: Valbracht
authors.forename: M K
authors.initials: MK
authors.lastname: Lotz
mesh_terms: D001693:Biological Transport, Active; D002358:Cartilage, Articular / Q000166:cytology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D015777:Eicosanoids / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D006031:Glycosylation; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D015777:Eicosanoids; D051272:Glucose Transporter Type 1; D007375:Interleukin-1; D015850:Interleukin-6; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003847:Deoxyglucose; D005947:Glucose