Bone is an active tissue that undergoes constant remodelling. Bone-forming osteoblasts use various energy sources to meet their energy demand, and one of the main energy sources of the cells is glucose. Glucose is transferred into the cell via passive transportation through the protein family of glucose transporters. In disorders of glucose metabolism, such as type 2 diabetes, bone metabolism is disturbed, and patients with type 2 diabetes have an increased risk of fragility fractures. Diabetes is characterized by elevated blood glucose levels, hyperglycaemia, and long-term hyperglycaemia impairs the functions of osteoblasts. The mechanisms responsible for these changes are complicated and not yet fully understood.

In this thesis, multiple glucose transporters were shown to be expressed and have unique functions in rat osteoblasts and their precursors, mesenchymal stromal cells, in vitro. Further, short- and long-term exposures to hyperglycaemia were shown to have different responses in the osteoblast transcriptome. Long-term hyperglycaemia decreased the proliferation of osteoblasts, whereas short-term exposure to hyperglycaemia increased the expression of genes related to osteoblast differentiation and function. In addition, a new recombinant antibody-based immunoassay was developed to measure osteoblast-specific, non-carboxylated form of osteocalcin in human blood samples. Negative associations between type 2 diabetes, blood glucose levels and bone formation were demonstrated with this assay.

In summary, osteoblasts rely on several glucose transporters to ensure sufficient energy, and long-term exposure to high glucose decreases the functions of osteoblasts. A proper balance in glucose metabolism is necessary for proper bone formation.