Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Dec 17:3:153.
doi: 10.3389/fendo.2012.00153. eCollection 2012.

Glucose: an energy currency and structural precursor in articular cartilage and bone with emerging roles as an extracellular signaling molecule and metabolic regulator

Ali Mobasheri  1
Affiliations

Glucose: an energy currency and structural precursor in articular cartilage and bone with emerging roles as an extracellular signaling molecule and metabolic regulator

Ali Mobasheri. Front Endocrinol (Lausanne). .

Abstract

In the skeletal system glucose serves as an essential source of energy for the development, growth, and maintenance of bone and articular cartilage. It is particularly needed for skeletal morphogenesis during embryonic growth and fetal development. Glucose is vital for osteogenesis and chondrogenesis, and is used as a precursor for the synthesis of glycosaminoglycans, glycoproteins, and glycolipids. Glucose sensors are present in tissues and organs that carry out bulk glucose fluxes (i.e., intestine, kidney, and liver). The beta cells of the pancreatic islets of Langerhans respond to changes in blood glucose concentration by varying the rate of insulin synthesis and secretion. Neuronal cells in the hypothalamus are also capable of sensing extracellular glucose. Glucosensing neurons use glucose as a signaling molecule to alter their action potential frequency in response to variations in ambient glucose levels. Skeletal muscle and adipose tissue can respond to changes in circulating glucose but much less is known about glucosensing in bone and cartilage. Recent research suggests that bone cells can influence (and be influenced by) systemic glucose metabolism. This focused review article discusses what we know about glucose transport and metabolism in bone and cartilage and highlights recent studies that have linked glucose metabolism, insulin signaling, and osteocalcin activity in bone. These new findings in bone cells raise important questions about nutrient sensing, uptake, storage and processing mechanisms and how they might contribute to overall energy homeostasis in health and disease. The role of glucose in modulating anabolic and catabolic gene expression in normal and osteoarthritic chondrocytes is also discussed. In summary, cartilage and bone cells are sensitive to extracellular glucose and adjust their gene expression and metabolism in response to varying extracellular glucose concentrations.

Keywords: articular cartilage; bone; extracellular signaling; glucose; glucose transport; glucosensing; hexokinase; osteocalcin.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Members of the extended GLUT/SLC2A family. The radial phylogram was derived from a multiple sequence alignment of the 14 known members of the human GLUT/SLC2A family. The tree was constructed using neighbor-joining analysis of a distance matrix generated with PHYLIP software. The family is divided into three classes of GLUT proteins; class I includes GLUTs1-4 and GLUT14; class II includes the fructose transporter GLUT5, GLUT7, GLUT9 and GLUT11; class III includes GLUT6, GLUT8, GLUT10, GLUT12, and the H+-coupled myo-inositol transporter, HMIT. Adapted and modified from Wood and Trayhurn (2003).
FIGURE 2
FIGURE 2
Glucosensing in the pancreatic β cell. A rise in blood glucose is an important metabolic signal that closes KATP channels, causing membrane depolarization, activation of voltage gated calcium channels (VGCC), free calcium entry and insulin release by exocytosis. It is thought that various additional effectors including phosphatidylinositol-4,5-bisphosphate (PIP2) and acyl CoAs modulate the ATP sensitivity of the KATP channel thereby affecting the coupling of pancreatic cell metabolism to insulin secretion. Adapted from Koster et al. (2005).
FIGURE 3
FIGURE 3
Glucosensing and transport in the gut. This schematic highlights the transport and regulatory mechanisms involved in glucose absorption by enterocytes in the small intestine.
FIGURE 4
FIGURE 4
Putative mechanism of insulin signaling and osteocalcin regulation in osteoblasts. Insulin released from pancreatic β cells binds the insulin receptor (InsR) on osteoblasts, which increases osteocalcin (OC) synthesis. This feeds back in a forward loop to β cells thus stimulating insulin secretion and also regulating glucose homeostasis potentially via GLUTs expressed in osteoblasts. Adapted from Fulzele and Clemens (2012).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bacchetta J., Boutroy S., Guebre-Egziabher F., Juillard L., Drai J., Pelletier S., et al. (2009). The relationship between adipokines, osteocalcin and bone quality in chronic kidney disease. Nephrol. Dial. Transplant. 24 3120–3125 - PubMed
    1. Bird T. A., Davies A., Baldwin S. A., Saklatvala J. (1990). Interleukin 1 stimulates hexose transport in fibroblasts by increasing the expression of glucose transporters. J. Biol. Chem. 265 13578–13583 - PubMed
    1. Buckwalter J. A., Mankin H. J., Grodzinsky A. J. (2005). Articular cartilage and osteoarthritis. Instr. Course Lect. 54 465–480 - PubMed
    1. Burr D. B., Gallant M. A. (2012). Bone remodelling in osteoarthritis. Nat. Rev. Rheumatol. 8 665–673 - PubMed
    1. Burstein D. E., Reder I., Weiser K., Tong T., Pritsker A., Haber R. S. (1998). GLUT1 glucose transporter: a highly sensitive marker of malignancy in body cavity effusions. Mod. Pathol. 11 392–396 - PubMed

LinkOut - more resources

  NODES
Association 1
twitter 2