Abstract

Glucose is an essential source of energy for embryonic growth and fetal development. Glucose is vital for chondroblasts during chondrogenesis and for articular and growth plate chondrocytes during post-natal development. Glucose also plays a key role in extracellular matrix synthesis as a precursor for glycosaminoglycans. The quantity of glucose available to cells in avascular connective tissues such as articular cartilage and intervertebral disc is normally significantly lower than plasma and synovial fluid. Glucose concentrations in cartilage can fluctuate depending on age, physical activity and endocrine status. Chondrocytes are glycolytic cells and must be able to sense the amount of glucose available to them in the extracellular matrix and respond appropriately by adjusting cellular metabolism. Studies are currently in progress to identify glucose sensors in tissues that carry out bulk glucose fluxes (intestine, kidney and liver) where the sodium dependent glucose transporter (SGLT1) has been proposed to be involved. GLUT2 and hexokinase have been identified as important components of the glucose sensing apparatus in the pancreas. Chondrocytes do not appear to express GLUT2 or SGLT1 and glucose sensing in these cells is likely to involve other facilitative glucose transporters. In this article we review selected literature on glucose sensing in the yeast, and in pancreas, kidney, brain and gut in an attempt to understand how different cells sense and respond to alterations in extracellular glucose. We present a new hypothesis that implicates the hypoxia responsive GLUT1 and GLUT3 glucose transporters and the hypoxiainducible transcription factor (HIF-1α) in glucose sensing in chondrocytes.

Keywords: Articular cartilage, intervertebral disc, chondrocyte, glucose sensing, glucose transporter, GLUT1, GLUT3, hypoxia, hypoxia-inducible factor 1, HIF-1